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NCT0426xxxx/NCT04267731.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267731</url>
</required_header>
<id_info>
<org_study_id>VMK1</org_study_id>
<nct_id>NCT04267731</nct_id>
</id_info>
<brief_title>Gut Health, Inflammation, Hormones</brief_title>
<official_title>Double Blinded, Randomized, Placebo Controlled Preliminary Pilot Exploratory Investigation Into the Effects of a Bifidobacterium Breve Extract, as VMK223, on Blood Inflammatory Markers, Gut Microbiota Composition and Tolerance in Healthy Adults Ages >50yrs Over a 3-week Period</official_title>
<sponsors>
<lead_sponsor>
<agency>Vemico Ltd.</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
<collaborator>
<agency>University of Roehampton</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>Vemico Ltd.</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Pilot exploratory study on the effect of a Bifidobacterium breve extract, as VMK223, on
plasma inflammatory markers, saliva hormones, gut microbiota and tolerance in females over
50years old. Participants are randomised in one of 4 arms: 0.25g/d VMK223, 0.5g/d VMK223,
0.75g/d VMK223, or placebo.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
The commensal bacteria colonising the gut and making up the microbiome perform a number of
functions through their normal life cycle, which provide benefits to their human hosts in
maintaining homeostasis. The relationship works both ways with the human host providing both
nutrition and an environment for the bacteria to flourish.

Ageing is a natural and multifactorial phenomenon characterised by the accumulation of
degenerative processes that are in turn underpinned by multiple alterations and damage within
molecular pathways. The alterations and damage ultimately compromise cell and tissue
functions. As such, ageing is the most profound risk factor for almost all non-communicable
diseases. Amongst the key processes involved [in ageing], inflammation is of particular
interest, because ageing is characterised by an increase in the concentration of a number of
pro-inflammatory molecules in the circulation, a phenomenon that has been termed
"inflammageing" and is a determinant of the speed of the ageing process and of lifespan.

Amongst the members of the human microbiome, Bifidobacterium spp. are resident microbiota
members throughout the invesstigator's lifetime, with their levels across the life course
aligning with key stages in immune maturation. Bifidobacteria influence this critical
homeostatic development and programming by impacting on specific immune populations and
signalling pathways associated with improved host well-being.

VMK223 is a heat treated Bifidobacterium breve extract, consisting of a low molecular weight
storage polysaccharide that targets the reduction of NF-κB activation.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">December 1, 2019</start_date>
<completion_date type="Actual">February 28, 2023</completion_date>
<primary_completion_date type="Actual">February 28, 2023</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>Double blinded, placebo controlled, randomised dose response study</intervention_model_description>
<primary_purpose>Prevention</primary_purpose>
<masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>Bowel Movements</measure>
<time_frame>3 weeks</time_frame>
<description>self reported daily number of bowel movements</description>
</primary_outcome>
<primary_outcome>
<measure>Stool form</measure>
<time_frame>3 weeks</time_frame>
<description>self reported daily using the bristol 7-point scale (1:hard to 7:watery)</description>
</primary_outcome>
<primary_outcome>
<measure>Flatulence</measure>
<time_frame>3 weeks</time_frame>
<description>self reported daily using a 4-point scale (0: none, 3: severe)</description>
</primary_outcome>
<primary_outcome>
<measure>Bloating</measure>
<time_frame>3 weeks</time_frame>
<description>self reported daily using a 4-point scale (0: none, 3: severe)</description>
</primary_outcome>
<primary_outcome>
<measure>Abdominal pain</measure>
<time_frame>3 weeks</time_frame>
<description>self reported daily using a 4-point scale (0: none, 3: severe)</description>
</primary_outcome>
<secondary_outcome>
<measure>C-Reactive protein</measure>
<time_frame>3 weeks</time_frame>
<description>Plasma measurement</description>
</secondary_outcome>
<secondary_outcome>
<measure>Interleukin-6</measure>
<time_frame>3 weeks</time_frame>
<description>Plasma measurement</description>
</secondary_outcome>
<secondary_outcome>
<measure>Tumor Necrosis Factor alpha</measure>
<time_frame>3 weeks</time_frame>
<description>Plasma measurement</description>
</secondary_outcome>
<secondary_outcome>
<measure>Interleukin-10</measure>
<time_frame>3 weeks</time_frame>
<description>Plasma measurement</description>
</secondary_outcome>
<secondary_outcome>
<measure>Interferon gamma</measure>
<time_frame>3 weeks</time_frame>
<description>Plasma measurement</description>
</secondary_outcome>
<secondary_outcome>
<measure>Human growth hormone</measure>
<time_frame>3 weeks</time_frame>
<description>Plasma measurement</description>
</secondary_outcome>
<secondary_outcome>
<measure>Cortisol</measure>
<time_frame>3 weeks</time_frame>
<description>Saliva</description>
</secondary_outcome>
<secondary_outcome>
<measure>Oestradiol</measure>
<time_frame>3 weeks</time_frame>
<description>saliva</description>
</secondary_outcome>
<secondary_outcome>
<measure>Oestriol</measure>
<time_frame>3 weeks</time_frame>
<description>saliva</description>
</secondary_outcome>
<secondary_outcome>
<measure>Progesterone</measure>
<time_frame>3 weeks</time_frame>
<description>Saliva</description>
</secondary_outcome>
<secondary_outcome>
<measure>Dehydroepiandrosterone</measure>
<time_frame>3 weeks</time_frame>
<description>Saliva</description>
</secondary_outcome>
<other_outcome>
<measure>Positive and Negative Affect Schedule</measure>
<time_frame>1 day</time_frame>
<description>Self reported positive/negative perception 5-point scale questionnaire. The positive affect score range is 10-50 and the negative affect score range is 10-50. Higher scores represent higher effect.</description>
</other_outcome>
<number_of_arms>4</number_of_arms>
<enrollment type="Actual">30</enrollment>
<condition>Aging Well</condition>
<arm_group>
<arm_group_label>Placebo</arm_group_label>
<arm_group_type>Placebo Comparator</arm_group_type>
<description>Cellulose 0.75g per day</description>
</arm_group>
<arm_group>
<arm_group_label>Low dose</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>0.25g VMK223 per day</description>
</arm_group>
<arm_group>
<arm_group_label>Middle dose</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>0.5g VMK223 per day</description>
</arm_group>
<arm_group>
<arm_group_label>High dose</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>0.75g VMK223 per day</description>
</arm_group>
<intervention>
<intervention_type>Dietary Supplement</intervention_type>
<intervention_name>VMK223</intervention_name>
<description>Heat killed and purified Bifidobacterium breve polysaccharide-based extract</description>
<arm_group_label>High dose</arm_group_label>
<arm_group_label>Low dose</arm_group_label>
<arm_group_label>Middle dose</arm_group_label>
<other_name>Bifidobacterium breve extract/lysate</other_name>
</intervention>
<intervention>
<intervention_type>Dietary Supplement</intervention_type>
<intervention_name>Cellulose</intervention_name>
<description>Bulking agent in food production without probiotic properties</description>
<arm_group_label>Placebo</arm_group_label>
<other_name>Cellulose microcrystalline</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Adults, aged 50 years to 65 years

- Not dieting within the last month and not having lost >5% body weight in the previous
year

- Not increased physical activity levels in the past 2-4 weeks or intending to modify
them during the study

- Understands and is willing, able and likely to comply with all study procedures and
restriction including being willing to follow the nutritional advice

- Able to eat most everyday foods

- Habitually consumes three standard meals a day

Exclusion Criteria:

- Significant health problems (e.g. hypercholesterolaemia, diabetes, GI disorders)

- Taking any medication or supplements known to affect immune system function within the
past month and/or during the study

- Pregnant, planning to become pregnant or breastfeeding

- History of anaphylaxis to food

- Known allergies or intolerance to foods and/or to the study materials (or closely
related compounds) or any of their stated ingredients

- Volunteers self-reporting currently dieting or having lost >5% body weight in the
previous year

- Participants with abnormal eating behaviour

- Participation in another experimental study or receipt of an investigational
drug/product within 30 days of the screening visit

- Volunteers who have significantly changed their physical activity in the past 2-4
weeks or who intend to change them during the study

- Participants receiving systemic or local treatment likely to interfere with the
evaluation of the study parameters

- Participants on specific food avoidance diets

- Participants who work in appetite or feeding related areas
</textblock>
</criteria>
<gender>Female</gender>
<gender_based>Yes</gender_based>
<minimum_age>50 Years</minimum_age>
<maximum_age>65 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Adele Costabile</last_name>
<role>Principal Investigator</role>
<affiliation>University of Roehampton</affiliation>
</overall_official>
<location>
<facility>
<name>University of Roehampton</name>
<address>
<city>London</city>
<zip>SW15 5PJ</zip>
<country>United Kingdom</country>
</address>
</facility>
</location>
<location_countries>
<country>United Kingdom</country>
</location_countries>
<verification_date>April 2022</verification_date>
<study_first_submitted>February 6, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>April 25, 2023</last_update_submitted>
<last_update_submitted_qc>April 25, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">April 26, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Gut microbiota</keyword>
<keyword>Postbiotics</keyword>
<keyword>Inflammation</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Inflammation</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>Yes</sharing_ipd>
<ipd_description>De-identified participants data for all outcomes will be made available.</ipd_description>
<ipd_info_type>Study Protocol</ipd_info_type>
<ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
<ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
<ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
<ipd_info_type>Analytic Code</ipd_info_type>
<ipd_time_frame>3 months after study completion</ipd_time_frame>
<ipd_access_criteria>Based on a data sharing agreement, a review panel will decide on all data sharing request</ipd_access_criteria>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Pilot exploratory study on the effect of a Bifidobacterium breve extract, as VMK223, on
plasma inflammatory markers, saliva hormones, gut microbiota and tolerance in females over
50years old. Participants are randomised in one of 4 arms: 0.25g/d VMK223, 0.5g/d VMK223,
0.75g/d VMK223, or placebo.
The commensal bacteria colonising the gut and making up the microbiome perform a number of
functions through their normal life cycle, which provide benefits to their human hosts in
maintaining homeostasis. The relationship works both ways with the human host providing both
nutrition and an environment for the bacteria to flourish.
Ageing is a natural and multifactorial phenomenon characterised by the accumulation of
degenerative processes that are in turn underpinned by multiple alterations and damage within
molecular pathways. The alterations and damage ultimately compromise cell and tissue
functions. As such, ageing is the most profound risk factor for almost all non-communicable
diseases. Amongst the key processes involved [in ageing], inflammation is of particular
interest, because ageing is characterised by an increase in the concentration of a number of
pro-inflammatory molecules in the circulation, a phenomenon that has been termed
"inflammageing" and is a determinant of the speed of the ageing process and of lifespan.
Amongst the members of the human microbiome, Bifidobacterium spp. are resident microbiota
members throughout the invesstigator's lifetime, with their levels across the life course
aligning with key stages in immune maturation. Bifidobacteria influence this critical
homeostatic development and programming by impacting on specific immune populations and
signalling pathways associated with improved host well-being.
VMK223 is a heat treated Bifidobacterium breve extract, consisting of a low molecular weight
storage polysaccharide that targets the reduction of NF-κB activation.
Inclusion Criteria:
- Adults, aged 50 years to 65 years
- Not dieting within the last month and not having lost >5% body weight in the previous
year
- Not increased physical activity levels in the past 2-4 weeks or intending to modify
them during the study
- Understands and is willing, able and likely to comply with all study procedures and
restriction including being willing to follow the nutritional advice
- Able to eat most everyday foods
- Habitually consumes three standard meals a day
Exclusion Criteria:
- Significant health problems (e.g. hypercholesterolaemia, diabetes, GI disorders)
- Taking any medication or supplements known to affect immune system function within the
past month and/or during the study
- Pregnant, planning to become pregnant or breastfeeding
- History of anaphylaxis to food
- Known allergies or intolerance to foods and/or to the study materials (or closely
related compounds) or any of their stated ingredients
- Volunteers self-reporting currently dieting or having lost >5% body weight in the
previous year
- Participants with abnormal eating behaviour
- Participation in another experimental study or receipt of an investigational
drug/product within 30 days of the screening visit
- Volunteers who have significantly changed their physical activity in the past 2-4
weeks or who intend to change them during the study
- Participants receiving systemic or local treatment likely to interfere with the
evaluation of the study parameters
- Participants on specific food avoidance diets
- Participants who work in appetite or feeding related areas
|
NCT0426xxxx/NCT04267744.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267744</url>
</required_header>
<id_info>
<org_study_id>201908180</org_study_id>
<nct_id>NCT04267744</nct_id>
</id_info>
<brief_title>Remote Monitoring of Multiple Indicators of Heart Failure</brief_title>
<official_title>Usability and Utility Assessment of Passive Remote Monitoring of Multiple Novel Indicators of Heart Failure</official_title>
<sponsors>
<lead_sponsor>
<agency>Washington University School of Medicine</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Healthcare Innovation Lab</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>MYIA Labs, Inc.</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>Washington University School of Medicine</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This study is intended to evaluate the impact of passive continuous remote patient monitoring
to assist in the outpatient management of heart failure (HF) patients.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
The study will prospectively evaluate the usability, utility, and efficacy of remote
monitoring using novel noninvasive technologies in HF patients in an outpatient setting.
Investigators will gather dynamic, longitudinal data from multiple sensors, in addition to
patient-reported and physician-reported data. Both the patient interface through interactions
with the sensors and mobile application, and the clinician interface through the monitoring
portal, will be evaluated for usability, utility and efficacy.

Patients will be recruited for the study from the Barnes Jewish Hospital Advanced Heart
Failure Clinic. Eligible individuals will receive onboarding instructions and a study
schedule detailing the required surveys and clinical activities they will be asked to
complete over a period of 7 months. In addition to onboarding instructions and a study
schedule, individuals will have the kit of sensors shipped to their home.

After the Myia Home Hub and Myia Sensor Suite are set up, data will begin to be transmitted.
Following a run in period where data is collected and delivered but not acted upon by
clinicians all eligible participants will move forward with 6 month interactive study
monitoring.

In addition to obtaining questionnaires and using the devices in the Myia kit, participants
will also be asked to obtain their blood pressure and weight daily.

During the course of the study, outpatient health status data for the group will be
collected, summarized and delivered to clinicians in an electronic dashboard. The format and
content of the data dashboard will be updated based on user feedback throughout the study.
Required changes deemed appropriate by the healthcare team will be incorporated into the
software platform alongside any standard updates.
</textblock>
</detailed_description>
<overall_status>Enrolling by invitation</overall_status>
<start_date type="Actual">February 11, 2020</start_date>
<completion_date type="Anticipated">March 1, 2024</completion_date>
<primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<intervention_model_description>Device: Myia Health platform and in-home suite of devices®</intervention_model_description>
<primary_purpose>Supportive Care</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Myia Platform feasibility: questionnaire</measure>
<time_frame>From baseline to 6 months (final)</time_frame>
<description>Patient perception of the Myia Platform will be assessed during the study using a structured questionnaire, delivered either electronically or by paper to patients by research staff.
Patient Platform satisfaction/usability/utility questionnaire: The formal title of the questionnaire is 'Check In Survey' and it consists of 17 questions with scaled options, 1-7 (1=most positive, 7=most negative) and it is administered at 3 time points. The lower the overall total the more positive the patient rating of the Myia Platform.</description>
</primary_outcome>
<secondary_outcome>
<measure>Persistence of minimally useful data acquisition of a remote patient monitoring platform to monitor the health status of patients living with heart failure.</measure>
<time_frame>From baseline to 6 months time (final)</time_frame>
<description>Acquisition of minimally useful data profile: Weeks where minimally useful data profile collected/total number of weeks. This endpoint will be defined retrospectively by the clinical team.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Persistence of daily data acquisition of a remote patient monitoring platform to monitor the health status of patients living with heart failure.</measure>
<time_frame>From baseline to 6 months time (final)</time_frame>
<description>Acquisition of any data point daily: Days with >1 data point collected/total number of days</description>
</secondary_outcome>
<secondary_outcome>
<measure>Persistence of weekly data acquisition of a remote patient monitoring platform to monitor the health status of patients living with heart failure.</measure>
<time_frame>From baseline to 6 months time (final)</time_frame>
<description>Acquisition of any data point weekly: Weeks with >1 data point collected/total number of weeks</description>
</secondary_outcome>
<secondary_outcome>
<measure>Persistence of vital sign data acquisition of a remote patient monitoring platform to monitor the health status of patients living with heart failure.</measure>
<time_frame>From baseline to 6 months time (final)</time_frame>
<description>Acquisition of continuous vital sign data variables daily: Days with >1 data point collected/total number of days</description>
</secondary_outcome>
<secondary_outcome>
<measure>Persistence of greater than 1 data point per week data acquisition of a remote patient monitoring platform to monitor the health status of patients living with heart failure.</measure>
<time_frame>From baseline to 6 months time (final)</time_frame>
<description>Acquisition of continuous data variables weekly: Weeks with >1 data point collected/total number of weeks</description>
</secondary_outcome>
<secondary_outcome>
<measure>Medication management: total number of medication changes</measure>
<time_frame>From baseline to 6 months time (final)</time_frame>
<description>Absolute count of heart failure medication changes per patient. This metric will be calculated on a per patient level. Any change in dose or frequency of medication will be considered a medication change.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Medication management: length of time to medication change</measure>
<time_frame>From baseline to 6 months time (final)</time_frame>
<description>Mean time to heart failure medication change per patient. Average time interval between a change to 1 or more heart failure drugs between the baseline and 6 month time points.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Medication management: target dose</measure>
<time_frame>From baseline to 6 months time (final)</time_frame>
<description>Distance from target dose of heart failure medication (< 50% target dose, 50%-75% of target dose, 75%-100% of target dose)
The baseline use and dose of the following heart failure medication categories will be examined for each patient at baseline:
Beta Blockers Digoxin ACE, ARB, ARNIs Hydralazine Nitrates Loop Diuretics Aldosterone Antagonists For each medication class, the presence and absence of absolute contraindications will be determined based on documentation in the medical record or as ascertained by study investigators. For each patient and each medication, available dose information will be reviewed in reference to recommended target doses by clinical practice guidelines. Distance to target dose will be assessed at baseline and follow-up. The difference in the relative proportion of people in the target dose categories will be compared between treatment and usual care groups.</description>
</secondary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Anticipated">199</enrollment>
<condition>Heart Failure</condition>
<arm_group>
<arm_group_label>Remote patient monitoring</arm_group_label>
<arm_group_type>Other</arm_group_type>
<description>After consenting to the study, the Myia in-home suite of devices, and mobile phone application if the patient owns a smart phone, will be provided to all recruited patients. The data flowing from the Myia platform will be available to clinicians and patients for the duration of the pilot and utilized to complete study activities.
Patients enrolled will transmit daily vital sign data to the Myia Health remote patient monitoring platforms for clinical review.
Enrolled patients will complete medication change/compliance survey monthly to assess for medication changes.
Enrolled patients will complete symptomatic assessments (KCCQ-12) at 0, 3, and 6 months.
Enrolled patients will complete a Check-In survey to assess utility and usability of the intervention at the 2, 4, and 6 month timepoints</description>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Myia Health® remote patient monitoring unblinded treatment arm</intervention_name>
<description>After consenting to the study, the Myia in-home suite of devices will be provided to all recruited patients. The data flowing from the Myia platform will be available to clinicians and patients for the duration of the pilot and utilized to complete study activities.
Device: Myia Health platform and in-home suite of devices®:
Emfit Ballistocardiograph® Withings Connected Scale® VitalScout (VivaLink) ECG Accelerometer® Omron Blood Pressure Monitor® (Sphygmomanometer) Cradlepoint - Hotspot / Adaptor® (LTE Connection) Samsung Galaxy Tab A 8.0"® (User Interface)</description>
<arm_group_label>Remote patient monitoring</arm_group_label>
<other_name>Myia Health platform and in-home suite of devices®</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Outpatients cared for by BJH Advanced Heart Failure Clinic, where BJH is their primary
cardiology care team

2. Age ≥ 18 years old at time of consent

3. HFrEF diagnosis in the BJH Advanced Heart Failure Clinic medical record

4. Has had an ER presentation or hospitalization related to their heart failure in last
12 months prior to enrollment

5. Most recent recorded Left Ventricular Ejection Fraction (LVEF) of < 50% and at least 1
recorded LVEF of < 40%

6. Scheduled clinic visit 90- 180 days after study enrollment.

7. NYHA Class II-IV

8. Sleeps in the same bed at ≥ 4 days per week

9. Able to ambulate

10. Willingness to complete the required surveys, measurements and study activities

Exclusion Criteria:

1. Current ventricular assist device or cardiac transplant.

2. Currently listed for cardiac transplantation

3. End-Stage Renal Disease on chronic dialysis

4. Malignancy diagnosis undergoing active treatment

5. Hospice or palliative care

6. Living in a skilled nursing facility or other chronic care facility (ambulatory
patients only)

7. Self-reported pregnancy or planned pregnancy in the next 6 months

8. Inability or unwillingness to consent and/or follow requirements of the study

9. Planned major surgeries or procedures requiring hospitalization in next 6 months

10. Use of Lifevest or other worn device that may affect ballistocardiogram measurements

11. Patient weight > 385 lbs at time of enrollment

12. Life expectancy <1 year
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Greg Ewald, MD</last_name>
<role>Principal Investigator</role>
<affiliation>Washington University School of Medicine</affiliation>
</overall_official>
<location>
<facility>
<name>Washington University School of Medicine</name>
<address>
<city>Saint Louis</city>
<state>Missouri</state>
<zip>63110</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<reference>
<citation>Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R, de Ferranti SD, Ferguson JF, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Lutsey PL, Mackey JS, Matchar DB, Matsushita K, Mussolino ME, Nasir K, O'Flaherty M, Palaniappan LP, Pandey A, Pandey DK, Reeves MJ, Ritchey MD, Rodriguez CJ, Roth GA, Rosamond WD, Sampson UKA, Satou GM, Shah SH, Spartano NL, Tirschwell DL, Tsao CW, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation. 2018 Mar 20;137(12):e67-e492. doi: 10.1161/CIR.0000000000000558. Epub 2018 Jan 31. No abstract available. Erratum In: Circulation. 2018 Mar 20;137(12 ):e493.</citation>
<PMID>29386200</PMID>
</reference>
<reference>
<citation>Chen J, Normand SL, Wang Y, Krumholz HM. National and regional trends in heart failure hospitalization and mortality rates for Medicare beneficiaries, 1998-2008. JAMA. 2011 Oct 19;306(15):1669-78. doi: 10.1001/jama.2011.1474.</citation>
<PMID>22009099</PMID>
</reference>
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<citation>Wolfel EE. Can we predict and prevent the onset of acute decompensated heart failure? Circulation. 2007 Oct 2;116(14):1526-9. doi: 10.1161/CIRCULATIONAHA.107.729608. No abstract available.</citation>
<PMID>17909113</PMID>
</reference>
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<citation>Ping W, Jin-Gang W, Xiao-Bo S, Wei H. The research of telemedicine system based on embedded computer. Conf Proc IEEE Eng Med Biol Soc. 2005;2006:114-7. doi: 10.1109/IEMBS.2005.1616355.</citation>
<PMID>17282124</PMID>
</reference>
<reference>
<citation>Abraham WT, Adamson PB, Bourge RC, Aaron MF, Costanzo MR, Stevenson LW, Strickland W, Neelagaru S, Raval N, Krueger S, Weiner S, Shavelle D, Jeffries B, Yadav JS; CHAMPION Trial Study Group. Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial. Lancet. 2011 Feb 19;377(9766):658-66. doi: 10.1016/S0140-6736(11)60101-3. Erratum In: Lancet. 2012 Feb 4;379(9814):412.</citation>
<PMID>21315441</PMID>
</reference>
<reference>
<citation>Boehmer JP, Hariharan R, Devecchi FG, Smith AL, Molon G, Capucci A, An Q, Averina V, Stolen CM, Thakur PH, Thompson JA, Wariar R, Zhang Y, Singh JP. A Multisensor Algorithm Predicts Heart Failure Events in Patients With Implanted Devices: Results From the MultiSENSE Study. JACC Heart Fail. 2017 Mar;5(3):216-225. doi: 10.1016/j.jchf.2016.12.011.</citation>
<PMID>28254128</PMID>
</reference>
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<citation>Weng SF, Reps J, Kai J, Garibaldi JM, Qureshi N. Can machine-learning improve cardiovascular risk prediction using routine clinical data? PLoS One. 2017 Apr 4;12(4):e0174944. doi: 10.1371/journal.pone.0174944. eCollection 2017.</citation>
<PMID>28376093</PMID>
</reference>
<reference>
<citation>Chan PS, Oetgen WJ, Spertus JA. The Improving Continuous Cardiac Care (IC(3)) program and outpatient quality improvement. Am J Med. 2010 Mar;123(3):217-9. doi: 10.1016/j.amjmed.2009.09.019. No abstract available. Erratum In: Am J Med. 2010 Oct;123(10):e13.</citation>
<PMID>20193826</PMID>
</reference>
<reference>
<citation>Ong MK, Romano PS, Edgington S, Aronow HU, Auerbach AD, Black JT, De Marco T, Escarce JJ, Evangelista LS, Hanna B, Ganiats TG, Greenberg BH, Greenfield S, Kaplan SH, Kimchi A, Liu H, Lombardo D, Mangione CM, Sadeghi B, Sadeghi B, Sarrafzadeh M, Tong K, Fonarow GC; Better Effectiveness After Transition-Heart Failure (BEAT-HF) Research Group. Effectiveness of Remote Patient Monitoring After Discharge of Hospitalized Patients With Heart Failure: The Better Effectiveness After Transition -- Heart Failure (BEAT-HF) Randomized Clinical Trial. JAMA Intern Med. 2016 Mar;176(3):310-8. doi: 10.1001/jamainternmed.2015.7712. Erratum In: JAMA Intern Med. 2016 Apr;176(4):568. JAMA Intern Med. 2016 Jun 1;176(6):871.</citation>
<PMID>26857383</PMID>
</reference>
<reference>
<citation>Krumholz HM, Merrill AR, Schone EM, Schreiner GC, Chen J, Bradley EH, Wang Y, Wang Y, Lin Z, Straube BM, Rapp MT, Normand SL, Drye EE. Patterns of hospital performance in acute myocardial infarction and heart failure 30-day mortality and readmission. Circ Cardiovasc Qual Outcomes. 2009 Sep;2(5):407-13. doi: 10.1161/CIRCOUTCOMES.109.883256. Epub 2009 Jul 9.</citation>
<PMID>20031870</PMID>
</reference>
<reference>
<citation>Chun S, Tu JV, Wijeysundera HC, Austin PC, Wang X, Levy D, Lee DS. Lifetime analysis of hospitalizations and survival of patients newly admitted with heart failure. Circ Heart Fail. 2012 Jul 1;5(4):414-21. doi: 10.1161/CIRCHEARTFAILURE.111.964791. Epub 2012 May 2.</citation>
<PMID>22556322</PMID>
</reference>
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<citation>Tung YC, Chou SH, Liu KL, Hsieh IC, Wu LS, Lin CP, Wen MS, Chu PH. Worse Prognosis in Heart Failure Patients with 30-Day Readmission. Acta Cardiol Sin. 2016 Nov;32(6):698-707. doi: 10.6515/acs20151113a.</citation>
<PMID>27899857</PMID>
</reference>
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<citation>Sud M, Yu B, Wijeysundera HC, Austin PC, Ko DT, Braga J, Cram P, Spertus JA, Domanski M, Lee DS. Associations Between Short or Long Length of Stay and 30-Day Readmission and Mortality in Hospitalized Patients With Heart Failure. JACC Heart Fail. 2017 Aug;5(8):578-588. doi: 10.1016/j.jchf.2017.03.012. Epub 2017 May 10.</citation>
<PMID>28501521</PMID>
</reference>
<reference>
<citation>Holland R, Rechel B, Stepien K, Harvey I, Brooksby I. Patients' self-assessed functional status in heart failure by New York Heart Association class: a prognostic predictor of hospitalizations, quality of life and death. J Card Fail. 2010 Feb;16(2):150-6. doi: 10.1016/j.cardfail.2009.08.010. Epub 2009 Oct 22.</citation>
<PMID>20142027</PMID>
</reference>
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<citation>Soto GE, Jones P, Weintraub WS, Krumholz HM, Spertus JA. Prognostic value of health status in patients with heart failure after acute myocardial infarction. Circulation. 2004 Aug 3;110(5):546-51. doi: 10.1161/01.CIR.0000136991.85540.A9. Epub 2004 Jul 19.</citation>
<PMID>15262843</PMID>
</reference>
<reference>
<citation>Green CP, Porter CB, Bresnahan DR, Spertus JA. Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure. J Am Coll Cardiol. 2000 Apr;35(5):1245-55. doi: 10.1016/s0735-1097(00)00531-3.</citation>
<PMID>10758967</PMID>
</reference>
<reference>
<citation>Greene SJ, Fonarow GC, Butler J. Reply: Titration of Guideline-Directed Medical Therapy Improves Patient-Centered Outcomes in Heart Failure With Reduced Ejection Fraction. J Am Coll Cardiol. 2019 Sep 10;74(10):1426-1427. doi: 10.1016/j.jacc.2019.06.061. No abstract available.</citation>
<PMID>31488284</PMID>
</reference>
<verification_date>April 2023</verification_date>
<study_first_submitted>February 5, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>April 24, 2023</last_update_submitted>
<last_update_submitted_qc>April 24, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">April 26, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>NYHA II-IV</keyword>
<keyword>Reduced Ejection Fraction</keyword>
<keyword>Cardiology</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Heart Failure</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This study is intended to evaluate the impact of passive continuous remote patient monitoring
to assist in the outpatient management of heart failure (HF) patients.
The study will prospectively evaluate the usability, utility, and efficacy of remote
monitoring using novel noninvasive technologies in HF patients in an outpatient setting.
Investigators will gather dynamic, longitudinal data from multiple sensors, in addition to
patient-reported and physician-reported data. Both the patient interface through interactions
with the sensors and mobile application, and the clinician interface through the monitoring
portal, will be evaluated for usability, utility and efficacy.
Patients will be recruited for the study from the Barnes Jewish Hospital Advanced Heart
Failure Clinic. Eligible individuals will receive onboarding instructions and a study
schedule detailing the required surveys and clinical activities they will be asked to
complete over a period of 7 months. In addition to onboarding instructions and a study
schedule, individuals will have the kit of sensors shipped to their home.
After the Myia Home Hub and Myia Sensor Suite are set up, data will begin to be transmitted.
Following a run in period where data is collected and delivered but not acted upon by
clinicians all eligible participants will move forward with 6 month interactive study
monitoring.
In addition to obtaining questionnaires and using the devices in the Myia kit, participants
will also be asked to obtain their blood pressure and weight daily.
During the course of the study, outpatient health status data for the group will be
collected, summarized and delivered to clinicians in an electronic dashboard. The format and
content of the data dashboard will be updated based on user feedback throughout the study.
Required changes deemed appropriate by the healthcare team will be incorporated into the
software platform alongside any standard updates.
Inclusion Criteria:
1. Outpatients cared for by BJH Advanced Heart Failure Clinic, where BJH is their primary
cardiology care team
2. Age ≥ 18 years old at time of consent
3. HFrEF diagnosis in the BJH Advanced Heart Failure Clinic medical record
4. Has had an ER presentation or hospitalization related to their heart failure in last
12 months prior to enrollment
5. Most recent recorded Left Ventricular Ejection Fraction (LVEF) of < 50% and at least 1
recorded LVEF of < 40%
6. Scheduled clinic visit 90- 180 days after study enrollment.
7. NYHA Class II-IV
8. Sleeps in the same bed at ≥ 4 days per week
9. Able to ambulate
10. Willingness to complete the required surveys, measurements and study activities
Exclusion Criteria:
1. Current ventricular assist device or cardiac transplant.
2. Currently listed for cardiac transplantation
3. End-Stage Renal Disease on chronic dialysis
4. Malignancy diagnosis undergoing active treatment
5. Hospice or palliative care
6. Living in a skilled nursing facility or other chronic care facility (ambulatory
patients only)
7. Self-reported pregnancy or planned pregnancy in the next 6 months
8. Inability or unwillingness to consent and/or follow requirements of the study
9. Planned major surgeries or procedures requiring hospitalization in next 6 months
10. Use of Lifevest or other worn device that may affect ballistocardiogram measurements
11. Patient weight > 385 lbs at time of enrollment
12. Life expectancy <1 year
|
NCT0426xxxx/NCT04267757.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267757</url>
</required_header>
<id_info>
<org_study_id>zagazig 2</org_study_id>
<nct_id>NCT04267757</nct_id>
</id_info>
<brief_title>Transperineal Repair of Primary Obstetric Rectovaginal Fistulas</brief_title>
<official_title>Transperineal Repair of Primary Obstetric Rectovaginal Fistulas With Fecal Incontinence Using Fistulectomy, Sphincteroplasty and With or Without Bulbocavernosus Muscle Flap:Surgical Pitfalls and Prevention of Recurrence</official_title>
<sponsors>
<lead_sponsor>
<agency>Zagazig University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Zagazig University</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Introduction: A rectovaginal fistula (RVF) is an epithelium-lined abnormal tract between the
rectum and the vagina and is often a challenging problem for both the patients and to the
surgeons. In literature, there is still debate regarding the best treatment options for
rectovaginal fistulas.

Aim: To assess the results of the treatment of rectovaginal fistulas with incontinence and
impaired anal tonus using fistulectomy, sphincteroplasty with or without bulbocavernosus
muscle (Martius) flap.

Materials and Methods: A total of 22 consecutive patients with simple RVFs were included and
assigned to transperineal repair. The patients were divided into two groups , group1: with
Martius flap; group2: without Martius flap .Postoperatively, patients were followed up for
one year at the outpatient clinic or through telephone interviews with specific questionnaires
to collect information on the status of fecal control, flatus, or fecal leakage from the
vagina.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Introduction:

Rectovaginal fistulas represent an often devastating condition in patients and a challenge for
surgeons because of their irritating and embarrassing symptoms and high failure rate after
repair.Patients with rectovaginal fistulas typically present with complaints of passage of
flatus or feces from the vagina with painful skin excoriation.

(1) The most common etiological cause of rectovaginal fistulas is obstetrical trauma. When
obstructed labor is unrelieved, the presenting fetal part is impacted against the soft
tissues of the pelvis leading to ischemic vascular injury and subsequent tissue necrosis and
fistula formation. Other predisposing factors include forceps delivery, midline episiotomy,
and third or fourth-degree perineal lacerations.( 2).

Evaluation of a patient with rectovaginal fistula includes a detailed history, examination of
the rectum, vagina, and perineal body. The perineal body is often thin or nearly nonexistent
in patients with sphincter injuries secondary to obstetrical trauma. Endoanal ultrasonography
and pelvic Magnetic Resonance Imaging (MRI) to confirm sphincter injury and may provide
valuable information before a planned repair. MR is the modality of choice for disease
staging (sensitivity 91%) (3).

( Sagittal T2 MR imaging shows communication between the rectum tumor and the vagina) The
experience of the surgeon and the previous attempts at repair are also important factors of
the success rate of the operations [4)

There are various operative procedures, such as the advancement flap, sphincteroplasty and
fistulectomy, coloanal anastomosis,and gracilis muscle repair to manage rectovaginal fistulas
[5].

The choice of the operative technique greatly depends on the status of the fistula and the
etiological rationale behind this medical complication [6.].

In this study, we have compared the outcomes of the fistulectomy and sphincteroplasty
procedures with or without concomitant bulbocavernosus flap. All patients were incontinent
and felt to have impaired anal tonus.

Patients and method:

Study design:

This prospective study involved 22 patients diagnosed with simple rectovaginal fistula from
January 2018 to January 2019 at the General surgical department, faculty of medicine Zagazig
University, Egypt. This study was approved by the institutional ethics board of our hospital.
All patients who participated in the study provided informed consent.

rectovaginal examination, endoanal ultrasonography, and pelvic MRI findings were collected to
assess the extension of the fistula. Colonoscopy was performed in selected patients with
severe bowel symptoms such as bloody diarrhea to exclude inflammatory bowel disease.
Decisions regarding operations were made cautiously and involved the whole medical team. All
cases underwent fistulectomy, sphincteroplasty and with or without bulbocavernosus flap
technique.All patients were evaluated for incontinence using Wexner Incontinence Score (WIS)
[7) Method of randomization: simple randomization with a balance.

Patient selection:

Inclusion criteria:

1. Rectovaginal fistula caused by obstetric problems

2. Female >20 years

Exclusion criteria:

1. other causes of rectovaginal fistula as Crohn's disease or malignant fistula

2. complex and recurrent fistula

Three patients did not undergo surgery. One because of patient's choice, one because of
minimal symptoms and one because fistula healed after medical therapy.

Methods:

Patients were given a mechanical bowel preparation the day before surgery and an enema on the
morning of the operation. The patient was placed in the lithotomy position under spinal
anesthesia. Antibiotics in the form of third generation cephalosporin and 500 mg of
Metronidazole were given.

Sub mucosal lidocain 5% in adrenalized saline at a ratio of 1: 100 000 was injected around
the fistula. Surgical excision of the fistula using scalpel was performed. Biopsies of rectal
mucosa and the fistula margin were also obtained for pathological evaluation to exclude an
underlying Crohn's disease or malignancy. A transverse perineal incision was done. Dissection
of the internal sphincter fibers away from the external sphincter fibers was performed,
allowing a tension free rectal closure at the fistulous site (Dissection of internal
sphincter fi bers from external sphincter fi ber s.). Closure of the fistulous opening at the
rectal side was done using Vicryl 3/0 sutures. This was followed by suturing of the
rectovaginal septum to the internal sphincteric fibers using Vicryl 3/0 sutures (Suturing of
internal sphincter fi bers to the rectovaginal septu m.). The bulbocavernosus muscle flap was
harvested from the left side in all patients at its anterior part, preserving the
posteroexternal vascular pedicle (Posterior muscle repair), through the same incision, and
sutured across the rectum to its counterpart on the other side (Vaginal advancement fl a p.&
Fig. 1 a The fistulae are indicated by the two forceps passing through them; b The finger
demonstrates the large recto-vaginal orifice) using 2/0 Vicryl sutures. The vaginal flap was
advanced at the fistula site and sutured to the perineal skin using Vicryl 3/0 sutures
(Preparation of the bulbocavernosus fl a p.& Fig. 3 a, b After a right labial incision, the
bulbocavernous muscle and the surrounding fibroadipose tissue were carefully mobilized,
avoiding possible damage of the postero-external vascular pedicle& Fig. 4 A subcutaneous
tunnel connecting the two incisions was created after transecting superior to the
bulbocavernous muscle& Fig. 5 The final set-up with the interrupted absorbable sutures over
the vaginal closure after sectioning of the longitudinal vaginal septum. The bulbocavernous
muscle is clearly visible after the lay open of the perineovaginal tract).

No suction drain was used. No covering stoma was done. Postoperatively, Soft, stool was
provided in the postoperative period at least for two weeks with the help of clear liquid
diet, plenty fluid intake, and the use of stool softeners. Oral broad-spectrum antibiotic
therapy was given for 3-5 days postoperatively. Sexual activity or any physical activities
more strenuous than a slow walk were avoided by the patients for three weeks after the
surgery. Follow up period up to one year.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">January 1, 2018</start_date>
<completion_date type="Actual">January 1, 2019</completion_date>
<primary_completion_date type="Actual">January 1, 2019</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>Single (Participant)</masking>
</study_design_info>
<primary_outcome>
<measure>rectovaginal fistula repair with or without Martius flap</measure>
<time_frame>1 year</time_frame>
<description>detect recurrence in rectovaginal fistula repair with or without Martius flap</description>
</primary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">4</enrollment>
<condition>Recto Vaginal Fistula</condition>
<arm_group>
<arm_group_label>group 1</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>RVF with Martius flap</description>
</arm_group>
<arm_group>
<arm_group_label>group 2</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>RVF without Martius flap</description>
</arm_group>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>rectovaginal fistula repair with Martius flap</intervention_name>
<description>rectovaginal fistula repair with Martius flap</description>
<arm_group_label>group 1</arm_group_label>
<arm_group_label>group 2</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- 1- Rectovaginal fistula caused by obstetric problems 2- Female >20 years

Exclusion Criteria:

1. other causes of rectovaginal fistula as Crohn's disease or malignant fistula

2. complex and recurrent fistula -
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>20 Years</minimum_age>
<maximum_age>50 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>tamer A. alnaimy, MD</last_name>
<role>Principal Investigator</role>
<affiliation>Zagazig University</affiliation>
</overall_official>
<location>
<facility>
<name>Tamer Alsaied Alnaimy</name>
<address>
<city>Zagazig</city>
<state>Sharkia</state>
<zip>055</zip>
<country>Egypt</country>
</address>
</facility>
</location>
<location_countries>
<country>Egypt</country>
</location_countries>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 9, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 12, 2020</last_update_submitted>
<last_update_submitted_qc>February 12, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Zagazig University</investigator_affiliation>
<investigator_full_name>Tamer Alsaied Alnaimy</investigator_full_name>
<investigator_title>assistant professour</investigator_title>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Rectovaginal Fistula</mesh_term>
<mesh_term>Vaginal Fistula</mesh_term>
<mesh_term>Fistula</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Introduction: A rectovaginal fistula (RVF) is an epithelium-lined abnormal tract between the
rectum and the vagina and is often a challenging problem for both the patients and to the
surgeons. In literature, there is still debate regarding the best treatment options for
rectovaginal fistulas.
Aim: To assess the results of the treatment of rectovaginal fistulas with incontinence and
impaired anal tonus using fistulectomy, sphincteroplasty with or without bulbocavernosus
muscle (Martius) flap.
Materials and Methods: A total of 22 consecutive patients with simple RVFs were included and
assigned to transperineal repair. The patients were divided into two groups , group1: with
Martius flap; group2: without Martius flap .Postoperatively, patients were followed up for
one year at the outpatient clinic or through telephone interviews with specific questionnaires
to collect information on the status of fecal control, flatus, or fecal leakage from the
vagina.
Introduction:
Rectovaginal fistulas represent an often devastating condition in patients and a challenge for
surgeons because of their irritating and embarrassing symptoms and high failure rate after
repair.Patients with rectovaginal fistulas typically present with complaints of passage of
flatus or feces from the vagina with painful skin excoriation.
(1) The most common etiological cause of rectovaginal fistulas is obstetrical trauma. When
obstructed labor is unrelieved, the presenting fetal part is impacted against the soft
tissues of the pelvis leading to ischemic vascular injury and subsequent tissue necrosis and
fistula formation. Other predisposing factors include forceps delivery, midline episiotomy,
and third or fourth-degree perineal lacerations.( 2).
Evaluation of a patient with rectovaginal fistula includes a detailed history, examination of
the rectum, vagina, and perineal body. The perineal body is often thin or nearly nonexistent
in patients with sphincter injuries secondary to obstetrical trauma. Endoanal ultrasonography
and pelvic Magnetic Resonance Imaging (MRI) to confirm sphincter injury and may provide
valuable information before a planned repair. MR is the modality of choice for disease
staging (sensitivity 91%) (3).
( Sagittal T2 MR imaging shows communication between the rectum tumor and the vagina) The
experience of the surgeon and the previous attempts at repair are also important factors of
the success rate of the operations [4)
There are various operative procedures, such as the advancement flap, sphincteroplasty and
fistulectomy, coloanal anastomosis,and gracilis muscle repair to manage rectovaginal fistulas
[5].
The choice of the operative technique greatly depends on the status of the fistula and the
etiological rationale behind this medical complication [6.].
In this study, we have compared the outcomes of the fistulectomy and sphincteroplasty
procedures with or without concomitant bulbocavernosus flap. All patients were incontinent
and felt to have impaired anal tonus.
Patients and method:
Study design:
This prospective study involved 22 patients diagnosed with simple rectovaginal fistula from
January 2018 to January 2019 at the General surgical department, faculty of medicine Zagazig
University, Egypt. This study was approved by the institutional ethics board of our hospital.
All patients who participated in the study provided informed consent.
rectovaginal examination, endoanal ultrasonography, and pelvic MRI findings were collected to
assess the extension of the fistula. Colonoscopy was performed in selected patients with
severe bowel symptoms such as bloody diarrhea to exclude inflammatory bowel disease.
Decisions regarding operations were made cautiously and involved the whole medical team. All
cases underwent fistulectomy, sphincteroplasty and with or without bulbocavernosus flap
technique.All patients were evaluated for incontinence using Wexner Incontinence Score (WIS)
[7) Method of randomization: simple randomization with a balance.
Patient selection:
Inclusion criteria:
1. Rectovaginal fistula caused by obstetric problems
2. Female >20 years
Exclusion criteria:
1. other causes of rectovaginal fistula as Crohn's disease or malignant fistula
2. complex and recurrent fistula
Three patients did not undergo surgery. One because of patient's choice, one because of
minimal symptoms and one because fistula healed after medical therapy.
Methods:
Patients were given a mechanical bowel preparation the day before surgery and an enema on the
morning of the operation. The patient was placed in the lithotomy position under spinal
anesthesia. Antibiotics in the form of third generation cephalosporin and 500 mg of
Metronidazole were given.
Sub mucosal lidocain 5% in adrenalized saline at a ratio of 1: 100 000 was injected around
the fistula. Surgical excision of the fistula using scalpel was performed. Biopsies of rectal
mucosa and the fistula margin were also obtained for pathological evaluation to exclude an
underlying Crohn's disease or malignancy. A transverse perineal incision was done. Dissection
of the internal sphincter fibers away from the external sphincter fibers was performed,
allowing a tension free rectal closure at the fistulous site (Dissection of internal
sphincter fi bers from external sphincter fi ber s.). Closure of the fistulous opening at the
rectal side was done using Vicryl 3/0 sutures. This was followed by suturing of the
rectovaginal septum to the internal sphincteric fibers using Vicryl 3/0 sutures (Suturing of
internal sphincter fi bers to the rectovaginal septu m.). The bulbocavernosus muscle flap was
harvested from the left side in all patients at its anterior part, preserving the
posteroexternal vascular pedicle (Posterior muscle repair), through the same incision, and
sutured across the rectum to its counterpart on the other side (Vaginal advancement fl a p.&
Fig. 1 a The fistulae are indicated by the two forceps passing through them; b The finger
demonstrates the large recto-vaginal orifice) using 2/0 Vicryl sutures. The vaginal flap was
advanced at the fistula site and sutured to the perineal skin using Vicryl 3/0 sutures
(Preparation of the bulbocavernosus fl a p.& Fig. 3 a, b After a right labial incision, the
bulbocavernous muscle and the surrounding fibroadipose tissue were carefully mobilized,
avoiding possible damage of the postero-external vascular pedicle& Fig. 4 A subcutaneous
tunnel connecting the two incisions was created after transecting superior to the
bulbocavernous muscle& Fig. 5 The final set-up with the interrupted absorbable sutures over
the vaginal closure after sectioning of the longitudinal vaginal septum. The bulbocavernous
muscle is clearly visible after the lay open of the perineovaginal tract).
No suction drain was used. No covering stoma was done. Postoperatively, Soft, stool was
provided in the postoperative period at least for two weeks with the help of clear liquid
diet, plenty fluid intake, and the use of stool softeners. Oral broad-spectrum antibiotic
therapy was given for 3-5 days postoperatively. Sexual activity or any physical activities
more strenuous than a slow walk were avoided by the patients for three weeks after the
surgery. Follow up period up to one year.
Inclusion Criteria:
- 1- Rectovaginal fistula caused by obstetric problems 2- Female >20 years
Exclusion Criteria:
1. other causes of rectovaginal fistula as Crohn's disease or malignant fistula
2. complex and recurrent fistula -
|
NCT0426xxxx/NCT04267770.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267770</url>
</required_header>
<id_info>
<org_study_id>17HH4255</org_study_id>
<nct_id>NCT04267770</nct_id>
</id_info>
<brief_title>Flat and Circadian Insulin Infusion Rates in Continuous Subcutaneous Insulin Infusion</brief_title>
<acronym>FIRST1D</acronym>
<official_title>A Study of Flat and Circadian Insulin Infusion Rates in Continuous Subcutaneous Insulin Infusion (CSII) in Adults With Type 1 Diabetes</official_title>
<sponsors>
<lead_sponsor>
<agency>Imperial College London</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Imperial College London</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Randomised controlled trial to contribute to the evidence base for the optimal initial
insulin profile for adults with type 1 diabetes commencing insulin pump therapy.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Initiation of insulin pump therapy in people with type 1 diabetes requires conversion of a
basal insulin dose, given as once or twice daily long-acting insulin, to a continuous basal
infusion regimen. This conversion may be based on basal insulin dose only, or total daily
insulin dose, and may result in a flat basal insulin profile or an initial variable basal
rate.

Initial variable basal rates aim to replicate circadian changes in insulin requirements and
are derived from total basal insulin in adults over 24 years old, and from weight in adults
aged 18 to 24 years. Initial rates were developed from 63 well-controlled people with type 1
diabetes over 14 years of age and have been assessed against a flat basal rate in a small
randomised controlled trial with 12 participants. Mean glucose was lower in the circadian
basal rate group with particular differences noted in the early morning when glucose rises
were more pronounced in the flat basal rate group1.

In 50 people with type 1 diabetes treated with insulin pump therapy, HbA1c was lower in those
with lower basal rates at midnight, and in those with higher basal rates in the afternoon,
suggesting a benefit of circadian patterns2. In 33 people with type 1 diabetes over 16 years
of age basal rate distribution established at commencement of pump therapy did not alter over
6 months3. However, a 6 month cross-over study of circadian rates and oligophasic basal rates
showed no difference in HbA1c4.

Following initiation on insulin pump therapy basal rates are personalised to capillary blood
and continuous interstitial fluid glucose monitoring.

In adults with type 1 diabetes starting insulin pump therapy there are limited data to guide
the optimal insulin profile to rapidly achieve target glucose and minimise healthcare
professional input.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">April 10, 2018</start_date>
<completion_date type="Actual">November 9, 2018</completion_date>
<primary_completion_date type="Actual">November 9, 2018</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Supportive Care</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Change in Basal Insulin Rate</measure>
<time_frame>over 24 hours after 3 rounds of basal rate testing</time_frame>
<description>Absolute change in insulin basal rate over 24 hours after 3 rounds of basal rate testing (calculated by the sum of absolute changes for each 1 hour block compared with baseline)</description>
</primary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">17</enrollment>
<condition>Type 1 Diabetes</condition>
<arm_group>
<arm_group_label>circadian insulin infusion rates</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Initial variable basal rates aim to replicate circadian changes in insulin requirements and are derived from total basal insulin in adults over 24 years old, and from weight in adults aged 18 to 24 years.</description>
</arm_group>
<arm_group>
<arm_group_label>flat rates</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>flat basal rate</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Insulin (circadian)</intervention_name>
<description>Participant's own insulin adjusted to circadian infusion rates</description>
<arm_group_label>circadian insulin infusion rates</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Insulin (flat rate)</intervention_name>
<description>Participant's own insulin set to flat basal rates</description>
<arm_group_label>flat rates</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Adults ≥18 years of age

- Diagnosis of T1DM for > 1 year

- On MDI with decision made to commence CSII

- Structured education in previous 3 years

- HbA1c ≤ 75mmol/mol (9%)

- Stimulated c-peptide <200pmol/L

- No severe hypoglycaemia (defined as needing 3rd party assistance) in previous year

Exclusion Criteria:

- Previous CSII

- Night or shift worker

- Recurrent severe hypoglycaemia

- Pregnant or planning pregnancy

- Breastfeeding

- Enrolled in other clinical trials

- Have active malignancy or under investigation for malignancy

- Addison's Disease

- Gastroparesis

- Autonomic neuropathy

- Concomitant use of GLP-1 analogues and gliptins

- Visual impairment

- Reduced manual dexterity
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<location>
<facility>
<name>Imperial College Clinical Research Facility</name>
<address>
<city>London</city>
<country>United Kingdom</country>
</address>
</facility>
</location>
<location_countries>
<country>United Kingdom</country>
</location_countries>
<verification_date>March 2020</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<results_first_submitted>March 3, 2020</results_first_submitted>
<results_first_submitted_qc>March 19, 2020</results_first_submitted_qc>
<results_first_posted type="Actual">March 31, 2020</results_first_posted>
<last_update_submitted>March 19, 2020</last_update_submitted>
<last_update_submitted_qc>March 19, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">March 31, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Diabetes Mellitus, Type 1</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Insulin</mesh_term>
<mesh_term>Insulin, Globin Zinc</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<provided_document_section>
<provided_document>
<document_type>Study Protocol and Statistical Analysis Plan</document_type>
<document_has_protocol>Yes</document_has_protocol>
<document_has_icf>No</document_has_icf>
<document_has_sap>Yes</document_has_sap>
<document_date>February 23, 2018</document_date>
<document_url>https://ClinicalTrials.gov/ProvidedDocs/70/NCT04267770/Prot_SAP_000.pdf</document_url>
</provided_document>
</provided_document_section>
<clinical_results>
<participant_flow>
<group_list>
<group group_id="P1">
<title>Circadian Insulin Infusion Rates</title>
<description>Initial variable basal rates aim to replicate circadian changes in insulin requirements and are derived from total basal insulin in adults over 24 years old, and from weight in adults aged 18 to 24 years.
Insulin (circadian): Participant's own insulin adjusted to circadian infusion rates</description>
</group>
<group group_id="P2">
<title>Flat Rates</title>
<description>flat basal rate
Insulin (flat rate): Participant's own insulin set to flat basal rates</description>
</group>
</group_list>
<period_list>
<period>
<title>Overall Study</title>
<milestone_list>
<milestone>
<title>STARTED</title>
<participants_list>
<participants group_id="P1" count="9"/>
<participants group_id="P2" count="8"/>
</participants_list>
</milestone>
<milestone>
<title>COMPLETED</title>
<participants_list>
<participants group_id="P1" count="9"/>
<participants group_id="P2" count="8"/>
</participants_list>
</milestone>
<milestone>
<title>NOT COMPLETED</title>
<participants_list>
<participants group_id="P1" count="0"/>
<participants group_id="P2" count="0"/>
</participants_list>
</milestone>
</milestone_list>
</period>
</period_list>
</participant_flow>
<baseline>
<group_list>
<group group_id="B1">
<title>Circadian Insulin Infusion Rates</title>
<description>Initial variable basal rates aim to replicate circadian changes in insulin requirements and are derived from total basal insulin in adults over 24 years old, and from weight in adults aged 18 to 24 years.
Insulin (circadian): Participant's own insulin adjusted to circadian infusion rates</description>
</group>
<group group_id="B2">
<title>Flat Rates</title>
<description>flat basal rate
Insulin (flat rate): Participant's own insulin set to flat basal rates</description>
</group>
<group group_id="B3">
<title>Total</title>
<description>Total of all reporting groups</description>
</group>
</group_list>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Overall</scope>
<count_list>
<count group_id="B1" value="9"/>
<count group_id="B2" value="8"/>
<count group_id="B3" value="17"/>
</count_list>
</analyzed>
</analyzed_list>
<measure_list>
<measure>
<title>Age</title>
<units>years</units>
<param>Mean</param>
<dispersion>Standard Deviation</dispersion>
<class_list>
<class>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="9"/>
<count group_id="B2" value="8"/>
<count group_id="B3" value="17"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="33.3" spread="8.6"/>
<measurement group_id="B2" value="33.3" spread="8.6"/>
<measurement group_id="B3" value="33.3" spread="8.6"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
<measure>
<title>Sex: Female, Male</title>
<units>Participants</units>
<param>Count of Participants</param>
<class_list>
<class>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="9"/>
<count group_id="B2" value="8"/>
<count group_id="B3" value="17"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<title>Female</title>
<measurement_list>
<measurement group_id="B1" value="8"/>
<measurement group_id="B2" value="3"/>
<measurement group_id="B3" value="11"/>
</measurement_list>
</category>
<category>
<title>Male</title>
<measurement_list>
<measurement group_id="B1" value="1"/>
<measurement group_id="B2" value="5"/>
<measurement group_id="B3" value="6"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
<measure>
<title>Race and Ethnicity Not Collected</title>
<population>Race and Ethnicity were not collected from any participant.</population>
<units>Participants</units>
<param>Count of Participants</param>
<class_list>
<class>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="0"/>
<count group_id="B2" value="0"/>
<count group_id="B3" value="0"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<measurement_list>
<measurement group_id="B3" value="0"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
</measure_list>
</baseline>
<outcome_list>
<outcome>
<type>Primary</type>
<title>Change in Basal Insulin Rate</title>
<description>Absolute change in insulin basal rate over 24 hours after 3 rounds of basal rate testing (calculated by the sum of absolute changes for each 1 hour block compared with baseline)</description>
<time_frame>over 24 hours after 3 rounds of basal rate testing</time_frame>
<group_list>
<group group_id="O1">
<title>Circadian Insulin Infusion Rates</title>
<description>Initial variable basal rates aim to replicate circadian changes in insulin requirements and are derived from total basal insulin in adults over 24 years old, and from weight in adults aged 18 to 24 years.
Insulin (circadian): Participant's own insulin adjusted to circadian infusion rates</description>
</group>
<group group_id="O2">
<title>Flat Rates</title>
<description>flat basal rate
Insulin (flat rate): Participant's own insulin set to flat basal rates</description>
</group>
</group_list>
<measure>
<title>Change in Basal Insulin Rate</title>
<description>Absolute change in insulin basal rate over 24 hours after 3 rounds of basal rate testing (calculated by the sum of absolute changes for each 1 hour block compared with baseline)</description>
<units>Units of insulin</units>
<param>Median</param>
<dispersion>Inter-Quartile Range</dispersion>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Measure</scope>
<count_list>
<count group_id="O1" value="9"/>
<count group_id="O2" value="8"/>
</count_list>
</analyzed>
</analyzed_list>
<class_list>
<class>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="1.8" lower_limit="0.63" upper_limit="2.99"/>
<measurement group_id="O2" value="1.49" lower_limit="0.83" upper_limit="1.94"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
</outcome>
</outcome_list>
<reported_events>
<time_frame>28 days</time_frame>
<group_list>
<group group_id="E1">
<title>Circadian Insulin Infusion Rates</title>
<description>Initial variable basal rates aim to replicate circadian changes in insulin requirements and are derived from total basal insulin in adults over 24 years old, and from weight in adults aged 18 to 24 years.
Insulin (circadian): Participant's own insulin adjusted to circadian infusion rates</description>
</group>
<group group_id="E2">
<title>Flat Rates</title>
<description>flat basal rate
Insulin (flat rate): Participant's own insulin set to flat basal rates</description>
</group>
</group_list>
<serious_events>
<category_list>
<category>
<title>Total</title>
<event_list>
<event>
<sub_title>Total, all-cause mortality</sub_title>
<counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
<counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
</event>
<event>
<sub_title>Total, serious adverse events</sub_title>
<counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
<counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
</event>
</event_list>
</category>
</category_list>
</serious_events>
<other_events>
<frequency_threshold>0</frequency_threshold>
<category_list>
<category>
<title>Total</title>
<event_list>
<event>
<sub_title>Total, other adverse events</sub_title>
<counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
<counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
</event>
</event_list>
</category>
</category_list>
</other_events>
</reported_events>
<certain_agreements>
<pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
<restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
</certain_agreements>
<point_of_contact>
<name_or_title>Nick Oliver</name_or_title>
<organization>Imperial College London</organization>
<phone>+44 20 7594 1796</phone>
<email>nick.oliver@imperial.ac.uk</email>
</point_of_contact>
</clinical_results>
</clinical_study>
|
Randomised controlled trial to contribute to the evidence base for the optimal initial
insulin profile for adults with type 1 diabetes commencing insulin pump therapy.
Initiation of insulin pump therapy in people with type 1 diabetes requires conversion of a
basal insulin dose, given as once or twice daily long-acting insulin, to a continuous basal
infusion regimen. This conversion may be based on basal insulin dose only, or total daily
insulin dose, and may result in a flat basal insulin profile or an initial variable basal
rate.
Initial variable basal rates aim to replicate circadian changes in insulin requirements and
are derived from total basal insulin in adults over 24 years old, and from weight in adults
aged 18 to 24 years. Initial rates were developed from 63 well-controlled people with type 1
diabetes over 14 years of age and have been assessed against a flat basal rate in a small
randomised controlled trial with 12 participants. Mean glucose was lower in the circadian
basal rate group with particular differences noted in the early morning when glucose rises
were more pronounced in the flat basal rate group1.
In 50 people with type 1 diabetes treated with insulin pump therapy, HbA1c was lower in those
with lower basal rates at midnight, and in those with higher basal rates in the afternoon,
suggesting a benefit of circadian patterns2. In 33 people with type 1 diabetes over 16 years
of age basal rate distribution established at commencement of pump therapy did not alter over
6 months3. However, a 6 month cross-over study of circadian rates and oligophasic basal rates
showed no difference in HbA1c4.
Following initiation on insulin pump therapy basal rates are personalised to capillary blood
and continuous interstitial fluid glucose monitoring.
In adults with type 1 diabetes starting insulin pump therapy there are limited data to guide
the optimal insulin profile to rapidly achieve target glucose and minimise healthcare
professional input.
Inclusion Criteria:
- Adults ≥18 years of age
- Diagnosis of T1DM for > 1 year
- On MDI with decision made to commence CSII
- Structured education in previous 3 years
- HbA1c ≤ 75mmol/mol (9%)
- Stimulated c-peptide <200pmol/L
- No severe hypoglycaemia (defined as needing 3rd party assistance) in previous year
Exclusion Criteria:
- Previous CSII
- Night or shift worker
- Recurrent severe hypoglycaemia
- Pregnant or planning pregnancy
- Breastfeeding
- Enrolled in other clinical trials
- Have active malignancy or under investigation for malignancy
- Addison's Disease
- Gastroparesis
- Autonomic neuropathy
- Concomitant use of GLP-1 analogues and gliptins
- Visual impairment
- Reduced manual dexterity
|
NCT0426xxxx/NCT04267783.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267783</url>
</required_header>
<id_info>
<org_study_id>2018-02267</org_study_id>
<nct_id>NCT04267783</nct_id>
</id_info>
<brief_title>Prediction of Uterine Atony After Vaginal Delivery by Elastography</brief_title>
<official_title>Prediction of Uterine Atony After Vaginal Delivery by Shear Wave Elastography: a Feasibility Study</official_title>
<sponsors>
<lead_sponsor>
<agency>Centre Hospitalier Universitaire Vaudois</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Centre Hospitalier Universitaire Vaudois</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Prospective study evaluating the feasibility of shear-wave elastography of the uterus during
the third stage of labour and following placental delivery. The investigators hypothesize
that the stiffness of the myometrium can be measured by using shear-wave technology. This
study involves 30 patients with a healthy pregnancy and spontaneous vaginal delivery. One
co-investigator will carry out measurements at the uterine fundus, at three different time
points: after fetal delivery, after placental delivery and 30 minutes after placental
delivery.
</textblock>
</brief_summary>
<overall_status>Completed</overall_status>
<start_date type="Actual">May 1, 2019</start_date>
<completion_date type="Actual">May 30, 2020</completion_date>
<primary_completion_date type="Actual">April 30, 2020</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Stiffness of the myometrium</measure>
<time_frame>Third labor stage to 30 minutes post placenta delivery</time_frame>
<description>Difference in median myometrial shear wave velocity between each time point: after fetal delivery, after placental delivery and 30 minutes after placental delivery.</description>
</primary_outcome>
<secondary_outcome>
<measure>Blood loss</measure>
<time_frame>Two hours following the childbirth</time_frame>
<description>Measurement of total blood loss</description>
</secondary_outcome>
<enrollment type="Actual">30</enrollment>
<condition>Postpartum Hemorrhage</condition>
<intervention>
<intervention_type>Diagnostic Test</intervention_type>
<intervention_name>Shear wave elastography</intervention_name>
<description>Investigate the feasibility of use of shear-wave elastography of the uterus during the third stage of labour and following placental delivery in order to predict uterine atony .</description>
</intervention>
<eligibility>
<study_pop>
<textblock>
Women above 37 weeks of gestation without known risk factors for postpartum hemorrhage who
have vaginal births in our centre will be eligible for this study
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- singleton pregnancy

- cephalic presentation

- maternal age > 18 years old

- nulliparous

- healthy uncomplicated pregnancy

- gestational age between 37-42 weeks of gestation

- spontaneous labour and delivery

- uncomplicated progression of labour (cervical dilatation at >1 cm/h)

- administration of less than 3 units of oxytocin during the second stage of labour

- patient having read, accepted and signed the consent form

Exclusion Criteria:

- antepartum hemorrhage in the present pregnancy

- protracted second stage of labour (more than two hours from full dilatation to
delivery)

- more than 30 minutes of active pushing

- BMI > 35 kg/m2

- distance from skin to uterus > 8 cm

- age > 35 years old

- instrumental deliveries

- bleeding disorders

- polyhydramnios

- diabetes

- pre-eclampsia

- high blood pressure

- use of anticoagulant medications

- clinical chorioamnionitis

- placental abnormality (low-lying or abruption)

- fetal macrosomia

- uterine fibroids

- uterine anomalies

- previous uterine scar

- multiple pregnancy

- placental retention

- inability to follow procedures or insufficient knowledge of project language

- inability to give consent

- refusal to participate
</textblock>
</criteria>
<gender>Female</gender>
<gender_based>Yes</gender_based>
<gender_description>Pregnant women</gender_description>
<minimum_age>18 Years</minimum_age>
<maximum_age>35 Years</maximum_age>
</eligibility>
<location>
<facility>
<name>University Hospital of Lausanne</name>
<address>
<city>Lausanne</city>
<state>Vaud</state>
<zip>1011</zip>
<country>Switzerland</country>
</address>
</facility>
</location>
<location_countries>
<country>Switzerland</country>
</location_countries>
<verification_date>August 2020</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>August 31, 2020</last_update_submitted>
<last_update_submitted_qc>August 31, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">September 2, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Centre Hospitalier Universitaire Vaudois</investigator_affiliation>
<investigator_full_name>DAVID DESSEAUVE</investigator_full_name>
<investigator_title>Principal investigator</investigator_title>
</responsible_party>
<keyword>postpartum hemorrhage</keyword>
<keyword>uterine atony</keyword>
<keyword>shear wave</keyword>
<keyword>elastography</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Postpartum Hemorrhage</mesh_term>
<mesh_term>Uterine Inertia</mesh_term>
<mesh_term>Hemorrhage</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>Undecided</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Prospective study evaluating the feasibility of shear-wave elastography of the uterus during
the third stage of labour and following placental delivery. The investigators hypothesize
that the stiffness of the myometrium can be measured by using shear-wave technology. This
study involves 30 patients with a healthy pregnancy and spontaneous vaginal delivery. One
co-investigator will carry out measurements at the uterine fundus, at three different time
points: after fetal delivery, after placental delivery and 30 minutes after placental
delivery.
Women above 37 weeks of gestation without known risk factors for postpartum hemorrhage who
have vaginal births in our centre will be eligible for this study
Inclusion Criteria:
- singleton pregnancy
- cephalic presentation
- maternal age > 18 years old
- nulliparous
- healthy uncomplicated pregnancy
- gestational age between 37-42 weeks of gestation
- spontaneous labour and delivery
- uncomplicated progression of labour (cervical dilatation at >1 cm/h)
- administration of less than 3 units of oxytocin during the second stage of labour
- patient having read, accepted and signed the consent form
Exclusion Criteria:
- antepartum hemorrhage in the present pregnancy
- protracted second stage of labour (more than two hours from full dilatation to
delivery)
- more than 30 minutes of active pushing
- BMI > 35 kg/m2
- distance from skin to uterus > 8 cm
- age > 35 years old
- instrumental deliveries
- bleeding disorders
- polyhydramnios
- diabetes
- pre-eclampsia
- high blood pressure
- use of anticoagulant medications
- clinical chorioamnionitis
- placental abnormality (low-lying or abruption)
- fetal macrosomia
- uterine fibroids
- uterine anomalies
- previous uterine scar
- multiple pregnancy
- placental retention
- inability to follow procedures or insufficient knowledge of project language
- inability to give consent
- refusal to participate
|
NCT0426xxxx/NCT04267796.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267796</url>
</required_header>
<id_info>
<org_study_id>2019-0634</org_study_id>
<secondary_id>NCI-2019-07636</secondary_id>
<secondary_id>2019-0634</secondary_id>
<nct_id>NCT04267796</nct_id>
</id_info>
<brief_title>Lifestyle Intervention for the Reduction of Breast Cancer Risk in Normal Weight Women</brief_title>
<official_title>Reducing Breast Cancer Risk Through Modifying Body Composition and Decreasing Inflammation in Normal Weight Women</official_title>
<sponsors>
<lead_sponsor>
<agency>M.D. Anderson Cancer Center</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>National Cancer Institute (NCI)</agency>
<agency_class>NIH</agency_class>
</collaborator>
<collaborator>
<agency>Foundation for Women's Cancers</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>M.D. Anderson Cancer Center</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This trial studies how well a lifestyle intervention works in reducing breast cancer risk
through changing body composition and decreasing inflammation in normal weight women. This
trial may help researchers learn more about diet and exercise programs designed to decrease
body fat in postmenopausal women who are of normal weight but have an elevated risk of breast
cancer because of excess body fat.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
PRIMARY OBJECTIVE:

I. Evaluate the feasibility of a diet and exercise intervention to decrease body fat in
postmenopausal women with normal body mass index (BMI) but high body fat (trunk fat mass 9.4
kg, the 50th percentile of normal BMI women in the Women's Health Initiative [WHI]).

SECONDARY OBJECTIVE:

I. Assess preliminary efficacy of the intervention by evaluating the post-intervention
differences between the intervention and control groups in:

IIa. Circulating markers of inflammation and metabolic dysfunction linked to both excess
adiposity and breast cancer (high sensitivity C-reactive protein [hsCRP], fasting insulin,
leptin, IL-6, triglycerides, sex hormone binding globulin [SHBG], adiponectin, and high
density lipoprotein [HDL] cholesterol).

IIb. Body composition body fat, trunk fat mass, fat mass, lean mass, fat-free mass).

EXPLORATORY OBJECTIVE:

I. Exploratory outcomes include fitness (oxygen consumption VO2 peak, sit-to-stand test),
behavior (physical activity, energy intake, macronutrient consumption), and quality of life
(global health-related quality of life, physical functioning, sleep, menopausal symptoms).

OUTLINE: Participants are randomized to 1 of 2 groups.

GROUP I: Participants complete lifestyle intervention consisting of 1-3 sets of
high-resistance circuit training sessions per week, up to 150 minutes of aerobic training per
week, and diet recommendations from a health coach or registered dietitian twice per week for
16 weeks.

GROUP II: Participants are placed on a wait-list and then complete lifestyle intervention
after 4 months.
</textblock>
</detailed_description>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">November 22, 2021</start_date>
<completion_date type="Anticipated">April 30, 2025</completion_date>
<primary_completion_date type="Anticipated">April 30, 2025</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Prevention</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Evaluate the feasibility of a diet intervention to decrease body fat in postmenopausal women with normal BMI but high body. fat.</measure>
<time_frame>up to 16 weeks</time_frame>
<description>Will assessed by the calculated rates, frequencies, and 95% confidence intervals (CIs) for these measures</description>
</primary_outcome>
<primary_outcome>
<measure>Evaluate the exercise intervention to decrease body fat in postmenopausal women with normal BMI but high body. fat.</measure>
<time_frame>up to 16 weeks</time_frame>
<description>Will assessed by the calculated rates, frequencies, and 95% confidence intervals (CIs) for these measures</description>
</primary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">62</enrollment>
<condition>Breast Carcinoma</condition>
<arm_group>
<arm_group_label>Group I (lifestyle intervention)</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Participants complete lifestyle intervention consisting of 1-3 sets of high-resistance circuit training sessions per week, up to 150 minutes of aerobic training per week, and diet recommendations from a health coach or registered dietitian twice per week for 16 weeks.</description>
</arm_group>
<arm_group>
<arm_group_label>Group II (wait-list, lifestyle intervention)</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Participants are placed on a wait-list and then complete lifestyle intervention after 4 months.</description>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Aerobic Exercise</intervention_name>
<description>Complete aerobic training</description>
<arm_group_label>Group I (lifestyle intervention)</arm_group_label>
<arm_group_label>Group II (wait-list, lifestyle intervention)</arm_group_label>
<other_name>Aerobic Activity</other_name>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Dietary Intervention</intervention_name>
<description>Receive diet recommendations from health coach or registered dietitian</description>
<arm_group_label>Group I (lifestyle intervention)</arm_group_label>
<arm_group_label>Group II (wait-list, lifestyle intervention)</arm_group_label>
<other_name>Dietary Modification</other_name>
<other_name>intervention, dietary</other_name>
<other_name>Nutrition Intervention</other_name>
<other_name>Nutrition Interventions</other_name>
<other_name>Nutritional Interventions</other_name>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Quality-of-Life Assessment</intervention_name>
<description>Ancillary studies</description>
<arm_group_label>Group I (lifestyle intervention)</arm_group_label>
<arm_group_label>Group II (wait-list, lifestyle intervention)</arm_group_label>
<other_name>Quality of Life Assessment</other_name>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Questionnaire Administration</intervention_name>
<description>Ancillary studies</description>
<arm_group_label>Group I (lifestyle intervention)</arm_group_label>
<arm_group_label>Group II (wait-list, lifestyle intervention)</arm_group_label>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Resistance Training</intervention_name>
<description>Complete high-resistance circuit training sessions</description>
<arm_group_label>Group I (lifestyle intervention)</arm_group_label>
<arm_group_label>Group II (wait-list, lifestyle intervention)</arm_group_label>
<other_name>Strength Training</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Employee at MD Anderson Cancer Center

- Postmenopausal woman (absence of menstruation for at least one year, or history of
bilateral oophorectomy)

- Self-reported height and weight indicating a BMI >= 18.5 and < 25 kg/m^2

- No contraindications to exercise (either no positive responses on the Physical
Activity Readiness Questionnaire, or clearance from a health care provider certifying
that the participant is healthy enough to exercise)

- No history of invasive cancer, other than non-melanoma skin cancer

- No history of renal disease

- Able to walk without an assistive device

- Not within 3 months of major surgery

- Able to speak/read/write in English

- Has internet access on a computer or mobile device

- A trunk fat mass >= 9.4 kg as indicated by a dual x-ray absorptiometry (DXA) scan

- Height and weight indicating a BMI of >= 18.5 and < 25 kg/m^2 verified at the
screening visit

Exclusion Criteria:

- MD Anderson employees that report to the principal investigator of this study

- Participants that cannot engage in the exercise program for more than three weeks
during the study period

- Participants that are currently doing strength exercises that work all major muscle
groups wo or more times per week
</textblock>
</criteria>
<gender>Female</gender>
<minimum_age>50 Years</minimum_age>
<maximum_age>69 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Karen M Basen-Engquist</last_name>
<role>Principal Investigator</role>
<affiliation>M.D. Anderson Cancer Center</affiliation>
</overall_official>
<overall_contact>
<last_name>Karen M. Basen-Engquist</last_name>
<phone>713-745-3123</phone>
<email>kbasenen@mdanderson.org</email>
</overall_contact>
<location>
<facility>
<name>M D Anderson Cancer Center</name>
<address>
<city>Houston</city>
<state>Texas</state>
<zip>77030</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Karen M. Basen-Engquist</last_name>
<phone>713-745-3123</phone>
</contact>
<investigator>
<last_name>Karen M. Basen-Engquist</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<link>
<url>http://www.mdanderson.org</url>
<description>MD Anderson Cancer Center Website</description>
</link>
<verification_date>September 2023</verification_date>
<study_first_submitted>November 26, 2019</study_first_submitted>
<study_first_submitted_qc>February 10, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>September 1, 2023</last_update_submitted>
<last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">September 6, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Breast Neoplasms</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This trial studies how well a lifestyle intervention works in reducing breast cancer risk
through changing body composition and decreasing inflammation in normal weight women. This
trial may help researchers learn more about diet and exercise programs designed to decrease
body fat in postmenopausal women who are of normal weight but have an elevated risk of breast
cancer because of excess body fat.
PRIMARY OBJECTIVE:
I. Evaluate the feasibility of a diet and exercise intervention to decrease body fat in
postmenopausal women with normal body mass index (BMI) but high body fat (trunk fat mass 9.4
kg, the 50th percentile of normal BMI women in the Women's Health Initiative [WHI]).
SECONDARY OBJECTIVE:
I. Assess preliminary efficacy of the intervention by evaluating the post-intervention
differences between the intervention and control groups in:
IIa. Circulating markers of inflammation and metabolic dysfunction linked to both excess
adiposity and breast cancer (high sensitivity C-reactive protein [hsCRP], fasting insulin,
leptin, IL-6, triglycerides, sex hormone binding globulin [SHBG], adiponectin, and high
density lipoprotein [HDL] cholesterol).
IIb. Body composition body fat, trunk fat mass, fat mass, lean mass, fat-free mass).
EXPLORATORY OBJECTIVE:
I. Exploratory outcomes include fitness (oxygen consumption VO2 peak, sit-to-stand test),
behavior (physical activity, energy intake, macronutrient consumption), and quality of life
(global health-related quality of life, physical functioning, sleep, menopausal symptoms).
OUTLINE: Participants are randomized to 1 of 2 groups.
GROUP I: Participants complete lifestyle intervention consisting of 1-3 sets of
high-resistance circuit training sessions per week, up to 150 minutes of aerobic training per
week, and diet recommendations from a health coach or registered dietitian twice per week for
16 weeks.
GROUP II: Participants are placed on a wait-list and then complete lifestyle intervention
after 4 months.
Inclusion Criteria:
- Employee at MD Anderson Cancer Center
- Postmenopausal woman (absence of menstruation for at least one year, or history of
bilateral oophorectomy)
- Self-reported height and weight indicating a BMI >= 18.5 and < 25 kg/m^2
- No contraindications to exercise (either no positive responses on the Physical
Activity Readiness Questionnaire, or clearance from a health care provider certifying
that the participant is healthy enough to exercise)
- No history of invasive cancer, other than non-melanoma skin cancer
- No history of renal disease
- Able to walk without an assistive device
- Not within 3 months of major surgery
- Able to speak/read/write in English
- Has internet access on a computer or mobile device
- A trunk fat mass >= 9.4 kg as indicated by a dual x-ray absorptiometry (DXA) scan
- Height and weight indicating a BMI of >= 18.5 and < 25 kg/m^2 verified at the
screening visit
Exclusion Criteria:
- MD Anderson employees that report to the principal investigator of this study
- Participants that cannot engage in the exercise program for more than three weeks
during the study period
- Participants that are currently doing strength exercises that work all major muscle
groups wo or more times per week
|
NCT0426xxxx/NCT04267809.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267809</url>
</required_header>
<id_info>
<org_study_id>Met-YF-001</org_study_id>
<nct_id>NCT04267809</nct_id>
</id_info>
<brief_title>Modulate Cellular Stress in the Immune Cells to Reduce Rate of Symptomatic Viral Infection</brief_title>
<official_title>Modulating Endoplasmic Reticulum Stress as a Prophylactic Approach Against Symptomatic Viral Infection</official_title>
<sponsors>
<lead_sponsor>
<agency>Singapore General Hospital</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Duke-NUS Graduate Medical School</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>Singapore General Hospital</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
To determine the efficacy of metformin in reducing the rate of symptomatic YF17D infection,
and to elucidate the effects of metformin on YF17D viremia and the downstream adaptive immune
response, we hereby propose a randomised, double-blind, placebo-controlled clinical trial
that is coupled with a system biology approach. We plan to recruit 44 healthy volunteers aged
21-40 years, with a Body Mass Index of 20-25 kg/m2, have no known drug allergies and are not
currently receiving regular immune-modulating therapy such as metformin, NSAIDs, paracetamol,
corticosteroids or statins. The age range that we propose will ensure that our volunteers are
likely to be healthy and not be on long-term medication for other concurrent medical
conditions. This would abrogate the confounding effect of YF17D infection enhancement by
cross reactive antibodies that we have previously shown.

Informed written consent will be obtained before any physical examination is performed. All
consented subjects will undergo screening which includes a full physical examination, vital
signs measurement, clinical laboratory tests and urine pregnancy test (for female subjects of
child-bearing potential) Eligible subjects will be randomized 1:1 to either metformin 1000mg
or placebo twice daily for 7 consecutive days (Days 1-7). On Day 4, subjects will be
administered one dose of YF17D before study drug dosing.

Aim 1 tests the hypothesis that prophylactic metformin reduces ER stress and thus attenuates
the post-infection pro-inflammatory response for reduced rate of symptomatic outcome. The
primary objective for Aim 1 is to determine the efficacy of metformin in reducing the rate of
symptomatic YF17D infection using a randomized placebo-controlled clinical trial.

Aim 2 explores the effectiveness of metformin, either through its action on ER stress or
other pathways that differentially regulate the expression of pro- and anti-viral host
factors, in inhibiting live attenuated vaccine infection and downstream adaptive immune
responses. The primary objective for Aim 2 is to elucidate the effects of metformin on YF17D
viremia and the downstream adaptive immune response.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Criteria for Recruitment and Recruitment Process: Subjects will be recruited from SingHealth
Investigational Medicine Unit (IMU) healthy volunteer database and recruitment posters.
Subjects will be given a copy of the Participant Information and Informed Consent Form to
read upon their arrival. A briefing session on the study will be conducted by the
Investigator. Thereafter, subjects will be ushered into a private room where informed consent
is obtained and where questions about the study can be asked freely. Subjects will not be
rushed into making a decision to participate in the study. They will be encouraged to speak
to their family members about participation in the study; and allowed to defer their decision
(without any prejudice) to participate till after discussion with their family members.

Screening Visits and Procedures: Subjects will be recruited via the SingHealth
Investigational Medicine Unit (IMU). Informed written consent will be obtained before any
study related procedure or assessment is performed. All subjects' eligibility for recruitment
into the study must be assessed during screening visit. Subjects must satisfy all inclusion
and exclusion criteria outlined in Section 3.3 and Section 3.4 respectively to be eligible
for enrolment into the study. Eligibility criteria must be confirmed before dosing. All
clinical laboratory tests scheduled for screening will be collected to establish pre-dose
baseline. Other procedures that must be completed before the study begins include a full
physical examination and urinary pregnancy test (for female subjects of child-bearing
potential).

Study Visits and Procedures: All eligible subjects will proceed to Day 1, where they will be
randomized 1:1 to either metformin 1000mg or placebo twice daily for 7 consecutive days (Days
1-7). On Day 4, subjects will be administered one dose of YF17D before study drug dosing.
Subjects will report to the SingHealth IMU on Day 1 (pre-study drug), Day 4 (pre-YF17D), Days
5, 7, 11, 14, 18 (only for participants who consent to scRNA-seq and T-cell studies) and Day
32 for research blood sampling. The schedule for blood draws will be identical for all study
groups. All research blood samples will be stored at -80oC until recruitment is completed
before analysis. Subject recruitment and blood collection will be conducted as an outpatient
study in the SingHealth Investigational Medicine Unit (IMU), a dedicated early phase clinical
trial facility. From our prior experience, we anticipate we will not have difficulty
recruiting the required number of participants into our study necessary to meet our target
sample size.

Post Study Follow up and Procedures: There is no requirement for post-study follow-up or
procedures.

Safety Monitoring Plan: The study may be evaluated by government inspectors/regulatory
authorities who must be allowed access to e-CRFs, source documents, and other study files.
The inspectors will review CRFs and compare them with source documents to verify accurate and
complete collection of data and confirm that the study is being conducted according to the
protocol, ICH-Good Clinical Practices (ICH-GCP) and all applicable regulations.

Known common adverse events of metformin include diarrhoea, nausea, stomach pain, heartburn
and bloatedness. Rare AEs include lactic acidosis and hypoglycaemia. Limiting the duration of
metformin dosing to 10 days would further reduce the risk of these serious AEs. Subjects will
be trained to look out for early symptoms associated with these AEs and to report to IMU
immediately should they experience any of these symptoms. Details of AE event terminology,
date and time of event start and end, severity, using the CTCAE or treatment given, impact on
work and to the continuation of the study, and final outcome of the event will be recorded on
the case report until resolution of the event.

During the study, the investigator will recruit the subjects, as well as perform full history
taking and physical examination at both scheduled and unscheduled visits. The investigator
will also review the subject's diaries for any potential side effects and manage the AEs
based on best clinical practice should they arise. Compliance to study protocol will be
checked by taking a medication history, and pill count and inspection of diary as well as
measurement of metformin drug level at specific time points.

Data Quality Assurance: The PI and Co-Is will review the study periodically for data and
safety monitoring. Internal quality checks will be performed by two CRCs who are study team
members. The data entered by one CRC will be checked by another using the source documents.
The study may also be picked for monitoring by SingHealth Office of Research Integrity and
Compliance (ORIC) or evaluated by government inspectors/regulatory authorities who must be
allowed access to e-CRFs, source documents, and other study files. The monitors/inspectors
may review CRFs and compare them with source documents to verify accurate and complete
collection of data and confirm that the study is being conducted according to the protocol,
ICH-Good Clinical Practices (ICH-GCP) and all applicable regulations.

Data Entry and Storage: All participant's data will be de-identified upon recruitment.
Hardcopy research data collection forms such as CRFs, logs and diaries will be kept in the
Investigator's Site File and stored in SingHealth IMU under lock and key, accessible only to
delegated study team members. Direct data capture of demographic and clinical data will be
captured on source documents. Identifiers will be kept in a separate file in another office
and every effort will be made to protect the privacy of the participants. The data to be
analysed will contain only de-identified data. An electronic data capture system will be
used. All electronic data will be password protected and can only be accessed by study team
members. Specimens, test results or pathogen data will be stored at Duke-NUS EID laboratory
in a stand-alone PC whereby access is password protected.

Determination of Sample Size: A sample size of 20 per arm will give 80% power to detect a
reduction in systemic symptoms from 50% to 10% (risk difference = 0.4 reduction ratio = 0.8)
in participants who receive placebo versus who are pre-treated with metformin versus placebo
group at a 2-sided 5% type I error rate (PASS 13 Software). Factoring in a potential dropout
rate of 10%, the total sample size is 44 in total (22 per arm). From our previous experience
with subject recruitment in the YF vaccine trial, there were no dropouts during the 1-month
follow-up period. Therefore, we are confident that we can recruit the required number of
subjects within the trial period.

Statistical analysis: Fisher's exact test will be used to assess difference in systemic
symptom rate between placebo and metformin pre-treatment arm. Confidence intervals (CI) for
AE rates will be estimated using the exact method. CI for risk difference will be estimated
using the Newcombe's score method.

Diagnostic plots will be used to determine the choice of using the raw data or
log-transformed data in parametric analyses or non-parametric analyses. Differences in
anti-YF neutralizing antibody titer at day 28, viremia and SBREP-1 expression will be
compared between placebo and metformin groups. Relationship between systemic symptoms,
molecular correlates of immunogenicity, viremia, antibody titer and metformin will be
explored with regression methods. Differences in background characteristics between subjects
who do and do not have systemic symptom onset will be included in covariate-adjusted
analysis.

Determination of study drug blood level: Study drug levels will be measured via a liquid
chromatography-tandem mass spectrometric (LC-MS/MS) assay method. The assay will be performed
on a Shimadzu 8060 LC-MS/MS system, which is available at the Singapore General Hospital.

Gene expression studies: Gene expression in whole blood would be carried out using Nanostring
nCounter assay. This assay provides a multiplex approach to identify the genes that the
investigator have previously used to validate the hits from the microarray that identified
adaptive ER stress as a susceptibility factor for symptomatic YF17D infection (see
preliminary data). Importantly, the investigator have worked with Nanostring, to customize a
comprehensive set of probes that are able to directly quantify mRNA transcripts in the ER
stress and TCA cycle pathways, which would be the target genes in this trial. This approach
is also chosen due to the CSA budget constraint. Nonetheless, the study team will collect
extra clinical samples as backup and explore the use of RNAseq to discover the
pharmacogenomics of metformin through additional funding from other grant sources.

This proposed gene expression study will be carried out at the Viral Research and
Experimental Medicine Centre @ SingHealth Duke-NUS (ViREMiCS). ViREMiCS was established by
the PI and collaborator, Eng Eong Ooi as a research centre in the SingHealth Duke-NUS
Academic Medicine Centre partnership. It has established a suite of molecular and systems
biology tools to support and accelerate proof-of concept clinical trials. The investigators
thus do not anticipate any problem in using this approach to measure gene expression in blood
samples.

Proteomics and Metabolomic profiling: Plasma metabolomics will be examined using capillary
electrophoresis/mass spectrometry (CE/MS), and liquid chromatography/mass spectrometry
LC-MS/MS as we have previously employed to measure the polar metabolites from glycolysis and
TCA cycle [18, 25]. Proteomics will be measured using LC-MS/MS. These assays will be carried
out using the core equipment available in the Programme in Emerging Infectious Diseases and
Metabolomics Core Facility, both in Duke-NUS. This will enable a multi-omics approach to
support enhanced biological insights.

Chemokine and Cytokine: Serum chemokine and cytokine levels will be measured using the
Luminex or Olink assay that enables more than 40 serum chemokines and cytokines to be
measured simultaneously.

YF Viremia and PRNT titres: YF viremia loads will be assessed using quantitative real-time
PCR (qRT-PCR). Anti-YF neutralising antibody titres will be measured by plaque reduction
neutralisation test (PRNT). Briefly, 50 PFU (plaque forming units) of YF17D virus will be
incubated with 2-fold serial dilutions of human serum for one hour at 37oC, and then added to
a monolayer of Vero cells in 24-well plates. One hour later, media will be aspirated and
cells overlaid with carboxymethyl cellulose 1% in maintenance media. After 5 days, cells will
be fixed, washed and stained with crystal violet. The number of plaques will be counted and
PRNT50 titres determined using a sigmoid dose-response curve fit as reciprocal values.

scRNA-seq and T-cell Studies: Single cell RNA sequencing (scRNA-seq) will be performed on
PBMCs isolated before and after metformin treatment to determine the impact of metformin
treatment on different immune cell subsets. This proposed study will be carried out in
collaboration with the Genome Biology Facility at Duke-NUS. Subsequently, using the findings
of scRNA-seq as a guide, we will then assess T-cell function and activity using either flow
cytometry or enzyme-linked immune absorbent spot (ELISPOT) assay. These assays will be
carried out using core equipment available in the Programme in Emerging Infectious Diseases
in Duke-NUS.
</textblock>
</detailed_description>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">October 22, 2021</start_date>
<completion_date type="Anticipated">July 2023</completion_date>
<primary_completion_date type="Anticipated">July 2023</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>Enrolled subjects will be randomized into one of two groups in the same ratio (1:1). As this is an open-label study, random block sizes will be used to avoid selection bias yet ensure balance over time. Randomization will be performed via a web-based randomization system: http://www.randomization.com by an independent person who has no direct contact with the subjects. Randomization opaque envelopes will be prepared by an independent team in accordance to the Master Randomization List generated. The randomization envelopes are to be opened sequentially for each enrollment by the study team and will determine the subject's allocation to one of the two groups.</intervention_model_description>
<primary_purpose>Basic Science</primary_purpose>
<masking>Double (Participant, Investigator)</masking>
<masking_description>This is a randomized, double-blind, placebo-controlled clinical trial of metformin in 44 healthy adults.</masking_description>
</study_design_info>
<primary_outcome>
<measure>Rate of symptomatic outcome</measure>
<time_frame>Day 0 to Day 18</time_frame>
<description>We will employ the definitions of systemic symptoms, based on the WHO guidelines for surveillance of YF vaccine-related AEs, and graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 as previously published. For pain symptoms (i.e. headache, myalgia, arthralgia), a standardized Numerical pain Rating Scale (NRS) will be used. Subjects will be monitored over a 2-week period starting immediately after YF vaccination</description>
</primary_outcome>
<secondary_outcome>
<measure>Reduction in pro-inflammatory and innate immune responses at day 1 post-infection</measure>
<time_frame>Day 0 to Day 32</time_frame>
<description>The rationale for this is that we have previously shown that expression of genes in these pathways at day 1 post-YF17D infection correlated with the development of symptoms at a median time of 6 days post-infection. Measurements of these genes will be done using the panel of Nanostring nCounter probes we have established in ViREMiCS.</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">44</enrollment>
<condition>Endoplasmic Reticulum Stress</condition>
<condition>Viral Infection</condition>
<condition>Yellow Fever</condition>
<arm_group>
<arm_group_label>Metformin group</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>22 subjects will receive Metformin 1000mg twice daily for 7 consecutive days (Days 1-7). On Day 4, subjects will be administered one dose of YF17D before metformin dosing.</description>
</arm_group>
<arm_group>
<arm_group_label>Placebo group</arm_group_label>
<arm_group_type>Placebo Comparator</arm_group_type>
<description>22 subjects will receive placebo twice daily for 7 consecutive days (Days 1-7). On Day 4, subjects will be administered one dose of YF17D before placebo dosing.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Metformin Hydrochloride</intervention_name>
<description>Metformin 500mg tablets are registered and licensed in Singapore. For the study, we will be sourcing the Metformin tablets from Singapore General Hospital Formulary.</description>
<arm_group_label>Metformin group</arm_group_label>
<other_name>Metformin</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Calcium and Vitamin D</intervention_name>
<description>Calcium and Vitamin D tablets are registered and licensed in Singapore. For the study, we will be sourcing the Calcium and Vitamin D tablets from Singapore General Hospital Formulary.</description>
<arm_group_label>Placebo group</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Healthy adults, 21-40 years of age at time of screening

2. Body Mass Index of 20-25 kg/m2

3. No known drug allergies and are not currently receiving regular immune-modulating
therapy such as metformin, NSAIDs, paracetamol, corticosteroids or statins.

4. Subjects who give written informed consent approved by the Ethical Review Board
governing the site.

5. Satisfactory baseline medical assessment as assessed by physical examination and a
stable health status. The laboratory values must be within the normal range of the
assessing site or show abnormalities that are deemed not clinically significant as
judged by the investigator. A stable health status is defined as the absence of a
health event satisfying the definition of a serious adverse event.

6. Female subjects of childbearing potential may be enrolled in the study if they have
negative urine pregnancy tests on the day of screening.

7. Negative for diabetes mellitus by HbA1c

8. Accessible vein at the forearm for blood collection.

9. Subjects who are willing to comply with the requirements of the study protocol and
scheduled visits. (e.g., completion of the subject diary, return for follow-up visits)
and who are willing to make themselves available for the duration of the study, with
access to a consistent means of telephone contact, which may be either at home or at
the workplace, land line, or mobile, but NOT a pay phone or other multiple-user device
(i.e. a common-use phone serving multiple rooms or apartments).

Exclusion Criteria:

1. History of severe drug and/or food allergies and/or known allergies to the trial
product or its components and any ingredients in the placebo pill.

2. Any condition that, in the opinion of the investigator, would complicate or compromise
the study or wellbeing of the subject.

3. Woman who is pregnant or breast feeding.

4. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,
neuropsychiatric, or immunosuppressive disorders that would be a risk factor when
administered the Investigational Product (IP).

5. Diagnosed with cancer or on treatment for cancer within the 3 years prior to the
screening.

6. Evidence of clinically significant anemia and other any significant active
hematological disease, or having donated > 450 mL of blood within the past three
months.

7. Evidence of substance abuse, or previous substance abuse.

8. Participation in a study involving administration of an investigational compound
within the past four months, or planned participation during the duration of this
study.

9. Subjects who are on long term immune-modulating therapy (e.g. NSAIDs, Paracetamol,
Corticosteroids, Statins etc.) for other medical condition for the last 6 months.

10. Subject who are on long term medication for concurrent medical conditions.

11. Administration of any licensed vaccine within 30 days before the first study vaccine
dose.

12. Subject who has been vaccinated with YF vaccine previously.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>21 Years</minimum_age>
<maximum_age>40 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Jenny GH Low, MRCP (UK)</last_name>
<role>Principal Investigator</role>
<affiliation>Singapore General Hospital</affiliation>
</overall_official>
<overall_contact>
<last_name>Rachel Lee</last_name>
<phone>63237572</phone>
<email>rachel.lee.heng@singhealth.com.sg</email>
</overall_contact>
<overall_contact_backup>
<last_name>Lavanya Lakshmi Jeeva</last_name>
<phone>63237532</phone>
<email>lavanya.lakshmi.jeeva@singhealth.com.sg</email>
</overall_contact_backup>
<location>
<facility>
<name>Singhealth Investigational Medicine Unit</name>
<address>
<city>Singapore</city>
<zip>169608</zip>
<country>Singapore</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Rachel Lee</last_name>
<phone>63237572</phone>
<email>rachel.lee.heng@singhealth.com.sg</email>
</contact>
<contact_backup>
<last_name>Lavanya Lakshmi Jeeva</last_name>
<phone>63237532</phone>
<email>lavanya.lakshmi.jeeva@singhealth.com.sg</email>
</contact_backup>
<investigator>
<last_name>Jenny Low Guek Hong, MBBS</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location_countries>
<country>Singapore</country>
</location_countries>
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<verification_date>May 2023</verification_date>
<study_first_submitted>February 5, 2020</study_first_submitted>
<study_first_submitted_qc>February 10, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>May 4, 2023</last_update_submitted>
<last_update_submitted_qc>May 4, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">May 6, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Metformin</keyword>
<keyword>Endoplasmic Reticulum Stress</keyword>
<keyword>YF17D infection</keyword>
<keyword>Symptomatic</keyword>
<keyword>Metabolic</keyword>
<keyword>Immunometabolism</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Infections</mesh_term>
<mesh_term>Communicable Diseases</mesh_term>
<mesh_term>Virus Diseases</mesh_term>
<mesh_term>Yellow Fever</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Vitamin D</mesh_term>
<mesh_term>Metformin</mesh_term>
<mesh_term>Calcium</mesh_term>
</intervention_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
To determine the efficacy of metformin in reducing the rate of symptomatic YF17D infection,
and to elucidate the effects of metformin on YF17D viremia and the downstream adaptive immune
response, we hereby propose a randomised, double-blind, placebo-controlled clinical trial
that is coupled with a system biology approach. We plan to recruit 44 healthy volunteers aged
21-40 years, with a Body Mass Index of 20-25 kg/m2, have no known drug allergies and are not
currently receiving regular immune-modulating therapy such as metformin, NSAIDs, paracetamol,
corticosteroids or statins. The age range that we propose will ensure that our volunteers are
likely to be healthy and not be on long-term medication for other concurrent medical
conditions. This would abrogate the confounding effect of YF17D infection enhancement by
cross reactive antibodies that we have previously shown.
Informed written consent will be obtained before any physical examination is performed. All
consented subjects will undergo screening which includes a full physical examination, vital
signs measurement, clinical laboratory tests and urine pregnancy test (for female subjects of
child-bearing potential) Eligible subjects will be randomized 1:1 to either metformin 1000mg
or placebo twice daily for 7 consecutive days (Days 1-7). On Day 4, subjects will be
administered one dose of YF17D before study drug dosing.
Aim 1 tests the hypothesis that prophylactic metformin reduces ER stress and thus attenuates
the post-infection pro-inflammatory response for reduced rate of symptomatic outcome. The
primary objective for Aim 1 is to determine the efficacy of metformin in reducing the rate of
symptomatic YF17D infection using a randomized placebo-controlled clinical trial.
Aim 2 explores the effectiveness of metformin, either through its action on ER stress or
other pathways that differentially regulate the expression of pro- and anti-viral host
factors, in inhibiting live attenuated vaccine infection and downstream adaptive immune
responses. The primary objective for Aim 2 is to elucidate the effects of metformin on YF17D
viremia and the downstream adaptive immune response.
Criteria for Recruitment and Recruitment Process: Subjects will be recruited from SingHealth
Investigational Medicine Unit (IMU) healthy volunteer database and recruitment posters.
Subjects will be given a copy of the Participant Information and Informed Consent Form to
read upon their arrival. A briefing session on the study will be conducted by the
Investigator. Thereafter, subjects will be ushered into a private room where informed consent
is obtained and where questions about the study can be asked freely. Subjects will not be
rushed into making a decision to participate in the study. They will be encouraged to speak
to their family members about participation in the study; and allowed to defer their decision
(without any prejudice) to participate till after discussion with their family members.
Screening Visits and Procedures: Subjects will be recruited via the SingHealth
Investigational Medicine Unit (IMU). Informed written consent will be obtained before any
study related procedure or assessment is performed. All subjects' eligibility for recruitment
into the study must be assessed during screening visit. Subjects must satisfy all inclusion
and exclusion criteria outlined in Section 3.3 and Section 3.4 respectively to be eligible
for enrolment into the study. Eligibility criteria must be confirmed before dosing. All
clinical laboratory tests scheduled for screening will be collected to establish pre-dose
baseline. Other procedures that must be completed before the study begins include a full
physical examination and urinary pregnancy test (for female subjects of child-bearing
potential).
Study Visits and Procedures: All eligible subjects will proceed to Day 1, where they will be
randomized 1:1 to either metformin 1000mg or placebo twice daily for 7 consecutive days (Days
1-7). On Day 4, subjects will be administered one dose of YF17D before study drug dosing.
Subjects will report to the SingHealth IMU on Day 1 (pre-study drug), Day 4 (pre-YF17D), Days
5, 7, 11, 14, 18 (only for participants who consent to scRNA-seq and T-cell studies) and Day
32 for research blood sampling. The schedule for blood draws will be identical for all study
groups. All research blood samples will be stored at -80oC until recruitment is completed
before analysis. Subject recruitment and blood collection will be conducted as an outpatient
study in the SingHealth Investigational Medicine Unit (IMU), a dedicated early phase clinical
trial facility. From our prior experience, we anticipate we will not have difficulty
recruiting the required number of participants into our study necessary to meet our target
sample size.
Post Study Follow up and Procedures: There is no requirement for post-study follow-up or
procedures.
Safety Monitoring Plan: The study may be evaluated by government inspectors/regulatory
authorities who must be allowed access to e-CRFs, source documents, and other study files.
The inspectors will review CRFs and compare them with source documents to verify accurate and
complete collection of data and confirm that the study is being conducted according to the
protocol, ICH-Good Clinical Practices (ICH-GCP) and all applicable regulations.
Known common adverse events of metformin include diarrhoea, nausea, stomach pain, heartburn
and bloatedness. Rare AEs include lactic acidosis and hypoglycaemia. Limiting the duration of
metformin dosing to 10 days would further reduce the risk of these serious AEs. Subjects will
be trained to look out for early symptoms associated with these AEs and to report to IMU
immediately should they experience any of these symptoms. Details of AE event terminology,
date and time of event start and end, severity, using the CTCAE or treatment given, impact on
work and to the continuation of the study, and final outcome of the event will be recorded on
the case report until resolution of the event.
During the study, the investigator will recruit the subjects, as well as perform full history
taking and physical examination at both scheduled and unscheduled visits. The investigator
will also review the subject's diaries for any potential side effects and manage the AEs
based on best clinical practice should they arise. Compliance to study protocol will be
checked by taking a medication history, and pill count and inspection of diary as well as
measurement of metformin drug level at specific time points.
Data Quality Assurance: The PI and Co-Is will review the study periodically for data and
safety monitoring. Internal quality checks will be performed by two CRCs who are study team
members. The data entered by one CRC will be checked by another using the source documents.
The study may also be picked for monitoring by SingHealth Office of Research Integrity and
Compliance (ORIC) or evaluated by government inspectors/regulatory authorities who must be
allowed access to e-CRFs, source documents, and other study files. The monitors/inspectors
may review CRFs and compare them with source documents to verify accurate and complete
collection of data and confirm that the study is being conducted according to the protocol,
ICH-Good Clinical Practices (ICH-GCP) and all applicable regulations.
Data Entry and Storage: All participant's data will be de-identified upon recruitment.
Hardcopy research data collection forms such as CRFs, logs and diaries will be kept in the
Investigator's Site File and stored in SingHealth IMU under lock and key, accessible only to
delegated study team members. Direct data capture of demographic and clinical data will be
captured on source documents. Identifiers will be kept in a separate file in another office
and every effort will be made to protect the privacy of the participants. The data to be
analysed will contain only de-identified data. An electronic data capture system will be
used. All electronic data will be password protected and can only be accessed by study team
members. Specimens, test results or pathogen data will be stored at Duke-NUS EID laboratory
in a stand-alone PC whereby access is password protected.
Determination of Sample Size: A sample size of 20 per arm will give 80% power to detect a
reduction in systemic symptoms from 50% to 10% (risk difference = 0.4 reduction ratio = 0.8)
in participants who receive placebo versus who are pre-treated with metformin versus placebo
group at a 2-sided 5% type I error rate (PASS 13 Software). Factoring in a potential dropout
rate of 10%, the total sample size is 44 in total (22 per arm). From our previous experience
with subject recruitment in the YF vaccine trial, there were no dropouts during the 1-month
follow-up period. Therefore, we are confident that we can recruit the required number of
subjects within the trial period.
Statistical analysis: Fisher's exact test will be used to assess difference in systemic
symptom rate between placebo and metformin pre-treatment arm. Confidence intervals (CI) for
AE rates will be estimated using the exact method. CI for risk difference will be estimated
using the Newcombe's score method.
Diagnostic plots will be used to determine the choice of using the raw data or
log-transformed data in parametric analyses or non-parametric analyses. Differences in
anti-YF neutralizing antibody titer at day 28, viremia and SBREP-1 expression will be
compared between placebo and metformin groups. Relationship between systemic symptoms,
molecular correlates of immunogenicity, viremia, antibody titer and metformin will be
explored with regression methods. Differences in background characteristics between subjects
who do and do not have systemic symptom onset will be included in covariate-adjusted
analysis.
Determination of study drug blood level: Study drug levels will be measured via a liquid
chromatography-tandem mass spectrometric (LC-MS/MS) assay method. The assay will be performed
on a Shimadzu 8060 LC-MS/MS system, which is available at the Singapore General Hospital.
Gene expression studies: Gene expression in whole blood would be carried out using Nanostring
nCounter assay. This assay provides a multiplex approach to identify the genes that the
investigator have previously used to validate the hits from the microarray that identified
adaptive ER stress as a susceptibility factor for symptomatic YF17D infection (see
preliminary data). Importantly, the investigator have worked with Nanostring, to customize a
comprehensive set of probes that are able to directly quantify mRNA transcripts in the ER
stress and TCA cycle pathways, which would be the target genes in this trial. This approach
is also chosen due to the CSA budget constraint. Nonetheless, the study team will collect
extra clinical samples as backup and explore the use of RNAseq to discover the
pharmacogenomics of metformin through additional funding from other grant sources.
This proposed gene expression study will be carried out at the Viral Research and
Experimental Medicine Centre @ SingHealth Duke-NUS (ViREMiCS). ViREMiCS was established by
the PI and collaborator, Eng Eong Ooi as a research centre in the SingHealth Duke-NUS
Academic Medicine Centre partnership. It has established a suite of molecular and systems
biology tools to support and accelerate proof-of concept clinical trials. The investigators
thus do not anticipate any problem in using this approach to measure gene expression in blood
samples.
Proteomics and Metabolomic profiling: Plasma metabolomics will be examined using capillary
electrophoresis/mass spectrometry (CE/MS), and liquid chromatography/mass spectrometry
LC-MS/MS as we have previously employed to measure the polar metabolites from glycolysis and
TCA cycle [18, 25]. Proteomics will be measured using LC-MS/MS. These assays will be carried
out using the core equipment available in the Programme in Emerging Infectious Diseases and
Metabolomics Core Facility, both in Duke-NUS. This will enable a multi-omics approach to
support enhanced biological insights.
Chemokine and Cytokine: Serum chemokine and cytokine levels will be measured using the
Luminex or Olink assay that enables more than 40 serum chemokines and cytokines to be
measured simultaneously.
YF Viremia and PRNT titres: YF viremia loads will be assessed using quantitative real-time
PCR (qRT-PCR). Anti-YF neutralising antibody titres will be measured by plaque reduction
neutralisation test (PRNT). Briefly, 50 PFU (plaque forming units) of YF17D virus will be
incubated with 2-fold serial dilutions of human serum for one hour at 37oC, and then added to
a monolayer of Vero cells in 24-well plates. One hour later, media will be aspirated and
cells overlaid with carboxymethyl cellulose 1% in maintenance media. After 5 days, cells will
be fixed, washed and stained with crystal violet. The number of plaques will be counted and
PRNT50 titres determined using a sigmoid dose-response curve fit as reciprocal values.
scRNA-seq and T-cell Studies: Single cell RNA sequencing (scRNA-seq) will be performed on
PBMCs isolated before and after metformin treatment to determine the impact of metformin
treatment on different immune cell subsets. This proposed study will be carried out in
collaboration with the Genome Biology Facility at Duke-NUS. Subsequently, using the findings
of scRNA-seq as a guide, we will then assess T-cell function and activity using either flow
cytometry or enzyme-linked immune absorbent spot (ELISPOT) assay. These assays will be
carried out using core equipment available in the Programme in Emerging Infectious Diseases
in Duke-NUS.
Inclusion Criteria:
1. Healthy adults, 21-40 years of age at time of screening
2. Body Mass Index of 20-25 kg/m2
3. No known drug allergies and are not currently receiving regular immune-modulating
therapy such as metformin, NSAIDs, paracetamol, corticosteroids or statins.
4. Subjects who give written informed consent approved by the Ethical Review Board
governing the site.
5. Satisfactory baseline medical assessment as assessed by physical examination and a
stable health status. The laboratory values must be within the normal range of the
assessing site or show abnormalities that are deemed not clinically significant as
judged by the investigator. A stable health status is defined as the absence of a
health event satisfying the definition of a serious adverse event.
6. Female subjects of childbearing potential may be enrolled in the study if they have
negative urine pregnancy tests on the day of screening.
7. Negative for diabetes mellitus by HbA1c
8. Accessible vein at the forearm for blood collection.
9. Subjects who are willing to comply with the requirements of the study protocol and
scheduled visits. (e.g., completion of the subject diary, return for follow-up visits)
and who are willing to make themselves available for the duration of the study, with
access to a consistent means of telephone contact, which may be either at home or at
the workplace, land line, or mobile, but NOT a pay phone or other multiple-user device
(i.e. a common-use phone serving multiple rooms or apartments).
Exclusion Criteria:
1. History of severe drug and/or food allergies and/or known allergies to the trial
product or its components and any ingredients in the placebo pill.
2. Any condition that, in the opinion of the investigator, would complicate or compromise
the study or wellbeing of the subject.
3. Woman who is pregnant or breast feeding.
4. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,
neuropsychiatric, or immunosuppressive disorders that would be a risk factor when
administered the Investigational Product (IP).
5. Diagnosed with cancer or on treatment for cancer within the 3 years prior to the
screening.
6. Evidence of clinically significant anemia and other any significant active
hematological disease, or having donated > 450 mL of blood within the past three
months.
7. Evidence of substance abuse, or previous substance abuse.
8. Participation in a study involving administration of an investigational compound
within the past four months, or planned participation during the duration of this
study.
9. Subjects who are on long term immune-modulating therapy (e.g. NSAIDs, Paracetamol,
Corticosteroids, Statins etc.) for other medical condition for the last 6 months.
10. Subject who are on long term medication for concurrent medical conditions.
11. Administration of any licensed vaccine within 30 days before the first study vaccine
dose.
12. Subject who has been vaccinated with YF vaccine previously.
|
NCT0426xxxx/NCT04267822.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267822</url>
</required_header>
<id_info>
<org_study_id>REVC006</org_study_id>
<secondary_id>C5241011</secondary_id>
<nct_id>NCT04267822</nct_id>
</id_info>
<brief_title>Study of RV521 in the Treatment of Adult Subjects Who Have Undergone HCT With an URTI With RSV</brief_title>
<acronym>REVIRAL2</acronym>
<official_title>Randomized, Double-blind, Placebo-controlled Trial of the Safety, Tolerability, and Efficacy of RV521 in the Treatment of Adult Subjects Who Have Undergone Hematopoietic Cell Transplantation (HCT) With a Documented Upper Respiratory Tract Infection (URTI) With Respiratory Syncytial Virus (RSV)</official_title>
<sponsors>
<lead_sponsor>
<agency>Pfizer</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
</sponsors>
<source>Pfizer</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
RV521 is to being developed to treat RSV infection and disease in susceptible individuals at
high risk for complications. This is an international, multicenter, placebo-controlled study.
Eligible subjects are adults with a documented symptomatic RSV infection who have undergone
HCT transplantation and are moderately to severely immunocompromised. Qualified subjects will
be randomized in a 1:1 ratio to receive RV521 or placebo, twice daily for 10 days.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
The purpose of this study is to compare the viral load, safety, tolerability, and clinical
efficacy of RV521 compared to placebo. This is a Phase 2, international, multicenter,
randomized, double-blind, placebo-controlled study. Up to 200 adult subjects with a
documented symptomatic RSV URTI who have undergone HCT within 1 year of randomization and who
are moderately to severely immunocompromised will be randomized.

Qualified subjects will be randomized in a 1:1 ratio to receive RV521 capsules or matching
placebo twice daily for 10 days. After the completion of the 10-day double-blind treatment
period, subjects will be followed for an additional 28 days. Study drug may be taken on an
outpatient or inpatient basis, depending on clinical status and site practices. Randomization
will be stratified by type of HCT graft and ALC count. There are 9 clinic visits planned for
this study.
</textblock>
</detailed_description>
<overall_status>Withdrawn</overall_status>
<why_stopped>
No recruitment
</why_stopped>
<start_date type="Anticipated">June 15, 2020</start_date>
<completion_date type="Anticipated">July 31, 2023</completion_date>
<primary_completion_date type="Anticipated">June 30, 2023</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>A Phase 2, international, multicenter, randomized, double-blind, placebo-controlled study.</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
<masking_description>The Investigators, Sponsor, Independent Adjudication Committee members, and any personnel involved in the subject's care, assessment, monitoring, data collection, or analysis will be blinded to the subject treatment assignment throughout the conduct of the study. Exceptions to this are limited to a fire-walled-protected, unblinded Data Safety Monitoring Board (DSMB) statistician at the Contract Research Organization (CRO) who will prepare output for the closed session of all DSMB meetings.</masking_description>
</study_design_info>
<primary_outcome>
<measure>Proportion of subjects with a progression to Lower Respiratory Tract Complication (LRTC) during the study</measure>
<time_frame>Pre-dose baseline (Day 1) through Visit 8 (Day 28)</time_frame>
<description>Progression to LRTC during the study defined as one of the following:
Primary LRTI caused by RSV
Secondary bacterial LRTI
LRTI caused by another pathogen
LRTC of unknown etiology</description>
</primary_outcome>
<primary_outcome>
<measure>Change in RSV nasal viral load (via RT-qPCR)</measure>
<time_frame>Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28)</time_frame>
<description>RSV change measured by the time-weighted average (DAVG) viral load using RT qPCR</description>
</primary_outcome>
<secondary_outcome>
<measure>Percent of participants who experience AEs, TEAEs, SAEs and withdrawals due to TEAEs</measure>
<time_frame>First dose of study drug through Visit 8 (Day 28)</time_frame>
<description>Safety analyses will include a summary of AEs, including but not limited to n (%) of subjects in each treatment group and overall.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Evaluate safety and tolerability of RV521 by assessing changes from baseline in systolic and diastolic BP (vital sign parameters)</measure>
<time_frame>Baseline through Visit 8 (Day 28)</time_frame>
<description>BP will be collected in mm Hg. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Evaluate safety and tolerability of RV521 by assessing changes from baseline in body temperature (vital sign parameters)</measure>
<time_frame>Baseline through Visit 8 (Day 28)</time_frame>
<description>Body Temperature will be collected in degrees Fahrenheit (°F) or degrees Celsius (°C). Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Evaluate safety and tolerability of RV521 by assessing changes from baseline in respiration rate (vital sign parameters)</measure>
<time_frame>Baseline through Visit 8 (Day 28)</time_frame>
<description>Respiration rate will be measured in breaths per minute. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Evaluate safety and tolerability of RV521 by assessing changes from baseline in pulse/heart rate (vital sign parameters)</measure>
<time_frame>Baseline through Visit 8 (Day 28)</time_frame>
<description>Heart rate will be measured in beats per minute. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Evaluate safety and tolerability of RV521 by assessing changes from baseline weight/BMI</measure>
<time_frame>Baseline through Visit 8 (Day 28)</time_frame>
<description>Weight and height will be collected and combined to report BMI</description>
</secondary_outcome>
<secondary_outcome>
<measure>Evaluate the proportion of subjects with changes and shifts in hematology/clinical chemistry/urinalysis laboratory values (laboratory tests read by a central lab) from baseline.</measure>
<time_frame>Collected at Visit 2/Day 1 (pre-dose), Visit 4/Day 3, Visit 6/Day 14 and Visit 8/Day 28</time_frame>
<description>Results at each visit will be summarized using the statistics n, mean, standard deviation, median, minimum and maximum. Also, change from baseline will also be summarized by post baseline visits.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Evaluate the proportion of subjects with changes in ECG measurements and changes in clinical impression from baseline</measure>
<time_frame>Measurements will be taken at Day 1/Visit 2 (pre-dose and at 5-hours post-dose), on Day 3/Visit 4 (at 5 hours post-dose), and at Visit 6 (Day 14)</time_frame>
<description>ECGs will be taken with a centrally supplied ECG machine and electronically transmitted to a central ECG repository. ECG will only be evaluated by the Investigator for normal, abnormal NCS and abnormal CS.
Parameters collected will be:
Ventricular Heart Rate (bpm)
PR Interval (msec)
QRS Interval (msec)
QT Interval (msec)
QTcB Interval (msec)
Results at each visit will be summarized using the statistics: n (number of observations), mean, SD, median, minimum and maximum.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Relationship between plasma exposures of RV521 and RSV viral loads measured in nasal swabs by RT-qPCR</measure>
<time_frame>Pre-dose baseline (Day 1) and every visit through Visit 8 (Day 28)</time_frame>
<description>Nasal swabs will be collected for analysis of viral load and RSV F protein gene sequencing at a central laboratory. Viral load will be assessed at intervals from nasal swabs by RT-qPCR.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Relationship between plasma exposures of RV521 and RSV viral loads measured in nasal swabs by CBIA</measure>
<time_frame>Pre-dose baseline (Day 1) and every visit through Visit 8 (Day 28)</time_frame>
<description>Nasal swabs will be collected for analysis of viral load and RSV F protein gene sequencing at a central laboratory. Viral load will be assessed at intervals from nasal swabs by CBIA.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mean change in RSV viral load assessed via CBIA</measure>
<time_frame>Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28)</time_frame>
<description>change measured by the time weighted average (DAVG) viral load using CBIA</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mean change from baseline in viral RNA shedding</measure>
<time_frame>Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28)</time_frame>
<description>RSV assessed via nasal swabs collected at each visit and analyzed at a central laboratory.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Proportion of subjects who no longer shed RSV assessed by both RT-qPCR and CBIA at each timepoint</measure>
<time_frame>Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28)</time_frame>
<description>RSV assessed via nasal swabs collected at each visit and analyzed at a central laboratory.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Time to improvement in RSV-related symptoms</measure>
<time_frame>Daily from baseline (Day 1) through Visit 8 (Day 28)</time_frame>
<description>Defined as all symptoms present at initiation of therapy are mild or no longer present. (absent/resolved)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Time to total resolution of all RSV-related symptoms</measure>
<time_frame>Daily from baseline (Day 1) through Visit 8 (Day 28)</time_frame>
<description>Defined as all symptoms are no longer present.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Proportion of days with lowest daily SpO2 ≥ 90% on room air</measure>
<time_frame>Daily from baseline (Day 1) through Visit 8 (Day 28)</time_frame>
<description>SpO2 measured at every visit. For subjects on oxygen or who are mechanically ventilated may have this waived.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of days where supplementary oxygen was required</measure>
<time_frame>Baseline (Day 1) through Visit 8 (Day 28)</time_frame>
<description>Use of daily supplementary oxygen will be collected throughout the study.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Proportion of subjects who require hospitalization during the study</measure>
<time_frame>Baseline (Day 1) through Visit 8 (Day 28)</time_frame>
<description>Daily hospitalization utilization will be collected</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mean number of days of hospitalization during the study</measure>
<time_frame>Baseline (Day 1) through Visit 8 (Day 28)</time_frame>
<description>Daily hospitalization utilization will be collected</description>
</secondary_outcome>
<secondary_outcome>
<measure>Proportion of subjects requiring ICU</measure>
<time_frame>Baseline (Day 1) through Visit 8 (Day 28)</time_frame>
<description>Daily ICU utilization will be collected</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mean number of days in ICU</measure>
<time_frame>Baseline (Day 1) through Visit 8 (Day 28)</time_frame>
<description>Daily ICU utilization will be collected</description>
</secondary_outcome>
<secondary_outcome>
<measure>Proportion of subjects requiring mechanical ventilation</measure>
<time_frame>Baseline (Day 1) through Visit 8 (Day 28)</time_frame>
<description>Daily mechanical ventilation requirements will be collected</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of subjects who experience death (all-cause mortality)</measure>
<time_frame>First dose of study drug through Visit 8 (Day 28)</time_frame>
<description>Patient outcome will be followed and collected</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of subjects who experience death attributable to LRTC</measure>
<time_frame>First dose of study drug through Visit 8 (Day 28)</time_frame>
<description>Patient outcome will be followed and collected</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">0</enrollment>
<condition>RSV Infection</condition>
<condition>Stem Cell Transplant Complications</condition>
<condition>Lower Resp Tract Infection</condition>
<arm_group>
<arm_group_label>RV521 Capsules</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>RV521 is formulated as a dry powder blend of RV521 drug substance with mannitol as excipient. They are a white, opaque capsule and administered orally.</description>
</arm_group>
<arm_group>
<arm_group_label>RV521 Placebo Capsules</arm_group_label>
<arm_group_type>Placebo Comparator</arm_group_type>
<description>RV521 placebo capsules will contain mannitol and microcrystalline cellulose only. They are a white, opaque capsule and administered orally.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>RV521 oral tablet</intervention_name>
<description>Each RV521 dose is four 50 mg dry powder blend capsules, taken orally twice daily for 10 days (20 doses total; 80 capsules total)</description>
<arm_group_label>RV521 Capsules</arm_group_label>
<other_name>sisunatovir</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Placebo oral tablet</intervention_name>
<description>Each placebo dose is four capsules, taken orally twice daily for 10 days (20 doses total; 80 capsules total)</description>
<arm_group_label>RV521 Placebo Capsules</arm_group_label>
<other_name>vehicle</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Has undergone autologous or allogeneic HCT using any conditioning regimen within 1
year of randomization. Subjects who have undergone HCT more than 1 year before
Randomization are eligible if all other inclusion/exclusion criteria are satisfied and
under at least one of the following conditions:

1. Diagnosed with Chronic Graft-vs-Host Disease (GVHD), or

2. Has used systemic corticosteroids in the 30 days prior to RSV infection

2. Has moderate to severe immunocompromise, defined as a score ≥ 5 on the ISI-RSV and/or
an ALC of ≤ 500 cells/ mm3

3. Documentation of positive RSV infection in the upper airway

Exclusion Criteria:

1. Use of non-marketed investigational agents within 30 days, OR use of an
investigational monoclonal anti-RSV antibodies within 4 months or 5 half-lives of
screening, whichever is longer, OR use of any investigational RSV vaccines after HCT.

2. Receiving a prescription, OTC, or herbal medication that is a potent inducer or
inhibitor of CYP3A4, within 2 weeks of Randomization.

3. Receiving a prescription, OTC, or herbal medication that is a substrate of CYP3A4 with
a narrow therapeutic index where monitoring blood levels is not possible.

4. Known chronic infection with hepatitis B, C, or HIV.

5. Is in the pre-engraftment period during RSV infection.

6. Admitted to the hospital primarily for lower respiratory tract disease of any cause as
determined by the Investigator.

7. Any condition requiring mechanical ventilation or vasopressor support at the time of
randomization.

8. Clinically significant bacteremia or fungemia within 5 days prior to Screening that
has not been adequately treated.

9. Clinically significant bacterial, fungal, or viral pneumonia within 2 weeks prior to
Screening that has not been adequately treated.

10. Excessive nausea/vomiting at Screening or an inability to swallow capsules.

11. Elevation of hepatic enzymes or renal compromise.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>75 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>PfizerCT.gov Call Center</last_name>
<role>Study Director</role>
<affiliation>Pfizer</affiliation>
</overall_official>
<removed_countries>
<country>Australia</country>
<country>Brazil</country>
<country>Korea, Republic of</country>
<country>Taiwan</country>
<country>United States</country>
</removed_countries>
<verification_date>May 2023</verification_date>
<study_first_submitted>February 5, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>May 4, 2023</last_update_submitted>
<last_update_submitted_qc>May 4, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">May 8, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>RV521</keyword>
<keyword>lower respiratory tract complication</keyword>
<keyword>HCT</keyword>
<keyword>hematopoietic cell transplantation</keyword>
<keyword>LRTI</keyword>
<keyword>Respiratory tract infection</keyword>
<keyword>immunocompromise</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Infections</mesh_term>
<mesh_term>Communicable Diseases</mesh_term>
<mesh_term>Respiratory Tract Infections</mesh_term>
<mesh_term>Respiratory Syncytial Virus Infections</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>Yes</sharing_ipd>
<ipd_description>Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.</ipd_description>
<ipd_url>https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests</ipd_url>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
RV521 is to being developed to treat RSV infection and disease in susceptible individuals at
high risk for complications. This is an international, multicenter, placebo-controlled study.
Eligible subjects are adults with a documented symptomatic RSV infection who have undergone
HCT transplantation and are moderately to severely immunocompromised. Qualified subjects will
be randomized in a 1:1 ratio to receive RV521 or placebo, twice daily for 10 days.
The purpose of this study is to compare the viral load, safety, tolerability, and clinical
efficacy of RV521 compared to placebo. This is a Phase 2, international, multicenter,
randomized, double-blind, placebo-controlled study. Up to 200 adult subjects with a
documented symptomatic RSV URTI who have undergone HCT within 1 year of randomization and who
are moderately to severely immunocompromised will be randomized.
Qualified subjects will be randomized in a 1:1 ratio to receive RV521 capsules or matching
placebo twice daily for 10 days. After the completion of the 10-day double-blind treatment
period, subjects will be followed for an additional 28 days. Study drug may be taken on an
outpatient or inpatient basis, depending on clinical status and site practices. Randomization
will be stratified by type of HCT graft and ALC count. There are 9 clinic visits planned for
this study.
Inclusion Criteria:
1. Has undergone autologous or allogeneic HCT using any conditioning regimen within 1
year of randomization. Subjects who have undergone HCT more than 1 year before
Randomization are eligible if all other inclusion/exclusion criteria are satisfied and
under at least one of the following conditions:
1. Diagnosed with Chronic Graft-vs-Host Disease (GVHD), or
2. Has used systemic corticosteroids in the 30 days prior to RSV infection
2. Has moderate to severe immunocompromise, defined as a score ≥ 5 on the ISI-RSV and/or
an ALC of ≤ 500 cells/ mm3
3. Documentation of positive RSV infection in the upper airway
Exclusion Criteria:
1. Use of non-marketed investigational agents within 30 days, OR use of an
investigational monoclonal anti-RSV antibodies within 4 months or 5 half-lives of
screening, whichever is longer, OR use of any investigational RSV vaccines after HCT.
2. Receiving a prescription, OTC, or herbal medication that is a potent inducer or
inhibitor of CYP3A4, within 2 weeks of Randomization.
3. Receiving a prescription, OTC, or herbal medication that is a substrate of CYP3A4 with
a narrow therapeutic index where monitoring blood levels is not possible.
4. Known chronic infection with hepatitis B, C, or HIV.
5. Is in the pre-engraftment period during RSV infection.
6. Admitted to the hospital primarily for lower respiratory tract disease of any cause as
determined by the Investigator.
7. Any condition requiring mechanical ventilation or vasopressor support at the time of
randomization.
8. Clinically significant bacteremia or fungemia within 5 days prior to Screening that
has not been adequately treated.
9. Clinically significant bacterial, fungal, or viral pneumonia within 2 weeks prior to
Screening that has not been adequately treated.
10. Excessive nausea/vomiting at Screening or an inability to swallow capsules.
11. Elevation of hepatic enzymes or renal compromise.
|
NCT0426xxxx/NCT04267835.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267835</url>
</required_header>
<id_info>
<org_study_id>PKU MICS study</org_study_id>
<nct_id>NCT04267835</nct_id>
</id_info>
<brief_title>Prospective Cohort Study on Minimal Invasive Coronary Surgery</brief_title>
<acronym>PCSMICS</acronym>
<official_title>Prospective Cohort Study on Mid-term Safety and Effectiveness of Minimal Invasive Coronary Artery Bypass Grafting</official_title>
<sponsors>
<lead_sponsor>
<agency>Peking University Third Hospital</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Peking University Third Hospital</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
CABG technology is recognized as the preferred treatment, and its major adverse cardiac and
cerebral event(MACCE) incidence and mortality are lower than percutaneous coronary
intervention(PCI). However, the traditional CABG procedure requires sternal incision, large
trauma and long recovery period after surgery.

How to reduce trauma and treat multiple complex coronary lesions under minimally invasive
conditions has become a hot spot. MIDCAB surgery can complete the coronary anastomosis only
by a 6-8 cm incision in the left chest. It has been more than ten years since the first
literature report in the world, however, due to the technical bottleneck, a unified and
standardized surgical procedure has not yet been formed. Some centers are still in the
exploratory stage, and internationally Large-scale studies of clinical outcomes (mostly less
than 150 cases) have not been reported. Assessing the minimally invasive procedure's safety
and effectiveness has become an urgent problem to be solved.

At present, our center has completed nearly 200 cases of small incision multi-coronary
coronary artery bypass graft surgery. The investigators evaluate the patency of the graft by
the postoperative of angiography, the patency of grafts is more than 95%, and there is no
statistical difference with conventional OPCABG. On the other hand, focus on the
postoperative complications, there was no significant difference in the incidence of MACCE
and revascularization between the MIDCAB group and conventional surgery during
hospitalization. The investigators assume that the early results of this procedure are safe
and effective. MIDCAB has a congenital advantage because of its' reduction of the trauma of
the thoracotomy and the aesthetics of the incision. Therefore, if a larger sample size study
and mid-term follow-up results are obtained, and the conclusion prove that the safety of the
small incision surgery and the patency of the grafts are not inferior to conventional
surgery. The investigators can consider that minimal invasive coronary surgery(MICS) is a
technique worth trying to promote.

Through this prospective cohort study, the investigators evaluated the safety of MICS through
mid-term follow-up results and asses the efficiency by the results of grafts patency
(angiography or CT within 30 days after surgery) and medical outcomes study-short from
scores(SF-36), establish the surgical standard and perioperative management method.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
1. MIDCAB procedure introduction

1. Surgery preparation:

General anesthesia, double lumen tracheal intubation. In the supine position, tilt
15° to the right. An automatic defibrillation electrode is attached to the right
front and left rear chest wall, and the external defibrillator is connected. A
small incision of 8-10 cm into the left anterior lateral 5th intercostal space was
performed into the chest.

2. Internal mammary artery acquisition:

After entering the chest, the IMA is exposed through a new minimal invasive
retraction system. Single or bilateral IMA is obtained as needed. Separate the IMA
From the middle segment (non-fat muscle coverage area) applied with an electric
scalpel (15J), and the free range was up to the first rib to the fifth or sixth
intercostal(IMA bifurcation).

3. Bypass strategy:

All procedures were performed under a non-cardiopulmonary situation, and vascular
anastomosis was performed with the aid of a laparoscopic cardiac stabilizer. The
stabilizer is smaller and does not occupy the operating space. The head of
stabilizer can be rotated 360 degrees and the target vessel can be fixed at any
angle. Bilateral internal mammary artery, radial artery and saphenous vein can be
used as graft vessels. The bypass strategy is not particularly different from
conventional bypass surgery, including aorta(AO)-saphenous vein graft (SVG) or
radial artery(RA)-X1-X2-...( sequential anastomosis), left internal mammary
artery(LIMA)-right internal mammary artery(RIMA) -RA or SVG(Y)-X, RIMA-left
anterior descending(LAD), LIMA-RA or RIMA or SVG(I)-X1-X2 and so on.

4. Vascular anastomosis:

The target vessel is exposed through the pericardial suture, the heart is locally
fixed with the aid of a cardiac stabilizer, and the target vessel is inserted shunt
to avoid hemodynamic disorder and arrhythmia. Vascular anastomosis is performed by
8-0 polypropylene suture.

5. Aortic exposure and proximal anastomosis:

Place gauze behind the aorta, expose the aorta with the right pericardial
suspension suture, temporary block aortic anterior wall with a soft-chain sidewall
clamp, Punch on the aortic anterior wall with 3.5mm puncher, anastomose SVG or RA
on AO with 6-0 polypropylene suture.

6. postoperative management: Patients go to the cardiac ICU ward postoperatively. The
investigators closely observe the electrocardiogram and myocardial enzyme changes,
maintain a mean arterial pressure more than 70 mmHg perfusion pressure, and the use
of nitrate ester drug to relax coronary, Begin with oral aspirin (100 mg, qd)
antiplatelet therapy as soon as tracheal intubation is removed. Complete chest
X-ray, cardiac ultrasound and coronary angiography before discharge.

7. Patient selection Because MIDCAB requires the heart to be exposed through the
lateral incision, it is necessary to avoid the difficulty of exposure caused by
thoracic deformity, adhesion or obesity; it is not suitable for MIDCAB in patients
with extremely low cardiac function and severe heart enlargement; Because of the
necessity of single-side ventilation, such as patients with severe pulmonary
dysfunction before surgery, should also avoid small incision surgery. See the
eligible and exclusion criteria for details.

2. Baseline matching problem MIDCAB is more rigorous in terms of patient selection, such as
weight, EF%, and lung function, thus the study will use a propensity score method to
match the baseline of two groups to eliminate the baseline bias.

Baseline factor： General: gender, age, BMI History and comorbidities：Smoke, Diabetes
(diagnostic criteria: oral hypoglycemic agents, insulin therapy, HbA1c greater than
7.0%, postprandial blood glucose greater than 11.1mmol/L, fasting plasma glucose greater
than 7.0mmol/L), previous stroke(CT showed large area softening lesion) and presence of
neurological dysfunction (paralysis, weak muscles, aphasia, paresthesia, and difficulty
urinating), Hyperlipidemia (administered or admitted to hospital serum cholesterol
greater than 5.17mmol / L or 200mg / dl), high blood pressure (blood pressure greater
than 140 / 90 mmHg without medication), renal insufficiency (dialysis or serum
creatinine level greater than 140mmol / L ), Peripheral vascular disease (preoperative
ultrasound or CT confirmed peripheral vascular stenosis greater than 50%), previous
history of cardiac surgery, previous PCI history (balloon dilatation or stent
implantation)

Preoperative status: Classification of angina (stable angina pectoris, unstable angina
pectoris, non st-t segment elevation myocardial infarction, st-t segment elevation
myocardial infarction), previous myocardial infarction history(pathological Q wave on
ECG, abnormal segment motion on lesion area accompany with low EF% or clear and
definitely evidence of elevation of creatine kinase(CK-MB) or troponin(cTnI), New York
Heart Association(NYHA) heart function classification.

Preoperative examination:creatinine(Cr), N-terminal pro brain natriuretic
peptide(NT-proBNP), total cholesterol(TG) and low density lipoprotein(LDL) level,
preoperative cardiac function (EF%, LVEDmm), SYNTAX score (evaluation by cardiologist).

Preoperative medication (within 1 week): aspirin, clopidogrel

3. statistical methods The primary endpoint of 12 months MACCE will be analysis by
non-inferiority method. The small incision surgery has advantage of little trauma and
the aesthetics of the incision. According to the results of previous studies and
literature reports, the 1 year graft's patency is assumed to be 96% in the MICS group,
96% in the control group, test performance β=90%, in the single-tail test α=0.025,
△=0.06, the investigators expected the sample size of each group is required to be 168,
and assume drop rate is about 15%, and finally 190-200 cases are needed in each group.
In the OPCABG group, considering the propensity score matching efficiency of 0.5, it may
be need more cases.

The other primary endpoints of Physical Component Scale (PCS) will be analysis by superior
effect test. The higher the PCS score of SF-36 scale, the better the patient's physiological
health. According to previous studies and literature reports, the average PCS score of SF-36
scale on the 30th day after CABG was 43 with a standard deviation of 10. The PCS difference
of SF-36 scale with the smallest clinical significance reported in literature was 2. Through
previous studies, the average PCS score on the 30th day after CABG in MICS group was 50.
Assuming that the lower line of 95% confidence interval of PCS score difference between
MICS-CABG group and OPCABG group is greater than 2, it is considered that the PCS score of
MICS-CABG group is better than OPCABG group, with inspection level α=0.025 (one side) and
inspection efficiency 1-β=0.80. The sample size of OPCABG group and MICS group is calculated
to be 65 cases, with an estimated miss rate of 20%, and each group needs to include at least
82 people.

Based on the above conclusions, The investigators calculated sample size is 200 cases in each
group.

After establishing the database, the logistic regression model will be established，the
dependent variable is surgery procedure（MICS surgery）, the independent variable are baseline
factor, and the receiver operating characteristic curve(ROC) will be drawn. The logistic
regression model will be used to calculate the prone score(PS) of each subject. The nearest
neighbor matching method will be used to select the thoracotomy OPCABG cases in a 1:1 ratio
according to the priority matching method.

According to the basic principles of Intention-to-Treat (ITT), the whole analysis set was
used. The analysis of the main indicators will include all randomized subjects, whether or
not they will complete the test, the data will be included in the analysis.

Statistics data include baseline analysis, primary endpoints, secondary endpoints,
observations, and compliance indicators. Measurement data that conformed to the normal
distribution will be statistically described using mean ± standard deviation (χ ± S，using t
test). Non-normally distributed measurement data will be statistically described using median
and quartiles (using variance or nonparametric tests). The grade data will be tested using
rank sum test. The count data will be statistically described as a percentage, and two or
more independent sample rates will be compared using a chi-square test. Fisher's exact
probability analysis will be used for indicators with low index positives (expected value
<5). Survival-related data will be applied by proportional hazards model(COX) regression and
survival curve risk.

Describe the missing value processing method: The estimation of the missing value of the main
indicator is carried forward using the closest observation when selecting the full analysis
set for statistical analysis,

5、 Ethics and safety Ethics: This research has been reviewed and filed by the Ethics
Committee of the Third Hospital of Peking University. Informed consent will be signed before
each participating patient was enrolled Safety: Through pre-research, MICS is a safe and
effective new surgical procedure. At present, the investigators have completed more than 200
MICS operations. Only 2 of these patients died, and the postoperative complications and
mid-term follow-up results were counted. The rate of graft patency and complications is not
inferior to thoracotomy OPCABG surgery.

6、 Quality control Access system: MICS surgery is limited by the operation space. Although
the multiple minimal invasive bypass surgery can be achieved routinely at present in our
center, this surgery requires high skill and long learning curve. The cardiac surgery will
strictly implement the surgeon's access qualification and have regular bypass surgery 300.
For example, in the case of a small incision, only 50 patients with more than one bypass
surgery, after a discussion within the department and approved by the core group, can perform
small incision multi-bridge surgery.

Safeguard plan: For each case of small incision surgery, the patient's clinical data will be
evaluate preoperative in our center by more than 3 senior surgeons. The surgical plan is
strictly according to the standard of admission; Femoral arteriovenous will be routinely
prepared for emergency cardiopulmonary bypass(CPB) and intraaortic balloon pumping(IABP)
implantation. Transformation to thoracotomy surgery will be carried out if hemorrhage,
uncontrollable hemodynamic disorder and malignant arrhythmia occured.

Termination of research criteria:

To ensure the safety of all candidates, a quality and safety management team will be
established to monitor the complications and major safety indicators of the MICS group. The
data were collected monthly to monitor serious complications (death, MACCE, unplanned
revascularization, reoperation etc.) Our research will be terminated when any of the serious
complications happen more than 5 cases .
</textblock>
</detailed_description>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">April 4, 2020</start_date>
<completion_date type="Anticipated">December 31, 2025</completion_date>
<primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Rate of 1 years graft occlusion rate</measure>
<time_frame>12 months after the MIDCAB or OPCABG surgery</time_frame>
<description>12 months occlusion rate of graft(Evaluate by angiography of CT angiography )</description>
</primary_outcome>
<primary_outcome>
<measure>30 days PCS scores</measure>
<time_frame>30days after the MIDCAB or OPCABG surgery</time_frame>
<description>PCS scores calculated from the SF-36</description>
</primary_outcome>
<primary_outcome>
<measure>30 days mental health summary scales(MCS) of SF-36 scores</measure>
<time_frame>30days after the MIDCAB or OPCABG surgery</time_frame>
<description>MCS scores calculated from the SF-36</description>
</primary_outcome>
<secondary_outcome>
<measure>Rate of 30 days graft occlusion rate</measure>
<time_frame>within 30days after the MIDCAB or OPCABG surgery</time_frame>
<description>perioperative occlusion rate of graft(Evaluate by angiography of CT angiography )</description>
</secondary_outcome>
<secondary_outcome>
<measure>MCS scores</measure>
<time_frame>7 days, 3 months, 6 months and 12 months after the MIDCAB or OPCABG surgery</time_frame>
<description>MCS scores calculated from the SF-36</description>
</secondary_outcome>
<secondary_outcome>
<measure>PCS scores</measure>
<time_frame>7 days, 3 months, 6 months and 12 months after the MIDCAB or OPCABG surgery</time_frame>
<description>PCS scores calculated from the SF-36</description>
</secondary_outcome>
<secondary_outcome>
<measure>Rate of Perioperative MACCE</measure>
<time_frame>Within 30 days of the MIDCAB or OPCABG surgery</time_frame>
<description>Major adverse cardiovascular and cerebrovascular events（ Composite endpoint of Myocardial infarction, Stroke and death)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Rate of mid-term MACCE incidence</measure>
<time_frame>12 months after the MIDCAB or OPCABG surgery</time_frame>
<description>Major adverse cardiovascular and cerebrovascular events（ Composite endpoint of Myocardial infarction, Stroke and death)</description>
</secondary_outcome>
<other_outcome>
<measure>Number of Transfusion volume</measure>
<time_frame>Within 30 days after the MIDCAB or OPCABG surgery</time_frame>
<description>Perioperative transfusion number(U) of red blood cell</description>
</other_outcome>
<other_outcome>
<measure>mechanical ventilation time (hours)</measure>
<time_frame>Within 30 days after the MIDCAB or OPCABG surgery</time_frame>
<description>Perioperative mechanical ventilation time</description>
</other_outcome>
<other_outcome>
<measure>Rate of wound infection</measure>
<time_frame>Within 90 days of the MIDCAB or OPCABG surgery</time_frame>
<description>wound infection performed as redness, exudation, cracking, delayed healing that need surgical suture</description>
</other_outcome>
<other_outcome>
<measure>Rate of secondary surgery</measure>
<time_frame>Within 30 days after the MIDCAB or OPCABG surgery</time_frame>
<description>All cause secondary surgery event such as bleeding, hemodynamic instability, sternum fracture or wound infection etc.</description>
</other_outcome>
<other_outcome>
<measure>Rate of other complications</measure>
<time_frame>Within 30 days after the MIDCAB or OPCABG surgery</time_frame>
<description>Renal failure、atrial fibrillation、postoperativeIABP implantation、postoperative extracorporeal membrane oxygenation(ECMO) implantation etc.</description>
</other_outcome>
<other_outcome>
<measure>Rate of Perioperative mortality</measure>
<time_frame>Within 30 days of the MIDCAB or OPCABG surgery</time_frame>
<description>all cause death no matter cardiogenic death or non-cardiogenic death</description>
</other_outcome>
<other_outcome>
<measure>Rate of Mid-term mortality</measure>
<time_frame>Within 12 months after the MIDCAB or OPCABG surgery</time_frame>
<description>all cause death no matter cardiogenic death or non-cardiogenic death</description>
</other_outcome>
<other_outcome>
<measure>Rate of Revascularization</measure>
<time_frame>Within 12 months after the MIDCAB or OPCABG surgery</time_frame>
<description>Receive PCI or Redo-CABG because of graft stenosis or occlusion</description>
</other_outcome>
<number_of_groups>2</number_of_groups>
<enrollment type="Anticipated">400</enrollment>
<condition>Coronary Artery Bypass, Off-Pump</condition>
<arm_group>
<arm_group_label>MICS (Minimal invasive coronary surgery)</arm_group_label>
<description>Patients undergoing MIDCAB surgery.</description>
</arm_group>
<arm_group>
<arm_group_label>OPCABG (thoracotomy off-pump CABG)</arm_group_label>
<description>Patients undergoing thoracotomy OPCABG surgery</description>
</arm_group>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>MIDCAB</intervention_name>
<description>Surgery: MIDCAB</description>
<arm_group_label>MICS (Minimal invasive coronary surgery)</arm_group_label>
</intervention>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>thoracotomy OPCABG</intervention_name>
<description>Surgery: thoracotomy OPCABG</description>
<arm_group_label>OPCABG (thoracotomy off-pump CABG)</arm_group_label>
</intervention>
<eligibility>
<study_pop>
<textblock>
Patients are planned for undergoing off-pump coronary artery bypass surgery.
</textblock>
</study_pop>
<sampling_method>Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

Patients are planned for undergoing off-pump coronary artery bypass surgery.

Exclusion Criteria:

1. BMI greater than 28

2. trauma, surgical or radiotherapy history of left chest

3. EF less than 40%

4. Simultaneous other cardiac surgery or planned cardiopulmonary bypass

5. Preoperative critical situation: acute myocardial infarction, heart failure and other
conditions require emergency surgery. Preoperative nitrate drugs are difficult to
control angina and needs IABP implantation.

6. Respiratory function: severe hypoxemia (pO2 less than 60 mmHg without Oxygen
inhalation), carbon dioxide retention (pCO2 > 50 mmHg), severe chronic obstructive
pulmonary disease (FEV1/forced vital capacity less than 70% and FEV1 less than 50%)

7. Aortic lesions: patients with ascending aorta calcification confirmed by preoperative
CT

8. Peripheral vascular lesions:By the preoperative assessment with ultrasound or CT，LIMA
and left subclavian artery stenosis>70% ,or bilateral femoral artery calcification,
stenosis>50%

9. Drug therapy: Preoperative antiplatelet or anticoagulant therapy (except aspirin and
clopidogrel)

10. Others: Exclusion criteria and contraindications of CABG
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>25 Years</minimum_age>
<maximum_age>85 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Yunpeng Ling, Doctor</last_name>
<role>Study Chair</role>
<affiliation>Peking University Third Hospital</affiliation>
</overall_official>
<overall_official>
<last_name>Yichen Gong, Doctor</last_name>
<role>Principal Investigator</role>
<affiliation>Peking University Third Hospital</affiliation>
</overall_official>
<overall_contact>
<last_name>Yichen Gong, Doctor</last_name>
<phone>8618611693463</phone>
<email>18611693463@126.com</email>
</overall_contact>
<location>
<facility>
<name>Peking University Third Hospital</name>
<address>
<city>Beijing</city>
<state>Beijing</state>
<zip>100191</zip>
<country>China</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Yichen Gong, Doctor</last_name>
<phone>8618611693463</phone>
<email>18611693463@126.com</email>
</contact>
<contact_backup>
<last_name>Yunpeng Ling, Doctor</last_name>
<phone>8613910315963</phone>
<email>yunpengling@163.com</email>
</contact_backup>
</location>
<location_countries>
<country>China</country>
</location_countries>
<verification_date>February 2020</verification_date>
<study_first_submitted>May 19, 2019</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>November 5, 2020</last_update_submitted>
<last_update_submitted_qc>November 5, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">November 9, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Coronary artery bypass grafting</keyword>
<keyword>Minimally Invasive Surgical Procedures</keyword>
<keyword>Off-pump CABG</keyword>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
CABG technology is recognized as the preferred treatment, and its major adverse cardiac and
cerebral event(MACCE) incidence and mortality are lower than percutaneous coronary
intervention(PCI). However, the traditional CABG procedure requires sternal incision, large
trauma and long recovery period after surgery.
How to reduce trauma and treat multiple complex coronary lesions under minimally invasive
conditions has become a hot spot. MIDCAB surgery can complete the coronary anastomosis only
by a 6-8 cm incision in the left chest. It has been more than ten years since the first
literature report in the world, however, due to the technical bottleneck, a unified and
standardized surgical procedure has not yet been formed. Some centers are still in the
exploratory stage, and internationally Large-scale studies of clinical outcomes (mostly less
than 150 cases) have not been reported. Assessing the minimally invasive procedure's safety
and effectiveness has become an urgent problem to be solved.
At present, our center has completed nearly 200 cases of small incision multi-coronary
coronary artery bypass graft surgery. The investigators evaluate the patency of the graft by
the postoperative of angiography, the patency of grafts is more than 95%, and there is no
statistical difference with conventional OPCABG. On the other hand, focus on the
postoperative complications, there was no significant difference in the incidence of MACCE
and revascularization between the MIDCAB group and conventional surgery during
hospitalization. The investigators assume that the early results of this procedure are safe
and effective. MIDCAB has a congenital advantage because of its' reduction of the trauma of
the thoracotomy and the aesthetics of the incision. Therefore, if a larger sample size study
and mid-term follow-up results are obtained, and the conclusion prove that the safety of the
small incision surgery and the patency of the grafts are not inferior to conventional
surgery. The investigators can consider that minimal invasive coronary surgery(MICS) is a
technique worth trying to promote.
Through this prospective cohort study, the investigators evaluated the safety of MICS through
mid-term follow-up results and asses the efficiency by the results of grafts patency
(angiography or CT within 30 days after surgery) and medical outcomes study-short from
scores(SF-36), establish the surgical standard and perioperative management method.
1. MIDCAB procedure introduction
1. Surgery preparation:
General anesthesia, double lumen tracheal intubation. In the supine position, tilt
15° to the right. An automatic defibrillation electrode is attached to the right
front and left rear chest wall, and the external defibrillator is connected. A
small incision of 8-10 cm into the left anterior lateral 5th intercostal space was
performed into the chest.
2. Internal mammary artery acquisition:
After entering the chest, the IMA is exposed through a new minimal invasive
retraction system. Single or bilateral IMA is obtained as needed. Separate the IMA
From the middle segment (non-fat muscle coverage area) applied with an electric
scalpel (15J), and the free range was up to the first rib to the fifth or sixth
intercostal(IMA bifurcation).
3. Bypass strategy:
All procedures were performed under a non-cardiopulmonary situation, and vascular
anastomosis was performed with the aid of a laparoscopic cardiac stabilizer. The
stabilizer is smaller and does not occupy the operating space. The head of
stabilizer can be rotated 360 degrees and the target vessel can be fixed at any
angle. Bilateral internal mammary artery, radial artery and saphenous vein can be
used as graft vessels. The bypass strategy is not particularly different from
conventional bypass surgery, including aorta(AO)-saphenous vein graft (SVG) or
radial artery(RA)-X1-X2-...( sequential anastomosis), left internal mammary
artery(LIMA)-right internal mammary artery(RIMA) -RA or SVG(Y)-X, RIMA-left
anterior descending(LAD), LIMA-RA or RIMA or SVG(I)-X1-X2 and so on.
4. Vascular anastomosis:
The target vessel is exposed through the pericardial suture, the heart is locally
fixed with the aid of a cardiac stabilizer, and the target vessel is inserted shunt
to avoid hemodynamic disorder and arrhythmia. Vascular anastomosis is performed by
8-0 polypropylene suture.
5. Aortic exposure and proximal anastomosis:
Place gauze behind the aorta, expose the aorta with the right pericardial
suspension suture, temporary block aortic anterior wall with a soft-chain sidewall
clamp, Punch on the aortic anterior wall with 3.5mm puncher, anastomose SVG or RA
on AO with 6-0 polypropylene suture.
6. postoperative management: Patients go to the cardiac ICU ward postoperatively. The
investigators closely observe the electrocardiogram and myocardial enzyme changes,
maintain a mean arterial pressure more than 70 mmHg perfusion pressure, and the use
of nitrate ester drug to relax coronary, Begin with oral aspirin (100 mg, qd)
antiplatelet therapy as soon as tracheal intubation is removed. Complete chest
X-ray, cardiac ultrasound and coronary angiography before discharge.
7. Patient selection Because MIDCAB requires the heart to be exposed through the
lateral incision, it is necessary to avoid the difficulty of exposure caused by
thoracic deformity, adhesion or obesity; it is not suitable for MIDCAB in patients
with extremely low cardiac function and severe heart enlargement; Because of the
necessity of single-side ventilation, such as patients with severe pulmonary
dysfunction before surgery, should also avoid small incision surgery. See the
eligible and exclusion criteria for details.
2. Baseline matching problem MIDCAB is more rigorous in terms of patient selection, such as
weight, EF%, and lung function, thus the study will use a propensity score method to
match the baseline of two groups to eliminate the baseline bias.
Baseline factor： General: gender, age, BMI History and comorbidities：Smoke, Diabetes
(diagnostic criteria: oral hypoglycemic agents, insulin therapy, HbA1c greater than
7.0%, postprandial blood glucose greater than 11.1mmol/L, fasting plasma glucose greater
than 7.0mmol/L), previous stroke(CT showed large area softening lesion) and presence of
neurological dysfunction (paralysis, weak muscles, aphasia, paresthesia, and difficulty
urinating), Hyperlipidemia (administered or admitted to hospital serum cholesterol
greater than 5.17mmol / L or 200mg / dl), high blood pressure (blood pressure greater
than 140 / 90 mmHg without medication), renal insufficiency (dialysis or serum
creatinine level greater than 140mmol / L ), Peripheral vascular disease (preoperative
ultrasound or CT confirmed peripheral vascular stenosis greater than 50%), previous
history of cardiac surgery, previous PCI history (balloon dilatation or stent
implantation)
Preoperative status: Classification of angina (stable angina pectoris, unstable angina
pectoris, non st-t segment elevation myocardial infarction, st-t segment elevation
myocardial infarction), previous myocardial infarction history(pathological Q wave on
ECG, abnormal segment motion on lesion area accompany with low EF% or clear and
definitely evidence of elevation of creatine kinase(CK-MB) or troponin(cTnI), New York
Heart Association(NYHA) heart function classification.
Preoperative examination:creatinine(Cr), N-terminal pro brain natriuretic
peptide(NT-proBNP), total cholesterol(TG) and low density lipoprotein(LDL) level,
preoperative cardiac function (EF%, LVEDmm), SYNTAX score (evaluation by cardiologist).
Preoperative medication (within 1 week): aspirin, clopidogrel
3. statistical methods The primary endpoint of 12 months MACCE will be analysis by
non-inferiority method. The small incision surgery has advantage of little trauma and
the aesthetics of the incision. According to the results of previous studies and
literature reports, the 1 year graft's patency is assumed to be 96% in the MICS group,
96% in the control group, test performance β=90%, in the single-tail test α=0.025,
△=0.06, the investigators expected the sample size of each group is required to be 168,
and assume drop rate is about 15%, and finally 190-200 cases are needed in each group.
In the OPCABG group, considering the propensity score matching efficiency of 0.5, it may
be need more cases.
The other primary endpoints of Physical Component Scale (PCS) will be analysis by superior
effect test. The higher the PCS score of SF-36 scale, the better the patient's physiological
health. According to previous studies and literature reports, the average PCS score of SF-36
scale on the 30th day after CABG was 43 with a standard deviation of 10. The PCS difference
of SF-36 scale with the smallest clinical significance reported in literature was 2. Through
previous studies, the average PCS score on the 30th day after CABG in MICS group was 50.
Assuming that the lower line of 95% confidence interval of PCS score difference between
MICS-CABG group and OPCABG group is greater than 2, it is considered that the PCS score of
MICS-CABG group is better than OPCABG group, with inspection level α=0.025 (one side) and
inspection efficiency 1-β=0.80. The sample size of OPCABG group and MICS group is calculated
to be 65 cases, with an estimated miss rate of 20%, and each group needs to include at least
82 people.
Based on the above conclusions, The investigators calculated sample size is 200 cases in each
group.
After establishing the database, the logistic regression model will be established，the
dependent variable is surgery procedure（MICS surgery）, the independent variable are baseline
factor, and the receiver operating characteristic curve(ROC) will be drawn. The logistic
regression model will be used to calculate the prone score(PS) of each subject. The nearest
neighbor matching method will be used to select the thoracotomy OPCABG cases in a 1:1 ratio
according to the priority matching method.
According to the basic principles of Intention-to-Treat (ITT), the whole analysis set was
used. The analysis of the main indicators will include all randomized subjects, whether or
not they will complete the test, the data will be included in the analysis.
Statistics data include baseline analysis, primary endpoints, secondary endpoints,
observations, and compliance indicators. Measurement data that conformed to the normal
distribution will be statistically described using mean ± standard deviation (χ ± S，using t
test). Non-normally distributed measurement data will be statistically described using median
and quartiles (using variance or nonparametric tests). The grade data will be tested using
rank sum test. The count data will be statistically described as a percentage, and two or
more independent sample rates will be compared using a chi-square test. Fisher's exact
probability analysis will be used for indicators with low index positives (expected value
<5). Survival-related data will be applied by proportional hazards model(COX) regression and
survival curve risk.
Describe the missing value processing method: The estimation of the missing value of the main
indicator is carried forward using the closest observation when selecting the full analysis
set for statistical analysis,
5、 Ethics and safety Ethics: This research has been reviewed and filed by the Ethics
Committee of the Third Hospital of Peking University. Informed consent will be signed before
each participating patient was enrolled Safety: Through pre-research, MICS is a safe and
effective new surgical procedure. At present, the investigators have completed more than 200
MICS operations. Only 2 of these patients died, and the postoperative complications and
mid-term follow-up results were counted. The rate of graft patency and complications is not
inferior to thoracotomy OPCABG surgery.
6、 Quality control Access system: MICS surgery is limited by the operation space. Although
the multiple minimal invasive bypass surgery can be achieved routinely at present in our
center, this surgery requires high skill and long learning curve. The cardiac surgery will
strictly implement the surgeon's access qualification and have regular bypass surgery 300.
For example, in the case of a small incision, only 50 patients with more than one bypass
surgery, after a discussion within the department and approved by the core group, can perform
small incision multi-bridge surgery.
Safeguard plan: For each case of small incision surgery, the patient's clinical data will be
evaluate preoperative in our center by more than 3 senior surgeons. The surgical plan is
strictly according to the standard of admission; Femoral arteriovenous will be routinely
prepared for emergency cardiopulmonary bypass(CPB) and intraaortic balloon pumping(IABP)
implantation. Transformation to thoracotomy surgery will be carried out if hemorrhage,
uncontrollable hemodynamic disorder and malignant arrhythmia occured.
Termination of research criteria:
To ensure the safety of all candidates, a quality and safety management team will be
established to monitor the complications and major safety indicators of the MICS group. The
data were collected monthly to monitor serious complications (death, MACCE, unplanned
revascularization, reoperation etc.) Our research will be terminated when any of the serious
complications happen more than 5 cases .
Patients are planned for undergoing off-pump coronary artery bypass surgery.
Inclusion Criteria:
Patients are planned for undergoing off-pump coronary artery bypass surgery.
Exclusion Criteria:
1. BMI greater than 28
2. trauma, surgical or radiotherapy history of left chest
3. EF less than 40%
4. Simultaneous other cardiac surgery or planned cardiopulmonary bypass
5. Preoperative critical situation: acute myocardial infarction, heart failure and other
conditions require emergency surgery. Preoperative nitrate drugs are difficult to
control angina and needs IABP implantation.
6. Respiratory function: severe hypoxemia (pO2 less than 60 mmHg without Oxygen
inhalation), carbon dioxide retention (pCO2 > 50 mmHg), severe chronic obstructive
pulmonary disease (FEV1/forced vital capacity less than 70% and FEV1 less than 50%)
7. Aortic lesions: patients with ascending aorta calcification confirmed by preoperative
CT
8. Peripheral vascular lesions:By the preoperative assessment with ultrasound or CT，LIMA
and left subclavian artery stenosis>70% ,or bilateral femoral artery calcification,
stenosis>50%
9. Drug therapy: Preoperative antiplatelet or anticoagulant therapy (except aspirin and
clopidogrel)
10. Others: Exclusion criteria and contraindications of CABG
|
NCT0426xxxx/NCT04267848.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267848</url>
</required_header>
<id_info>
<org_study_id>NCI-2020-00751</org_study_id>
<secondary_id>NCI-2020-00751</secondary_id>
<secondary_id>A081801</secondary_id>
<secondary_id>A081801</secondary_id>
<secondary_id>U10CA180821</secondary_id>
<nct_id>NCT04267848</nct_id>
</id_info>
<brief_title>Testing the Addition of a Type of Drug Called Immunotherapy to the Usual Chemotherapy Treatment for Non-Small Cell Lung Cancer (An ALCHEMIST Treatment Trial)</brief_title>
<official_title>Integration of Immunotherapy Into Adjuvant Therapy for Resected NSCLC: ALCHEMIST Chemo-IO (ACCIO)</official_title>
<sponsors>
<lead_sponsor>
<agency>National Cancer Institute (NCI)</agency>
<agency_class>NIH</agency_class>
</lead_sponsor>
</sponsors>
<source>National Cancer Institute (NCI)</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This phase III ALCHEMIST trial tests the addition of pembrolizumab to usual chemotherapy for
the treatment of stage IIA, IIB IIIA or IIIB non-small cell lung cancer that has been removed
by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the
body's immune system attack the cancer, and may interfere with the ability of tumor cells to
grow and spread. Chemotherapy drugs, such as cisplatin, pemetrexed, carboplatin, gemcitabine
hydrochloride, and paclitaxel, work in different ways to stop the growth of tumor cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Giving pembrolizumab with usual chemotherapy may help increase survival times in
patients with stage IIA, IIB IIIA or IIIB non-small cell lung cancer.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
PRIMARY OBJECTIVE:

I. To compare the disease free survival (DFS) between Arm B versus (vs) Arm C in patients
with stage IIA-IIIB (T3-4N2) non-small cell lung cancer.

SECONDARY OBJECTIVES:

I. To compare the overall survival (OS) between the two treatment arms in patients with stage
IIA-IIIB (T3-4N2) non-small cell lung cancer.

II. To compare the adverse event rates and drug discontinuation rates due to adverse events
in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer.

III. To compare the adverse event (AE) rates for Arms B and C with A (prior to Update #7) and
estimate the DFS and OS in Arm A.

IV. To compare the DFS and OS in patients with stage IIA-IIIB (T3-4N2) non-small cell lung
cancer that receive at least 2 cycles of initial adjuvant chemotherapy.

QUALITY OF LIFE OBJECTIVES:

I. To compare patient-reported quality of life (QOL) one year after randomization as assessed
by the European Organization for the Research and Treatment of Cancer Quality of Life
Questionnaire (EORTC QLQ)-Core (C)30 between patients randomized to receive adjuvant
chemotherapy followed by pembrolizumab (Arm B), and those randomized to receive adjuvant
chemotherapy + pembrolizumab concomitantly (Arm C).

II. To compare patient-reported QOL at completion of chemotherapy as assessed by the EORTC
QLQ-C30 between patients randomized to receive adjuvant chemotherapy followed by
pembrolizumab (Arm B) and those randomized to receive adjuvant chemotherapy + pembrolizumab
concomitantly (Arm C).

III. To present longitudinal trajectories by arm of patient-reported dyspnea and coughing as
assessed by the EORTC QLQ-Lung Cancer (LC13).

CORRELATIVE SCIENCE OBJECTIVES:

I. To compare the DFS and OS in the PD-L1 subgroup of patients with PD-L1 expression status
(>= 1% vs < 1%).

II. To compare the DFS and OS by tumor mutational burden status (high vs. low) in patients
with stage IIA-IIIB (T3-4N2) non-small cell lung cancer.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A (CLOSED AS OF UPDATE #7):

INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating
physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease
progression or unacceptable toxicity.

CONTINUANCE THERAPY: Patients then undergo observation.

ARM B:

INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating
physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease
progression or unacceptable toxicity.

CONTINUANCE THERAPY: Patients then receive pembrolizumab intravenously (IV) over 25-40
minutes on day 1. Treatment repeats every 21 days for 17 cycles or every 6 weeks for 16
cycles (patients enrolled after 10/14/2020) in the absence of disease progression or
unacceptable toxicity.

ARM C:

INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating
physician's choice and pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every
21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1.
Treatment repeats every 21 days for 13 cycles or every 6 weeks for 12 cycles (patients
enrolled after 10/14/2020) in the absence of disease progression or unacceptable toxicity.

*ACCEPTABLE REGIMENS: DOUBLET I: Patients receive cisplatin IV over 1-2 hours and pemetrexed
IV over 10 minutes on day 1 of each cycle.

DOUBLET II: Patients receive carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes
on day 1 of each cycle.

DOUBLET III: Patients receive cisplatin IV over 1-2 hours on day 1 of each cycle and
gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 of each cycle.

DOUBLET IV: Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on
day 1 of each cycle.

After completion of study treatment, patients are followed up at 6 weeks, then every 3 months
for 2 years from randomization, every 6 months for years 2-4, and then annually for up to 10
years from randomization.
</textblock>
</detailed_description>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">June 3, 2020</start_date>
<completion_date type="Anticipated">December 15, 2024</completion_date>
<primary_completion_date type="Anticipated">December 15, 2024</primary_completion_date>
<phase>Phase 3</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Disease free survival (DFS)</measure>
<time_frame>From randomization to the first of either disease recurrence or death from any cause, assessed up to 5 years after accrual completion</time_frame>
<description>Will be estimated using the Kaplan-Meier method, where the stratified log-rank test (using the central PD-L1 result for the PD-L1 expression status) will be used to compare the distributions across the treatment arms. DFS rates at 1 year, 2 years, and 5 years will also be reported, along with 95% confidence intervals. Univariable and multivariable Cox models stratified by the stratification factors (using the central PD-L1 result for the PD-L1 expression status) used in the randomization will be assessed as well.</description>
</primary_outcome>
<secondary_outcome>
<measure>Overall survival (OS)</measure>
<time_frame>From randomization to death from any cause, assessed up to 8 years after accrual completion</time_frame>
<description>Will be estimated using the Kaplan-Meier method, where the stratified log-rank test (using the central PD-L1 result for the PD-L1 expression status) will be used to compare the distributions across the treatment arms. OS rates at 1 year, 2 years, and 5 years will also be reported, along with 95% confidence intervals. Univariable and multivariable Cox models stratified by the stratification factors (using the central PD-L1 result for the PD-L1 expression status) used in the randomization will be assessed as well.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Incidence of adverse events</measure>
<time_frame>Up to 10 years</time_frame>
<description>The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5. The frequency and percentage of grade 3+ adverse events will be compared between the 2 experimental treatment arms and the control as well as between the two experimental arms. We will also compare the rate of drug discontinuation due to adverse events between the experimental treatment arms and control, and between the two experimental arms. Comparisons between arms will be made by using the Chi-square test. Analysis of the overall adverse event rates, as well as specific events of interest will involve Chi-square tests or Fisher's exact tests.</description>
</secondary_outcome>
<secondary_outcome>
<measure>DFS between each experimental pembrolizumab plus standard of care arms vs. standard of care</measure>
<time_frame>From randomization to the first of either disease recurrence or death from any cause, assessed up to 5 years after accrual completion</time_frame>
<description>Assessed by PD-L1 expression status (tumor proportion score >= 50% vs. tumor proportion score < 50%). Univariable and multivariable Cox models stratified by the stratification factors used in the randomization will be used as the primary analytical method, where all baseline covariates will be considered in the univariable models and subsequently in the multivariable models based on the criteria for selection for the multivariable models.</description>
</secondary_outcome>
<secondary_outcome>
<measure>OS between each experimental pembrolizumab plus standard of care arms vs. standard of care</measure>
<time_frame>From randomization to death from any cause, assessed up to 8 years after accrual completion</time_frame>
<description>Assessed by PD-L1 expression status. Univariable and multivariable Cox models stratified by the stratification factors used in the randomization will be used as the primary analytical method, where all baseline covariates will be considered in the univariable models and subsequently in the multivariable models based on the criteria for selection for the multivariable models.</description>
</secondary_outcome>
<number_of_arms>3</number_of_arms>
<enrollment type="Anticipated">1210</enrollment>
<condition>Lung Non-Small Cell Carcinoma</condition>
<condition>Lung Non-Small Cell Squamous Carcinoma</condition>
<condition>Lung Non-Squamous Non-Small Cell Carcinoma</condition>
<condition>Stage II Lung Cancer AJCC v8</condition>
<condition>Stage IIA Lung Cancer AJCC v8</condition>
<condition>Stage IIB Lung Cancer AJCC v8</condition>
<condition>Stage IIIA Lung Cancer AJCC v8</condition>
<condition>Stage IIIB Lung Cancer AJCC v8</condition>
<arm_group>
<arm_group_label>Arm A (platinum doublet, observation)</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then undergo observation.
(CLOSED AS OF UPDATE #7)</description>
</arm_group>
<arm_group>
<arm_group_label>Arm B (platinum doublet, sequential pembrolizumab)</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 17 cycles or every 6 weeks for 16 cycles (patients enrolled after 10/14/2020) in the absence of disease progression or unacceptable toxicity.</description>
</arm_group>
<arm_group>
<arm_group_label>Arm C (platinum doublet, combination pembrolizumab)</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice and pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 13 cycles or every 6 weeks for 12 cycles (patients enrolled after 10/14/2020) in the absence of disease progression or unacceptable toxicity.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Carboplatin</intervention_name>
<description>Given IV</description>
<arm_group_label>Arm A (platinum doublet, observation)</arm_group_label>
<arm_group_label>Arm B (platinum doublet, sequential pembrolizumab)</arm_group_label>
<arm_group_label>Arm C (platinum doublet, combination pembrolizumab)</arm_group_label>
<other_name>Blastocarb</other_name>
<other_name>Carboplat</other_name>
<other_name>Carboplatin Hexal</other_name>
<other_name>Carboplatino</other_name>
<other_name>Carboplatinum</other_name>
<other_name>Carbosin</other_name>
<other_name>Carbosol</other_name>
<other_name>Carbotec</other_name>
<other_name>CBDCA</other_name>
<other_name>Displata</other_name>
<other_name>Ercar</other_name>
<other_name>JM-8</other_name>
<other_name>JM8</other_name>
<other_name>Nealorin</other_name>
<other_name>Novoplatinum</other_name>
<other_name>Paraplatin</other_name>
<other_name>Paraplatin AQ</other_name>
<other_name>Paraplatine</other_name>
<other_name>Platinwas</other_name>
<other_name>Ribocarbo</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Cisplatin</intervention_name>
<description>Given IV</description>
<arm_group_label>Arm A (platinum doublet, observation)</arm_group_label>
<arm_group_label>Arm B (platinum doublet, sequential pembrolizumab)</arm_group_label>
<arm_group_label>Arm C (platinum doublet, combination pembrolizumab)</arm_group_label>
<other_name>Abiplatin</other_name>
<other_name>Blastolem</other_name>
<other_name>Briplatin</other_name>
<other_name>CDDP</other_name>
<other_name>Cis-diammine-dichloroplatinum</other_name>
<other_name>Cis-diamminedichloridoplatinum</other_name>
<other_name>Cis-diamminedichloro Platinum (II)</other_name>
<other_name>Cis-diamminedichloroplatinum</other_name>
<other_name>Cis-dichloroammine Platinum (II)</other_name>
<other_name>Cis-platinous Diamine Dichloride</other_name>
<other_name>Cis-platinum</other_name>
<other_name>Cis-platinum II</other_name>
<other_name>Cis-platinum II Diamine Dichloride</other_name>
<other_name>Cismaplat</other_name>
<other_name>Cisplatina</other_name>
<other_name>Cisplatinum</other_name>
<other_name>Cisplatyl</other_name>
<other_name>Citoplatino</other_name>
<other_name>Citosin</other_name>
<other_name>Cysplatyna</other_name>
<other_name>DDP</other_name>
<other_name>Lederplatin</other_name>
<other_name>Metaplatin</other_name>
<other_name>Neoplatin</other_name>
<other_name>Peyrone's Chloride</other_name>
<other_name>Peyrone's Salt</other_name>
<other_name>Placis</other_name>
<other_name>Plastistil</other_name>
<other_name>Platamine</other_name>
<other_name>Platiblastin</other_name>
<other_name>Platiblastin-S</other_name>
<other_name>Platinex</other_name>
<other_name>Platinol</other_name>
<other_name>Platinol- AQ</other_name>
<other_name>Platinol-AQ</other_name>
<other_name>Platinol-AQ VHA Plus</other_name>
<other_name>Platinoxan</other_name>
<other_name>Platinum</other_name>
<other_name>Platinum Diamminodichloride</other_name>
<other_name>Platiran</other_name>
<other_name>Platistin</other_name>
<other_name>Platosin</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Gemcitabine Hydrochloride</intervention_name>
<description>Given IV</description>
<arm_group_label>Arm A (platinum doublet, observation)</arm_group_label>
<arm_group_label>Arm B (platinum doublet, sequential pembrolizumab)</arm_group_label>
<arm_group_label>Arm C (platinum doublet, combination pembrolizumab)</arm_group_label>
<other_name>dFdCyd</other_name>
<other_name>Difluorodeoxycytidine Hydrochloride</other_name>
<other_name>Gemcitabine HCI</other_name>
<other_name>Gemzar</other_name>
<other_name>LY-188011</other_name>
<other_name>LY188011</other_name>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Observation</intervention_name>
<description>Undergo observation</description>
<arm_group_label>Arm A (platinum doublet, observation)</arm_group_label>
<other_name>Inspection</other_name>
<other_name>Visual Inspection</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Paclitaxel</intervention_name>
<description>Given IV</description>
<arm_group_label>Arm A (platinum doublet, observation)</arm_group_label>
<arm_group_label>Arm B (platinum doublet, sequential pembrolizumab)</arm_group_label>
<arm_group_label>Arm C (platinum doublet, combination pembrolizumab)</arm_group_label>
<other_name>Anzatax</other_name>
<other_name>Asotax</other_name>
<other_name>Bristaxol</other_name>
<other_name>Praxel</other_name>
<other_name>Taxol</other_name>
<other_name>Taxol Konzentrat</other_name>
</intervention>
<intervention>
<intervention_type>Biological</intervention_type>
<intervention_name>Pembrolizumab</intervention_name>
<description>Given IV</description>
<arm_group_label>Arm B (platinum doublet, sequential pembrolizumab)</arm_group_label>
<arm_group_label>Arm C (platinum doublet, combination pembrolizumab)</arm_group_label>
<other_name>BCD-201</other_name>
<other_name>Keytruda</other_name>
<other_name>Lambrolizumab</other_name>
<other_name>MK-3475</other_name>
<other_name>Pembrolizumab Biosimilar BCD-201</other_name>
<other_name>SCH 900475</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Pemetrexed Disodium</intervention_name>
<description>Given IV</description>
<arm_group_label>Arm A (platinum doublet, observation)</arm_group_label>
<arm_group_label>Arm B (platinum doublet, sequential pembrolizumab)</arm_group_label>
<arm_group_label>Arm C (platinum doublet, combination pembrolizumab)</arm_group_label>
<other_name>Alimta</other_name>
<other_name>Almita</other_name>
<other_name>LY231514</other_name>
<other_name>N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt</other_name>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Quality-of-Life Assessment</intervention_name>
<description>Ancillary studies</description>
<arm_group_label>Arm A (platinum doublet, observation)</arm_group_label>
<arm_group_label>Arm B (platinum doublet, sequential pembrolizumab)</arm_group_label>
<arm_group_label>Arm C (platinum doublet, combination pembrolizumab)</arm_group_label>
<other_name>Quality of Life Assessment</other_name>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Questionnaire Administration</intervention_name>
<description>Ancillary studies</description>
<arm_group_label>Arm A (platinum doublet, observation)</arm_group_label>
<arm_group_label>Arm B (platinum doublet, sequential pembrolizumab)</arm_group_label>
<arm_group_label>Arm C (platinum doublet, combination pembrolizumab)</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Previously registered to A151216 (NCT02194738)

- Central and/or local testing of EGFR with no EGFR exon 19 deletion or EGFR L858 R
mutation (applicable to non-squamous patients only)

- Central and/or local testing of ALK with no ALK rearrangement (failed testing is
considered negative) (applicable to non-squamous patients only)

- Central and/or local testing of PD-L1 immunohistochemistry (IHC) using one of the
following assays: DAKO 22C3, DAKO 28-8, EIL3N or SP263

- Note: Local testing results of EGFR and ALK by a local Clinical Laboratory
Improvement Act (CLIA) certified laboratory is acceptable. The report must
indicate the result as well as the CLIA number of the laboratory that performed
the assay. Local result of PD-L1 by DAKO 22C3, Dako 28-8, EIL3N or SP263 are
acceptable for enrollment on A081801. Patients with local results for EGFR, ALK
and PD-L1 still need to be registered to A151216 and follow all the submissions
requirements but do NOT need to wait for the results to proceed to A081801
registration

- Completely resected stage IIA, IIB IIIA or IIIB (T3-4N2) non-small cell lung cancer
(NSCLC) (squamous or non-squamous) with negative margins (complete R0 resection).
Patients will be staged according to the 8th edition of the American Joint Committee
on Cancer (AJCC) Staging Manual, 2017

- Note: Patients with pathologic N2 disease, completely resected, are eligible.
However, patients known to have N2 disease prior to surgery are not eligible;
guidelines do not recommend up-front surgery for this population

- Complete recovery from surgery. Registration to A081801 must be 30-77 days following
surgery

- No prior neoadjuvant or adjuvant therapy for current lung cancer diagnosis

- No prior allogeneic tissue/solid organ transplant

- No current pneumonitis or history of (non-infectious) pneumonitis that required
steroids

- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial

- Age >= 18 years

- Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1

- No active auto-immune disease that has required systemic treatment within the last 2
years (e.g., disease-modifying agents, corticosteroids, or immunosuppressive drugs).
Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid release
therapy for adrenal or pituitary insufficiency) is not considered a form of systemic
treatment

- Not pregnant and not nursing, because this study involves an agent that has known
genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing
potential only, a negative pregnancy test done =< 7 days prior to registration is
required

- No patients with a "currently active" second malignancy that is progressing or has
required active treatment within the last 3 years. Participants with non-melanoma skin
cancers or carcinoma in situ (e.g., breast carcinoma or cervical cancer in situ) that
have undergone potentially curative therapy are eligible

- No hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients

- No live vaccine within 30 days prior to registration. Examples of live vaccines
include, but are not limited to, the following: measles, mumps, rubella,
varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG),
and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed
virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist)
are live attenuated vaccines and are not allowed

- No known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]
reactive) or known hepatitis C virus (defined as HCV ribonucleic acid [RNA]
[qualitative] is detected) infection

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- Hemoglobin >= 8 gm/dl

- Calculated (Calc.) creatinine clearance >= 45 mL/min

- Total bilirubin =< 1.5 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 x upper limit
of normal (ULN)

Exclusion Criteria:

- Patients must NOT have uncontrolled intercurrent illness including, but not limited
to, serious ongoing or active infection, symptomatic congestive heart failure,
uncontrolled cardiac arrhythmia, unstable angina pectoris, that would limit compliance
with study requirements
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Jacob M Sands</last_name>
<role>Principal Investigator</role>
<affiliation>Alliance for Clinical Trials in Oncology</affiliation>
</overall_official>
<location>
<facility>
<name>Anchorage Associates in Radiation Medicine</name>
<address>
<city>Anchorage</city>
<state>Alaska</state>
<zip>98508</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Anchorage Radiation Therapy Center</name>
<address>
<city>Anchorage</city>
<state>Alaska</state>
<zip>99504</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Alaska Breast Care and Surgery LLC</name>
<address>
<city>Anchorage</city>
<state>Alaska</state>
<zip>99508</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Alaska Oncology and Hematology LLC</name>
<address>
<city>Anchorage</city>
<state>Alaska</state>
<zip>99508</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Alaska Women's Cancer Care</name>
<address>
<city>Anchorage</city>
<state>Alaska</state>
<zip>99508</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Anchorage Oncology Centre</name>
<address>
<city>Anchorage</city>
<state>Alaska</state>
<zip>99508</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Katmai Oncology Group</name>
<address>
<city>Anchorage</city>
<state>Alaska</state>
<zip>99508</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>907-212-6871</phone>
<email>AKPAMC.OncologyResearchSupport@providence.org</email>
</contact>
<investigator>
<last_name>Alison K. Conlin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Providence Alaska Medical Center</name>
<address>
<city>Anchorage</city>
<state>Alaska</state>
<zip>99508</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Fairbanks Memorial Hospital</name>
<address>
<city>Fairbanks</city>
<state>Alaska</state>
<zip>99701</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>907-458-3043</phone>
<email>Veronica.Stevenson@foundationhealth.org</email>
</contact>
<investigator>
<last_name>Nicholas DiBella</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Banner MD Anderson Cancer Center</name>
<address>
<city>Gilbert</city>
<state>Arizona</state>
<zip>85234</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kingman Regional Medical Center</name>
<address>
<city>Kingman</city>
<state>Arizona</state>
<zip>86401</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer Center at Saint Joseph's</name>
<address>
<city>Phoenix</city>
<state>Arizona</state>
<zip>85004</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Banner Boswell Medical Center</name>
<address>
<city>Sun City</city>
<state>Arizona</state>
<zip>85351</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>480-440-7458</phone>
<email>BMDACCResearch@bannerhealth.com</email>
</contact>
<investigator>
<last_name>Jiaxin (Jason) Niu</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Banner University Medical Center - Tucson</name>
<address>
<city>Tucson</city>
<state>Arizona</state>
<zip>85719</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>University of Arizona Cancer Center-North Campus</name>
<address>
<city>Tucson</city>
<state>Arizona</state>
<zip>85719</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Mercy Hospital Fort Smith</name>
<address>
<city>Fort Smith</city>
<state>Arkansas</state>
<zip>72903</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>CHI Saint Vincent Cancer Center Hot Springs</name>
<address>
<city>Hot Springs</city>
<state>Arkansas</state>
<zip>71913</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro</name>
<address>
<city>Jonesboro</city>
<state>Arkansas</state>
<zip>72401</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>870-936-7066</phone>
<email>Emily.Carvell@bmhcc.org</email>
</contact>
<investigator>
<last_name>Philip E. Lammers</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Anaheim</name>
<address>
<city>Anaheim</city>
<state>California</state>
<zip>92806</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-398-3996</phone>
<email>clinical.trials@kp.org</email>
</contact>
<investigator>
<last_name>Eric C. McGary</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Deer Valley Medical Center</name>
<address>
<city>Antioch</city>
<state>California</state>
<zip>94531</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mission Hope Medical Oncology - Arroyo Grande</name>
<address>
<city>Arroyo Grande</city>
<state>California</state>
<zip>93420</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>PCR Oncology</name>
<address>
<city>Arroyo Grande</city>
<state>California</state>
<zip>93420</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Sutter Auburn Faith Hospital</name>
<address>
<city>Auburn</city>
<state>California</state>
<zip>95602</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>Melanie.Cook@sutterhealth.org</email>
</contact>
<investigator>
<last_name>Edmund W. Tai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sutter Cancer Centers Radiation Oncology Services-Auburn</name>
<address>
<city>Auburn</city>
<state>California</state>
<zip>95603</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente-Baldwin Park</name>
<address>
<city>Baldwin Park</city>
<state>California</state>
<zip>91706</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-398-3996</phone>
<email>clinical.trials@kp.org</email>
</contact>
<investigator>
<last_name>Eric C. McGary</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Bellflower</name>
<address>
<city>Bellflower</city>
<state>California</state>
<zip>90706</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-398-3996</phone>
<email>clinical.trials@kp.org</email>
</contact>
<investigator>
<last_name>Eric C. McGary</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Alta Bates Summit Medical Center-Herrick Campus</name>
<address>
<city>Berkeley</city>
<state>California</state>
<zip>94704</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>Melanie.Cook@sutterhealth.org</email>
</contact>
<investigator>
<last_name>Edmund W. Tai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Providence Saint Joseph Medical Center/Disney Family Cancer Center</name>
<address>
<city>Burbank</city>
<state>California</state>
<zip>91505</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Mills-Peninsula Medical Center</name>
<address>
<city>Burlingame</city>
<state>California</state>
<zip>94010</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Sutter Cancer Centers Radiation Oncology Services-Cameron Park</name>
<address>
<city>Cameron Park</city>
<state>California</state>
<zip>95682</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Eden Hospital Medical Center</name>
<address>
<city>Castro Valley</city>
<state>California</state>
<zip>94546</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>John Muir Medical Center-Concord Campus</name>
<address>
<city>Concord</city>
<state>California</state>
<zip>94520</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>925-674-2580</phone>
</contact>
<investigator>
<last_name>Gigi Q. Chen</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sutter Davis Hospital</name>
<address>
<city>Davis</city>
<state>California</state>
<zip>95616</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>City of Hope Comprehensive Cancer Center</name>
<address>
<city>Duarte</city>
<state>California</state>
<zip>91010</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Epic Care-Dublin</name>
<address>
<city>Dublin</city>
<state>California</state>
<zip>94568</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>925-875-1677</phone>
</contact>
<investigator>
<last_name>Lisa Bailey</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente Dublin</name>
<address>
<city>Dublin</city>
<state>California</state>
<zip>94568</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Bay Area Breast Surgeons Inc</name>
<address>
<city>Emeryville</city>
<state>California</state>
<zip>94608</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Epic Care Partners in Cancer Care</name>
<address>
<city>Emeryville</city>
<state>California</state>
<zip>94608</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>510-629-6682</phone>
</contact>
<investigator>
<last_name>Lisa Bailey</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Fontana</name>
<address>
<city>Fontana</city>
<state>California</state>
<zip>92335</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-398-3996</phone>
<email>clinical.trials@kp.org</email>
</contact>
<investigator>
<last_name>Eric C. McGary</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Fremont</name>
<address>
<city>Fremont</city>
<state>California</state>
<zip>94538</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Palo Alto Medical Foundation-Fremont</name>
<address>
<city>Fremont</city>
<state>California</state>
<zip>94538</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>Melanie.Cook@sutterhealth.org</email>
</contact>
<investigator>
<last_name>Edmund W. Tai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Fresno</name>
<address>
<city>Fresno</city>
<state>California</state>
<zip>93720</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente - Harbor City</name>
<address>
<city>Harbor City</city>
<state>California</state>
<zip>90710</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-398-3996</phone>
<email>clinical.trials@kp.org</email>
</contact>
<investigator>
<last_name>Eric C. McGary</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Irvine</name>
<address>
<city>Irvine</city>
<state>California</state>
<zip>92618</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-398-3996</phone>
<email>clinical.trials@kp.org</email>
</contact>
<investigator>
<last_name>Eric C. McGary</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UC San Diego Moores Cancer Center</name>
<address>
<city>La Jolla</city>
<state>California</state>
<zip>92093</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>858-822-5354</phone>
<email>cancercto@ucsd.edu</email>
</contact>
<investigator>
<last_name>Lyudmila A. Bazhenova</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Loma Linda University Medical Center</name>
<address>
<city>Loma Linda</city>
<state>California</state>
<zip>92354</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>909-558-4050</phone>
</contact>
<investigator>
<last_name>Hamid R. Mirshahidi</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Tibor Rubin VA Medical Center</name>
<address>
<city>Long Beach</city>
<state>California</state>
<zip>90822</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>562-826-8000</phone>
</contact>
<investigator>
<last_name>Pankaj Gupta</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente Los Angeles Medical Center</name>
<address>
<city>Los Angeles</city>
<state>California</state>
<zip>90027</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-398-3996</phone>
<email>clinical.trials@kp.org</email>
</contact>
<investigator>
<last_name>Eric C. McGary</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente West Los Angeles</name>
<address>
<city>Los Angeles</city>
<state>California</state>
<zip>90034</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-398-3996</phone>
<email>clinical.trials@kp.org</email>
</contact>
<investigator>
<last_name>Eric C. McGary</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Contra Costa Regional Medical Center</name>
<address>
<city>Martinez</city>
<state>California</state>
<zip>94553-3156</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>925-957-5400</phone>
</contact>
<investigator>
<last_name>Lisa Bailey</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Fremont - Rideout Cancer Center</name>
<address>
<city>Marysville</city>
<state>California</state>
<zip>95901</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>530-749-4400</phone>
</contact>
<investigator>
<last_name>David R. Gandara</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Memorial Medical Center</name>
<address>
<city>Modesto</city>
<state>California</state>
<zip>95355</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>Melanie.Cook@sutterhealth.org</email>
</contact>
<investigator>
<last_name>Edmund W. Tai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Modesto</name>
<address>
<city>Modesto</city>
<state>California</state>
<zip>95356</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Palo Alto Medical Foundation-Camino Division</name>
<address>
<city>Mountain View</city>
<state>California</state>
<zip>94040</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>Melanie.Cook@sutterhealth.org</email>
</contact>
<investigator>
<last_name>Edmund W. Tai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Palo Alto Medical Foundation-Gynecologic Oncology</name>
<address>
<city>Mountain View</city>
<state>California</state>
<zip>94040</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Alta Bates Summit Medical Center - Summit Campus</name>
<address>
<city>Oakland</city>
<state>California</state>
<zip>94609</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Bay Area Tumor Institute</name>
<address>
<city>Oakland</city>
<state>California</state>
<zip>94609</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente Oakland-Broadway</name>
<address>
<city>Oakland</city>
<state>California</state>
<zip>94611</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente-Oakland</name>
<address>
<city>Oakland</city>
<state>California</state>
<zip>94611</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Ontario</name>
<address>
<city>Ontario</city>
<state>California</state>
<zip>91761</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-398-3996</phone>
<email>clinical.trials@kp.org</email>
</contact>
<investigator>
<last_name>Eric C. McGary</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Joseph Hospital - Orange</name>
<address>
<city>Orange</city>
<state>California</state>
<zip>92868</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>714-734-6220</phone>
</contact>
<investigator>
<last_name>Timothy E. Byun</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Palo Alto Medical Foundation Health Care</name>
<address>
<city>Palo Alto</city>
<state>California</state>
<zip>94301</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>Melanie.Cook@sutterhealth.org</email>
</contact>
<investigator>
<last_name>Edmund W. Tai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente - Panorama City</name>
<address>
<city>Panorama City</city>
<state>California</state>
<zip>91402</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-398-3996</phone>
<email>clinical.trials@kp.org</email>
</contact>
<investigator>
<last_name>Eric C. McGary</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Rancho Cordova Cancer Center</name>
<address>
<city>Rancho Cordova</city>
<state>California</state>
<zip>95670</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Eisenhower Medical Center</name>
<address>
<city>Rancho Mirage</city>
<state>California</state>
<zip>92270</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>760-834-3798</phone>
</contact>
<investigator>
<last_name>Davood Vafai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mercy Regional Cancer Center</name>
<address>
<city>Redding</city>
<state>California</state>
<zip>96001</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Mercy Oncology Center</name>
<address>
<city>Redding</city>
<state>California</state>
<zip>96002</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente- Marshall Medical Offices</name>
<address>
<city>Redwood City</city>
<state>California</state>
<zip>94063</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente-Redwood City</name>
<address>
<city>Redwood City</city>
<state>California</state>
<zip>94063</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente-Richmond</name>
<address>
<city>Richmond</city>
<state>California</state>
<zip>94801</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Riverside</name>
<address>
<city>Riverside</city>
<state>California</state>
<zip>92505</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-398-3996</phone>
<email>clinical.trials@kp.org</email>
</contact>
<investigator>
<last_name>Eric C. McGary</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Rohnert Park Cancer Center</name>
<address>
<city>Rohnert Park</city>
<state>California</state>
<zip>94928</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente-Roseville</name>
<address>
<city>Roseville</city>
<state>California</state>
<zip>95661</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sutter Cancer Centers Radiation Oncology Services-Roseville</name>
<address>
<city>Roseville</city>
<state>California</state>
<zip>95661</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Sutter Roseville Medical Center</name>
<address>
<city>Roseville</city>
<state>California</state>
<zip>95661</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>Melanie.Cook@sutterhealth.org</email>
</contact>
<investigator>
<last_name>Edmund W. Tai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>The Permanente Medical Group-Roseville Radiation Oncology</name>
<address>
<city>Roseville</city>
<state>California</state>
<zip>95678</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente Downtown Commons</name>
<address>
<city>Sacramento</city>
<state>California</state>
<zip>95814</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sutter Medical Center Sacramento</name>
<address>
<city>Sacramento</city>
<state>California</state>
<zip>95816</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>Melanie.Cook@sutterhealth.org</email>
</contact>
<investigator>
<last_name>Edmund W. Tai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University of California Davis Comprehensive Cancer Center</name>
<address>
<city>Sacramento</city>
<state>California</state>
<zip>95817</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>916-734-3089</phone>
</contact>
<investigator>
<last_name>David R. Gandara</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-South Sacramento</name>
<address>
<city>Sacramento</city>
<state>California</state>
<zip>95823</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>South Sacramento Cancer Center</name>
<address>
<city>Sacramento</city>
<state>California</state>
<zip>95823</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Helena Hospital</name>
<address>
<city>Saint Helena</city>
<state>California</state>
<zip>94574</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>707-967-3698</phone>
</contact>
<investigator>
<last_name>Tyler Y. Kang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-San Diego Zion</name>
<address>
<city>San Diego</city>
<state>California</state>
<zip>92120</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-398-3996</phone>
<email>clinical.trials@kp.org</email>
</contact>
<investigator>
<last_name>Eric C. McGary</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>California Pacific Medical Center-Pacific Campus</name>
<address>
<city>San Francisco</city>
<state>California</state>
<zip>94115</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>Melanie.Cook@sutterhealth.org</email>
</contact>
<investigator>
<last_name>Edmund W. Tai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-San Francisco</name>
<address>
<city>San Francisco</city>
<state>California</state>
<zip>94115</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Veterans Affairs Medical Center - San Francisco</name>
<address>
<city>San Francisco</city>
<state>California</state>
<zip>94121</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>415-221-4810</phone>
</contact>
<investigator>
<last_name>Sunny Wang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Santa Teresa-San Jose</name>
<address>
<city>San Jose</city>
<state>California</state>
<zip>95119</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente San Leandro</name>
<address>
<city>San Leandro</city>
<state>California</state>
<zip>94577</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Pacific Central Coast Health Center-San Luis Obispo</name>
<address>
<city>San Luis Obispo</city>
<state>California</state>
<zip>93401</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>805-219-4673</phone>
<email>ResearchInstituteInquiries@CommonSpirit.org</email>
</contact>
<investigator>
<last_name>Shahzad Siddique</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-San Marcos</name>
<address>
<city>San Marcos</city>
<state>California</state>
<zip>92078</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-398-3996</phone>
<email>clinical.trials@kp.org</email>
</contact>
<investigator>
<last_name>Eric C. McGary</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mills Health Center</name>
<address>
<city>San Mateo</city>
<state>California</state>
<zip>94401</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser San Rafael-Gallinas</name>
<address>
<city>San Rafael</city>
<state>California</state>
<zip>94903</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente Medical Center - Santa Clara</name>
<address>
<city>Santa Clara</city>
<state>California</state>
<zip>95051</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Dominican Santa Cruz Hospital</name>
<address>
<city>Santa Cruz</city>
<state>California</state>
<zip>95065</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>831-462-7770</phone>
</contact>
<investigator>
<last_name>Michael P. Alexander</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Palo Alto Medical Foundation-Santa Cruz</name>
<address>
<city>Santa Cruz</city>
<state>California</state>
<zip>95065</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>Melanie.Cook@sutterhealth.org</email>
</contact>
<investigator>
<last_name>Edmund W. Tai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mission Hope Medical Oncology - Santa Maria</name>
<address>
<city>Santa Maria</city>
<state>California</state>
<zip>93444</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente-Santa Rosa</name>
<address>
<city>Santa Rosa</city>
<state>California</state>
<zip>95403</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sutter Pacific Medical Foundation</name>
<address>
<city>Santa Rosa</city>
<state>California</state>
<zip>95403</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>City of Hope South Pasadena</name>
<address>
<city>South Pasadena</city>
<state>California</state>
<zip>91030</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Kaiser Permanente Cancer Treatment Center</name>
<address>
<city>South San Francisco</city>
<state>California</state>
<zip>94080</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente-South San Francisco</name>
<address>
<city>South San Francisco</city>
<state>California</state>
<zip>94080</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Stockton</name>
<address>
<city>Stockton</city>
<state>California</state>
<zip>95210</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Palo Alto Medical Foundation-Sunnyvale</name>
<address>
<city>Sunnyvale</city>
<state>California</state>
<zip>94086</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>Melanie.Cook@sutterhealth.org</email>
</contact>
<investigator>
<last_name>Edmund W. Tai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Gene Upshaw Memorial Tahoe Forest Cancer Center</name>
<address>
<city>Truckee</city>
<state>California</state>
<zip>96161</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>530-582-6450</phone>
</contact>
<investigator>
<last_name>David R. Gandara</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>City of Hope Upland</name>
<address>
<city>Upland</city>
<state>California</state>
<zip>91786</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Northbay Cancer Center</name>
<address>
<city>Vacaville</city>
<state>California</state>
<zip>95687</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Sutter Cancer Centers Radiation Oncology Services-Vacaville</name>
<address>
<city>Vacaville</city>
<state>California</state>
<zip>95687</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente Medical Center-Vacaville</name>
<address>
<city>Vacaville</city>
<state>California</state>
<zip>95688</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Vallejo</name>
<address>
<city>Vallejo</city>
<state>California</state>
<zip>94589</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sutter Solano Medical Center/Cancer Center</name>
<address>
<city>Vallejo</city>
<state>California</state>
<zip>94589</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>Melanie.Cook@sutterhealth.org</email>
</contact>
<investigator>
<last_name>Edmund W. Tai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Walnut Creek</name>
<address>
<city>Walnut Creek</city>
<state>California</state>
<zip>94596</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-642-4691</phone>
<email>Kpoct@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Epic Care Cyberknife Center</name>
<address>
<city>Walnut Creek</city>
<state>California</state>
<zip>94597</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>510-465-8016</phone>
<email>somega@bati.org</email>
</contact>
<investigator>
<last_name>Lisa Bailey</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>John Muir Medical Center-Walnut Creek</name>
<address>
<city>Walnut Creek</city>
<state>California</state>
<zip>94598</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>925-941-4246</phone>
</contact>
<investigator>
<last_name>Gigi Q. Chen</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Presbyterian Intercommunity Hospital</name>
<address>
<city>Whittier</city>
<state>California</state>
<zip>90602</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente-Woodland Hills</name>
<address>
<city>Woodland Hills</city>
<state>California</state>
<zip>91367</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-398-3996</phone>
<email>clinical.trials@kp.org</email>
</contact>
<investigator>
<last_name>Eric C. McGary</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers-Aurora</name>
<address>
<city>Aurora</city>
<state>Colorado</state>
<zip>80012</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>303-777-2663</phone>
<email>info@westernstatesncorp.org</email>
</contact>
<investigator>
<last_name>Nicholas DiBella</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>The Medical Center of Aurora</name>
<address>
<city>Aurora</city>
<state>Colorado</state>
<zip>80012</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>UCHealth University of Colorado Hospital</name>
<address>
<city>Aurora</city>
<state>Colorado</state>
<zip>80045</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Boulder Community Hospital</name>
<address>
<city>Boulder</city>
<state>Colorado</state>
<zip>80301</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>303-777-2663</phone>
<email>jbloomfield@co-cancerresearch.org</email>
</contact>
<investigator>
<last_name>Nicholas DiBella</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Boulder Community Foothills Hospital</name>
<address>
<city>Boulder</city>
<state>Colorado</state>
<zip>80303</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers-Boulder</name>
<address>
<city>Boulder</city>
<state>Colorado</state>
<zip>80304</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>303-777-2663</phone>
<email>info@westernstatesncorp.org</email>
</contact>
<investigator>
<last_name>Nicholas DiBella</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers - Centennial</name>
<address>
<city>Centennial</city>
<state>Colorado</state>
<zip>80112</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>303-777-2663</phone>
<email>info@westernstatesncorp.org</email>
</contact>
<investigator>
<last_name>Nicholas DiBella</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Penrose-Saint Francis Healthcare</name>
<address>
<city>Colorado Springs</city>
<state>Colorado</state>
<zip>80907</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers-Penrose</name>
<address>
<city>Colorado Springs</city>
<state>Colorado</state>
<zip>80907</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>UCHealth Memorial Hospital Central</name>
<address>
<city>Colorado Springs</city>
<state>Colorado</state>
<zip>80909</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>719-365-2406</phone>
</contact>
<investigator>
<last_name>Tejas Patil</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Memorial Hospital North</name>
<address>
<city>Colorado Springs</city>
<state>Colorado</state>
<zip>80920</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>719-364-6700</phone>
</contact>
<investigator>
<last_name>Tejas Patil</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Center of Colorado at Sloan's Lake</name>
<address>
<city>Denver</city>
<state>Colorado</state>
<zip>80204</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente-Franklin</name>
<address>
<city>Denver</city>
<state>Colorado</state>
<zip>80205</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>303-720-2685</phone>
<email>kristi.m.bronkan@kp.org</email>
</contact>
<investigator>
<last_name>Alexander Menter</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>National Jewish Health-Main Campus</name>
<address>
<city>Denver</city>
<state>Colorado</state>
<zip>80206</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-225-5654</phone>
<email>glicht@co-cancerresearch.org</email>
</contact>
<investigator>
<last_name>Laurie L. Carr</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>The Women's Imaging Center</name>
<address>
<city>Denver</city>
<state>Colorado</state>
<zip>80209</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Porter Adventist Hospital</name>
<address>
<city>Denver</city>
<state>Colorado</state>
<zip>80210</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Colorado Blood Cancer Institute</name>
<address>
<city>Denver</city>
<state>Colorado</state>
<zip>80218</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Presbyterian - Saint Lukes Medical Center - Health One</name>
<address>
<city>Denver</city>
<state>Colorado</state>
<zip>80218</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers-Midtown</name>
<address>
<city>Denver</city>
<state>Colorado</state>
<zip>80218</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>303-777-2663</phone>
<email>info@westernstatesncorp.org</email>
</contact>
<investigator>
<last_name>Nicholas DiBella</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>SCL Health Saint Joseph Hospital</name>
<address>
<city>Denver</city>
<state>Colorado</state>
<zip>80218</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers-Rose</name>
<address>
<city>Denver</city>
<state>Colorado</state>
<zip>80220</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>303-777-2663</phone>
<email>info@westernstatesncorp.org</email>
</contact>
<investigator>
<last_name>Nicholas DiBella</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Rose Medical Center</name>
<address>
<city>Denver</city>
<state>Colorado</state>
<zip>80220</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Western Surgical Care</name>
<address>
<city>Denver</city>
<state>Colorado</state>
<zip>80220</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Mercy Medical Center</name>
<address>
<city>Durango</city>
<state>Colorado</state>
<zip>81301</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Southwest Oncology PC</name>
<address>
<city>Durango</city>
<state>Colorado</state>
<zip>81301</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Mountain Blue Cancer Care Center - Swedish</name>
<address>
<city>Englewood</city>
<state>Colorado</state>
<zip>80113</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers - Swedish</name>
<address>
<city>Englewood</city>
<state>Colorado</state>
<zip>80113</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>303-777-2663</phone>
<email>info@westernstatesncorp.org</email>
</contact>
<investigator>
<last_name>Nicholas DiBella</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Swedish Medical Center</name>
<address>
<city>Englewood</city>
<state>Colorado</state>
<zip>80113</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>The Melanoma and Skin Cancer Institute</name>
<address>
<city>Englewood</city>
<state>Colorado</state>
<zip>80113</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Poudre Valley Hospital</name>
<address>
<city>Fort Collins</city>
<state>Colorado</state>
<zip>80524</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>970-297-6150</phone>
</contact>
<investigator>
<last_name>Tejas Patil</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Care and Hematology-Fort Collins</name>
<address>
<city>Fort Collins</city>
<state>Colorado</state>
<zip>80528</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Tejas Patil</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>National Jewish Health-Western Hematology Oncology</name>
<address>
<city>Golden</city>
<state>Colorado</state>
<zip>80401</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>303-777-2663</phone>
<email>glicht@co-cancerresearch.org</email>
</contact>
<investigator>
<last_name>Laurie L. Carr</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Mary's Hospital and Regional Medical Center</name>
<address>
<city>Grand Junction</city>
<state>Colorado</state>
<zip>81501</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>North Colorado Medical Center</name>
<address>
<city>Greeley</city>
<state>Colorado</state>
<zip>80631</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>UCHealth Greeley Hospital</name>
<address>
<city>Greeley</city>
<state>Colorado</state>
<zip>80631</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Tejas Patil</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Good Samaritan Medical Center</name>
<address>
<city>Lafayette</city>
<state>Colorado</state>
<zip>80026</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente-Rock Creek</name>
<address>
<city>Lafayette</city>
<state>Colorado</state>
<zip>80026</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>303-720-2685</phone>
<email>kristi.m.bronkan@kp.org</email>
</contact>
<investigator>
<last_name>Alexander Menter</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers-Lakewood</name>
<address>
<city>Lakewood</city>
<state>Colorado</state>
<zip>80228</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Anthony Hospital</name>
<address>
<city>Lakewood</city>
<state>Colorado</state>
<zip>80228</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers-Littleton</name>
<address>
<city>Littleton</city>
<state>Colorado</state>
<zip>80120</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>303-777-2663</phone>
<email>info@westernstatesncorp.org</email>
</contact>
<investigator>
<last_name>Nicholas DiBella</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Littleton Adventist Hospital</name>
<address>
<city>Littleton</city>
<state>Colorado</state>
<zip>80122</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>719-776-6550</phone>
<email>ResearchTracking@Centura.Org</email>
</contact>
<investigator>
<last_name>Shahzad Siddique</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Lone Tree</name>
<address>
<city>Lone Tree</city>
<state>Colorado</state>
<zip>80124</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>303-720-2685</phone>
<email>kristi.m.bronkan@kp.org</email>
</contact>
<investigator>
<last_name>Alexander Menter</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers-Sky Ridge</name>
<address>
<city>Lone Tree</city>
<state>Colorado</state>
<zip>80124</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>303-777-2663</phone>
<email>info@westernstatesncorp.org</email>
</contact>
<investigator>
<last_name>Nicholas DiBella</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sky Ridge Medical Center</name>
<address>
<city>Lone Tree</city>
<state>Colorado</state>
<zip>80124</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Longmont United Hospital</name>
<address>
<city>Longmont</city>
<state>Colorado</state>
<zip>80501</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>719-776-6550</phone>
<email>ResearchTracking@Centura.Org</email>
</contact>
<investigator>
<last_name>Shahzad Siddique</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers-Longmont</name>
<address>
<city>Longmont</city>
<state>Colorado</state>
<zip>80501</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Medical Center of the Rockies</name>
<address>
<city>Loveland</city>
<state>Colorado</state>
<zip>80538</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>970-203-7083</phone>
</contact>
<investigator>
<last_name>Tejas Patil</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>McKee Medical Center</name>
<address>
<city>Loveland</city>
<state>Colorado</state>
<zip>80539</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Parker Adventist Hospital</name>
<address>
<city>Parker</city>
<state>Colorado</state>
<zip>80138</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>719-776-6550</phone>
<email>ResearchTracking@Centura.Org</email>
</contact>
<investigator>
<last_name>Shahzad Siddique</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Mary Corwin Medical Center</name>
<address>
<city>Pueblo</city>
<state>Colorado</state>
<zip>81004</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>National Jewish Health-Northern Hematology Oncology</name>
<address>
<city>Thornton</city>
<state>Colorado</state>
<zip>80260</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>303-777-2663</phone>
<email>glicht@co-cancerresearch.org</email>
</contact>
<investigator>
<last_name>Laurie L. Carr</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers-Thornton</name>
<address>
<city>Thornton</city>
<state>Colorado</state>
<zip>80260</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Smilow Cancer Hospital-Derby Care Center</name>
<address>
<city>Derby</city>
<state>Connecticut</state>
<zip>06418</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>203-785-5702</phone>
<email>canceranswers@yale.edu</email>
</contact>
<investigator>
<last_name>Ashita Talsania</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Smilow Cancer Hospital Care Center-Fairfield</name>
<address>
<city>Fairfield</city>
<state>Connecticut</state>
<zip>06824</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>203-785-5702</phone>
<email>canceranswers@yale.edu</email>
</contact>
<investigator>
<last_name>Ashita Talsania</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Smilow Cancer Hospital Care Center at Greenwich</name>
<address>
<city>Greenwich</city>
<state>Connecticut</state>
<zip>06830</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>203-785-5702</phone>
<email>canceranswers@yale.edu</email>
</contact>
<investigator>
<last_name>Ashita Talsania</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Smilow Cancer Hospital Care Center - Guilford</name>
<address>
<city>Guilford</city>
<state>Connecticut</state>
<zip>06437</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>203-785-5702</phone>
<email>canceranswers@yale.edu</email>
</contact>
<investigator>
<last_name>Ashita Talsania</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Smilow Cancer Hospital Care Center at Saint Francis</name>
<address>
<city>Hartford</city>
<state>Connecticut</state>
<zip>06105</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>203-785-5702</phone>
<email>canceranswers@yale.edu</email>
</contact>
<investigator>
<last_name>Ashita Talsania</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Smilow Cancer Center/Yale-New Haven Hospital</name>
<address>
<city>New Haven</city>
<state>Connecticut</state>
<zip>06510</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Yale University</name>
<address>
<city>New Haven</city>
<state>Connecticut</state>
<zip>06520</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>203-785-5702</phone>
<email>canceranswers@yale.edu</email>
</contact>
<investigator>
<last_name>Ashita Talsania</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Yale-New Haven Hospital North Haven Medical Center</name>
<address>
<city>North Haven</city>
<state>Connecticut</state>
<zip>06473</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>203-785-5702</phone>
<email>canceranswers@yale.edu</email>
</contact>
<investigator>
<last_name>Ashita Talsania</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Smilow Cancer Hospital-Orange Care Center</name>
<address>
<city>Orange</city>
<state>Connecticut</state>
<zip>06477</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>203-785-5702</phone>
<email>canceranswers@yale.edu</email>
</contact>
<investigator>
<last_name>Ashita Talsania</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Stamford Hospital/Bennett Cancer Center</name>
<address>
<city>Stamford</city>
<state>Connecticut</state>
<zip>06904</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>203-323-8944</phone>
</contact>
<investigator>
<last_name>Salvatore A. Del Prete</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Smilow Cancer Hospital-Torrington Care Center</name>
<address>
<city>Torrington</city>
<state>Connecticut</state>
<zip>06790</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>203-785-5702</phone>
<email>canceranswers@yale.edu</email>
</contact>
<investigator>
<last_name>Ashita Talsania</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Smilow Cancer Hospital Care Center-Trumbull</name>
<address>
<city>Trumbull</city>
<state>Connecticut</state>
<zip>06611</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>203-785-5702</phone>
<email>canceranswers@yale.edu</email>
</contact>
<investigator>
<last_name>Ashita Talsania</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Smilow Cancer Hospital-Waterbury Care Center</name>
<address>
<city>Waterbury</city>
<state>Connecticut</state>
<zip>06708</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>203-785-5702</phone>
<email>canceranswers@yale.edu</email>
</contact>
<investigator>
<last_name>Ashita Talsania</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Smilow Cancer Hospital Care Center - Waterford</name>
<address>
<city>Waterford</city>
<state>Connecticut</state>
<zip>06385</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>203-785-5702</phone>
<email>canceranswers@yale.edu</email>
</contact>
<investigator>
<last_name>Ashita Talsania</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Veterans Affairs Connecticut Healthcare System-West Haven Campus</name>
<address>
<city>West Haven</city>
<state>Connecticut</state>
<zip>06516</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>203-937-3421</phone>
<phone_ext>2832</phone_ext>
</contact>
<investigator>
<last_name>Herta H. Chao</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Beebe South Coastal Health Campus</name>
<address>
<city>Frankford</city>
<state>Delaware</state>
<zip>19945</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>302-291-6730</phone>
<email>research@beebehealthcare.org</email>
</contact>
<investigator>
<last_name>Gregory A. Masters</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Beebe Medical Center</name>
<address>
<city>Lewes</city>
<state>Delaware</state>
<zip>19958</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Delaware Clinical and Laboratory Physicians PA</name>
<address>
<city>Newark</city>
<state>Delaware</state>
<zip>19713</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Helen F Graham Cancer Center</name>
<address>
<city>Newark</city>
<state>Delaware</state>
<zip>19713</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>302-623-4450</phone>
<email>lbarone@christianacare.org</email>
</contact>
<investigator>
<last_name>Gregory A. Masters</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Medical Oncology Hematology Consultants PA</name>
<address>
<city>Newark</city>
<state>Delaware</state>
<zip>19713</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>302-623-4450</phone>
<email>lbarone@christianacare.org</email>
</contact>
<investigator>
<last_name>Gregory A. Masters</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Christiana Care Health System-Christiana Hospital</name>
<address>
<city>Newark</city>
<state>Delaware</state>
<zip>19718</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Beebe Health Campus</name>
<address>
<city>Rehoboth Beach</city>
<state>Delaware</state>
<zip>19971</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>302-291-6730</phone>
<email>research@beebehealthcare.org</email>
</contact>
<investigator>
<last_name>Gregory A. Masters</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>TidalHealth Nanticoke / Allen Cancer Center</name>
<address>
<city>Seaford</city>
<state>Delaware</state>
<zip>19973</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Christiana Care Health System-Wilmington Hospital</name>
<address>
<city>Wilmington</city>
<state>Delaware</state>
<zip>19801</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente-Capitol Hill Medical Center</name>
<address>
<city>Washington</city>
<state>District of Columbia</state>
<zip>20002</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>301-548-5743</phone>
</contact>
<investigator>
<last_name>Leon C. Hwang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>MedStar Georgetown University Hospital</name>
<address>
<city>Washington</city>
<state>District of Columbia</state>
<zip>20007</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>MedStar Washington Hospital Center</name>
<address>
<city>Washington</city>
<state>District of Columbia</state>
<zip>20010</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>202-877-8839</phone>
</contact>
<investigator>
<last_name>Joshua E. Reuss</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mount Sinai Comprehensive Cancer Center at Aventura</name>
<address>
<city>Aventura</city>
<state>Florida</state>
<zip>33180</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Holy Cross Hospital</name>
<address>
<city>Fort Lauderdale</city>
<state>Florida</state>
<zip>33308</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Regional Cancer Center-Lee Memorial Health System</name>
<address>
<city>Fort Myers</city>
<state>Florida</state>
<zip>33905</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Venkata K. Parsa</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Memorial Regional Hospital/Joe DiMaggio Children's Hospital</name>
<address>
<city>Hollywood</city>
<state>Florida</state>
<zip>33021</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Baptist MD Anderson Cancer Center</name>
<address>
<city>Jacksonville</city>
<state>Florida</state>
<zip>32207</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>904-202-7468</phone>
</contact>
<investigator>
<last_name>John H. Vu</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mount Sinai Medical Center</name>
<address>
<city>Miami Beach</city>
<state>Florida</state>
<zip>33140</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Orlando Health Cancer Institute</name>
<address>
<city>Orlando</city>
<state>Florida</state>
<zip>32806</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Memorial Hospital West</name>
<address>
<city>Pembroke Pines</city>
<state>Florida</state>
<zip>33028</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Moffitt Cancer Center-International Plaza</name>
<address>
<city>Tampa</city>
<state>Florida</state>
<zip>33607</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Moffitt Cancer Center - McKinley Campus</name>
<address>
<city>Tampa</city>
<state>Florida</state>
<zip>33612</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Moffitt Cancer Center</name>
<address>
<city>Tampa</city>
<state>Florida</state>
<zip>33612</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-679-0775</phone>
<email>ClinicalTrials@moffitt.org</email>
</contact>
<investigator>
<last_name>Jhanelle E. Gray</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Northside Hospital</name>
<address>
<city>Atlanta</city>
<state>Georgia</state>
<zip>30342</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>404-303-3355</phone>
<email>ClinicalTrials@northside.com</email>
</contact>
<investigator>
<last_name>Ioana Bonta</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Northeast Georgia Medical Center Braselton</name>
<address>
<city>Braselton</city>
<state>Georgia</state>
<zip>30517</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Northside Hospital - Duluth</name>
<address>
<city>Duluth</city>
<state>Georgia</state>
<zip>30096</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>404-303-3355</phone>
<email>Clinical.trials@northside.com</email>
</contact>
<investigator>
<last_name>Ioana Bonta</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Northeast Georgia Medical Center-Gainesville</name>
<address>
<city>Gainesville</city>
<state>Georgia</state>
<zip>30501</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>770-219-8800</phone>
<email>cancerpatient.navigator@nghs.com</email>
</contact>
<investigator>
<last_name>Charles H. Nash</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Northside Hospital - Gwinnett</name>
<address>
<city>Lawrenceville</city>
<state>Georgia</state>
<zip>30046</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>404-303-3355</phone>
<email>Clinical.trials@northside.com</email>
</contact>
<investigator>
<last_name>Ioana Bonta</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lewis Cancer and Research Pavilion at Saint Joseph's/Candler</name>
<address>
<city>Savannah</city>
<state>Georgia</state>
<zip>31405</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>912-819-5704</phone>
<email>underberga@sjchs.org</email>
</contact>
<investigator>
<last_name>Mark A. Taylor</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Suburban Hematology Oncology Associates - Snellville</name>
<address>
<city>Snellville</city>
<state>Georgia</state>
<zip>30078</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Hawaii Cancer Care - Westridge</name>
<address>
<city>'Aiea</city>
<state>Hawaii</state>
<zip>96701</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Pali Momi Medical Center</name>
<address>
<city>'Aiea</city>
<state>Hawaii</state>
<zip>96701</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Queen's Cancer Center - Pearlridge</name>
<address>
<city>'Aiea</city>
<state>Hawaii</state>
<zip>96701</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>The Cancer Center of Hawaii-Pali Momi</name>
<address>
<city>'Aiea</city>
<state>Hawaii</state>
<zip>96701</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>The Queen's Medical Center - West Oahu</name>
<address>
<city>'Ewa Beach</city>
<state>Hawaii</state>
<zip>96706</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Hawaii Cancer Care Inc - Waterfront Plaza</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96813</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Island Urology</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96813</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Queen's Cancer Cenrer - POB I</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96813</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Queen's Medical Center</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96813</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Straub Clinic and Hospital</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96813</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>University of Hawaii Cancer Center</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96813</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Hawaii Cancer Care Inc-Liliha</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96817</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Hawaii Diagnostic Radiology Services LLC</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96817</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kuakini Medical Center</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96817</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Queen's Cancer Center - Kuakini</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96817</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>The Cancer Center of Hawaii-Liliha</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96817</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente Moanalua Medical Center</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96819</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>808-432-5195</phone>
<email>shelley.a.clark@kp.org</email>
</contact>
<investigator>
<last_name>Jennifer M. Suga</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kapiolani Medical Center for Women and Children</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96826</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Straub Medical Center - Kahului Clinic</name>
<address>
<city>Kahului</city>
<state>Hawaii</state>
<zip>96732</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Castle Medical Center</name>
<address>
<city>Kailua</city>
<state>Hawaii</state>
<zip>96734</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Wilcox Memorial Hospital and Kauai Medical Clinic</name>
<address>
<city>Lihue</city>
<state>Hawaii</state>
<zip>96766</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Alphonsus Cancer Care Center-Boise</name>
<address>
<city>Boise</city>
<state>Idaho</state>
<zip>83706</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>734-712-3671</phone>
<email>stephanie.couch@stjoeshealth.org</email>
</contact>
<investigator>
<last_name>John M. Schallenkamp</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Luke's Cancer Institute - Boise</name>
<address>
<city>Boise</city>
<state>Idaho</state>
<zip>83712</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>208-381-2774</phone>
<email>eslinget@slhs.org</email>
</contact>
<investigator>
<last_name>Alison K. Conlin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Alphonsus Cancer Care Center-Caldwell</name>
<address>
<city>Caldwell</city>
<state>Idaho</state>
<zip>83605</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>734-712-3671</phone>
<email>stephanie.couch@stjoeshealth.org</email>
</contact>
<investigator>
<last_name>John M. Schallenkamp</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kootenai Health - Coeur d'Alene</name>
<address>
<city>Coeur d'Alene</city>
<state>Idaho</state>
<zip>83814</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>406-969-6060</phone>
<email>mccinfo@mtcancer.org</email>
</contact>
<investigator>
<last_name>John M. Schallenkamp</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Walter Knox Memorial Hospital</name>
<address>
<city>Emmett</city>
<state>Idaho</state>
<zip>83617</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Luke's Cancer Institute - Fruitland</name>
<address>
<city>Fruitland</city>
<state>Idaho</state>
<zip>83619</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>208-381-2774</phone>
<email>eslinget@slhs.org</email>
</contact>
<investigator>
<last_name>Alison K. Conlin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Idaho Urologic Institute-Meridian</name>
<address>
<city>Meridian</city>
<state>Idaho</state>
<zip>83642</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Luke's Cancer Institute - Meridian</name>
<address>
<city>Meridian</city>
<state>Idaho</state>
<zip>83642</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>208-381-2774</phone>
<email>eslinget@slhs.org</email>
</contact>
<investigator>
<last_name>Alison K. Conlin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Luke's Cancer Institute - Nampa</name>
<address>
<city>Nampa</city>
<state>Idaho</state>
<zip>83686</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>208-381-2774</phone>
<email>eslinget@slhs.org</email>
</contact>
<investigator>
<last_name>Alison K. Conlin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Alphonsus Cancer Care Center-Nampa</name>
<address>
<city>Nampa</city>
<state>Idaho</state>
<zip>83687</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>406-969-6060</phone>
<email>mccinfo@mtcancer.org</email>
</contact>
<investigator>
<last_name>John M. Schallenkamp</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kootenai Clinic Cancer Services - Post Falls</name>
<address>
<city>Post Falls</city>
<state>Idaho</state>
<zip>83854</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>406-969-6060</phone>
<email>mccinfo@mtcancer.org</email>
</contact>
<investigator>
<last_name>John M. Schallenkamp</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kootenai Cancer Clinic</name>
<address>
<city>Sandpoint</city>
<state>Idaho</state>
<zip>83864</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>406-969-6060</phone>
<email>mccinfo@mtcancer.org</email>
</contact>
<investigator>
<last_name>John M. Schallenkamp</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Luke's Cancer Institute - Twin Falls</name>
<address>
<city>Twin Falls</city>
<state>Idaho</state>
<zip>83301</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>208-381-2774</phone>
<email>eslinget@slhs.org</email>
</contact>
<investigator>
<last_name>Alison K. Conlin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Anthony's Health</name>
<address>
<city>Alton</city>
<state>Illinois</state>
<zip>62002</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Rush - Copley Medical Center</name>
<address>
<city>Aurora</city>
<state>Illinois</state>
<zip>60504</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Illinois CancerCare-Bloomington</name>
<address>
<city>Bloomington</city>
<state>Illinois</state>
<zip>61704</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>309-243-3605</phone>
<email>andersonj@illinoiscancercare.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Illinois CancerCare-Canton</name>
<address>
<city>Canton</city>
<state>Illinois</state>
<zip>61520</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>309-243-3605</phone>
<email>andersonj@illinoiscancercare.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Memorial Hospital of Carbondale</name>
<address>
<city>Carbondale</city>
<state>Illinois</state>
<zip>62902</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>SIH Cancer Institute</name>
<address>
<city>Carterville</city>
<state>Illinois</state>
<zip>62918</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>618-985-3333</phone>
<email>clinical.research@sih.net</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Illinois CancerCare-Carthage</name>
<address>
<city>Carthage</city>
<state>Illinois</state>
<zip>62321</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>309-243-3605</phone>
<email>andersonj@illinoiscancercare.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Centralia Oncology Clinic</name>
<address>
<city>Centralia</city>
<state>Illinois</state>
<zip>62801</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>217-876-4762</phone>
<email>morganthaler.jodi@mhsil.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Northwestern University</name>
<address>
<city>Chicago</city>
<state>Illinois</state>
<zip>60611</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>312-695-1301</phone>
<email>cancer@northwestern.edu</email>
</contact>
<investigator>
<last_name>Nisha A. Mohindra</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>John H Stroger Jr Hospital of Cook County</name>
<address>
<city>Chicago</city>
<state>Illinois</state>
<zip>60612</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>312-864-5204</phone>
</contact>
<investigator>
<last_name>Thomas E. Lad</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University of Illinois</name>
<address>
<city>Chicago</city>
<state>Illinois</state>
<zip>60612</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>312-355-3046</phone>
</contact>
<investigator>
<last_name>Lawrence E. Feldman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University of Chicago Comprehensive Cancer Center</name>
<address>
<city>Chicago</city>
<state>Illinois</state>
<zip>60637</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-8222</phone>
<email>cancerclinicaltrials@bsd.uchicago.edu</email>
</contact>
<investigator>
<last_name>Christine M. Bestvina</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Advocate Illinois Masonic Medical Center</name>
<address>
<city>Chicago</city>
<state>Illinois</state>
<zip>60657</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-296-5360</phone>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>AMG Crystal Lake - Oncology</name>
<address>
<city>Crystal Lake</city>
<state>Illinois</state>
<zip>60014</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>630-929-6129</phone>
<email>advocateresearch@advocate.com</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Carle at The Riverfront</name>
<address>
<city>Danville</city>
<state>Illinois</state>
<zip>61832</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-446-5532</phone>
<email>Research@Carle.com</email>
</contact>
<investigator>
<last_name>Vamsi K. Vasireddy</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Care Specialists of Illinois - Decatur</name>
<address>
<city>Decatur</city>
<state>Illinois</state>
<zip>62526</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>217-876-4762</phone>
<email>morganthaler.jodi@mhsil.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Decatur Memorial Hospital</name>
<address>
<city>Decatur</city>
<state>Illinois</state>
<zip>62526</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>217-876-4762</phone>
<email>morganthaler.jodi@mhsil.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Illinois CancerCare-Dixon</name>
<address>
<city>Dixon</city>
<state>Illinois</state>
<zip>61021</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>815-285-7800</phone>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Advocate Good Samaritan Hospital</name>
<address>
<city>Downers Grove</city>
<state>Illinois</state>
<zip>60515</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>630-275-1270</phone>
<email>Barbara.barhamand@advocatehealth.com</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Carle Physician Group-Effingham</name>
<address>
<city>Effingham</city>
<state>Illinois</state>
<zip>62401</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-446-5532</phone>
<email>Research@carle.com</email>
</contact>
<investigator>
<last_name>Vamsi K. Vasireddy</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Crossroads Cancer Center</name>
<address>
<city>Effingham</city>
<state>Illinois</state>
<zip>62401</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>217-876-4762</phone>
<email>morganthaler.jodi@mhsil.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Illinois CancerCare-Eureka</name>
<address>
<city>Eureka</city>
<state>Illinois</state>
<zip>61530</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>309-243-3605</phone>
<email>andersonj@illinoiscancercare.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>NorthShore University HealthSystem-Evanston Hospital</name>
<address>
<city>Evanston</city>
<state>Illinois</state>
<zip>60201</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>847-570-2109</phone>
</contact>
<investigator>
<last_name>Thomas A. Hensing</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Illinois CancerCare-Galesburg</name>
<address>
<city>Galesburg</city>
<state>Illinois</state>
<zip>61401</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>309-243-3605</phone>
<email>andersonj@illinoiscancercare.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Western Illinois Cancer Treatment Center</name>
<address>
<city>Galesburg</city>
<state>Illinois</state>
<zip>61401</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>NorthShore University HealthSystem-Glenbrook Hospital</name>
<address>
<city>Glenview</city>
<state>Illinois</state>
<zip>60026</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>847-570-2109</phone>
</contact>
<investigator>
<last_name>Thomas A. Hensing</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>NorthShore University HealthSystem-Highland Park Hospital</name>
<address>
<city>Highland Park</city>
<state>Illinois</state>
<zip>60035</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>847-570-2109</phone>
</contact>
<investigator>
<last_name>Thomas A. Hensing</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Edward Hines Jr VA Hospital</name>
<address>
<city>Hines</city>
<state>Illinois</state>
<zip>60141</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>708-202-8387</phone>
</contact>
<investigator>
<last_name>Cheryl M. Czerlanis</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Duly Health and Care Joliet</name>
<address>
<city>Joliet</city>
<state>Illinois</state>
<zip>60435</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>815-730-3098</phone>
<email>Karen.Sceniak@dulyhealthandcare.com</email>
</contact>
<investigator>
<last_name>Nafisa D. Burhani</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Illinois CancerCare-Kewanee Clinic</name>
<address>
<city>Kewanee</city>
<state>Illinois</state>
<zip>61443</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>309-243-3605</phone>
<email>andersonj@illinoiscancercare.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Condell Memorial Hospital</name>
<address>
<city>Libertyville</city>
<state>Illinois</state>
<zip>60048</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>630-929-6129</phone>
<email>advocateresearch@advocatehealth.com</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Illinois CancerCare-Macomb</name>
<address>
<city>Macomb</city>
<state>Illinois</state>
<zip>61455</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>309-243-3605</phone>
<email>andersonj@illinoiscancercare.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Carle Physician Group-Mattoon/Charleston</name>
<address>
<city>Mattoon</city>
<state>Illinois</state>
<zip>61938</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-446-5532</phone>
<email>Research@carle.com</email>
</contact>
<investigator>
<last_name>Vamsi K. Vasireddy</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Loyola University Medical Center</name>
<address>
<city>Maywood</city>
<state>Illinois</state>
<zip>60153</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>708-226-4357</phone>
</contact>
<investigator>
<last_name>Cheryl M. Czerlanis</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Trinity Medical Center</name>
<address>
<city>Moline</city>
<state>Illinois</state>
<zip>61265</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Good Samaritan Regional Health Center</name>
<address>
<city>Mount Vernon</city>
<state>Illinois</state>
<zip>62864</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>618-242-4600</phone>
</contact>
<investigator>
<last_name>Jay W. Carlson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UC Comprehensive Cancer Center at Silver Cross</name>
<address>
<city>New Lenox</city>
<state>Illinois</state>
<zip>60451</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-8222</phone>
<email>cancerclinicaltrials@bsd.uchicago.edu</email>
</contact>
<investigator>
<last_name>Christine M. Bestvina</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Care Center of O'Fallon</name>
<address>
<city>O'Fallon</city>
<state>Illinois</state>
<zip>62269</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>217-876-4762</phone>
<email>morganthaler.jodi@mhsil.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Advocate Christ Medical Center</name>
<address>
<city>Oak Lawn</city>
<state>Illinois</state>
<zip>60453-2699</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-323-8622</phone>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University of Chicago Medicine-Orland Park</name>
<address>
<city>Orland Park</city>
<state>Illinois</state>
<zip>60462</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-8222</phone>
<email>cancerclinicaltrials@bsd.uchicago.edu</email>
</contact>
<investigator>
<last_name>Christine M. Bestvina</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Illinois CancerCare-Ottawa Clinic</name>
<address>
<city>Ottawa</city>
<state>Illinois</state>
<zip>61350</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>309-243-3605</phone>
<email>andersonj@illinoiscancercare.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Advocate Lutheran General Hospital</name>
<address>
<city>Park Ridge</city>
<state>Illinois</state>
<zip>60068</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>847-384-3621</phone>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Illinois CancerCare-Pekin</name>
<address>
<city>Pekin</city>
<state>Illinois</state>
<zip>61554</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>309-243-3605</phone>
<email>andersonj@illinoiscancercare.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center</name>
<address>
<city>Pekin</city>
<state>Illinois</state>
<zip>61554</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Illinois CancerCare-Peoria</name>
<address>
<city>Peoria</city>
<state>Illinois</state>
<zip>61615</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>309-243-3605</phone>
<email>andersonj@illinoiscancercare.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>OSF Saint Francis Radiation Oncology at Peoria Cancer Center</name>
<address>
<city>Peoria</city>
<state>Illinois</state>
<zip>61615</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Methodist Medical Center of Illinois</name>
<address>
<city>Peoria</city>
<state>Illinois</state>
<zip>61636</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>OSF Saint Francis Medical Center</name>
<address>
<city>Peoria</city>
<state>Illinois</state>
<zip>61637</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Illinois CancerCare-Peru</name>
<address>
<city>Peru</city>
<state>Illinois</state>
<zip>61354</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>309-243-3605</phone>
<email>andersonj@illinoiscancercare.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Valley Radiation Oncology</name>
<address>
<city>Peru</city>
<state>Illinois</state>
<zip>61354</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Illinois CancerCare-Princeton</name>
<address>
<city>Princeton</city>
<state>Illinois</state>
<zip>61356</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>309-243-3605</phone>
<email>andersonj@illinoiscancercare.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>OSF Saint Anthony Medical Center</name>
<address>
<city>Rockford</city>
<state>Illinois</state>
<zip>61108</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>815-227-2633</phone>
</contact>
<investigator>
<last_name>Iftekhar U. Ahmad</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>SwedishAmerican Regional Cancer Center/ACT</name>
<address>
<city>Rockford</city>
<state>Illinois</state>
<zip>61114</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>779-696-9378</phone>
<email>lkline@uwhealth.org</email>
</contact>
<investigator>
<last_name>Harvey E. Einhorn</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Genesis Cancer Center - Silvis</name>
<address>
<city>Silvis</city>
<state>Illinois</state>
<zip>61282</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>563-421-1908</phone>
<email>turnerk@genesishealth.com</email>
</contact>
<investigator>
<last_name>David M. Spector</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Southern Illinois University School of Medicine</name>
<address>
<city>Springfield</city>
<state>Illinois</state>
<zip>62702</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>217-545-7929</phone>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Springfield Clinic</name>
<address>
<city>Springfield</city>
<state>Illinois</state>
<zip>62702</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-444-7541</phone>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Memorial Medical Center</name>
<address>
<city>Springfield</city>
<state>Illinois</state>
<zip>62781</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Southwest Illinois Health Services LLP</name>
<address>
<city>Swansea</city>
<state>Illinois</state>
<zip>62226</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Carle Cancer Center</name>
<address>
<city>Urbana</city>
<state>Illinois</state>
<zip>61801</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-446-5532</phone>
<email>Research@carle.com</email>
</contact>
<investigator>
<last_name>Vamsi K. Vasireddy</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>The Carle Foundation Hospital</name>
<address>
<city>Urbana</city>
<state>Illinois</state>
<zip>61801</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Illinois CancerCare - Washington</name>
<address>
<city>Washington</city>
<state>Illinois</state>
<zip>61571</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>309-243-3605</phone>
<email>andersonj@illinoiscancercare.com</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Rush-Copley Healthcare Center</name>
<address>
<city>Yorkville</city>
<state>Illinois</state>
<zip>60560</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Northwest Cancer Center - Main Campus</name>
<address>
<city>Crown Point</city>
<state>Indiana</state>
<zip>46307</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>219-310-2550</phone>
</contact>
<investigator>
<last_name>Vamsi K. Vasireddy</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Northwest Oncology LLC</name>
<address>
<city>Dyer</city>
<state>Indiana</state>
<zip>46311</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>219-924-8178</phone>
</contact>
<investigator>
<last_name>Vamsi K. Vasireddy</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Parkview Regional Medical Center</name>
<address>
<city>Fort Wayne</city>
<state>Indiana</state>
<zip>46845</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-784-4673</phone>
</contact>
<investigator>
<last_name>Sarah Y. Wang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Northwest Cancer Center - Hobart</name>
<address>
<city>Hobart</city>
<state>Indiana</state>
<zip>46342</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>219-947-1795</phone>
</contact>
<investigator>
<last_name>Vamsi K. Vasireddy</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Mary Medical Center</name>
<address>
<city>Hobart</city>
<state>Indiana</state>
<zip>46342</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>219-836-6875</phone>
<email>CancerResearch@COMHS.org</email>
</contact>
<investigator>
<last_name>Vamsi K. Vasireddy</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Franciscan Health Indianapolis</name>
<address>
<city>Indianapolis</city>
<state>Indiana</state>
<zip>46237</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Catherine Hospital</name>
<address>
<city>Indianapolis</city>
<state>Indiana</state>
<zip>46312</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Vamsi K. Vasireddy</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Franciscan Saint Elizabeth Health - Lafayette East</name>
<address>
<city>Lafayette</city>
<state>Indiana</state>
<zip>47905</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Woodland Cancer Care Center</name>
<address>
<city>Michigan City</city>
<state>Indiana</state>
<zip>46360</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Franciscan Health Mooresville</name>
<address>
<city>Mooresville</city>
<state>Indiana</state>
<zip>46158</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Franciscan Health Munster</name>
<address>
<city>Munster</city>
<state>Indiana</state>
<zip>46321</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>219-922-7469</phone>
</contact>
<investigator>
<last_name>Harsha Ranganath</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>The Community Hospital</name>
<address>
<city>Munster</city>
<state>Indiana</state>
<zip>46321</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>219-836-3349</phone>
</contact>
<investigator>
<last_name>Vamsi K. Vasireddy</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Women's Diagnostic Center - Munster</name>
<address>
<city>Munster</city>
<state>Indiana</state>
<zip>46321</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>219-934-8869</phone>
<email>mnicholson@comhs.org</email>
</contact>
<investigator>
<last_name>Vamsi K. Vasireddy</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Baptist Health Floyd</name>
<address>
<city>New Albany</city>
<state>Indiana</state>
<zip>47150</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Reid Health</name>
<address>
<city>Richmond</city>
<state>Indiana</state>
<zip>47374</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>937-528-2900</phone>
<email>clinical.trials@daytonncorp.org</email>
</contact>
<investigator>
<last_name>Howard M. Gross</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Memorial Hospital of South Bend</name>
<address>
<city>South Bend</city>
<state>Indiana</state>
<zip>46601</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-284-7370</phone>
</contact>
<investigator>
<last_name>Muhammad O. Toor</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Union Hospital</name>
<address>
<city>Terre Haute</city>
<state>Indiana</state>
<zip>47804</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Northwest Cancer Center - Valparaiso</name>
<address>
<city>Valparaiso</city>
<state>Indiana</state>
<zip>46383</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>219-836-6875</phone>
<email>CancerResearch@COMHS.org</email>
</contact>
<investigator>
<last_name>Vamsi K. Vasireddy</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mary Greeley Medical Center</name>
<address>
<city>Ames</city>
<state>Iowa</state>
<zip>50010</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>515-956-4132</phone>
</contact>
<investigator>
<last_name>Joseph J. Merchant</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>McFarland Clinic - Ames</name>
<address>
<city>Ames</city>
<state>Iowa</state>
<zip>50010</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>515-239-4734</phone>
<email>ksoder@mcfarlandclinic.com</email>
</contact>
<investigator>
<last_name>Joseph J. Merchant</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>McFarland Clinic - Boone</name>
<address>
<city>Boone</city>
<state>Iowa</state>
<zip>50036</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>515-956-4132</phone>
</contact>
<investigator>
<last_name>Joseph J. Merchant</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Anthony Regional Hospital</name>
<address>
<city>Carroll</city>
<state>Iowa</state>
<zip>51401</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>515-689-7658</phone>
<email>sbenson@iora.org</email>
</contact>
<investigator>
<last_name>Joshua Lukenbill</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Physicians' Clinic of Iowa PC</name>
<address>
<city>Cedar Rapids</city>
<state>Iowa</state>
<zip>52402</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>319-297-2900</phone>
</contact>
<investigator>
<last_name>William P. Fusselman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mercy Hospital</name>
<address>
<city>Cedar Rapids</city>
<state>Iowa</state>
<zip>52403</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>319-365-4673</phone>
</contact>
<investigator>
<last_name>Deborah W. Wilbur</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Oncology Associates at Mercy Medical Center</name>
<address>
<city>Cedar Rapids</city>
<state>Iowa</state>
<zip>52403</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>319-363-2690</phone>
</contact>
<investigator>
<last_name>Deborah W. Wilbur</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Medical Oncology and Hematology Associates-West Des Moines</name>
<address>
<city>Clive</city>
<state>Iowa</state>
<zip>50325</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Mercy Cancer Center-West Lakes</name>
<address>
<city>Clive</city>
<state>Iowa</state>
<zip>50325</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Alegent Health Mercy Hospital</name>
<address>
<city>Council Bluffs</city>
<state>Iowa</state>
<zip>51503</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Heartland Oncology and Hematology LLP</name>
<address>
<city>Council Bluffs</city>
<state>Iowa</state>
<zip>51503</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>712-322-4136</phone>
</contact>
<investigator>
<last_name>Robert M. Langdon</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Greater Regional Medical Center</name>
<address>
<city>Creston</city>
<state>Iowa</state>
<zip>50801</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Genesis Medical Center - East Campus</name>
<address>
<city>Davenport</city>
<state>Iowa</state>
<zip>52803</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>563-421-1908</phone>
<email>turnerk@genesishealth.com</email>
</contact>
<investigator>
<last_name>David M. Spector</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Genesis Cancer Care Institute</name>
<address>
<city>Davenport</city>
<state>Iowa</state>
<zip>52804</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>563-421-1908</phone>
<email>turnerk@genesishealth.com</email>
</contact>
<investigator>
<last_name>David M. Spector</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Iowa Cancer Specialists</name>
<address>
<city>Davenport</city>
<state>Iowa</state>
<zip>52807</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>563-421-1908</phone>
<email>turnerk@genesishealth.com</email>
</contact>
<investigator>
<last_name>David M. Spector</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Iowa Methodist Medical Center</name>
<address>
<city>Des Moines</city>
<state>Iowa</state>
<zip>50309</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Medical Oncology and Hematology Associates-Des Moines</name>
<address>
<city>Des Moines</city>
<state>Iowa</state>
<zip>50309</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>515-241-3305</phone>
</contact>
<investigator>
<last_name>Joshua Lukenbill</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Broadlawns Medical Center</name>
<address>
<city>Des Moines</city>
<state>Iowa</state>
<zip>50314</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>515-282-2200</phone>
</contact>
<investigator>
<last_name>Joshua Lukenbill</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mercy Medical Center - Des Moines</name>
<address>
<city>Des Moines</city>
<state>Iowa</state>
<zip>50314</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>515-358-6613</phone>
<email>cancerresearch@mercydesmoines.org</email>
</contact>
<investigator>
<last_name>Richard L. Deming</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mission Cancer and Blood - Laurel</name>
<address>
<city>Des Moines</city>
<state>Iowa</state>
<zip>50314</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Iowa Lutheran Hospital</name>
<address>
<city>Des Moines</city>
<state>Iowa</state>
<zip>50316</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>McFarland Clinic - Trinity Cancer Center</name>
<address>
<city>Fort Dodge</city>
<state>Iowa</state>
<zip>50501</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>515-956-4132</phone>
</contact>
<investigator>
<last_name>Joseph J. Merchant</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Trinity Regional Medical Center</name>
<address>
<city>Fort Dodge</city>
<state>Iowa</state>
<zip>50501</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>McFarland Clinic - Jefferson</name>
<address>
<city>Jefferson</city>
<state>Iowa</state>
<zip>50129</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>515-956-4132</phone>
</contact>
<investigator>
<last_name>Joseph J. Merchant</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>McFarland Clinic - Marshalltown</name>
<address>
<city>Marshalltown</city>
<state>Iowa</state>
<zip>50158</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>515-956-4132</phone>
</contact>
<investigator>
<last_name>Joseph J. Merchant</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Siouxland Regional Cancer Center</name>
<address>
<city>Sioux City</city>
<state>Iowa</state>
<zip>51101</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>712-252-9326</phone>
<email>HoopingarnerT@jencc.com</email>
</contact>
<investigator>
<last_name>Donald B. Wender</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Methodist West Hospital</name>
<address>
<city>West Des Moines</city>
<state>Iowa</state>
<zip>50266-7700</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Mercy Medical Center-West Lakes</name>
<address>
<city>West Des Moines</city>
<state>Iowa</state>
<zip>50266</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer Center of Kansas - Chanute</name>
<address>
<city>Chanute</city>
<state>Kansas</state>
<zip>66720</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer Center of Kansas - Dodge City</name>
<address>
<city>Dodge City</city>
<state>Kansas</state>
<zip>67801</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer Center of Kansas - El Dorado</name>
<address>
<city>El Dorado</city>
<state>Kansas</state>
<zip>67042</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Central Care Cancer Center - Garden City</name>
<address>
<city>Garden City</city>
<state>Kansas</state>
<zip>67846</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Central Care Cancer Center - Great Bend</name>
<address>
<city>Great Bend</city>
<state>Kansas</state>
<zip>67530</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>HaysMed University of Kansas Health System</name>
<address>
<city>Hays</city>
<state>Kansas</state>
<zip>67601</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>785-623-5774</phone>
</contact>
<investigator>
<last_name>Chao H. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Center of Kansas-Independence</name>
<address>
<city>Independence</city>
<state>Kansas</state>
<zip>67301</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>University of Kansas Cancer Center</name>
<address>
<city>Kansas City</city>
<state>Kansas</state>
<zip>66160</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>913-588-3671</phone>
<email>KUCC_Navigation@kumc.edu</email>
</contact>
<investigator>
<last_name>Chao H. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Center of Kansas-Kingman</name>
<address>
<city>Kingman</city>
<state>Kansas</state>
<zip>67068</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Lawrence Memorial Hospital</name>
<address>
<city>Lawrence</city>
<state>Kansas</state>
<zip>66044</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>785-505-2800</phone>
<email>Stephanie.Norris@LMH.ORG</email>
</contact>
<investigator>
<last_name>Chao H. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Center of Kansas-Liberal</name>
<address>
<city>Liberal</city>
<state>Kansas</state>
<zip>67905</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer Center of Kansas-Manhattan</name>
<address>
<city>Manhattan</city>
<state>Kansas</state>
<zip>66502</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer Center of Kansas - McPherson</name>
<address>
<city>McPherson</city>
<state>Kansas</state>
<zip>67460</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer Center of Kansas - Newton</name>
<address>
<city>Newton</city>
<state>Kansas</state>
<zip>67114</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Olathe Health Cancer Center</name>
<address>
<city>Olathe</city>
<state>Kansas</state>
<zip>66061</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>913-355-8000</phone>
<email>Jeni.wakefield@olathehealth.org</email>
</contact>
<investigator>
<last_name>Chao H. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University of Kansas Cancer Center-Overland Park</name>
<address>
<city>Overland Park</city>
<state>Kansas</state>
<zip>66210</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>913-588-3671</phone>
<email>KUCC_Navigation@kumc.edu</email>
</contact>
<investigator>
<last_name>Chao H. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Luke's South Hospital</name>
<address>
<city>Overland Park</city>
<state>Kansas</state>
<zip>66213</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer Center of Kansas - Parsons</name>
<address>
<city>Parsons</city>
<state>Kansas</state>
<zip>67357</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Ascension Via Christi - Pittsburg</name>
<address>
<city>Pittsburg</city>
<state>Kansas</state>
<zip>66762</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>620-235-7900</phone>
<email>jennifer.jameson@ascension.org</email>
</contact>
<investigator>
<last_name>Chao H. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Center of Kansas - Pratt</name>
<address>
<city>Pratt</city>
<state>Kansas</state>
<zip>67124</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer Center of Kansas - Salina</name>
<address>
<city>Salina</city>
<state>Kansas</state>
<zip>67401</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Salina Regional Health Center</name>
<address>
<city>Salina</city>
<state>Kansas</state>
<zip>67401</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>785-452-7038</phone>
<email>mleepers@srhc.com</email>
</contact>
<investigator>
<last_name>Chao H. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cotton O'Neil Cancer Center / Stormont Vail Health</name>
<address>
<city>Topeka</city>
<state>Kansas</state>
<zip>66606</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>785-270-4939</phone>
</contact>
<investigator>
<last_name>David E. Einspahr</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University of Kansas Health System Saint Francis Campus</name>
<address>
<city>Topeka</city>
<state>Kansas</state>
<zip>66606</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>785-295-8000</phone>
</contact>
<investigator>
<last_name>Chao H. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Center of Kansas - Wellington</name>
<address>
<city>Wellington</city>
<state>Kansas</state>
<zip>67152</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>University of Kansas Hospital-Westwood Cancer Center</name>
<address>
<city>Westwood</city>
<state>Kansas</state>
<zip>66205</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>913-588-3671</phone>
<email>KUCC_Navigation@kumc.edu</email>
</contact>
<investigator>
<last_name>Chao H. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Center of Kansas-Wichita Medical Arts Tower</name>
<address>
<city>Wichita</city>
<state>Kansas</state>
<zip>67208</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>316-291-4774</phone>
<email>research@viachristi.org</email>
</contact>
<investigator>
<last_name>Shaker R. Dakhil</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ascension Via Christi Hospitals Wichita</name>
<address>
<city>Wichita</city>
<state>Kansas</state>
<zip>67214</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>316-291-4774</phone>
<email>research@viachristi.org</email>
</contact>
<investigator>
<last_name>Shaker R. Dakhil</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Center of Kansas - Wichita</name>
<address>
<city>Wichita</city>
<state>Kansas</state>
<zip>67214</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>316-291-4774</phone>
<email>research@viachristi.org</email>
</contact>
<investigator>
<last_name>Shaker R. Dakhil</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Center of Kansas - Winfield</name>
<address>
<city>Winfield</city>
<state>Kansas</state>
<zip>67156</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Flaget Memorial Hospital</name>
<address>
<city>Bardstown</city>
<state>Kentucky</state>
<zip>40004</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Baptist Health Corbin</name>
<address>
<city>Corbin</city>
<state>Kentucky</state>
<zip>40701</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Commonwealth Cancer Center-Corbin</name>
<address>
<city>Corbin</city>
<state>Kentucky</state>
<zip>40701</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Elizabeth Healthcare Edgewood</name>
<address>
<city>Edgewood</city>
<state>Kentucky</state>
<zip>41017</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Baptist Health Hardin</name>
<address>
<city>Elizabethtown</city>
<state>Kentucky</state>
<zip>42701</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Elizabeth Fort Thomas</name>
<address>
<city>Fort Thomas</city>
<state>Kentucky</state>
<zip>41075</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Baptist Health Lexington</name>
<address>
<city>Lexington</city>
<state>Kentucky</state>
<zip>40503</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Joseph Radiation Oncology Resource Center</name>
<address>
<city>Lexington</city>
<state>Kentucky</state>
<zip>40504</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Joseph Hospital East</name>
<address>
<city>Lexington</city>
<state>Kentucky</state>
<zip>40509</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>University of Kentucky/Markey Cancer Center</name>
<address>
<city>Lexington</city>
<state>Kentucky</state>
<zip>40536</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>859-257-3379</phone>
</contact>
<investigator>
<last_name>Susanne M. Arnold</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Joseph London</name>
<address>
<city>London</city>
<state>Kentucky</state>
<zip>40741</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Jewish Hospital</name>
<address>
<city>Louisville</city>
<state>Kentucky</state>
<zip>40202</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Baptist Health Louisville</name>
<address>
<city>Louisville</city>
<state>Kentucky</state>
<zip>40207</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>502-897-8592</phone>
<email>Cbcresearch@bhsi.com</email>
</contact>
<investigator>
<last_name>Firas B. Badin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saints Mary and Elizabeth Hospital</name>
<address>
<city>Louisville</city>
<state>Kentucky</state>
<zip>40215</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>UofL Health Medical Center Northeast</name>
<address>
<city>Louisville</city>
<state>Kentucky</state>
<zip>40245</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Baptist Health Madisonville/Merle Mahr Cancer Center</name>
<address>
<city>Madisonville</city>
<state>Kentucky</state>
<zip>42431</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Baptist Health Paducah</name>
<address>
<city>Paducah</city>
<state>Kentucky</state>
<zip>42003</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Jewish Hospital Medical Center South</name>
<address>
<city>Shepherdsville</city>
<state>Kentucky</state>
<zip>40165</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Christus Saint Frances Cabrini Hospital</name>
<address>
<city>Alexandria</city>
<state>Louisiana</state>
<zip>71301</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>318-448-6976</phone>
<email>tammy.debona@christushealth.org</email>
</contact>
<investigator>
<last_name>Marc R. Matrana</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>LSU Health Baton Rouge-North Clinic</name>
<address>
<city>Baton Rouge</city>
<state>Louisiana</state>
<zip>70805</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>225-765-7659</phone>
<email>research@ololrmc.com</email>
</contact>
<investigator>
<last_name>Marshall P. Stagg</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Louisiana Hematology Oncology Associates LLC</name>
<address>
<city>Baton Rouge</city>
<state>Louisiana</state>
<zip>70809</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>225-215-1353</phone>
<email>clinicalresearch@marybird.com</email>
</contact>
<investigator>
<last_name>Victor T. Lin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mary Bird Perkins Cancer Center</name>
<address>
<city>Baton Rouge</city>
<state>Louisiana</state>
<zip>70809</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>225-215-1353</phone>
<email>clinicalresearch@marybird.com</email>
</contact>
<investigator>
<last_name>Victor T. Lin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Our Lady of the Lake Physicians Group - Medical Oncology</name>
<address>
<city>Baton Rouge</city>
<state>Louisiana</state>
<zip>70809</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>225-765-7659</phone>
<email>research@ololrmc.com</email>
</contact>
<investigator>
<last_name>Marshall P. Stagg</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Medical Center of Baton Rouge</name>
<address>
<city>Baton Rouge</city>
<state>Louisiana</state>
<zip>70816</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Ochsner High Grove</name>
<address>
<city>Baton Rouge</city>
<state>Louisiana</state>
<zip>70836</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Northshore Oncology Associates-Covington</name>
<address>
<city>Covington</city>
<state>Louisiana</state>
<zip>70433</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Ochsner Hematology Oncology North Shore - Covington (West Region)</name>
<address>
<city>Covington</city>
<state>Louisiana</state>
<zip>70433</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>985-809-5668</phone>
<email>Cheryl.kesler@ochsner.org</email>
</contact>
<investigator>
<last_name>Marc R. Matrana</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Terrebonne General Medical Center</name>
<address>
<city>Houma</city>
<state>Louisiana</state>
<zip>70360</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>985-850-6300</phone>
<email>ann.hooks@tgmc.com</email>
</contact>
<investigator>
<last_name>Victor T. Lin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ochsner Medical Center Kenner</name>
<address>
<city>Kenner</city>
<state>Louisiana</state>
<zip>70065</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>504-464-8789</phone>
<email>awendt@ochsner.org</email>
</contact>
<investigator>
<last_name>Marc R. Matrana</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Louisiana State University Health Science Center</name>
<address>
<city>New Orleans</city>
<state>Louisiana</state>
<zip>70112</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>University Medical Center New Orleans</name>
<address>
<city>New Orleans</city>
<state>Louisiana</state>
<zip>70112</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>504-210-3539</phone>
<email>emede1@lsuhsc.edu</email>
</contact>
<investigator>
<last_name>Brian C. Boulmay</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ochsner Medical Center Jefferson</name>
<address>
<city>New Orleans</city>
<state>Louisiana</state>
<zip>70121</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>504-842-8084</phone>
<email>Elisemarie.curry@ochsner.org</email>
</contact>
<investigator>
<last_name>Marc R. Matrana</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>CHRISTUS Highland Medical Center</name>
<address>
<city>Shreveport</city>
<state>Louisiana</state>
<zip>71105</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>318-681-4763</phone>
<email>Nancy.hassan@christushealth.org</email>
</contact>
<investigator>
<last_name>Marc R. Matrana</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ochsner Hematology Oncology North Shore - Slidell (East Region)</name>
<address>
<city>Slidell</city>
<state>Louisiana</state>
<zip>70458</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Tammany Hospital Service District #2 / Slidell Memorial Hospital</name>
<address>
<city>Slidell</city>
<state>Louisiana</state>
<zip>70458</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Harold Alfond Center for Cancer Care</name>
<address>
<city>Augusta</city>
<state>Maine</state>
<zip>04330</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>207-626-4855</phone>
</contact>
<investigator>
<last_name>Peter Rubin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Eastern Maine Medical Center</name>
<address>
<city>Bangor</city>
<state>Maine</state>
<zip>04401</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>207-973-4274</phone>
</contact>
<investigator>
<last_name>Sarah J. Sinclair</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Waldo County General Hospital</name>
<address>
<city>Belfast</city>
<state>Maine</state>
<zip>04915</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>207-338-2500</phone>
</contact>
<investigator>
<last_name>Peter Rubin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford</name>
<address>
<city>Biddeford</city>
<state>Maine</state>
<zip>04005</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>LLemire@mmc.org</email>
</contact>
<investigator>
<last_name>Peter Rubin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lafayette Family Cancer Center-EMMC</name>
<address>
<city>Brewer</city>
<state>Maine</state>
<zip>04412</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-987-3005</phone>
</contact>
<investigator>
<last_name>Sarah J. Sinclair</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Stephens Memorial Hospital</name>
<address>
<city>Norway</city>
<state>Maine</state>
<zip>04268</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Penobscot Bay Medical Center</name>
<address>
<city>Rockport</city>
<state>Maine</state>
<zip>04856</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>207-396-8670</phone>
<email>ClinicalResearch@mmc.org</email>
</contact>
<investigator>
<last_name>Peter Rubin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford</name>
<address>
<city>Sanford</city>
<state>Maine</state>
<zip>04073</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>LLemire@mmc.org</email>
</contact>
<investigator>
<last_name>Peter Rubin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Maine Medical Partners - South Portland</name>
<address>
<city>South Portland</city>
<state>Maine</state>
<zip>04106</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>207-396-8670</phone>
<email>ClinicalResearch@mmc.org</email>
</contact>
<investigator>
<last_name>Peter Rubin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Anne Arundel Medical Center</name>
<address>
<city>Annapolis</city>
<state>Maryland</state>
<zip>21401</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>University of Maryland/Greenebaum Cancer Center</name>
<address>
<city>Baltimore</city>
<state>Maryland</state>
<zip>21201</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Greater Baltimore Medical Center</name>
<address>
<city>Baltimore</city>
<state>Maryland</state>
<zip>21204</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>443-849-3706</phone>
</contact>
<investigator>
<last_name>Mei Tang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sinai Hospital of Baltimore</name>
<address>
<city>Baltimore</city>
<state>Maryland</state>
<zip>21215</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>410-601-6120</phone>
<email>pridgely@lifebridgehealth.org</email>
</contact>
<investigator>
<last_name>Qiwei W. Gai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Woodlawn Medical Center</name>
<address>
<city>Baltimore</city>
<state>Maryland</state>
<zip>21244</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>301-816-7218</phone>
</contact>
<investigator>
<last_name>Leon C. Hwang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Johns Hopkins University/Sidney Kimmel Cancer Center</name>
<address>
<city>Baltimore</city>
<state>Maryland</state>
<zip>21287</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>410-955-8804</phone>
<email>jhcccro@jhmi.edu</email>
</contact>
<investigator>
<last_name>Patrick M. Forde</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UM Upper Chesapeake Medical Center</name>
<address>
<city>Bel Air</city>
<state>Maryland</state>
<zip>21014</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>443-643-3010</phone>
</contact>
<investigator>
<last_name>Ashkan Bahrani</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Western Maryland</name>
<address>
<city>Cumberland</city>
<state>Maryland</state>
<zip>21502</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>240-964-1400</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Gaithersburg Medical Center</name>
<address>
<city>Gaithersburg</city>
<state>Maryland</state>
<zip>20879</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>301-816-7218</phone>
</contact>
<investigator>
<last_name>Leon C. Hwang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UM Baltimore Washington Medical Center/Tate Cancer Center</name>
<address>
<city>Glen Burnie</city>
<state>Maryland</state>
<zip>21061</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Kaiser Permanente - Kensington Medical Center</name>
<address>
<city>Kensington</city>
<state>Maryland</state>
<zip>20895</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>301-816-7218</phone>
</contact>
<investigator>
<last_name>Leon C. Hwang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente - Largo Medical Center</name>
<address>
<city>Largo</city>
<state>Maryland</state>
<zip>20774</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>301-816-7446</phone>
</contact>
<investigator>
<last_name>Leon C. Hwang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente Lutherville - Timonium Medical Center</name>
<address>
<city>Lutherville</city>
<state>Maryland</state>
<zip>21093</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>410-847-3000</phone>
</contact>
<investigator>
<last_name>Leon C. Hwang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>TidalHealth Richard A Henson Cancer Institute</name>
<address>
<city>Ocean Pines</city>
<state>Maryland</state>
<zip>21811</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>410-543-7067</phone>
<email>carol.messick@peninsula.org</email>
</contact>
<investigator>
<last_name>Justin R. Kucinski</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Northwest Hospital Center</name>
<address>
<city>Randallstown</city>
<state>Maryland</state>
<zip>21133</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>TidalHealth Peninsula Regional</name>
<address>
<city>Salisbury</city>
<state>Maryland</state>
<zip>21801</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>410-543-7032</phone>
<email>monika.naegeli@peninsula.org</email>
</contact>
<investigator>
<last_name>Justin R. Kucinski</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>William E Kahlert Regional Cancer Center/Sinai Hospital</name>
<address>
<city>Westminster</city>
<state>Maryland</state>
<zip>21157</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>410-871-6400</phone>
</contact>
<investigator>
<last_name>Qiwei W. Gai</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Beverly Hospital</name>
<address>
<city>Beverly</city>
<state>Massachusetts</state>
<zip>01915</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>978-922-3000</phone>
<phone_ext>2405</phone_ext>
</contact>
<investigator>
<last_name>Paul J. Hesketh</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Boston Medical Center</name>
<address>
<city>Boston</city>
<state>Massachusetts</state>
<zip>02118</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>617-638-8265</phone>
</contact>
<investigator>
<last_name>Umit Tapan</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Beth Israel Deaconess Medical Center</name>
<address>
<city>Boston</city>
<state>Massachusetts</state>
<zip>02215</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>617-667-9925</phone>
</contact>
<investigator>
<last_name>Daniel B. Costa</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Dana-Farber Cancer Institute</name>
<address>
<city>Boston</city>
<state>Massachusetts</state>
<zip>02215</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-442-3324</phone>
</contact>
<investigator>
<last_name>Jacob M. Sands</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Steward Saint Elizabeth's Medical Center</name>
<address>
<city>Brighton</city>
<state>Massachusetts</state>
<zip>02135</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>617-789-2903</phone>
</contact>
<investigator>
<last_name>Christopher S. Lathan</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lahey Hospital and Medical Center</name>
<address>
<city>Burlington</city>
<state>Massachusetts</state>
<zip>01805</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>781-744-3421</phone>
<email>lhmc-cancer-clinical-trials@lahey.org</email>
</contact>
<investigator>
<last_name>Paul J. Hesketh</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Dana-Farber Cancer Institute at Foxborough</name>
<address>
<city>Foxboro</city>
<state>Massachusetts</state>
<zip>02035</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-338-7425</phone>
</contact>
<investigator>
<last_name>Naeem Tahir</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Addison Gilbert Hospital</name>
<address>
<city>Gloucester</city>
<state>Massachusetts</state>
<zip>01930</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>978-283-4000</phone>
<phone_ext>559</phone_ext>
</contact>
<investigator>
<last_name>Paul J. Hesketh</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Dana Farber-Merrimack Valley</name>
<address>
<city>Methuen</city>
<state>Massachusetts</state>
<zip>01844</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-338-7425</phone>
</contact>
<investigator>
<last_name>Pedro M. Sanz-Altamira</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Dana-Farber/Brigham and Women's Cancer Center at Milford Regional</name>
<address>
<city>Milford</city>
<state>Massachusetts</state>
<zip>01757</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-332-4294</phone>
</contact>
<investigator>
<last_name>Alexandra S. Bailey</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lahey Medical Center-Peabody</name>
<address>
<city>Peabody</city>
<state>Massachusetts</state>
<zip>01960</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>781-744-3421</phone>
<email>lhmc-cancer-clinical-trials@lahey.org</email>
</contact>
<investigator>
<last_name>Paul J. Hesketh</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Berkshire Medical Center - Cancer Center</name>
<address>
<city>Pittsfield</city>
<state>Massachusetts</state>
<zip>01201</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Dana-Farber/Brigham and Women's Cancer Center at South Shore</name>
<address>
<city>South Weymouth</city>
<state>Massachusetts</state>
<zip>02190</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>781-624-5000</phone>
</contact>
<investigator>
<last_name>Prabhsimranjot Singh</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mercy Medical Center</name>
<address>
<city>Springfield</city>
<state>Massachusetts</state>
<zip>01104</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Winchester Hospital</name>
<address>
<city>Winchester</city>
<state>Massachusetts</state>
<zip>01890</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>888-823-5923</phone>
<email>ctsucontact@westat.com</email>
</contact>
<investigator>
<last_name>Paul J. Hesketh</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UMass Memorial Medical Center - University Campus</name>
<address>
<city>Worcester</city>
<state>Massachusetts</state>
<zip>01655</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>508-856-3216</phone>
<email>cancer.research@umassmed.edu</email>
</contact>
<investigator>
<last_name>William V. Walsh</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hickman Cancer Center</name>
<address>
<city>Adrian</city>
<state>Michigan</state>
<zip>49221</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>MyMichigan Medical Center Gratiot</name>
<address>
<city>Alma</city>
<state>Michigan</state>
<zip>48801</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>MyMichigan Medical Center Alpena</name>
<address>
<city>Alpena</city>
<state>Michigan</state>
<zip>49707</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Saint Joseph Mercy Hospital</name>
<address>
<city>Ann Arbor</city>
<state>Michigan</state>
<zip>48106</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>734-712-7251</phone>
<email>MCRCwebsitecontactform@stjoeshealth.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Bronson Battle Creek</name>
<address>
<city>Battle Creek</city>
<state>Michigan</state>
<zip>49017</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>616-391-1230</phone>
<email>crcwm-regulatory@crcwm.org</email>
</contact>
<investigator>
<last_name>Kathleen J. Yost</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Joseph Mercy Brighton</name>
<address>
<city>Brighton</city>
<state>Michigan</state>
<zip>48114</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>734-712-7251</phone>
<email>MCRCwebsitecontactform@stjoeshealth.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Trinity Health IHA Medical Group Hematology Oncology - Brighton</name>
<address>
<city>Brighton</city>
<state>Michigan</state>
<zip>48114</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>734-712-7251</phone>
<email>MCRCwebsitecontactform@stjoeshealth.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Henry Ford Cancer Institute-Downriver</name>
<address>
<city>Brownstown</city>
<state>Michigan</state>
<zip>48183</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Joseph Mercy Canton</name>
<address>
<city>Canton</city>
<state>Michigan</state>
<zip>48188</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>734-712-7251</phone>
<email>MCRCwebsitecontactform@stjoeshealth.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Trinity Health IHA Medical Group Hematology Oncology - Canton</name>
<address>
<city>Canton</city>
<state>Michigan</state>
<zip>48188</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>734-712-7251</phone>
<email>MCRCwebsitecontactform@stjoeshealth.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Caro Cancer Center</name>
<address>
<city>Caro</city>
<state>Michigan</state>
<zip>48723</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Joseph Mercy Chelsea</name>
<address>
<city>Chelsea</city>
<state>Michigan</state>
<zip>48118</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>734-712-7251</phone>
<email>MCRCwebsitecontactform@stjoeshealth.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital</name>
<address>
<city>Chelsea</city>
<state>Michigan</state>
<zip>48118</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>734-712-7251</phone>
<email>MCRCwebsitecontactform@stjoeshealth.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hematology Oncology Consultants-Clarkston</name>
<address>
<city>Clarkston</city>
<state>Michigan</state>
<zip>48346</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Newland Medical Associates-Clarkston</name>
<address>
<city>Clarkston</city>
<state>Michigan</state>
<zip>48346</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Henry Ford Macomb Hospital-Clinton Township</name>
<address>
<city>Clinton Township</city>
<state>Michigan</state>
<zip>48038</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Beaumont Hospital - Dearborn</name>
<address>
<city>Dearborn</city>
<state>Michigan</state>
<zip>48124</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>248-551-7695</phone>
</contact>
<investigator>
<last_name>Joseph M. Anderson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Henry Ford Medical Center-Fairlane</name>
<address>
<city>Dearborn</city>
<state>Michigan</state>
<zip>48126</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Henry Ford Hospital</name>
<address>
<city>Detroit</city>
<state>Michigan</state>
<zip>48202</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>313-916-3721</phone>
<email>CTOResearch@hfhs.org</email>
</contact>
<investigator>
<last_name>Haythem Y. Ali</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ascension Saint John Hospital</name>
<address>
<city>Detroit</city>
<state>Michigan</state>
<zip>48236</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>313-343-3166</phone>
<email>karen.forman@ascension.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Great Lakes Cancer Management Specialists-Doctors Park</name>
<address>
<city>East China Township</city>
<state>Michigan</state>
<zip>48054</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>313-343-3166</phone>
<email>karen.forman@ascension.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Beaumont Hospital - Farmington Hills</name>
<address>
<city>Farmington Hills</city>
<state>Michigan</state>
<zip>48336</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>248-551-7695</phone>
</contact>
<investigator>
<last_name>Joseph M. Anderson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Genesee Cancer and Blood Disease Treatment Center</name>
<address>
<city>Flint</city>
<state>Michigan</state>
<zip>48503</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>810-762-8038</phone>
<email>wstrong@ghci.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Genesee Hematology Oncology PC</name>
<address>
<city>Flint</city>
<state>Michigan</state>
<zip>48503</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>810-762-8038</phone>
<email>wstrong@ghci.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Genesys Hurley Cancer Institute</name>
<address>
<city>Flint</city>
<state>Michigan</state>
<zip>48503</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>810-762-8038</phone>
<email>wstrong@ghci.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hurley Medical Center</name>
<address>
<city>Flint</city>
<state>Michigan</state>
<zip>48503</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>810-762-8038</phone>
<email>wstrong@ghci.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>MyMichigan Medical Center Gladwin</name>
<address>
<city>Gladwin</city>
<state>Michigan</state>
<zip>48624</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Helen DeVos Children's Hospital at Spectrum Health</name>
<address>
<city>Grand Rapids</city>
<state>Michigan</state>
<zip>49503</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Spectrum Health at Butterworth Campus</name>
<address>
<city>Grand Rapids</city>
<state>Michigan</state>
<zip>49503</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>616-391-1230</phone>
<email>crcwm-regulatory@crcwm.org</email>
</contact>
<investigator>
<last_name>Kathleen J. Yost</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Trinity Health Grand Rapids Hospital</name>
<address>
<city>Grand Rapids</city>
<state>Michigan</state>
<zip>49503</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Academic Hematology Oncology Specialists</name>
<address>
<city>Grosse Pointe Woods</city>
<state>Michigan</state>
<zip>48236</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>313-343-3166</phone>
<email>karen.forman@ascension.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Great Lakes Cancer Management Specialists-Van Elslander Cancer Center</name>
<address>
<city>Grosse Pointe Woods</city>
<state>Michigan</state>
<zip>48236</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>313-343-3166</phone>
<email>karen.forman@ascension.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Michigan Breast Specialists-Grosse Pointe Woods</name>
<address>
<city>Grosse Pointe Woods</city>
<state>Michigan</state>
<zip>48236</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Allegiance Health</name>
<address>
<city>Jackson</city>
<state>Michigan</state>
<zip>49201</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Bronson Methodist Hospital</name>
<address>
<city>Kalamazoo</city>
<state>Michigan</state>
<zip>49007</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>616-391-1230</phone>
<email>crcwm-regulatory@crcwm.org</email>
</contact>
<investigator>
<last_name>Kathleen J. Yost</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>West Michigan Cancer Center</name>
<address>
<city>Kalamazoo</city>
<state>Michigan</state>
<zip>49007</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>616-391-1230</phone>
<email>crcwm-regulatory@crcwm.org</email>
</contact>
<investigator>
<last_name>Kathleen J. Yost</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ascension Borgess Cancer Center</name>
<address>
<city>Kalamazoo</city>
<state>Michigan</state>
<zip>49009</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>616-391-1230</phone>
<email>crcwm-regulatory@crcwm.org</email>
</contact>
<investigator>
<last_name>Kathleen J. Yost</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Borgess Medical Center</name>
<address>
<city>Kalamazoo</city>
<state>Michigan</state>
<zip>49048</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Sparrow Hospital</name>
<address>
<city>Lansing</city>
<state>Michigan</state>
<zip>48912</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>517-364-9400</phone>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hope Cancer Clinic</name>
<address>
<city>Livonia</city>
<state>Michigan</state>
<zip>48154</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Trinity Health Saint Mary Mercy Livonia Hospital</name>
<address>
<city>Livonia</city>
<state>Michigan</state>
<zip>48154</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>734-712-7251</phone>
<email>MCRCwebsitecontactform@stjoeshealth.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Great Lakes Cancer Management Specialists-Macomb Medical Campus</name>
<address>
<city>Macomb</city>
<state>Michigan</state>
<zip>48044</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>313-343-3166</phone>
<email>karen.forman@ascension.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Michigan Breast Specialists-Macomb Township</name>
<address>
<city>Macomb</city>
<state>Michigan</state>
<zip>48044</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Mary's Oncology/Hematology Associates of Marlette</name>
<address>
<city>Marlette</city>
<state>Michigan</state>
<zip>48453</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>MyMichigan Medical Center Midland</name>
<address>
<city>Midland</city>
<state>Michigan</state>
<zip>48670</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Toledo Clinic Cancer Centers-Monroe</name>
<address>
<city>Monroe</city>
<state>Michigan</state>
<zip>48162</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Trinity Health Muskegon Hospital</name>
<address>
<city>Muskegon</city>
<state>Michigan</state>
<zip>49444</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>616-391-1230</phone>
<email>crcwm-regulatory@crcwm.org</email>
</contact>
<investigator>
<last_name>Kathleen J. Yost</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lakeland Hospital Niles</name>
<address>
<city>Niles</city>
<state>Michigan</state>
<zip>49120</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer and Hematology Centers of Western Michigan - Norton Shores</name>
<address>
<city>Norton Shores</city>
<state>Michigan</state>
<zip>49444</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>616-391-1230</phone>
<email>connie.szczepanek@crcwm.org</email>
</contact>
<investigator>
<last_name>Kathleen J. Yost</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ascension Providence Hospitals - Novi</name>
<address>
<city>Novi</city>
<state>Michigan</state>
<zip>48374</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>248-849-5332</phone>
<email>karen.fife@ascension.org</email>
</contact>
<investigator>
<last_name>Adam M. Forman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Henry Ford Medical Center-Columbus</name>
<address>
<city>Novi</city>
<state>Michigan</state>
<zip>48377</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>313-916-3721</phone>
<email>CTOResearch@hfhs.org</email>
</contact>
<investigator>
<last_name>Haythem Y. Ali</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>21st Century Oncology-Pontiac</name>
<address>
<city>Pontiac</city>
<state>Michigan</state>
<zip>48341</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Hope Cancer Center</name>
<address>
<city>Pontiac</city>
<state>Michigan</state>
<zip>48341</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Newland Medical Associates-Pontiac</name>
<address>
<city>Pontiac</city>
<state>Michigan</state>
<zip>48341</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Joseph Mercy Oakland</name>
<address>
<city>Pontiac</city>
<state>Michigan</state>
<zip>48341</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Spectrum Health Reed City Hospital</name>
<address>
<city>Reed City</city>
<state>Michigan</state>
<zip>49677</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>616-391-1230</phone>
<email>crcwm-regulatory@crcwm.org</email>
</contact>
<investigator>
<last_name>Kathleen J. Yost</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Great Lakes Cancer Management Specialists-Rochester Hills</name>
<address>
<city>Rochester Hills</city>
<state>Michigan</state>
<zip>48309</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Oakland Colon Rectal Associates</name>
<address>
<city>Royal Oak</city>
<state>Michigan</state>
<zip>48067</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer Care Associates PC</name>
<address>
<city>Royal Oak</city>
<state>Michigan</state>
<zip>48073</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Comprehensive Medical Center PLLC</name>
<address>
<city>Royal Oak</city>
<state>Michigan</state>
<zip>48073</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Hematology Oncology Consultants PC</name>
<address>
<city>Royal Oak</city>
<state>Michigan</state>
<zip>48073</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Oakland Medical Group</name>
<address>
<city>Royal Oak</city>
<state>Michigan</state>
<zip>48073</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>William Beaumont Hospital-Royal Oak</name>
<address>
<city>Royal Oak</city>
<state>Michigan</state>
<zip>48073</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>248-551-7695</phone>
</contact>
<investigator>
<last_name>Joseph M. Anderson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ascension Saint Mary's Hospital</name>
<address>
<city>Saginaw</city>
<state>Michigan</state>
<zip>48601</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>989-907-8411</phone>
<email>lori.srebinski@ascension.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Oncology Hematology Associates of Saginaw Valley PC</name>
<address>
<city>Saginaw</city>
<state>Michigan</state>
<zip>48604</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>989-907-8411</phone>
<email>lori.srebinski@ascension.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lakeland Medical Center Saint Joseph</name>
<address>
<city>Saint Joseph</city>
<state>Michigan</state>
<zip>49085</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Marie Yeager Cancer Center</name>
<address>
<city>Saint Joseph</city>
<state>Michigan</state>
<zip>49085</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>616-391-1230</phone>
<email>crcwm-regulatory@crcwm.org</email>
</contact>
<investigator>
<last_name>Kathleen J. Yost</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Henry Ford Macomb Health Center - Shelby Township</name>
<address>
<city>Shelby</city>
<state>Michigan</state>
<zip>48315</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Ascension Providence Hospitals - Southfield</name>
<address>
<city>Southfield</city>
<state>Michigan</state>
<zip>48075</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>248-849-5332</phone>
<email>karen.fife@ascension.org</email>
</contact>
<investigator>
<last_name>Adam M. Forman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Bhadresh Nayak MD PC-Sterling Heights</name>
<address>
<city>Sterling Heights</city>
<state>Michigan</state>
<zip>48312</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>313-343-3166</phone>
<email>karen.forman@ascension.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Premier Hematology Oncology Care</name>
<address>
<city>Sterling Heights</city>
<state>Michigan</state>
<zip>48312</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Ascension Saint Joseph Hospital</name>
<address>
<city>Tawas City</city>
<state>Michigan</state>
<zip>48764</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>989-907-8411</phone>
<email>lori.srebinski@ascension.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Munson Medical Center</name>
<address>
<city>Traverse City</city>
<state>Michigan</state>
<zip>49684</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>616-391-1230</phone>
<email>crcwm-regulatory@crcwm.org</email>
</contact>
<investigator>
<last_name>Kathleen J. Yost</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Michigan Institute of Urology-Town Center</name>
<address>
<city>Troy</city>
<state>Michigan</state>
<zip>48084</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>William Beaumont Hospital - Troy</name>
<address>
<city>Troy</city>
<state>Michigan</state>
<zip>48085</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>248-551-7695</phone>
</contact>
<investigator>
<last_name>Joseph M. Anderson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hematology Oncology Consultants PC-Troy</name>
<address>
<city>Troy</city>
<state>Michigan</state>
<zip>48098</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Advanced Breast Care Center PLLC</name>
<address>
<city>Warren</city>
<state>Michigan</state>
<zip>48088</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>313-343-3166</phone>
<email>karen.forman@ascension.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Great Lakes Cancer Management Specialists-Macomb Professional Building</name>
<address>
<city>Warren</city>
<state>Michigan</state>
<zip>48093</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>313-343-3166</phone>
<email>karen.forman@ascension.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Macomb Hematology Oncology PC</name>
<address>
<city>Warren</city>
<state>Michigan</state>
<zip>48093</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Michigan Breast Specialists-Warren</name>
<address>
<city>Warren</city>
<state>Michigan</state>
<zip>48093</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>313-343-3166</phone>
<email>karen.forman@ascension.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint John Macomb-Oakland Hospital</name>
<address>
<city>Warren</city>
<state>Michigan</state>
<zip>48093</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>313-343-3166</phone>
<email>karen.forman@ascension.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Henry Ford West Bloomfield Hospital</name>
<address>
<city>West Bloomfield</city>
<state>Michigan</state>
<zip>48322</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Mary's Oncology/Hematology Associates of West Branch</name>
<address>
<city>West Branch</city>
<state>Michigan</state>
<zip>48661</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>989-907-8411</phone>
<email>lori.srebinski@ascension.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University of Michigan Health - West</name>
<address>
<city>Wyoming</city>
<state>Michigan</state>
<zip>49519</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>616-391-1230</phone>
<email>crcwm-regulatory@crcwm.org</email>
</contact>
<investigator>
<last_name>Kathleen J. Yost</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Huron Gastroenterology PC</name>
<address>
<city>Ypsilanti</city>
<state>Michigan</state>
<zip>48106</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>734-712-7251</phone>
<email>MCRCwebsitecontactform@stjoeshealth.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus</name>
<address>
<city>Ypsilanti</city>
<state>Michigan</state>
<zip>48197</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>734-712-7251</phone>
<email>MCRCwebsitecontactform@stjoeshealth.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Riverwood Healthcare Center</name>
<address>
<city>Aitkin</city>
<state>Minnesota</state>
<zip>56431</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Sanford Joe Lueken Cancer Center</name>
<address>
<city>Bemidji</city>
<state>Minnesota</state>
<zip>56601</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>218-333-5000</phone>
<email>OncologyClinicalTrialsFargo@sanfordhealth.org</email>
</contact>
<investigator>
<last_name>Daniel Almquist</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Essentia Health Saint Joseph's Medical Center</name>
<address>
<city>Brainerd</city>
<state>Minnesota</state>
<zip>56401</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Fairview Ridges Hospital</name>
<address>
<city>Burnsville</city>
<state>Minnesota</state>
<zip>55337</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Minnesota Oncology - Burnsville</name>
<address>
<city>Burnsville</city>
<state>Minnesota</state>
<zip>55337</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cambridge Medical Center</name>
<address>
<city>Cambridge</city>
<state>Minnesota</state>
<zip>55008</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Mercy Hospital</name>
<address>
<city>Coon Rapids</city>
<state>Minnesota</state>
<zip>55433</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>952-993-1517</phone>
<email>mmcorc@healthpartners.com</email>
</contact>
<investigator>
<last_name>Daniel M. Anderson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Essentia Health - Deer River Clinic</name>
<address>
<city>Deer River</city>
<state>Minnesota</state>
<zip>56636</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>218-786-3308</phone>
<email>CancerTrials@EssentiaHealth.org</email>
</contact>
<investigator>
<last_name>Bret E. Friday</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Essentia Health Saint Mary's - Detroit Lakes Clinic</name>
<address>
<city>Detroit Lakes</city>
<state>Minnesota</state>
<zip>56501</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Essentia Health Cancer Center</name>
<address>
<city>Duluth</city>
<state>Minnesota</state>
<zip>55805</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>218-786-3308</phone>
<email>CancerTrials@EssentiaHealth.org</email>
</contact>
<investigator>
<last_name>Bret E. Friday</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Essentia Health Saint Mary's Medical Center</name>
<address>
<city>Duluth</city>
<state>Minnesota</state>
<zip>55805</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Miller-Dwan Hospital</name>
<address>
<city>Duluth</city>
<state>Minnesota</state>
<zip>55805</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Fairview Southdale Hospital</name>
<address>
<city>Edina</city>
<state>Minnesota</state>
<zip>55435</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>952-993-1517</phone>
<email>mmcorc@healthpartners.com</email>
</contact>
<investigator>
<last_name>Daniel M. Anderson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lake Region Healthcare Corporation-Cancer Care</name>
<address>
<city>Fergus Falls</city>
<state>Minnesota</state>
<zip>56537</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Essentia Health - Fosston</name>
<address>
<city>Fosston</city>
<state>Minnesota</state>
<zip>56542</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Unity Hospital</name>
<address>
<city>Fridley</city>
<state>Minnesota</state>
<zip>55432</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>952-993-1517</phone>
<email>mmcorc@healthpartners.com</email>
</contact>
<investigator>
<last_name>Daniel M. Anderson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Essentia Health Hibbing Clinic</name>
<address>
<city>Hibbing</city>
<state>Minnesota</state>
<zip>55746</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>218-786-3308</phone>
</contact>
<investigator>
<last_name>Bret E. Friday</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Fairview Clinics and Surgery Center Maple Grove</name>
<address>
<city>Maple Grove</city>
<state>Minnesota</state>
<zip>55369</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Minnesota Oncology Hematology PA-Maplewood</name>
<address>
<city>Maplewood</city>
<state>Minnesota</state>
<zip>55109</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint John's Hospital - Healtheast</name>
<address>
<city>Maplewood</city>
<state>Minnesota</state>
<zip>55109</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Abbott-Northwestern Hospital</name>
<address>
<city>Minneapolis</city>
<state>Minnesota</state>
<zip>55407</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Hennepin County Medical Center</name>
<address>
<city>Minneapolis</city>
<state>Minnesota</state>
<zip>55415</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>952-993-1517</phone>
<email>mmcorc@healthpartners.com</email>
</contact>
<investigator>
<last_name>Daniel M. Anderson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Minneapolis VA Medical Center</name>
<address>
<city>Minneapolis</city>
<state>Minnesota</state>
<zip>55417</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Health Partners Inc</name>
<address>
<city>Minneapolis</city>
<state>Minnesota</state>
<zip>55454</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Monticello Cancer Center</name>
<address>
<city>Monticello</city>
<state>Minnesota</state>
<zip>55362</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>New Ulm Medical Center</name>
<address>
<city>New Ulm</city>
<state>Minnesota</state>
<zip>56073</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Essentia Health - Park Rapids</name>
<address>
<city>Park Rapids</city>
<state>Minnesota</state>
<zip>56470</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Fairview Northland Medical Center</name>
<address>
<city>Princeton</city>
<state>Minnesota</state>
<zip>55371</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>North Memorial Medical Health Center</name>
<address>
<city>Robbinsdale</city>
<state>Minnesota</state>
<zip>55422</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>952-993-1517</phone>
<email>mmcorc@healthpartners.com</email>
</contact>
<investigator>
<last_name>Daniel M. Anderson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mayo Clinic in Rochester</name>
<address>
<city>Rochester</city>
<state>Minnesota</state>
<zip>55905</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>855-776-0015</phone>
</contact>
<investigator>
<last_name>Konstantinos Leventakos</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Coborn Cancer Center at Saint Cloud Hospital</name>
<address>
<city>Saint Cloud</city>
<state>Minnesota</state>
<zip>56303</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-229-4907</phone>
<email>coborncancercenter@centracare.com</email>
</contact>
<investigator>
<last_name>Donald J. Jurgens</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Park Nicollet Clinic - Saint Louis Park</name>
<address>
<city>Saint Louis Park</city>
<state>Minnesota</state>
<zip>55416</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Regions Hospital</name>
<address>
<city>Saint Paul</city>
<state>Minnesota</state>
<zip>55101</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>United Hospital</name>
<address>
<city>Saint Paul</city>
<state>Minnesota</state>
<zip>55102</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Essentia Health Sandstone</name>
<address>
<city>Sandstone</city>
<state>Minnesota</state>
<zip>55072</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>218-786-3308</phone>
<email>CancerTrials@EssentiaHealth.org</email>
</contact>
<investigator>
<last_name>Bret E. Friday</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Francis Regional Medical Center</name>
<address>
<city>Shakopee</city>
<state>Minnesota</state>
<zip>55379</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Lakeview Hospital</name>
<address>
<city>Stillwater</city>
<state>Minnesota</state>
<zip>55082</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Sanford Thief River Falls Medical Center</name>
<address>
<city>Thief River Falls</city>
<state>Minnesota</state>
<zip>56701</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Essentia Health Virginia Clinic</name>
<address>
<city>Virginia</city>
<state>Minnesota</state>
<zip>55792</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>218-786-3308</phone>
<email>CancerTrials@EssentiaHealth.org</email>
</contact>
<investigator>
<last_name>Bret E. Friday</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ridgeview Medical Center</name>
<address>
<city>Waconia</city>
<state>Minnesota</state>
<zip>55387</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Rice Memorial Hospital</name>
<address>
<city>Willmar</city>
<state>Minnesota</state>
<zip>56201</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Minnesota Oncology Hematology PA-Woodbury</name>
<address>
<city>Woodbury</city>
<state>Minnesota</state>
<zip>55125</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Sanford Cancer Center Worthington</name>
<address>
<city>Worthington</city>
<state>Minnesota</state>
<zip>56187</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Fairview Lakes Medical Center</name>
<address>
<city>Wyoming</city>
<state>Minnesota</state>
<zip>55092</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Baptist Memorial Hospital and Cancer Center-Golden Triangle</name>
<address>
<city>Columbus</city>
<state>Mississippi</state>
<zip>39705</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>901-226-1366</phone>
<email>BCCclintrials@bmhcc.org</email>
</contact>
<investigator>
<last_name>Philip E. Lammers</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Baptist Cancer Center-Grenada</name>
<address>
<city>Grenada</city>
<state>Mississippi</state>
<zip>38901</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>901-226-1366</phone>
<email>BCCclintrials@bmhcc.org</email>
</contact>
<investigator>
<last_name>Philip E. Lammers</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Gulfport Memorial Hospital</name>
<address>
<city>Gulfport</city>
<state>Mississippi</state>
<zip>39502</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Hattiesburg Clinic - Hematology/Oncology Clinic</name>
<address>
<city>Hattiesburg</city>
<state>Mississippi</state>
<zip>39401</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Forrest General Hospital / Cancer Center</name>
<address>
<city>Hattiesburg</city>
<state>Mississippi</state>
<zip>39404</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>University of Mississippi Medical Center</name>
<address>
<city>Jackson</city>
<state>Mississippi</state>
<zip>39216</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Baptist Memorial Hospital and Cancer Center-Union County</name>
<address>
<city>New Albany</city>
<state>Mississippi</state>
<zip>38652</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>901-226-1366</phone>
<email>BCCclintrials@bmhcc.org</email>
</contact>
<investigator>
<last_name>Philip E. Lammers</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Baptist Memorial Hospital and Cancer Center-Oxford</name>
<address>
<city>Oxford</city>
<state>Mississippi</state>
<zip>38655</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>901-226-1366</phone>
<email>BCCclintrials@bmhcc.org</email>
</contact>
<investigator>
<last_name>Philip E. Lammers</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Baptist Memorial Hospital and Cancer Center-Desoto</name>
<address>
<city>Southhaven</city>
<state>Mississippi</state>
<zip>38671</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>901-226-1366</phone>
<email>BCCclintrials@bmhcc.org</email>
</contact>
<investigator>
<last_name>Philip E. Lammers</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Louis Cancer and Breast Institute-Ballwin</name>
<address>
<city>Ballwin</city>
<state>Missouri</state>
<zip>63011</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Central Care Cancer Center - Bolivar</name>
<address>
<city>Bolivar</city>
<state>Missouri</state>
<zip>65613</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cox Cancer Center Branson</name>
<address>
<city>Branson</city>
<state>Missouri</state>
<zip>65616</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Francis Medical Center</name>
<address>
<city>Cape Girardeau</city>
<state>Missouri</state>
<zip>63703</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>573-334-2230</phone>
<email>sfmc@sfmc.net</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Southeast Cancer Center</name>
<address>
<city>Cape Girardeau</city>
<state>Missouri</state>
<zip>63703</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>MU Health - University Hospital/Ellis Fischel Cancer Center</name>
<address>
<city>Columbia</city>
<state>Missouri</state>
<zip>65212</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>573-882-7440</phone>
</contact>
<investigator>
<last_name>RuoBing Xue</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Siteman Cancer Center at West County Hospital</name>
<address>
<city>Creve Coeur</city>
<state>Missouri</state>
<zip>63141</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-600-3606</phone>
<email>info@siteman.wustl.edu</email>
</contact>
<investigator>
<last_name>Ramaswamy Govindan</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Parkland Health Center - Farmington</name>
<address>
<city>Farmington</city>
<state>Missouri</state>
<zip>63640</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>314-996-5569</phone>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Capital Region Southwest Campus</name>
<address>
<city>Jefferson City</city>
<state>Missouri</state>
<zip>65109</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>573-632-4814</phone>
<email>swooden@mail.crmc.org</email>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Freeman Health System</name>
<address>
<city>Joplin</city>
<state>Missouri</state>
<zip>64804</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>417-347-4030</phone>
<email>LJCrockett@freemanhealth.com</email>
</contact>
<investigator>
<last_name>Jay W. Carlson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mercy Hospital Joplin</name>
<address>
<city>Joplin</city>
<state>Missouri</state>
<zip>64804</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Truman Medical Centers</name>
<address>
<city>Kansas City</city>
<state>Missouri</state>
<zip>64108</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>816-404-4375</phone>
</contact>
<investigator>
<last_name>Chao H. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Luke's Hospital of Kansas City</name>
<address>
<city>Kansas City</city>
<state>Missouri</state>
<zip>64111</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>913-948-5588</phone>
<email>aroland@kccop.org</email>
</contact>
<investigator>
<last_name>Dhruv Bansal</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University of Kansas Cancer Center - North</name>
<address>
<city>Kansas City</city>
<state>Missouri</state>
<zip>64154</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>913-588-3671</phone>
<email>KUCC_Navigation@kumc.edu</email>
</contact>
<investigator>
<last_name>Chao H. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University of Kansas Cancer Center - Lee's Summit</name>
<address>
<city>Lee's Summit</city>
<state>Missouri</state>
<zip>64064</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>913-588-3671</phone>
<email>KUCC_Navigation@kumc.edu</email>
</contact>
<investigator>
<last_name>Chao H. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Luke's East - Lee's Summit</name>
<address>
<city>Lee's Summit</city>
<state>Missouri</state>
<zip>64086</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>University of Kansas Cancer Center at North Kansas City Hospital</name>
<address>
<city>North Kansas City</city>
<state>Missouri</state>
<zip>64116</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>913-588-3671</phone>
<email>KUCC_Navigation@kumc.edu</email>
</contact>
<investigator>
<last_name>Chao H. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Delbert Day Cancer Institute at PCRMC</name>
<address>
<city>Rolla</city>
<state>Missouri</state>
<zip>65401</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Mercy Clinic-Rolla-Cancer and Hematology</name>
<address>
<city>Rolla</city>
<state>Missouri</state>
<zip>65401</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Heartland Regional Medical Center</name>
<address>
<city>Saint Joseph</city>
<state>Missouri</state>
<zip>64506</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Louis Cancer and Breast Institute-South City</name>
<address>
<city>Saint Louis</city>
<state>Missouri</state>
<zip>63109</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Washington University School of Medicine</name>
<address>
<city>Saint Louis</city>
<state>Missouri</state>
<zip>63110</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-600-3606</phone>
<email>info@siteman.wustl.edu</email>
</contact>
<investigator>
<last_name>Ramaswamy Govindan</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Veteran's Affairs Medical Center - Saint Louis</name>
<address>
<city>Saint Louis</city>
<state>Missouri</state>
<zip>63125</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Mercy Hospital South</name>
<address>
<city>Saint Louis</city>
<state>Missouri</state>
<zip>63128</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Siteman Cancer Center-South County</name>
<address>
<city>Saint Louis</city>
<state>Missouri</state>
<zip>63129</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-600-3606</phone>
<email>info@siteman.wustl.edu</email>
</contact>
<investigator>
<last_name>Ramaswamy Govindan</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Missouri Baptist Medical Center</name>
<address>
<city>Saint Louis</city>
<state>Missouri</state>
<zip>63131</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>314-996-5569</phone>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Siteman Cancer Center at Christian Hospital</name>
<address>
<city>Saint Louis</city>
<state>Missouri</state>
<zip>63136</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-600-3606</phone>
<email>info@siteman.wustl.edu</email>
</contact>
<investigator>
<last_name>Ramaswamy Govindan</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mercy Hospital Saint Louis</name>
<address>
<city>Saint Louis</city>
<state>Missouri</state>
<zip>63141</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>314-251-7066</phone>
</contact>
<investigator>
<last_name>Jay W. Carlson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Siteman Cancer Center at Saint Peters Hospital</name>
<address>
<city>Saint Peters</city>
<state>Missouri</state>
<zip>63376</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-600-3606</phone>
<email>info@siteman.wustl.edu</email>
</contact>
<investigator>
<last_name>Ramaswamy Govindan</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sainte Genevieve County Memorial Hospital</name>
<address>
<city>Sainte Genevieve</city>
<state>Missouri</state>
<zip>63670</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>314-996-5569</phone>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mercy Hospital Springfield</name>
<address>
<city>Springfield</city>
<state>Missouri</state>
<zip>65804</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>CoxHealth South Hospital</name>
<address>
<city>Springfield</city>
<state>Missouri</state>
<zip>65807</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Missouri Baptist Sullivan Hospital</name>
<address>
<city>Sullivan</city>
<state>Missouri</state>
<zip>63080</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>314-996-5569</phone>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Missouri Baptist Outpatient Center-Sunset Hills</name>
<address>
<city>Sunset Hills</city>
<state>Missouri</state>
<zip>63127</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>314-996-5569</phone>
</contact>
<investigator>
<last_name>Bryan A. Faller</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mercy Hospital Washington</name>
<address>
<city>Washington</city>
<state>Missouri</state>
<zip>63090</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Community Hospital of Anaconda</name>
<address>
<city>Anaconda</city>
<state>Montana</state>
<zip>59711</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>406-969-6060</phone>
<email>mccinfo@mtcancer.org</email>
</contact>
<investigator>
<last_name>John M. Schallenkamp</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Billings Clinic Cancer Center</name>
<address>
<city>Billings</city>
<state>Montana</state>
<zip>59101</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-996-2663</phone>
<email>research@billingsclinic.org</email>
</contact>
<investigator>
<last_name>John M. Schallenkamp</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Vincent Healthcare</name>
<address>
<city>Billings</city>
<state>Montana</state>
<zip>59101</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Vincent Frontier Cancer Center</name>
<address>
<city>Billings</city>
<state>Montana</state>
<zip>59102</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Bozeman Deaconess Hospital</name>
<address>
<city>Bozeman</city>
<state>Montana</state>
<zip>59715</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>406-969-6060</phone>
<email>mccinfo@mtcancer.org</email>
</contact>
<investigator>
<last_name>John M. Schallenkamp</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint James Community Hospital and Cancer Treatment Center</name>
<address>
<city>Butte</city>
<state>Montana</state>
<zip>59701</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Benefis Healthcare- Sletten Cancer Institute</name>
<address>
<city>Great Falls</city>
<state>Montana</state>
<zip>59405</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>406-969-6060</phone>
<email>mccinfo@mtcancer.org</email>
</contact>
<investigator>
<last_name>John M. Schallenkamp</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Great Falls Clinic</name>
<address>
<city>Great Falls</city>
<state>Montana</state>
<zip>59405</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kalispell Regional Medical Center</name>
<address>
<city>Kalispell</city>
<state>Montana</state>
<zip>59901</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>406-969-6060</phone>
<email>mccinfo@mtcancer.org</email>
</contact>
<investigator>
<last_name>John M. Schallenkamp</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Patrick Hospital - Community Hospital</name>
<address>
<city>Missoula</city>
<state>Montana</state>
<zip>59802</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Community Medical Hospital</name>
<address>
<city>Missoula</city>
<state>Montana</state>
<zip>59804</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>406-969-6060</phone>
<email>mccinfo@mtcancer.org</email>
</contact>
<investigator>
<last_name>John M. Schallenkamp</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Nebraska Medicine-Bellevue</name>
<address>
<city>Bellevue</city>
<state>Nebraska</state>
<zip>68123</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>402-559-6941</phone>
<email>unmcrsa@unmc.edu</email>
</contact>
<investigator>
<last_name>Apar K. Ganti</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>CHI Health Saint Francis</name>
<address>
<city>Grand Island</city>
<state>Nebraska</state>
<zip>68803</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>CHI Health Good Samaritan</name>
<address>
<city>Kearney</city>
<state>Nebraska</state>
<zip>68847</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>308-865-7963</phone>
<email>ResearchInstituteInquiries@CommonSpirit.org</email>
</contact>
<investigator>
<last_name>Shahzad Siddique</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Elizabeth Regional Medical Center</name>
<address>
<city>Lincoln</city>
<state>Nebraska</state>
<zip>68510</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer Partners of Nebraska - Pine Lake</name>
<address>
<city>Lincoln</city>
<state>Nebraska</state>
<zip>68516</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>402-327-7363</phone>
<email>research@cancerpartners.com</email>
</contact>
<investigator>
<last_name>Joni A. Tilford</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Southeast Nebraska Cancer Center - 68th Street Place</name>
<address>
<city>Lincoln</city>
<state>Nebraska</state>
<zip>68516</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>402-327-7363</phone>
<email>research@cancerpartners.com</email>
</contact>
<investigator>
<last_name>Joni A. Tilford</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Nebraska Cancer Specialists/Oncology Hematology West PC - MECC</name>
<address>
<city>Omaha</city>
<state>Nebraska</state>
<zip>68114</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>402-334-4773</phone>
</contact>
<investigator>
<last_name>Robert M. Langdon</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Nebraska Methodist Hospital</name>
<address>
<city>Omaha</city>
<state>Nebraska</state>
<zip>68114</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>402-354-5144</phone>
</contact>
<investigator>
<last_name>Robert M. Langdon</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Oncology Associates PC</name>
<address>
<city>Omaha</city>
<state>Nebraska</state>
<zip>68114</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>402-354-5860</phone>
<email>info@oa-oc.com</email>
</contact>
<investigator>
<last_name>Robert M. Langdon</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Nebraska Medicine-Village Pointe</name>
<address>
<city>Omaha</city>
<state>Nebraska</state>
<zip>68118</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>402-559-5600</phone>
</contact>
<investigator>
<last_name>Apar K. Ganti</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Alegent Health Immanuel Medical Center</name>
<address>
<city>Omaha</city>
<state>Nebraska</state>
<zip>68122</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Alegent Health Bergan Mercy Medical Center</name>
<address>
<city>Omaha</city>
<state>Nebraska</state>
<zip>68124</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>402-717-1510</phone>
<email>ResearchInstituteInquiries@CommonSpirit.org</email>
</contact>
<investigator>
<last_name>Shahzad Siddique</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Alegent Health Lakeside Hospital</name>
<address>
<city>Omaha</city>
<state>Nebraska</state>
<zip>68130</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Creighton University Medical Center</name>
<address>
<city>Omaha</city>
<state>Nebraska</state>
<zip>68131</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>University of Nebraska Medical Center</name>
<address>
<city>Omaha</city>
<state>Nebraska</state>
<zip>68198</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>402-559-6941</phone>
<email>unmcrsa@unmc.edu</email>
</contact>
<investigator>
<last_name>Apar K. Ganti</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Midlands Community Hospital</name>
<address>
<city>Papillion</city>
<state>Nebraska</state>
<zip>68046</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Carson Tahoe Regional Medical Center</name>
<address>
<city>Carson City</city>
<state>Nevada</state>
<zip>89703</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer and Blood Specialists-Henderson</name>
<address>
<city>Henderson</city>
<state>Nevada</state>
<zip>89052</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Comprehensive Cancer Centers of Nevada - Henderson</name>
<address>
<city>Henderson</city>
<state>Nevada</state>
<zip>89052</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Comprehensive Cancer Centers of Nevada-Horizon Ridge</name>
<address>
<city>Henderson</city>
<state>Nevada</state>
<zip>89052</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Las Vegas Cancer Center-Henderson</name>
<address>
<city>Henderson</city>
<state>Nevada</state>
<zip>89052</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>OptumCare Cancer Care at Seven Hills</name>
<address>
<city>Henderson</city>
<state>Nevada</state>
<zip>89052</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Comprehensive Cancer Centers of Nevada-Southeast Henderson</name>
<address>
<city>Henderson</city>
<state>Nevada</state>
<zip>89074</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>GenesisCare USA - Henderson</name>
<address>
<city>Henderson</city>
<state>Nevada</state>
<zip>89074</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Las Vegas Urology - Green Valley</name>
<address>
<city>Henderson</city>
<state>Nevada</state>
<zip>89074</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Las Vegas Urology - Pebble</name>
<address>
<city>Henderson</city>
<state>Nevada</state>
<zip>89074</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Urology Specialists of Nevada - Green Valley</name>
<address>
<city>Henderson</city>
<state>Nevada</state>
<zip>89074</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Las Vegas Urology - Pecos</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89074</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Desert West Surgery</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89102</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>OptumCare Cancer Care at Charleston</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89102</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>702-384-0013</phone>
<email>research@sncrf.org</email>
</contact>
<investigator>
<last_name>John A. Ellerton</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University Medical Center of Southern Nevada</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89102</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Hope Cancer Care of Nevada</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89103</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer and Blood Specialists-Shadow</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89106</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Radiation Oncology Centers of Nevada Central</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89106</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Urology Specialists of Nevada - Central</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89106</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>GenesisCare USA - Las Vegas</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89109</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89109</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Sunrise Hospital and Medical Center</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89109</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>HealthCare Partners Medical Group Oncology/Hematology-San Martin</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89113</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Las Vegas Prostate Cancer Center</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89113</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Las Vegas Urology - Sunset</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89113</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Urology Specialists of Nevada - Southwest</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89113</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Radiation Oncology Centers of Nevada Southeast</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89119</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Ann M Wierman MD LTD</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89128</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cancer and Blood Specialists-Tenaya</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89128</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Comprehensive Cancer Centers of Nevada - Northwest</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89128</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>GenesisCare USA - Vegas Tenaya</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89128</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>HealthCare Partners Medical Group Oncology/Hematology-Tenaya</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89128</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Las Vegas Urology - Cathedral Rock</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89128</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Las Vegas Urology - Smoke Ranch</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89128</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>OptumCare Cancer Care at MountainView</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89128</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Urology Specialists of Nevada - Northwest</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89128</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Alliance for Childhood Diseases/Cure 4 the Kids Foundation</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89135</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Comprehensive Cancer Centers of Nevada - Town Center</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89144</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Comprehensive Cancer Centers of Nevada-Summerlin</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89144</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Summerlin Hospital Medical Center</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89144</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Las Vegas Cancer Center-Medical Center</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89148-2405</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Comprehensive Cancer Centers of Nevada</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89148</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>GenesisCare USA - Fort Apache</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89148</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>OptumCare Cancer Care at Fort Apache</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89148</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>702-384-0013</phone>
<email>research@sncrf.org</email>
</contact>
<investigator>
<last_name>John A. Ellerton</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89149</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Comprehensive Cancer Centers of Nevada - Central Valley</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89169</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>University Cancer Center</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89169</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Hope Cancer Care of Nevada-Pahrump</name>
<address>
<city>Pahrump</city>
<state>Nevada</state>
<zip>89048</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Renown Regional Medical Center</name>
<address>
<city>Reno</city>
<state>Nevada</state>
<zip>89502</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Mary's Regional Medical Center</name>
<address>
<city>Reno</city>
<state>Nevada</state>
<zip>89503</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Radiation Oncology Associates</name>
<address>
<city>Reno</city>
<state>Nevada</state>
<zip>89509</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>New Hampshire Oncology Hematology PA-Concord</name>
<address>
<city>Concord</city>
<state>New Hampshire</state>
<zip>03301</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>603-224-2556</phone>
</contact>
<investigator>
<last_name>Douglas J. Weckstein</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>The Dana-Farber Cancer Institute at Londonderry</name>
<address>
<city>Londonderry</city>
<state>New Hampshire</state>
<zip>03053</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Jeanna H. Walsh</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Elliot Hospital</name>
<address>
<city>Manchester</city>
<state>New Hampshire</state>
<zip>03103</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Solinsky Center for Cancer Care</name>
<address>
<city>Manchester</city>
<state>New Hampshire</state>
<zip>03103</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-339-6484</phone>
</contact>
<investigator>
<last_name>Douglas J. Weckstein</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cooper Hospital University Medical Center</name>
<address>
<city>Camden</city>
<state>New Jersey</state>
<zip>08103</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Virtua Samson Cancer Center</name>
<address>
<city>Moorestown</city>
<state>New Jersey</state>
<zip>08057</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Virtua Memorial</name>
<address>
<city>Mount Holly</city>
<state>New Jersey</state>
<zip>08060</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>The Valley Hospital-Luckow Pavilion</name>
<address>
<city>Paramus</city>
<state>New Jersey</state>
<zip>07652</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>201-634-5792</phone>
</contact>
<investigator>
<last_name>Jason Suh</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Neurosurgeons of New Jersey-Ridgewood</name>
<address>
<city>Ridgewood</city>
<state>New Jersey</state>
<zip>07450</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Valley Hospital</name>
<address>
<city>Ridgewood</city>
<state>New Jersey</state>
<zip>07450</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>201-634-5792</phone>
<email>cparish@valleyhealth.com</email>
</contact>
<investigator>
<last_name>Jason Suh</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Virtua Voorhees</name>
<address>
<city>Voorhees</city>
<state>New Jersey</state>
<zip>08043</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Valley Health System-Hematology/Oncology</name>
<address>
<city>Westwood</city>
<state>New Jersey</state>
<zip>07675</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Lovelace Medical Center-Saint Joseph Square</name>
<address>
<city>Albuquerque</city>
<state>New Mexico</state>
<zip>87102</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>University of New Mexico Cancer Center</name>
<address>
<city>Albuquerque</city>
<state>New Mexico</state>
<zip>87102</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>505-925-0348</phone>
<email>HSC-ClinicalTrialInfo@salud.unm.edu</email>
</contact>
<investigator>
<last_name>Atul Kumar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Presbyterian Kaseman Hospital</name>
<address>
<city>Albuquerque</city>
<state>New Mexico</state>
<zip>87110</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Presbyterian Rust Medical Center/Jorgensen Cancer Center</name>
<address>
<city>Rio Rancho</city>
<state>New Mexico</state>
<zip>87124</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>505-559-6113</phone>
<email>WBurman@phs.org</email>
</contact>
<investigator>
<last_name>Atul Kumar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hematology Oncology Associates of Central New York-Auburn</name>
<address>
<city>Auburn</city>
<state>New York</state>
<zip>13021</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Northwell Health Imbert Cancer Center</name>
<address>
<city>Bay Shore</city>
<state>New York</state>
<zip>11706</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Montefiore Medical Center-Einstein Campus</name>
<address>
<city>Bronx</city>
<state>New York</state>
<zip>10461</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>718-379-6866</phone>
<email>eskwak@montefiore.org</email>
</contact>
<investigator>
<last_name>Balazs Halmos</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Montefiore Medical Center-Weiler Hospital</name>
<address>
<city>Bronx</city>
<state>New York</state>
<zip>10461</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Montefiore Medical Center - Moses Campus</name>
<address>
<city>Bronx</city>
<state>New York</state>
<zip>10467</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>718-379-6866</phone>
<email>eskwak@montefiore.org</email>
</contact>
<investigator>
<last_name>Balazs Halmos</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>James J Peters VA Medical Center</name>
<address>
<city>Bronx</city>
<state>New York</state>
<zip>10468</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>718-584-9000</phone>
<email>kl2965@cumc.columbia.edu</email>
</contact>
<investigator>
<last_name>Yeun-Hee A. Park</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Maimonides Medical Center</name>
<address>
<city>Brooklyn</city>
<state>New York</state>
<zip>11219</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>718-765-2500</phone>
</contact>
<investigator>
<last_name>Kevin Becker</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Roswell Park Cancer Institute</name>
<address>
<city>Buffalo</city>
<state>New York</state>
<zip>14263</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-767-9355</phone>
<email>askroswell@roswellpark.org</email>
</contact>
<investigator>
<last_name>Edwin H. Yau</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mary Imogene Bassett Hospital</name>
<address>
<city>Cooperstown</city>
<state>New York</state>
<zip>13326</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-547-1750</phone>
<email>CancerClinicalTrials@bassett.org</email>
</contact>
<investigator>
<last_name>Jeffrey P. Allerton</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Institute at Saint Francis Hospital</name>
<address>
<city>East Hills</city>
<state>New York</state>
<zip>11548</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Edwin H. Yau</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hematology Oncology Associates of Central New York-East Syracuse</name>
<address>
<city>East Syracuse</city>
<state>New York</state>
<zip>13057</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>315-472-7504</phone>
</contact>
<investigator>
<last_name>Steven M. Duffy</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Glens Falls Hospital</name>
<address>
<city>Glens Falls</city>
<state>New York</state>
<zip>12801</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>518-926-6700</phone>
</contact>
<investigator>
<last_name>Aqeel A. Gillani</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Northwell Health/Center for Advanced Medicine</name>
<address>
<city>Lake Success</city>
<state>New York</state>
<zip>11042</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>516-734-8896</phone>
</contact>
<investigator>
<last_name>Kevin M. Sullivan</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Nyack Hospital</name>
<address>
<city>Nyack</city>
<state>New York</state>
<zip>10960</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Upstate Cancer Center at Oneida</name>
<address>
<city>Oneida</city>
<state>New York</state>
<zip>13421</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>315-464-8230</phone>
<email>McDowelE@upstate.edu</email>
</contact>
<investigator>
<last_name>Stephen L. Graziano</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Upstate Cancer Center at Oswego</name>
<address>
<city>Oswego</city>
<state>New York</state>
<zip>13126</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>315-464-8230</phone>
<email>McDowelE@upstate.edu</email>
</contact>
<investigator>
<last_name>Stephen L. Graziano</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Rochester General Hospital</name>
<address>
<city>Rochester</city>
<state>New York</state>
<zip>14621</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>585-922-3536</phone>
<email>tia.derosa@rochestergeneral.org</email>
</contact>
<investigator>
<last_name>Mehul P. Patel</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University of Rochester</name>
<address>
<city>Rochester</city>
<state>New York</state>
<zip>14642</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>585-275-5830</phone>
</contact>
<investigator>
<last_name>Yuhchyau Chen</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Phelps Memorial Hospital Center</name>
<address>
<city>Sleepy Hollow</city>
<state>New York</state>
<zip>10591</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>914-366-1600</phone>
</contact>
<investigator>
<last_name>Kevin M. Sullivan</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Stony Brook University Medical Center</name>
<address>
<city>Stony Brook</city>
<state>New York</state>
<zip>11794</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-862-2215</phone>
</contact>
<investigator>
<last_name>Roger S. Keresztes</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>State University of New York Upstate Medical University</name>
<address>
<city>Syracuse</city>
<state>New York</state>
<zip>13210</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>315-464-5476</phone>
</contact>
<investigator>
<last_name>Stephen L. Graziano</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hematology Oncology Associates of Central New York-Onondaga Hill</name>
<address>
<city>Syracuse</city>
<state>New York</state>
<zip>13215</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>315-472-7504</phone>
</contact>
<investigator>
<last_name>Steven M. Duffy</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>SUNY Upstate Medical Center-Community Campus</name>
<address>
<city>Syracuse</city>
<state>New York</state>
<zip>13215</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>315-464-5476</phone>
</contact>
<investigator>
<last_name>Stephen L. Graziano</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Good Samaritan Hospital Medical Center</name>
<address>
<city>West Islip</city>
<state>New York</state>
<zip>11795</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>631-417-8611</phone>
</contact>
<investigator>
<last_name>Edwin H. Yau</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Dickstein Cancer Treatment Center</name>
<address>
<city>White Plains</city>
<state>New York</state>
<zip>10601</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>914-849-7582</phone>
<email>mcortese@wphospital.org</email>
</contact>
<investigator>
<last_name>Joshua P. Raff</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Randolph Hospital</name>
<address>
<city>Asheboro</city>
<state>North Carolina</state>
<zip>27203</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cone Health Cancer Center at Alamance Regional</name>
<address>
<city>Burlington</city>
<state>North Carolina</state>
<zip>27215</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>336-832-0836</phone>
<email>stacey.phelps@conehealth.com</email>
</contact>
<investigator>
<last_name>Vinay K. Gudena</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Wake Forest University at Clemmons</name>
<address>
<city>Clemmons</city>
<state>North Carolina</state>
<zip>27012</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>888-716-9259</phone>
</contact>
<investigator>
<last_name>Jimmy Ruiz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Durham VA Medical Center</name>
<address>
<city>Durham</city>
<state>North Carolina</state>
<zip>27705</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Duke University Medical Center</name>
<address>
<city>Durham</city>
<state>North Carolina</state>
<zip>27710</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>888-275-3853</phone>
</contact>
<investigator>
<last_name>Jeffrey Crawford</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>CaroMont Regional Medical Center</name>
<address>
<city>Gastonia</city>
<state>North Carolina</state>
<zip>28054</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>704-834-2810</phone>
<email>tammy.cozad@caromonthealth.org</email>
</contact>
<investigator>
<last_name>James G. McGrath</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cone Health Cancer Center</name>
<address>
<city>Greensboro</city>
<state>North Carolina</state>
<zip>27403</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>336-832-0836</phone>
<email>stacey.phelps@conehealth.com</email>
</contact>
<investigator>
<last_name>Vinay K. Gudena</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cone Health Cancer Center at Drawbridge Parkway</name>
<address>
<city>Greensboro</city>
<state>North Carolina</state>
<zip>27410</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>336-832-0836</phone>
<email>stacey.phelps@conehealth.com</email>
</contact>
<investigator>
<last_name>Vinay K. Gudena</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Margaret R Pardee Memorial Hospital</name>
<address>
<city>Hendersonville</city>
<state>North Carolina</state>
<zip>28791</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>828-696-4716</phone>
<email>pardeecancerresearch@unchealth.unc.edu</email>
</contact>
<investigator>
<last_name>Praveen Vashist</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cone Heath Cancer Center at Mebane</name>
<address>
<city>Mebane</city>
<state>North Carolina</state>
<zip>27302</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>FirstHealth of the Carolinas-Moore Regional Hospital</name>
<address>
<city>Pinehurst</city>
<state>North Carolina</state>
<zip>28374</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>910-715-3500</phone>
<email>jcwilliams@firsthealth.org</email>
</contact>
<investigator>
<last_name>Charles S. Kuzma</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Duke Raleigh Hospital</name>
<address>
<city>Raleigh</city>
<state>North Carolina</state>
<zip>27609</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Annie Penn Memorial Hospital</name>
<address>
<city>Reidsville</city>
<state>North Carolina</state>
<zip>27320</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>336-832-0836</phone>
<email>stacey.phelps@conehealth.com</email>
</contact>
<investigator>
<last_name>Vinay K. Gudena</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Wake Forest Baptist Health - Hematology Oncology - Statesville</name>
<address>
<city>Statesville</city>
<state>North Carolina</state>
<zip>28677</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Wake Forest University Health Sciences</name>
<address>
<city>Winston-Salem</city>
<state>North Carolina</state>
<zip>27157</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>336-713-6771</phone>
</contact>
<investigator>
<last_name>Jimmy Ruiz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sanford Bismarck Medical Center</name>
<address>
<city>Bismarck</city>
<state>North Dakota</state>
<zip>58501</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>701-323-5760</phone>
<email>OncologyClinicalTrialsFargo@sanfordhealth.org</email>
</contact>
<investigator>
<last_name>Daniel Almquist</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Essentia Health Cancer Center-South University Clinic</name>
<address>
<city>Fargo</city>
<state>North Dakota</state>
<zip>58103</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Sanford South University Medical Center</name>
<address>
<city>Fargo</city>
<state>North Dakota</state>
<zip>58103</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Southpointe-Sanford Medical Center Fargo</name>
<address>
<city>Fargo</city>
<state>North Dakota</state>
<zip>58103</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Sanford Medical Center Fargo</name>
<address>
<city>Fargo</city>
<state>North Dakota</state>
<zip>58104</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Sanford Broadway Medical Center</name>
<address>
<city>Fargo</city>
<state>North Dakota</state>
<zip>58122</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>701-323-5760</phone>
<email>OncologyClinicalTrialsFargo@sanfordhealth.org</email>
</contact>
<investigator>
<last_name>Daniel Almquist</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sanford Roger Maris Cancer Center</name>
<address>
<city>Fargo</city>
<state>North Dakota</state>
<zip>58122</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>701-234-6161</phone>
<email>OncologyClinicalTrialsFargo@sanfordhealth.org</email>
</contact>
<investigator>
<last_name>Daniel Almquist</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Essentia Health - Jamestown Clinic</name>
<address>
<city>Jamestown</city>
<state>North Dakota</state>
<zip>58401</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cleveland Clinic Akron General</name>
<address>
<city>Akron</city>
<state>Ohio</state>
<zip>44307</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>866-223-8100</phone>
<email>CancerAnswer@ccf.org</email>
</contact>
<investigator>
<last_name>Kathryn M. Leininger</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aultman Alliance Community Hospital</name>
<address>
<city>Alliance</city>
<state>Ohio</state>
<zip>44601</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Indu and Raj Soin Medical Center</name>
<address>
<city>Beavercreek</city>
<state>Ohio</state>
<zip>45431</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Strecker Cancer Center-Belpre</name>
<address>
<city>Belpre</city>
<state>Ohio</state>
<zip>45714</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-523-3977</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Elizabeth Boardman Hospital</name>
<address>
<city>Boardman</city>
<state>Ohio</state>
<zip>44512</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Aultman Health Foundation</name>
<address>
<city>Canton</city>
<state>Ohio</state>
<zip>44710</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>330-363-7274</phone>
<email>ClinicalReserachDept@aultman.com</email>
</contact>
<investigator>
<last_name>Raza A. Khan</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Dayton Physicians LLC-Miami Valley South</name>
<address>
<city>Centerville</city>
<state>Ohio</state>
<zip>45459</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>937-528-2900</phone>
<email>clinical.trials@daytonncorp.org</email>
</contact>
<investigator>
<last_name>Howard M. Gross</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Miami Valley Hospital South</name>
<address>
<city>Centerville</city>
<state>Ohio</state>
<zip>45459</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Adena Regional Medical Center</name>
<address>
<city>Chillicothe</city>
<state>Ohio</state>
<zip>45601</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-779-7585</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Good Samaritan Hospital - Cincinnati</name>
<address>
<city>Cincinnati</city>
<state>Ohio</state>
<zip>45220</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Oncology Hematology Care Inc-Kenwood</name>
<address>
<city>Cincinnati</city>
<state>Ohio</state>
<zip>45236</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Bethesda North Hospital</name>
<address>
<city>Cincinnati</city>
<state>Ohio</state>
<zip>45242</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>TriHealth Cancer Institute-Westside</name>
<address>
<city>Cincinnati</city>
<state>Ohio</state>
<zip>45247</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>TriHealth Cancer Institute-Anderson</name>
<address>
<city>Cincinnati</city>
<state>Ohio</state>
<zip>45255</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>MetroHealth Medical Center</name>
<address>
<city>Cleveland</city>
<state>Ohio</state>
<zip>44109</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>216-778-8526</phone>
<email>dstrater@metrohealth.org</email>
</contact>
<investigator>
<last_name>William Tse</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cleveland Clinic Cancer Center/Fairview Hospital</name>
<address>
<city>Cleveland</city>
<state>Ohio</state>
<zip>44111</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>866-223-8100</phone>
<email>TaussigResearch@ccf.org</email>
</contact>
<investigator>
<last_name>Nathan A. Pennell</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cleveland Clinic Foundation</name>
<address>
<city>Cleveland</city>
<state>Ohio</state>
<zip>44195</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>866-223-8100</phone>
<email>TaussigResearch@ccf.org</email>
</contact>
<investigator>
<last_name>Nathan A. Pennell</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mount Carmel East Hospital</name>
<address>
<city>Columbus</city>
<state>Ohio</state>
<zip>43213</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>614-488-2118</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Columbus Oncology and Hematology Associates Inc</name>
<address>
<city>Columbus</city>
<state>Ohio</state>
<zip>43214</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>614-488-2118</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Riverside Methodist Hospital</name>
<address>
<city>Columbus</city>
<state>Ohio</state>
<zip>43214</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Grant Medical Center</name>
<address>
<city>Columbus</city>
<state>Ohio</state>
<zip>43215</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>614-566-4475</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>The Mark H Zangmeister Center</name>
<address>
<city>Columbus</city>
<state>Ohio</state>
<zip>43219</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>614-488-2118</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Mount Carmel Health Center West</name>
<address>
<city>Columbus</city>
<state>Ohio</state>
<zip>43222</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>614-234-5433</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Doctors Hospital</name>
<address>
<city>Columbus</city>
<state>Ohio</state>
<zip>43228</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>614-566-3275</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Miami Valley Hospital</name>
<address>
<city>Dayton</city>
<state>Ohio</state>
<zip>45409</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Dayton Physician LLC-Miami Valley Hospital North</name>
<address>
<city>Dayton</city>
<state>Ohio</state>
<zip>45415</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>937-528-2900</phone>
<email>clinical.trials@daytonncorp.org</email>
</contact>
<investigator>
<last_name>Howard M. Gross</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Miami Valley Hospital North</name>
<address>
<city>Dayton</city>
<state>Ohio</state>
<zip>45415</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Delaware Health Center-Grady Cancer Center</name>
<address>
<city>Delaware</city>
<state>Ohio</state>
<zip>43015</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>740-615-0227</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Grady Memorial Hospital</name>
<address>
<city>Delaware</city>
<state>Ohio</state>
<zip>43015</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>740-615-2403</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Dublin Methodist Hospital</name>
<address>
<city>Dublin</city>
<state>Ohio</state>
<zip>43016</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Armes Family Cancer Center</name>
<address>
<city>Findlay</city>
<state>Ohio</state>
<zip>45840</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>937-528-2900</phone>
<email>clinical.trials@daytonncorp.org</email>
</contact>
<investigator>
<last_name>Howard M. Gross</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Blanchard Valley Hospital</name>
<address>
<city>Findlay</city>
<state>Ohio</state>
<zip>45840</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Orion Cancer Care</name>
<address>
<city>Findlay</city>
<state>Ohio</state>
<zip>45840</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Atrium Medical Center-Middletown Regional Hospital</name>
<address>
<city>Franklin</city>
<state>Ohio</state>
<zip>45005-1066</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Dayton Physicians LLC-Atrium</name>
<address>
<city>Franklin</city>
<state>Ohio</state>
<zip>45005</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>937-528-2900</phone>
<email>clinical.trials@daytonncorp.org</email>
</contact>
<investigator>
<last_name>Howard M. Gross</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Central Ohio Breast and Endocrine Surgery</name>
<address>
<city>Gahanna</city>
<state>Ohio</state>
<zip>43230</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Dayton Physicians LLC-Wayne</name>
<address>
<city>Greenville</city>
<state>Ohio</state>
<zip>45331</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Wayne Hospital</name>
<address>
<city>Greenville</city>
<state>Ohio</state>
<zip>45331</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Mount Carmel Grove City Hospital</name>
<address>
<city>Grove City</city>
<state>Ohio</state>
<zip>43123</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Cleveland Clinic Cancer Center Independence</name>
<address>
<city>Independence</city>
<state>Ohio</state>
<zip>44131</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>866-223-8100</phone>
<email>TaussigResearch@ccf.org</email>
</contact>
<investigator>
<last_name>Nathan A. Pennell</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Greater Dayton Cancer Center</name>
<address>
<city>Kettering</city>
<state>Ohio</state>
<zip>45409</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>937-528-2900</phone>
<email>clinical.trials@daytonncorp.org</email>
</contact>
<investigator>
<last_name>Howard M. Gross</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>First Dayton Cancer Care</name>
<address>
<city>Kettering</city>
<state>Ohio</state>
<zip>45420</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kettering Medical Center</name>
<address>
<city>Kettering</city>
<state>Ohio</state>
<zip>45429</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>937-528-2900</phone>
<email>clinical.trials@daytonncorp.org</email>
</contact>
<investigator>
<last_name>Howard M. Gross</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Fairfield Medical Center</name>
<address>
<city>Lancaster</city>
<state>Ohio</state>
<zip>43130</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>740-687-8863</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Rita's Medical Center</name>
<address>
<city>Lima</city>
<state>Ohio</state>
<zip>45801</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>OhioHealth Mansfield Hospital</name>
<address>
<city>Mansfield</city>
<state>Ohio</state>
<zip>44903</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>419-526-8018</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cleveland Clinic Cancer Center Mansfield</name>
<address>
<city>Mansfield</city>
<state>Ohio</state>
<zip>44906</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>866-223-8100</phone>
<email>TaussigResearch@ccf.org</email>
</contact>
<investigator>
<last_name>Nathan A. Pennell</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Marietta Memorial Hospital</name>
<address>
<city>Marietta</city>
<state>Ohio</state>
<zip>45750</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-523-3977</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>OhioHealth Marion General Hospital</name>
<address>
<city>Marion</city>
<state>Ohio</state>
<zip>43302</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>614-488-2118</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hillcrest Hospital Cancer Center</name>
<address>
<city>Mayfield Heights</city>
<state>Ohio</state>
<zip>44124</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>866-223-8100</phone>
<email>TaussigResearch@ccf.org</email>
</contact>
<investigator>
<last_name>Nathan A. Pennell</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Knox Community Hospital</name>
<address>
<city>Mount Vernon</city>
<state>Ohio</state>
<zip>43050</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>740-393-9000</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Licking Memorial Hospital</name>
<address>
<city>Newark</city>
<state>Ohio</state>
<zip>43055</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>740-348-4000</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Newark Radiation Oncology</name>
<address>
<city>Newark</city>
<state>Ohio</state>
<zip>43055</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Mercy Health Perrysburg Cancer Center</name>
<address>
<city>Perrysburg</city>
<state>Ohio</state>
<zip>43551</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>614-488-2118</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Southern Ohio Medical Center</name>
<address>
<city>Portsmouth</city>
<state>Ohio</state>
<zip>45662</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>614-488-2118</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>North Coast Cancer Care</name>
<address>
<city>Sandusky</city>
<state>Ohio</state>
<zip>44870</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>866-223-8100</phone>
<email>TaussigResearch@ccf.org</email>
</contact>
<investigator>
<last_name>Nathan A. Pennell</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Springfield Regional Cancer Center</name>
<address>
<city>Springfield</city>
<state>Ohio</state>
<zip>45504</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>937-528-2900</phone>
<email>clinical.trials@daytonncorp.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Springfield Regional Medical Center</name>
<address>
<city>Springfield</city>
<state>Ohio</state>
<zip>45505</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Trinity's Tony Teramana Cancer Center</name>
<address>
<city>Steubenville</city>
<state>Ohio</state>
<zip>43952</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>888-874-7000</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>ProMedica Flower Hospital</name>
<address>
<city>Sylvania</city>
<state>Ohio</state>
<zip>43560</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>419-824-1842</phone>
<email>PCIOncResearch@promedica.org</email>
</contact>
<investigator>
<last_name>Jeffrey H. Muler</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Vincent Mercy Medical Center</name>
<address>
<city>Toledo</city>
<state>Ohio</state>
<zip>43608</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>University of Toledo</name>
<address>
<city>Toledo</city>
<state>Ohio</state>
<zip>43614</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Mercy Health - Saint Anne Hospital</name>
<address>
<city>Toledo</city>
<state>Ohio</state>
<zip>43623</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>614-488-2118</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Toledo Clinic Cancer Centers-Toledo</name>
<address>
<city>Toledo</city>
<state>Ohio</state>
<zip>43623</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-444-3561</phone>
</contact>
<investigator>
<last_name>Rex B. Mowat</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Dayton Physicians LLC - Troy</name>
<address>
<city>Troy</city>
<state>Ohio</state>
<zip>45373</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Upper Valley Medical Center</name>
<address>
<city>Troy</city>
<state>Ohio</state>
<zip>45373</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>South Pointe Hospital</name>
<address>
<city>Warrensville Heights</city>
<state>Ohio</state>
<zip>44122</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>866-223-8100</phone>
<email>TaussigResearch@ccf.org</email>
</contact>
<investigator>
<last_name>Nathan A. Pennell</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Joseph Warren Hospital</name>
<address>
<city>Warren</city>
<state>Ohio</state>
<zip>44484</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Ann's Hospital</name>
<address>
<city>Westerville</city>
<state>Ohio</state>
<zip>43081</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>614-234-5433</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cleveland Clinic Wooster Family Health and Surgery Center</name>
<address>
<city>Wooster</city>
<state>Ohio</state>
<zip>44691</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>866-223-8100</phone>
<email>TaussigResearch@ccf.org</email>
</contact>
<investigator>
<last_name>Nathan A. Pennell</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Wright-Patterson Medical Center</name>
<address>
<city>Wright-Patterson Air Force Base</city>
<state>Ohio</state>
<zip>45433</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>937-528-2900</phone>
<email>clinical.trials@daytonncorp.org</email>
</contact>
<investigator>
<last_name>McKayla Riggs</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Elizabeth Youngstown Hospital</name>
<address>
<city>Youngstown</city>
<state>Ohio</state>
<zip>44501</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Genesis Healthcare System Cancer Care Center</name>
<address>
<city>Zanesville</city>
<state>Ohio</state>
<zip>43701</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>740-454-5232</phone>
<email>sheree@columbusccop.org</email>
</contact>
<investigator>
<last_name>Timothy D. Moore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Centers of Southwest Oklahoma Research</name>
<address>
<city>Lawton</city>
<state>Oklahoma</state>
<zip>73505</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-231-4440</phone>
</contact>
<investigator>
<last_name>Raid Aljumaily</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University of Oklahoma Health Sciences Center</name>
<address>
<city>Oklahoma City</city>
<state>Oklahoma</state>
<zip>73104</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>405-271-8777</phone>
<email>ou-clinical-trials@ouhsc.edu</email>
</contact>
<investigator>
<last_name>Raid Aljumaily</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Integris Southwest Medical Center</name>
<address>
<city>Oklahoma City</city>
<state>Oklahoma</state>
<zip>73109</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Mercy Hospital Oklahoma City</name>
<address>
<city>Oklahoma City</city>
<state>Oklahoma</state>
<zip>73120</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>405-752-3402</phone>
</contact>
<investigator>
<last_name>Jay W. Carlson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Integris Cancer Institute of Oklahoma</name>
<address>
<city>Oklahoma City</city>
<state>Oklahoma</state>
<zip>73142</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Alphonsus Medical Center-Baker City</name>
<address>
<city>Baker City</city>
<state>Oregon</state>
<zip>97814</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Charles Health System</name>
<address>
<city>Bend</city>
<state>Oregon</state>
<zip>97701</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Clackamas Radiation Oncology Center</name>
<address>
<city>Clackamas</city>
<state>Oregon</state>
<zip>97015</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Providence Cancer Institute Clackamas Clinic</name>
<address>
<city>Clackamas</city>
<state>Oregon</state>
<zip>97015</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Bay Area Hospital</name>
<address>
<city>Coos Bay</city>
<state>Oregon</state>
<zip>97420</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Good Samaritan Hospital</name>
<address>
<city>Corvallis</city>
<state>Oregon</state>
<zip>97330</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>541-768-4352</phone>
<email>stmock@samhealth.org</email>
</contact>
<investigator>
<last_name>John Strother</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Three Rivers Community Hospital</name>
<address>
<city>Grants Pass</city>
<state>Oregon</state>
<zip>97527</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>541-472-7000</phone>
</contact>
<investigator>
<last_name>Alison D. Savage</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Rogue Valley Medical Center</name>
<address>
<city>Medford</city>
<state>Oregon</state>
<zip>97504</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>541-789-4673</phone>
<email>research@asante.org</email>
</contact>
<investigator>
<last_name>Alison D. Savage</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Providence Newberg Medical Center</name>
<address>
<city>Newberg</city>
<state>Oregon</state>
<zip>97132</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>503-215-2614</phone>
<email>CanRsrchStudies@providence.org</email>
</contact>
<investigator>
<last_name>Alison K. Conlin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Alphonsus Medical Center-Ontario</name>
<address>
<city>Ontario</city>
<state>Oregon</state>
<zip>97914</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>406-969-6060</phone>
<email>mccinfo@mtcancer.org</email>
</contact>
<investigator>
<last_name>John M. Schallenkamp</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Providence Portland Medical Center</name>
<address>
<city>Portland</city>
<state>Oregon</state>
<zip>97213</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>503-215-2614</phone>
<email>CanRsrchStudies@providence.org</email>
</contact>
<investigator>
<last_name>Alison K. Conlin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Providence Saint Vincent Medical Center</name>
<address>
<city>Portland</city>
<state>Oregon</state>
<zip>97225</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>503-215-2614</phone>
<email>CanRsrchStudies@providence.org</email>
</contact>
<investigator>
<last_name>Alison K. Conlin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente Northwest</name>
<address>
<city>Portland</city>
<state>Oregon</state>
<zip>97227</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>503-335-2400</phone>
<email>information@kpchr.org</email>
</contact>
<investigator>
<last_name>Abdul Hai Mansoor</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Charles Health System-Redmond</name>
<address>
<city>Redmond</city>
<state>Oregon</state>
<zip>97756</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Lehigh Valley Hospital-Cedar Crest</name>
<address>
<city>Allentown</city>
<state>Pennsylvania</state>
<zip>18103</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>610-402-9543</phone>
<email>Morgan_M.Horton@lvhn.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Altoona</name>
<address>
<city>Altoona</city>
<state>Pennsylvania</state>
<zip>16601</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC-Heritage Valley Health System Beaver</name>
<address>
<city>Beaver</city>
<state>Pennsylvania</state>
<zip>15009</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-389-5208</phone>
<email>haneydl@upmc.edu</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lehigh Valley Hospital - Muhlenberg</name>
<address>
<city>Bethlehem</city>
<state>Pennsylvania</state>
<zip>18017</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>610-402-9543</phone>
<email>Morgan_M.Horton@lvhn.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Bryn Mawr Hospital</name>
<address>
<city>Bryn Mawr</city>
<state>Pennsylvania</state>
<zip>19010</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>484-476-2649</phone>
<email>turzoe@mlhs.org</email>
</contact>
<investigator>
<last_name>Albert S. DeNittis</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Camp Hill</name>
<address>
<city>Camp Hill</city>
<state>Pennsylvania</state>
<zip>17011</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>717-975-8900</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Carlisle Regional Cancer Center</name>
<address>
<city>Carlisle</city>
<state>Pennsylvania</state>
<zip>17015</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Christiana Care Health System-Concord Health Center</name>
<address>
<city>Chadds Ford</city>
<state>Pennsylvania</state>
<zip>19317</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Chambersburg Hospital</name>
<address>
<city>Chambersburg</city>
<state>Pennsylvania</state>
<zip>17201</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>WellSpan Medical Oncology and Hematology</name>
<address>
<city>Chambersburg</city>
<state>Pennsylvania</state>
<zip>17201</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>717-217-6020</phone>
</contact>
<investigator>
<last_name>Dan Sotirescu</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Geisinger Medical Center</name>
<address>
<city>Danville</city>
<state>Pennsylvania</state>
<zip>17822</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>570-271-5251</phone>
<email>HemonCCTrials@geisinger.edu</email>
</contact>
<investigator>
<last_name>Ahmad Hanif</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Doylestown Hospital</name>
<address>
<city>Doylestown</city>
<state>Pennsylvania</state>
<zip>18901</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>215-345-2378</phone>
<email>lheacock@dh.org</email>
</contact>
<investigator>
<last_name>Nathaniel R. Evans</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Fox Chase Cancer Center - East Norriton Hospital Outpatient Center</name>
<address>
<city>East Norriton</city>
<state>Pennsylvania</state>
<zip>19401</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>888-823-5923</phone>
<email>ctsucontact@westat.com</email>
</contact>
<investigator>
<last_name>Martin J. Edelman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Pocono Medical Center</name>
<address>
<city>East Stroudsburg</city>
<state>Pennsylvania</state>
<zip>18301</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>610-402-9543</phone>
<email>Morgan_M.Horton@lvhn.org</email>
</contact>
<investigator>
<last_name>Christopher M. Reynolds</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ephrata Cancer Center</name>
<address>
<city>Ephrata</city>
<state>Pennsylvania</state>
<zip>17522</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>717-721-4840</phone>
</contact>
<investigator>
<last_name>Dan Sotirescu</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ephrata Community Hospital</name>
<address>
<city>Ephrata</city>
<state>Pennsylvania</state>
<zip>17522</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>UPMC Hillman Cancer Center Erie</name>
<address>
<city>Erie</city>
<state>Pennsylvania</state>
<zip>16505</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-389-5208</phone>
<email>haneydl@upmc.edu</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Cancer Center at UPMC Horizon</name>
<address>
<city>Farrell</city>
<state>Pennsylvania</state>
<zip>16121</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Adams Cancer Center</name>
<address>
<city>Gettysburg</city>
<state>Pennsylvania</state>
<zip>17325</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-441-7957</phone>
</contact>
<investigator>
<last_name>Dan Sotirescu</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Cancer Centers - Arnold Palmer Pavilion</name>
<address>
<city>Greensburg</city>
<state>Pennsylvania</state>
<zip>15601</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>724-838-1900</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Oncology Hematology Associates</name>
<address>
<city>Greenville</city>
<state>Pennsylvania</state>
<zip>16125</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cherry Tree Cancer Center</name>
<address>
<city>Hanover</city>
<state>Pennsylvania</state>
<zip>17331</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>717-632-1559</phone>
</contact>
<investigator>
<last_name>Dan Sotirescu</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Pinnacle Cancer Center/Community Osteopathic Campus</name>
<address>
<city>Harrisburg</city>
<state>Pennsylvania</state>
<zip>17109</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>717-724-6765</phone>
<email>klitchfield@PINNACLEHEALTH.org</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Geisinger Medical Center-Cancer Center Hazleton</name>
<address>
<city>Hazleton</city>
<state>Pennsylvania</state>
<zip>18201</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>570-459-2901</phone>
<email>HemonCCTrials@geisinger.edu</email>
</contact>
<investigator>
<last_name>Ahmad Hanif</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lehigh Valley Hospital-Hazleton</name>
<address>
<city>Hazleton</city>
<state>Pennsylvania</state>
<zip>18201</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>IRMC Cancer Center</name>
<address>
<city>Indiana</city>
<state>Pennsylvania</state>
<zip>15701</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-389-5208</phone>
<email>haneydl@upmc.edu</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC-Johnstown/John P. Murtha Regional Cancer Center</name>
<address>
<city>Johnstown</city>
<state>Pennsylvania</state>
<zip>15901</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>814-534-4724</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sechler Family Cancer Center</name>
<address>
<city>Lebanon</city>
<state>Pennsylvania</state>
<zip>17042</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>717-741-8303</phone>
<email>doxenberg@wellspan.org</email>
</contact>
<investigator>
<last_name>Dan Sotirescu</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Geisinger Medical Oncology-Lewisburg</name>
<address>
<city>Lewisburg</city>
<state>Pennsylvania</state>
<zip>17837</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>570-374-8555</phone>
<email>HemonCCTrials@geisinger.edu</email>
</contact>
<investigator>
<last_name>Ahmad Hanif</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lewistown Hospital</name>
<address>
<city>Lewistown</city>
<state>Pennsylvania</state>
<zip>17044</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>UPMC Cancer Center at UPMC McKeesport</name>
<address>
<city>McKeesport</city>
<state>Pennsylvania</state>
<zip>15132</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-647-8073</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion</name>
<address>
<city>Mechanicsburg</city>
<state>Pennsylvania</state>
<zip>17050</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-389-5208</phone>
<email>haneydl@upmc.edu</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Riddle Memorial Hospital</name>
<address>
<city>Media</city>
<state>Pennsylvania</state>
<zip>19063</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>484-476-2649</phone>
<email>turzoe@mlhs.org</email>
</contact>
<investigator>
<last_name>Albert S. DeNittis</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Hillman Cancer Center - Monroeville</name>
<address>
<city>Monroeville</city>
<state>Pennsylvania</state>
<zip>15146</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-389-5208</phone>
<email>haneydl@upmc.edu</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Hillman Cancer Center in Coraopolis</name>
<address>
<city>Moon</city>
<state>Pennsylvania</state>
<zip>15108</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-389-5208</phone>
<email>haneydl@upmc.edu</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Hillman Cancer Center - Part of Frick Hospital</name>
<address>
<city>Mount Pleasant</city>
<state>Pennsylvania</state>
<zip>15666</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-389-5208</phone>
<email>haneydl@upmc.edu</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Arnold Palmer Cancer Center Medical Oncology Norwin</name>
<address>
<city>N. Huntingdon</city>
<state>Pennsylvania</state>
<zip>15642</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-389-5208</phone>
<email>haneydl@upmc.edu</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Cancer Center-Natrona Heights</name>
<address>
<city>Natrona Heights</city>
<state>Pennsylvania</state>
<zip>15065</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>724-230-3030</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Hillman Cancer Center - New Castle</name>
<address>
<city>New Castle</city>
<state>Pennsylvania</state>
<zip>16105</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-389-5208</phone>
<email>haneydl@upmc.edu</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Paoli Memorial Hospital</name>
<address>
<city>Paoli</city>
<state>Pennsylvania</state>
<zip>19301</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>484-476-2649</phone>
<email>turzoe@mlhs.org</email>
</contact>
<investigator>
<last_name>Albert S. DeNittis</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Thomas Jefferson University Hospital</name>
<address>
<city>Philadelphia</city>
<state>Pennsylvania</state>
<zip>19107</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>215-600-9151</phone>
<email>ONCTrialNow@jefferson.edu</email>
</contact>
<investigator>
<last_name>Nathaniel R. Evans</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Fox Chase Cancer Center</name>
<address>
<city>Philadelphia</city>
<state>Pennsylvania</state>
<zip>19111</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>215-728-4790</phone>
</contact>
<investigator>
<last_name>Martin J. Edelman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Temple University Hospital</name>
<address>
<city>Philadelphia</city>
<state>Pennsylvania</state>
<zip>19140</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>215-728-2983</phone>
</contact>
<investigator>
<last_name>Martin J. Edelman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC-Saint Margaret</name>
<address>
<city>Pittsburgh</city>
<state>Pennsylvania</state>
<zip>15215</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-784-4900</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC-Mercy Hospital</name>
<address>
<city>Pittsburgh</city>
<state>Pennsylvania</state>
<zip>15219</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-533-8762</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University of Pittsburgh Cancer Institute (UPCI)</name>
<address>
<city>Pittsburgh</city>
<state>Pennsylvania</state>
<zip>15232</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-647-8073</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC-Shadyside Hospital</name>
<address>
<city>Pittsburgh</city>
<state>Pennsylvania</state>
<zip>15232</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>UPMC-Passavant Hospital</name>
<address>
<city>Pittsburgh</city>
<state>Pennsylvania</state>
<zip>15237</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-367-6454</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC-Saint Clair Hospital Cancer Center</name>
<address>
<city>Pittsburgh</city>
<state>Pennsylvania</state>
<zip>15243</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-502-3920</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Pottstown Hospital</name>
<address>
<city>Pottstown</city>
<state>Pennsylvania</state>
<zip>19464</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>610-327-7544</phone>
</contact>
<investigator>
<last_name>Jeffrey A. Stevens</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Geisinger Cancer Services-Pottsville</name>
<address>
<city>Pottsville</city>
<state>Pennsylvania</state>
<zip>17901</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-275-6401</phone>
<email>HemonCCTrials@geisinger.edu</email>
</contact>
<investigator>
<last_name>Ahmad Hanif</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Community Medical Center</name>
<address>
<city>Scranton</city>
<state>Pennsylvania</state>
<zip>18510</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>570-703-4768</phone>
<email>HemonCCTrials@geisinger.edu</email>
</contact>
<investigator>
<last_name>Ahmad Hanif</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Geisinger Medical Oncology-Selinsgrove</name>
<address>
<city>Selinsgrove</city>
<state>Pennsylvania</state>
<zip>17870</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>UPMC Cancer Center at UPMC Northwest</name>
<address>
<city>Seneca</city>
<state>Pennsylvania</state>
<zip>16346</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>814-676-7900</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Geisinger Medical Group</name>
<address>
<city>State College</city>
<state>Pennsylvania</state>
<zip>16801</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>UPMC Cancer Center-Uniontown</name>
<address>
<city>Uniontown</city>
<state>Pennsylvania</state>
<zip>15401</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Cancer Center-Washington</name>
<address>
<city>Washington</city>
<state>Pennsylvania</state>
<zip>15301</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC West Mifflin-Cancer Center Jefferson</name>
<address>
<city>West Mifflin</city>
<state>Pennsylvania</state>
<zip>15122</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>412-653-8100</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Reading Hospital</name>
<address>
<city>West Reading</city>
<state>Pennsylvania</state>
<zip>19611</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>610-988-9323</phone>
</contact>
<investigator>
<last_name>Terrence P. Cescon</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Geisinger Wyoming Valley/Henry Cancer Center</name>
<address>
<city>Wilkes-Barre</city>
<state>Pennsylvania</state>
<zip>18711</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>570-271-5251</phone>
<email>HemonCCTrials@geisinger.edu</email>
</contact>
<investigator>
<last_name>Ahmad Hanif</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Susquehanna</name>
<address>
<city>Williamsport</city>
<state>Pennsylvania</state>
<zip>17701</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-598-4282</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Divine Providence Hospital</name>
<address>
<city>Williamsport</city>
<state>Pennsylvania</state>
<zip>17754</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lankenau Medical Center</name>
<address>
<city>Wynnewood</city>
<state>Pennsylvania</state>
<zip>19096</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>484-476-2649</phone>
<email>turzoe@mlhs.org</email>
</contact>
<investigator>
<last_name>Albert S. DeNittis</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Care Associates of York</name>
<address>
<city>York</city>
<state>Pennsylvania</state>
<zip>17403</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>717-741-9229</phone>
</contact>
<investigator>
<last_name>Dan Sotirescu</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>WellSpan Health-York Cancer Center</name>
<address>
<city>York</city>
<state>Pennsylvania</state>
<zip>17403</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-441-7957</phone>
</contact>
<investigator>
<last_name>Dan Sotirescu</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>WellSpan Health-York Hospital</name>
<address>
<city>York</city>
<state>Pennsylvania</state>
<zip>17403</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-441-7957</phone>
</contact>
<investigator>
<last_name>Dan Sotirescu</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UPMC Memorial</name>
<address>
<city>York</city>
<state>Pennsylvania</state>
<zip>17408</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>717-724-6760</phone>
</contact>
<investigator>
<last_name>Liza C. Villaruz</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Roger Williams Medical Center</name>
<address>
<city>Providence</city>
<state>Rhode Island</state>
<zip>02908</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>401-456-2698</phone>
<email>fdallesandro@chartercare.org</email>
</contact>
<investigator>
<last_name>Ritesh Rathore</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Joseph's/Candler - Bluffton Campus</name>
<address>
<city>Bluffton</city>
<state>South Carolina</state>
<zip>29910</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>912-819-5704</phone>
<email>underberga@sjchs.org</email>
</contact>
<investigator>
<last_name>Mark A. Taylor</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Prisma Health Cancer Institute - Spartanburg</name>
<address>
<city>Boiling Springs</city>
<state>South Carolina</state>
<zip>29316</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>864-241-6251</phone>
</contact>
<investigator>
<last_name>Ki Y. Chung</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Roper Hospital</name>
<address>
<city>Charleston</city>
<state>South Carolina</state>
<zip>29401</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>843-724-2348</phone>
<email>Courtney.Roldan@RoperSaintFrancis.com</email>
</contact>
<investigator>
<last_name>Matthew A. Beldner</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lowcountry Hematology Oncology PA-North Charleston</name>
<address>
<city>Charleston</city>
<state>South Carolina</state>
<zip>29406</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Bon Secours Saint Francis Hospital</name>
<address>
<city>Charleston</city>
<state>South Carolina</state>
<zip>29414</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>843-724-2348</phone>
<email>Courtney.Roldan@RoperSaintFrancis.com</email>
</contact>
<investigator>
<last_name>Matthew A. Beldner</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lowcountry Hematology Oncology PA-West Ashley</name>
<address>
<city>Charleston</city>
<state>South Carolina</state>
<zip>29414</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Medical University of South Carolina</name>
<address>
<city>Charleston</city>
<state>South Carolina</state>
<zip>29425</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>843-792-9321</phone>
<email>hcc-clinical-trials@musc.edu</email>
</contact>
<investigator>
<last_name>Mariam Alexander</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Prisma Health Cancer Institute - Easley</name>
<address>
<city>Easley</city>
<state>South Carolina</state>
<zip>29640</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>864-522-2066</phone>
<email>Kim.Williams3@prismahealth.org</email>
</contact>
<investigator>
<last_name>Ki Y. Chung</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Gibbs Cancer Center-Gaffney</name>
<address>
<city>Gaffney</city>
<state>South Carolina</state>
<zip>29341</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>864-560-6104</phone>
<email>kmertz-rivera@gibbscc.org</email>
</contact>
<investigator>
<last_name>Vikas Dembla</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Francis Hospital</name>
<address>
<city>Greenville</city>
<state>South Carolina</state>
<zip>29601</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>864-603-6213</phone>
<email>melissa_beckman@bshsi.org</email>
</contact>
<investigator>
<last_name>Alex X. Yang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Prisma Health Cancer Institute - Butternut</name>
<address>
<city>Greenville</city>
<state>South Carolina</state>
<zip>29605</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>864-241-6251</phone>
</contact>
<investigator>
<last_name>Ki Y. Chung</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Prisma Health Cancer Institute - Faris</name>
<address>
<city>Greenville</city>
<state>South Carolina</state>
<zip>29605</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>864-241-6251</phone>
</contact>
<investigator>
<last_name>Ki Y. Chung</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Francis Cancer Center</name>
<address>
<city>Greenville</city>
<state>South Carolina</state>
<zip>29607</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>864-603-6213</phone>
<email>melissa_beckman@bshsi.org</email>
</contact>
<investigator>
<last_name>Alex X. Yang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Prisma Health Cancer Institute - Eastside</name>
<address>
<city>Greenville</city>
<state>South Carolina</state>
<zip>29615</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>864-241-6251</phone>
</contact>
<investigator>
<last_name>Ki Y. Chung</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Prisma Health Cancer Institute - Greer</name>
<address>
<city>Greer</city>
<state>South Carolina</state>
<zip>29650</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>864-241-6251</phone>
</contact>
<investigator>
<last_name>Ki Y. Chung</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Gibbs Cancer Center-Pelham</name>
<address>
<city>Greer</city>
<state>South Carolina</state>
<zip>29651</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>864-560-6104</phone>
<email>kmertz-rivera@gibbscc.org</email>
</contact>
<investigator>
<last_name>Vikas Dembla</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>South Carolina Cancer Specialists PC</name>
<address>
<city>Hilton Head Island</city>
<state>South Carolina</state>
<zip>29926-3827</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>912-819-5704</phone>
<email>underberga@sjchs.org</email>
</contact>
<investigator>
<last_name>Mark A. Taylor</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lowcountry Hematology Oncology PA-Mount Pleasant</name>
<address>
<city>Mount Pleasant</city>
<state>South Carolina</state>
<zip>29464</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Prisma Health Cancer Institute - Seneca</name>
<address>
<city>Seneca</city>
<state>South Carolina</state>
<zip>29672</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>864-241-6251</phone>
</contact>
<investigator>
<last_name>Ki Y. Chung</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Spartanburg Medical Center</name>
<address>
<city>Spartanburg</city>
<state>South Carolina</state>
<zip>29303</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>864-560-6104</phone>
<email>kmertz-rivera@gibbscc.org</email>
</contact>
<investigator>
<last_name>Vikas Dembla</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>MGC Hematology Oncology-Union</name>
<address>
<city>Union</city>
<state>South Carolina</state>
<zip>29379</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>864-560-6104</phone>
<email>kmertz-rivera@gibbscc.org</email>
</contact>
<investigator>
<last_name>Vikas Dembla</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Lexington Medical Center</name>
<address>
<city>West Columbia</city>
<state>South Carolina</state>
<zip>29169</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>803-791-2105</phone>
<email>LMCIRB@lexhealth.org</email>
</contact>
<investigator>
<last_name>Steven A. Madden</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sanford Cancer Center Oncology Clinic</name>
<address>
<city>Sioux Falls</city>
<state>South Dakota</state>
<zip>57104</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>605-312-3320</phone>
<email>OncologyClinicTrialsSF@sanfordhealth.org</email>
</contact>
<investigator>
<last_name>Daniel Almquist</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sanford USD Medical Center - Sioux Falls</name>
<address>
<city>Sioux Falls</city>
<state>South Dakota</state>
<zip>57117-5134</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>605-312-3320</phone>
<email>OncologyClinicalTrialsSF@SanfordHealth.org</email>
</contact>
<investigator>
<last_name>Daniel Almquist</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University Cancer Specialists - Alcoa</name>
<address>
<city>Alcoa</city>
<state>Tennessee</state>
<zip>37701</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>865-305-5120</phone>
<email>bherbert@utmck.edu</email>
</contact>
<investigator>
<last_name>Neil E. Faulkner</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Bristol Regional Medical Center</name>
<address>
<city>Bristol</city>
<state>Tennessee</state>
<zip>37620</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Ballad Health Cancer Care - Kingsport</name>
<address>
<city>Kingsport</city>
<state>Tennessee</state>
<zip>37660</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>423-578-8538</phone>
<email>Justin.reynolds@balladhealth.org</email>
</contact>
<investigator>
<last_name>Asheesh Shipstone</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Wellmont Holston Valley Hospital and Medical Center</name>
<address>
<city>Kingsport</city>
<state>Tennessee</state>
<zip>37660</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>University of Tennessee - Knoxville</name>
<address>
<city>Knoxville</city>
<state>Tennessee</state>
<zip>37920</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>865-544-9773</phone>
</contact>
<investigator>
<last_name>Neil E. Faulkner</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Baptist Memorial Hospital and Cancer Center-Memphis</name>
<address>
<city>Memphis</city>
<state>Tennessee</state>
<zip>38120</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>901-226-1366</phone>
<email>BCCclintrials@bmhcc.org</email>
</contact>
<investigator>
<last_name>Philip E. Lammers</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hendrick Medical Center</name>
<address>
<city>Abilene</city>
<state>Texas</state>
<zip>79601</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>325-670-6340</phone>
</contact>
<investigator>
<last_name>Mustapha A. Khalife</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>The Don and Sybil Harrington Cancer Center</name>
<address>
<city>Amarillo</city>
<state>Texas</state>
<zip>79106</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Dell Seton Medical Center at The University of Texas</name>
<address>
<city>Austin</city>
<state>Texas</state>
<zip>78701</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Houston Methodist San Jacinto Hospital</name>
<address>
<city>Baytown</city>
<state>Texas</state>
<zip>77521</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Jun Zhang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Joseph Regional Cancer Center</name>
<address>
<city>Bryan</city>
<state>Texas</state>
<zip>77802</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Parkland Memorial Hospital</name>
<address>
<city>Dallas</city>
<state>Texas</state>
<zip>75235</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>214-590-5582</phone>
<email>canceranswerline@UTSouthwestern.edu</email>
</contact>
<investigator>
<last_name>David E. Gerber</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UT Southwestern Simmons Cancer Center - RedBird</name>
<address>
<city>Dallas</city>
<state>Texas</state>
<zip>75237</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>214-648-7097</phone>
<email>canceranswerline@utsouthwestern.edu</email>
</contact>
<investigator>
<last_name>David E. Gerber</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UT Southwestern/Simmons Cancer Center-Dallas</name>
<address>
<city>Dallas</city>
<state>Texas</state>
<zip>75390</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>214-648-7097</phone>
<email>canceranswerline@UTSouthwestern.edu</email>
</contact>
<investigator>
<last_name>David E. Gerber</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UT Southwestern/Simmons Cancer Center-Fort Worth</name>
<address>
<city>Fort Worth</city>
<state>Texas</state>
<zip>76104</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>214-648-7097</phone>
<email>canceranswerline@UTSouthwestern.edu</email>
</contact>
<investigator>
<last_name>David E. Gerber</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center</name>
<address>
<city>Houston</city>
<state>Texas</state>
<zip>77030</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Ben Taub General Hospital</name>
<address>
<city>Houston</city>
<state>Texas</state>
<zip>77030</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Houston Methodist Hospital</name>
<address>
<city>Houston</city>
<state>Texas</state>
<zip>77030</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>713-790-2700</phone>
</contact>
<investigator>
<last_name>Jun Zhang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Methodist Willowbrook Hospital</name>
<address>
<city>Houston</city>
<state>Texas</state>
<zip>77070</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Houston Methodist West Hospital</name>
<address>
<city>Houston</city>
<state>Texas</state>
<zip>77094</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>832-522-2873</phone>
</contact>
<investigator>
<last_name>Jun Zhang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Houston Methodist Saint John Hospital</name>
<address>
<city>Nassau Bay</city>
<state>Texas</state>
<zip>77058</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>773-702-9171</phone>
<email>protocols@AllianceNCTN.org</email>
</contact>
<investigator>
<last_name>Jun Zhang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UT Southwestern Clinical Center at Richardson/Plano</name>
<address>
<city>Richardson</city>
<state>Texas</state>
<zip>75080</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>972-669-7044</phone>
<email>Suzanne.cole@utsouthwestern.edu</email>
</contact>
<investigator>
<last_name>David E. Gerber</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Houston Methodist Sugar Land Hospital</name>
<address>
<city>Sugar Land</city>
<state>Texas</state>
<zip>77479</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Houston Methodist The Woodlands Hospital</name>
<address>
<city>The Woodlands</city>
<state>Texas</state>
<zip>77385</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>713-790-2700</phone>
<email>hmthewoodlands@houstonmethodist.org</email>
</contact>
<investigator>
<last_name>Jun Zhang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Wellmont Medical Associates-Bristol</name>
<address>
<city>Bristol</city>
<state>Virginia</state>
<zip>24201</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>423-578-8538</phone>
<email>justin.reynolds@wellmont.org</email>
</contact>
<investigator>
<last_name>Asheesh Shipstone</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Kaiser Permanente-Burke Medical Center</name>
<address>
<city>Burke</city>
<state>Virginia</state>
<zip>22015</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>Diane.Fisher@nsmtp.kp.org</email>
</contact>
<investigator>
<last_name>Leon C. Hwang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University of Virginia Cancer Center</name>
<address>
<city>Charlottesville</city>
<state>Virginia</state>
<zip>22908</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>434-243-6303</phone>
<email>uvacancertrials@hscmail.mcc.virginia.edu</email>
</contact>
<investigator>
<last_name>Richard D. Hall</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Augusta Health Center for Cancer and Blood Disorders</name>
<address>
<city>Fishersville</city>
<state>Virginia</state>
<zip>22939</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>540-332-5960</phone>
</contact>
<investigator>
<last_name>Robert M. Kyler</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Centra Lynchburg Hematology-Oncology Clinic Inc</name>
<address>
<city>Lynchburg</city>
<state>Virginia</state>
<zip>24501</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>434-200-5925</phone>
<email>Kevin.Patel@centrahealth.com</email>
</contact>
<investigator>
<last_name>Renato G. Martins</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Sovah Health Martinsville</name>
<address>
<city>Martinsville</city>
<state>Virginia</state>
<zip>24115</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kaiser Permanente Tysons Corner Medical Center</name>
<address>
<city>McLean</city>
<state>Virginia</state>
<zip>22102</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>240-632-4284</phone>
</contact>
<investigator>
<last_name>Leon C. Hwang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Bon Secours Memorial Regional Medical Center</name>
<address>
<city>Mechanicsville</city>
<state>Virginia</state>
<zip>23116</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Bon Secours Westchester Emergency Center</name>
<address>
<city>Midlothian</city>
<state>Virginia</state>
<zip>23113</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Bon Secours Saint Francis Medical Center</name>
<address>
<city>Midlothian</city>
<state>Virginia</state>
<zip>23114</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Bon Secours DePaul Medical Center</name>
<address>
<city>Norfolk</city>
<state>Virginia</state>
<zip>23505</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Southwest VA Regional Cancer Center</name>
<address>
<city>Norton</city>
<state>Virginia</state>
<zip>24273</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>423-578-8538</phone>
<email>justin.reynolds@wellmont.org</email>
</contact>
<investigator>
<last_name>Asheesh Shipstone</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Bon Secours Maryview Medical Center</name>
<address>
<city>Portsmouth</city>
<state>Virginia</state>
<zip>23707</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Bon Secours Saint Mary's Hospital</name>
<address>
<city>Richmond</city>
<state>Virginia</state>
<zip>23226</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Virginia Cancer Institute</name>
<address>
<city>Richmond</city>
<state>Virginia</state>
<zip>23229</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>804-287-3000</phone>
<email>smoore@vacancer.com</email>
</contact>
<investigator>
<last_name>Renato G. Martins</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Bon Secours Cancer Institute at Reynolds Crossing</name>
<address>
<city>Richmond</city>
<state>Virginia</state>
<zip>23230</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>VCU Massey Cancer Center at Stony Point</name>
<address>
<city>Richmond</city>
<state>Virginia</state>
<zip>23235</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>ctoclinops@vcu.edu</email>
</contact>
<investigator>
<last_name>Renato G. Martins</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Virginia Commonwealth University/Massey Cancer Center</name>
<address>
<city>Richmond</city>
<state>Virginia</state>
<zip>23298</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>VCU Community Memorial Health Center</name>
<address>
<city>South Hill</city>
<state>Virginia</state>
<zip>23970</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>nemer.elmouallem@vcuhealth.org</email>
</contact>
<investigator>
<last_name>Renato G. Martins</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Bon Secours Health Center at Harbour View</name>
<address>
<city>Suffolk</city>
<state>Virginia</state>
<zip>23435</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Providence Regional Cancer System-Aberdeen</name>
<address>
<city>Aberdeen</city>
<state>Washington</state>
<zip>98520</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>MultiCare Auburn Medical Center</name>
<address>
<city>Auburn</city>
<state>Washington</state>
<zip>98001</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>253-887-9333</phone>
<email>research@multicare.org</email>
</contact>
<investigator>
<last_name>Jennifer Slim</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Overlake Medical Center</name>
<address>
<city>Bellevue</city>
<state>Washington</state>
<zip>98004</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>PeaceHealth Saint Joseph Medical Center</name>
<address>
<city>Bellingham</city>
<state>Washington</state>
<zip>98225</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Harrison HealthPartners Hematology and Oncology-Bremerton</name>
<address>
<city>Bremerton</city>
<state>Washington</state>
<zip>98310</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>308-398-6518</phone>
<email>clinicaltrials@sfmc-gi.org</email>
</contact>
<investigator>
<last_name>Richard L. Deming</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Harrison Medical Center</name>
<address>
<city>Bremerton</city>
<state>Washington</state>
<zip>98310</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Highline Medical Center-Main Campus</name>
<address>
<city>Burien</city>
<state>Washington</state>
<zip>98166</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Providence Regional Cancer System-Centralia</name>
<address>
<city>Centralia</city>
<state>Washington</state>
<zip>98531</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Swedish Cancer Institute-Edmonds</name>
<address>
<city>Edmonds</city>
<state>Washington</state>
<zip>98026</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Elizabeth Hospital</name>
<address>
<city>Enumclaw</city>
<state>Washington</state>
<zip>98022</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Providence Regional Cancer Partnership</name>
<address>
<city>Everett</city>
<state>Washington</state>
<zip>98201</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Francis Hospital</name>
<address>
<city>Federal Way</city>
<state>Washington</state>
<zip>98003</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>MultiCare Gig Harbor Medical Park</name>
<address>
<city>Gig Harbor</city>
<state>Washington</state>
<zip>98335</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>253-403-2394</phone>
<email>research@multicare.org</email>
</contact>
<investigator>
<last_name>Jennifer Slim</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Swedish Cancer Institute-Issaquah</name>
<address>
<city>Issaquah</city>
<state>Washington</state>
<zip>98029</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Kadlec Clinic Hematology and Oncology</name>
<address>
<city>Kennewick</city>
<state>Washington</state>
<zip>99336</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>509-783-4637</phone>
<email>research@kadlecmed.org</email>
</contact>
<investigator>
<last_name>Alison K. Conlin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Providence Regional Cancer System-Lacey</name>
<address>
<city>Lacey</city>
<state>Washington</state>
<zip>98503</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Saint Clare Hospital</name>
<address>
<city>Lakewood</city>
<state>Washington</state>
<zip>98499</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>PeaceHealth Saint John Medical Center</name>
<address>
<city>Longview</city>
<state>Washington</state>
<zip>98632</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>360-514-2016</phone>
<email>kmakin-bond@peacehealth.org</email>
</contact>
<investigator>
<last_name>Alison K. Conlin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Jefferson Healthcare</name>
<address>
<city>Port Townsend</city>
<state>Washington</state>
<zip>98368</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>360-344-3091</phone>
</contact>
<investigator>
<last_name>Nicholas DiBella</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Harrison HealthPartners Hematology and Oncology-Poulsbo</name>
<address>
<city>Poulsbo</city>
<state>Washington</state>
<zip>98370</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>MultiCare Good Samaritan Hospital</name>
<address>
<city>Puyallup</city>
<state>Washington</state>
<zip>98372</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-351-7955</phone>
<email>research@multicare.org</email>
</contact>
<investigator>
<last_name>Jennifer Slim</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Valley Medical Center</name>
<address>
<city>Renton</city>
<state>Washington</state>
<zip>98055</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>425-228-3440</phone>
<email>research@valleymed.org</email>
</contact>
<investigator>
<last_name>John A. Ellerton</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Pacific Gynecology Specialists</name>
<address>
<city>Seattle</city>
<state>Washington</state>
<zip>98104</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Swedish Medical Center-Ballard Campus</name>
<address>
<city>Seattle</city>
<state>Washington</state>
<zip>98107</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Swedish Medical Center-Cherry Hill</name>
<address>
<city>Seattle</city>
<state>Washington</state>
<zip>98122-5711</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Swedish Medical Center-First Hill</name>
<address>
<city>Seattle</city>
<state>Washington</state>
<zip>98122</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>PeaceHealth United General Medical Center</name>
<address>
<city>Sedro-Woolley</city>
<state>Washington</state>
<zip>98284</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Providence Regional Cancer System-Shelton</name>
<address>
<city>Shelton</city>
<state>Washington</state>
<zip>98584</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>MultiCare Deaconess Cancer and Blood Specialty Center - Downtown</name>
<address>
<city>Spokane</city>
<state>Washington</state>
<zip>99204</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>253-403-7249</phone>
<email>research@multicare.org</email>
</contact>
<investigator>
<last_name>Jennifer Slim</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>MultiCare Deaconess Cancer and Blood Specialty Center - North</name>
<address>
<city>Spokane</city>
<state>Washington</state>
<zip>99218</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>253-402-7249</phone>
<email>research@multicare.org</email>
</contact>
<investigator>
<last_name>Jennifer Slim</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Franciscan Research Center-Northwest Medical Plaza</name>
<address>
<city>Tacoma</city>
<state>Washington</state>
<zip>98405</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>MultiCare Tacoma General Hospital</name>
<address>
<city>Tacoma</city>
<state>Washington</state>
<zip>98405</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>253-403-3229</phone>
<email>research@multicare.org</email>
</contact>
<investigator>
<last_name>Jennifer Slim</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Northwest Medical Specialties PLLC</name>
<address>
<city>Tacoma</city>
<state>Washington</state>
<zip>98405</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>PeaceHealth Southwest Medical Center</name>
<address>
<city>Vancouver</city>
<state>Washington</state>
<zip>98664</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>360-514-3940</phone>
<email>kmakin-bond@peacehealth.org</email>
</contact>
<investigator>
<last_name>Alison K. Conlin</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Providence Saint Mary Regional Cancer Center</name>
<address>
<city>Walla Walla</city>
<state>Washington</state>
<zip>99362</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>North Star Lodge Cancer Center at Yakima Valley Memorial Hospital</name>
<address>
<city>Yakima</city>
<state>Washington</state>
<zip>98902</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Providence Regional Cancer System-Yelm</name>
<address>
<city>Yelm</city>
<state>Washington</state>
<zip>98597</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>United Hospital Center</name>
<address>
<city>Bridgeport</city>
<state>West Virginia</state>
<zip>26330</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>West Virginia University Charleston Division</name>
<address>
<city>Charleston</city>
<state>West Virginia</state>
<zip>25304</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>304-388-9944</phone>
</contact>
<investigator>
<last_name>Ahmed A. Khalid</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Edwards Comprehensive Cancer Center</name>
<address>
<city>Huntington</city>
<state>West Virginia</state>
<zip>25701</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>304-399-6566</phone>
<email>Christina.Cole@chhi.org</email>
</contact>
<investigator>
<last_name>Maria R. Tria Tirona</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>WVUH-Berkely Medical Center</name>
<address>
<city>Martinsburg</city>
<state>West Virginia</state>
<zip>25401</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>West Virginia University Healthcare</name>
<address>
<city>Morgantown</city>
<state>West Virginia</state>
<zip>26506</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>304-293-7374</phone>
<email>cancertrialsinfo@hsc.wvu.edu</email>
</contact>
<investigator>
<last_name>Mohammed Almubarak</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Camden Clark Medical Center</name>
<address>
<city>Parkersburg</city>
<state>West Virginia</state>
<zip>26101</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Langlade Hospital and Cancer Center</name>
<address>
<city>Antigo</city>
<state>Wisconsin</state>
<zip>54409</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>715-623-9869</phone>
<email>Juli.Alford@aspirus.org</email>
</contact>
<investigator>
<last_name>Andrew J. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>ThedaCare Regional Cancer Center</name>
<address>
<city>Appleton</city>
<state>Wisconsin</state>
<zip>54911</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>920-364-3604</phone>
<email>ResearchDept@thedacare.org</email>
</contact>
<investigator>
<last_name>Matthias Weiss</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ascension Saint Elizabeth Hospital</name>
<address>
<city>Appleton</city>
<state>Wisconsin</state>
<zip>54915</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-635-6420</phone>
<email>AWRI.inquiry@ascension.org</email>
</contact>
<investigator>
<last_name>Jonathan S. Treisman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Duluth Clinic Ashland</name>
<address>
<city>Ashland</city>
<state>Wisconsin</state>
<zip>54806</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>218-786-3308</phone>
<email>CancerTrials@EssentiaHealth.org</email>
</contact>
<investigator>
<last_name>Bret E. Friday</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Northwest Wisconsin Cancer Center</name>
<address>
<city>Ashland</city>
<state>Wisconsin</state>
<zip>54806</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Ascension Southeast Wisconsin Hospital - Elmbrook Campus</name>
<address>
<city>Brookfield</city>
<state>Wisconsin</state>
<zip>53045</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>AWRI.Inquiry@Ascension.org</email>
</contact>
<investigator>
<last_name>Jonathan S. Treisman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aurora Cancer Care-Southern Lakes VLCC</name>
<address>
<city>Burlington</city>
<state>Wisconsin</state>
<zip>53105</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ascension Calumet Hospital</name>
<address>
<city>Chilton</city>
<state>Wisconsin</state>
<zip>53014</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-635-6420</phone>
<email>AWRI.inquiry@ascension.org</email>
</contact>
<investigator>
<last_name>Jonathan S. Treisman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Marshfield Clinic-Chippewa Center</name>
<address>
<city>Chippewa Falls</city>
<state>Wisconsin</state>
<zip>54729</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Aurora Saint Luke's South Shore</name>
<address>
<city>Cudahy</city>
<state>Wisconsin</state>
<zip>53110</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>HSHS Sacred Heart Hospital</name>
<address>
<city>Eau Claire</city>
<state>Wisconsin</state>
<zip>54701</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>920-433-8889</phone>
<email>ewd_research_admin@hshs.org</email>
</contact>
<investigator>
<last_name>Anthony J. Jaslowski</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Marshfield Medical Center-EC Cancer Center</name>
<address>
<city>Eau Claire</city>
<state>Wisconsin</state>
<zip>54701</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-782-8581</phone>
<email>oncology.clinical.trials@marshfieldresearch.org</email>
</contact>
<investigator>
<last_name>Adedayo A. Onitilo</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Agnes Hospital/Agnesian Cancer Center</name>
<address>
<city>Fond Du Lac</city>
<state>Wisconsin</state>
<zip>54935</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Ascension Saint Francis - Reiman Cancer Center</name>
<address>
<city>Franklin</city>
<state>Wisconsin</state>
<zip>53132</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>AWRI.Inquiry@Ascension.org</email>
</contact>
<investigator>
<last_name>Jonathan S. Treisman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aurora Health Care Germantown Health Center</name>
<address>
<city>Germantown</city>
<state>Wisconsin</state>
<zip>53022</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aurora Cancer Care-Grafton</name>
<address>
<city>Grafton</city>
<state>Wisconsin</state>
<zip>53024</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Bellin Memorial Hospital</name>
<address>
<city>Green Bay</city>
<state>Wisconsin</state>
<zip>54301</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>920-435-8326</phone>
</contact>
<investigator>
<last_name>Kevin L. Mortara</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Vincent Hospital Cancer Center Green Bay</name>
<address>
<city>Green Bay</city>
<state>Wisconsin</state>
<zip>54301</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>920-433-8889</phone>
<email>ewd_research_admin@hshs.org</email>
</contact>
<investigator>
<last_name>Anthony J. Jaslowski</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Vincent Hospital Cancer Center at Saint Mary's</name>
<address>
<city>Green Bay</city>
<state>Wisconsin</state>
<zip>54303</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>920-433-8889</phone>
<email>ewd_research_admin@hshs.org</email>
</contact>
<investigator>
<last_name>Anthony J. Jaslowski</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aurora BayCare Medical Center</name>
<address>
<city>Green Bay</city>
<state>Wisconsin</state>
<zip>54311</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aurora Cancer Care-Kenosha South</name>
<address>
<city>Kenosha</city>
<state>Wisconsin</state>
<zip>53142</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Gundersen Lutheran Medical Center</name>
<address>
<city>La Crosse</city>
<state>Wisconsin</state>
<zip>54601</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>608-775-2385</phone>
<email>cancerctr@gundersenhealth.org</email>
</contact>
<investigator>
<last_name>Michael O. Ojelabi</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Marshfield Clinic - Ladysmith Center</name>
<address>
<city>Ladysmith</city>
<state>Wisconsin</state>
<zip>54848</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>William S Middleton VA Medical Center</name>
<address>
<city>Madison</city>
<state>Wisconsin</state>
<zip>53705</zip>
<country>United States</country>
</address>
</facility>
<status>Not yet recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>608-256-1901</phone>
<phone_ext>17007</phone_ext>
</contact>
<investigator>
<last_name>Justine Yang-Bruce</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>University of Wisconsin Carbone Cancer Center</name>
<address>
<city>Madison</city>
<state>Wisconsin</state>
<zip>53792</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-622-8922</phone>
</contact>
<investigator>
<last_name>Justine Yang-Bruce</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aurora Bay Area Medical Group-Marinette</name>
<address>
<city>Marinette</city>
<state>Wisconsin</state>
<zip>54143</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Marshfield Medical Center-Marshfield</name>
<address>
<city>Marshfield</city>
<state>Wisconsin</state>
<zip>54449</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-782-8581</phone>
<email>oncology.clinical.trials@marshfieldresearch.org</email>
</contact>
<investigator>
<last_name>Adedayo A. Onitilo</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aspirus Medford Hospital</name>
<address>
<city>Medford</city>
<state>Wisconsin</state>
<zip>54451</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>715-847-2353</phone>
<email>Beth.Knetter@aspirus.org</email>
</contact>
<investigator>
<last_name>Andrew J. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ascension Columbia Saint Mary's Hospital Ozaukee</name>
<address>
<city>Mequon</city>
<state>Wisconsin</state>
<zip>53097</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>AWRI.Inquiry@Ascension.org</email>
</contact>
<investigator>
<last_name>Jonathan S. Treisman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aurora Cancer Care-Milwaukee</name>
<address>
<city>Milwaukee</city>
<state>Wisconsin</state>
<zip>53209</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ascension Columbia Saint Mary's Hospital - Milwaukee</name>
<address>
<city>Milwaukee</city>
<state>Wisconsin</state>
<zip>53211</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>AWRI.Inquiry@Ascension.org</email>
</contact>
<investigator>
<last_name>Jonathan S. Treisman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aurora Saint Luke's Medical Center</name>
<address>
<city>Milwaukee</city>
<state>Wisconsin</state>
<zip>53215</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Medical College of Wisconsin</name>
<address>
<city>Milwaukee</city>
<state>Wisconsin</state>
<zip>53226</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-805-3666</phone>
</contact>
<investigator>
<last_name>Jonathan R. Thompson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aurora Sinai Medical Center</name>
<address>
<city>Milwaukee</city>
<state>Wisconsin</state>
<zip>53233</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Marshfield Clinic-Minocqua Center</name>
<address>
<city>Minocqua</city>
<state>Wisconsin</state>
<zip>54548</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-782-8581</phone>
<email>oncology.clinical.trials@marshfieldresearch.org</email>
</contact>
<investigator>
<last_name>Adedayo A. Onitilo</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>ProHealth D N Greenwald Center</name>
<address>
<city>Mukwonago</city>
<state>Wisconsin</state>
<zip>53149</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>research.institute@phci.org</email>
</contact>
<investigator>
<last_name>Timothy R. Wassenaar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>ThedaCare Regional Medical Center - Neenah</name>
<address>
<city>Neenah</city>
<state>Wisconsin</state>
<zip>54956</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>920-364-3605</phone>
<email>ResearchDept@thedacare.org</email>
</contact>
<investigator>
<last_name>Matthias Weiss</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Cancer Center of Western Wisconsin</name>
<address>
<city>New Richmond</city>
<state>Wisconsin</state>
<zip>54017</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>952-993-1517</phone>
<email>mmcorc@healthpartners.com</email>
</contact>
<investigator>
<last_name>Daniel M. Anderson</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>ProHealth Oconomowoc Memorial Hospital</name>
<address>
<city>Oconomowoc</city>
<state>Wisconsin</state>
<zip>53066</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>262-928-7878</phone>
</contact>
<investigator>
<last_name>Timothy R. Wassenaar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Vincent Hospital Cancer Center at Oconto Falls</name>
<address>
<city>Oconto Falls</city>
<state>Wisconsin</state>
<zip>54154</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>920-433-8889</phone>
<email>ewd_research_admin@hshs.org</email>
</contact>
<investigator>
<last_name>Anthony J. Jaslowski</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ascension Mercy Hospital</name>
<address>
<city>Oshkosh</city>
<state>Wisconsin</state>
<zip>54904</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>AWRI.inquiry@ascension.org</email>
</contact>
<investigator>
<last_name>Jonathan S. Treisman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Vince Lombardi Cancer Clinic - Oshkosh</name>
<address>
<city>Oshkosh</city>
<state>Wisconsin</state>
<zip>54904</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ascension All Saints Hospital</name>
<address>
<city>Racine</city>
<state>Wisconsin</state>
<zip>53405</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>AWRI.Inquiry@Ascension.org</email>
</contact>
<investigator>
<last_name>Jonathan S. Treisman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aurora Cancer Care-Racine</name>
<address>
<city>Racine</city>
<state>Wisconsin</state>
<zip>53406</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ascension Saint Mary's Hospital</name>
<address>
<city>Rhinelander</city>
<state>Wisconsin</state>
<zip>54501</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Marshfield Medical Center-Rice Lake</name>
<address>
<city>Rice Lake</city>
<state>Wisconsin</state>
<zip>54868</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-782-8581</phone>
<email>oncology.clinical.trials@marshfieldresearch.org</email>
</contact>
<investigator>
<last_name>Adedayo A. Onitilo</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Vince Lombardi Cancer Clinic-Sheboygan</name>
<address>
<city>Sheboygan</city>
<state>Wisconsin</state>
<zip>53081</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Ascension Saint Michael's Hospital</name>
<address>
<city>Stevens Point</city>
<state>Wisconsin</state>
<zip>54481</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Marshfield Medical Center-River Region at Stevens Point</name>
<address>
<city>Stevens Point</city>
<state>Wisconsin</state>
<zip>54482</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-782-8581</phone>
<email>oncology.clinical.trials@marshfieldresearch.org</email>
</contact>
<investigator>
<last_name>Adedayo A. Onitilo</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Vincent Hospital Cancer Center at Sturgeon Bay</name>
<address>
<city>Sturgeon Bay</city>
<state>Wisconsin</state>
<zip>54235-1495</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>920-433-8889</phone>
<email>ewd_research_admin@hshs.org</email>
</contact>
<investigator>
<last_name>Anthony J. Jaslowski</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aurora Medical Center in Summit</name>
<address>
<city>Summit</city>
<state>Wisconsin</state>
<zip>53066</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Vince Lombardi Cancer Clinic-Two Rivers</name>
<address>
<city>Two Rivers</city>
<state>Wisconsin</state>
<zip>54241</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>ProHealth Waukesha Memorial Hospital</name>
<address>
<city>Waukesha</city>
<state>Wisconsin</state>
<zip>53188</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>262-928-7632</phone>
</contact>
<investigator>
<last_name>Timothy R. Wassenaar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>UW Cancer Center at ProHealth Care</name>
<address>
<city>Waukesha</city>
<state>Wisconsin</state>
<zip>53188</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>262-928-5539</phone>
<email>Chanda.miller@phci.org</email>
</contact>
<investigator>
<last_name>Timothy R. Wassenaar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aspirus Regional Cancer Center</name>
<address>
<city>Wausau</city>
<state>Wisconsin</state>
<zip>54401</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>877-405-6866</phone>
</contact>
<investigator>
<last_name>Andrew J. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Marshfield Clinic-Wausau Center</name>
<address>
<city>Wausau</city>
<state>Wisconsin</state>
<zip>54401</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Ascension Medical Group Southeast Wisconsin - Mayfair Road</name>
<address>
<city>Wauwatosa</city>
<state>Wisconsin</state>
<zip>53226</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<email>AWRI.Inquiry@Ascension.org</email>
</contact>
<investigator>
<last_name>Jonathan S. Treisman</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aurora Cancer Care-Milwaukee West</name>
<address>
<city>Wauwatosa</city>
<state>Wisconsin</state>
<zip>53226</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aurora West Allis Medical Center</name>
<address>
<city>West Allis</city>
<state>Wisconsin</state>
<zip>53227</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>414-302-2304</phone>
<email>ncorp@aurora.org</email>
</contact>
<investigator>
<last_name>Rubina Qamar</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Marshfield Medical Center - Weston</name>
<address>
<city>Weston</city>
<state>Wisconsin</state>
<zip>54476</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>800-782-8581</phone>
<email>oncology.clinical.trials@marshfieldresearch.org</email>
</contact>
<investigator>
<last_name>Adedayo A. Onitilo</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Aspirus Cancer Care - Wisconsin Rapids</name>
<address>
<city>Wisconsin Rapids</city>
<state>Wisconsin</state>
<zip>54494</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Site Public Contact</last_name>
<phone>715-422-7718</phone>
</contact>
<investigator>
<last_name>Andrew J. Huang</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Marshfield Clinic - Wisconsin Rapids Center</name>
<address>
<city>Wisconsin Rapids</city>
<state>Wisconsin</state>
<zip>54494</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Cheyenne Regional Medical Center-West</name>
<address>
<city>Cheyenne</city>
<state>Wyoming</state>
<zip>82001</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Billings Clinic-Cody</name>
<address>
<city>Cody</city>
<state>Wyoming</state>
<zip>82414</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>Welch Cancer Center</name>
<address>
<city>Sheridan</city>
<state>Wyoming</state>
<zip>82801</zip>
<country>United States</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location>
<facility>
<name>FHP Health Center-Guam</name>
<address>
<city>Tamuning</city>
<zip>96913</zip>
<country>Guam</country>
</address>
</facility>
<status>Suspended</status>
</location>
<location_countries>
<country>Guam</country>
<country>United States</country>
</location_countries>
<verification_date>April 2023</verification_date>
<study_first_submitted>February 12, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>September 13, 2023</last_update_submitted>
<last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">September 14, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Carcinoma</mesh_term>
<mesh_term>Lung Neoplasms</mesh_term>
<mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
<mesh_term>Carcinoma, Squamous Cell</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Paclitaxel</mesh_term>
<mesh_term>Cisplatin</mesh_term>
<mesh_term>Carboplatin</mesh_term>
<mesh_term>Gemcitabine</mesh_term>
<mesh_term>Pembrolizumab</mesh_term>
<mesh_term>Pemetrexed</mesh_term>
<mesh_term>Albumin-Bound Paclitaxel</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>Yes</sharing_ipd>
<ipd_description>NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.</ipd_description>
<ipd_url>https://grants.nih.gov/policy/sharing.htm</ipd_url>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This phase III ALCHEMIST trial tests the addition of pembrolizumab to usual chemotherapy for
the treatment of stage IIA, IIB IIIA or IIIB non-small cell lung cancer that has been removed
by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the
body's immune system attack the cancer, and may interfere with the ability of tumor cells to
grow and spread. Chemotherapy drugs, such as cisplatin, pemetrexed, carboplatin, gemcitabine
hydrochloride, and paclitaxel, work in different ways to stop the growth of tumor cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Giving pembrolizumab with usual chemotherapy may help increase survival times in
patients with stage IIA, IIB IIIA or IIIB non-small cell lung cancer.
PRIMARY OBJECTIVE:
I. To compare the disease free survival (DFS) between Arm B versus (vs) Arm C in patients
with stage IIA-IIIB (T3-4N2) non-small cell lung cancer.
SECONDARY OBJECTIVES:
I. To compare the overall survival (OS) between the two treatment arms in patients with stage
IIA-IIIB (T3-4N2) non-small cell lung cancer.
II. To compare the adverse event rates and drug discontinuation rates due to adverse events
in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer.
III. To compare the adverse event (AE) rates for Arms B and C with A (prior to Update #7) and
estimate the DFS and OS in Arm A.
IV. To compare the DFS and OS in patients with stage IIA-IIIB (T3-4N2) non-small cell lung
cancer that receive at least 2 cycles of initial adjuvant chemotherapy.
QUALITY OF LIFE OBJECTIVES:
I. To compare patient-reported quality of life (QOL) one year after randomization as assessed
by the European Organization for the Research and Treatment of Cancer Quality of Life
Questionnaire (EORTC QLQ)-Core (C)30 between patients randomized to receive adjuvant
chemotherapy followed by pembrolizumab (Arm B), and those randomized to receive adjuvant
chemotherapy + pembrolizumab concomitantly (Arm C).
II. To compare patient-reported QOL at completion of chemotherapy as assessed by the EORTC
QLQ-C30 between patients randomized to receive adjuvant chemotherapy followed by
pembrolizumab (Arm B) and those randomized to receive adjuvant chemotherapy + pembrolizumab
concomitantly (Arm C).
III. To present longitudinal trajectories by arm of patient-reported dyspnea and coughing as
assessed by the EORTC QLQ-Lung Cancer (LC13).
CORRELATIVE SCIENCE OBJECTIVES:
I. To compare the DFS and OS in the PD-L1 subgroup of patients with PD-L1 expression status
(>= 1% vs < 1%).
II. To compare the DFS and OS by tumor mutational burden status (high vs. low) in patients
with stage IIA-IIIB (T3-4N2) non-small cell lung cancer.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A (CLOSED AS OF UPDATE #7):
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating
physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease
progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then undergo observation.
ARM B:
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating
physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease
progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab intravenously (IV) over 25-40
minutes on day 1. Treatment repeats every 21 days for 17 cycles or every 6 weeks for 16
cycles (patients enrolled after 10/14/2020) in the absence of disease progression or
unacceptable toxicity.
ARM C:
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating
physician's choice and pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every
21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1.
Treatment repeats every 21 days for 13 cycles or every 6 weeks for 12 cycles (patients
enrolled after 10/14/2020) in the absence of disease progression or unacceptable toxicity.
*ACCEPTABLE REGIMENS: DOUBLET I: Patients receive cisplatin IV over 1-2 hours and pemetrexed
IV over 10 minutes on day 1 of each cycle.
DOUBLET II: Patients receive carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes
on day 1 of each cycle.
DOUBLET III: Patients receive cisplatin IV over 1-2 hours on day 1 of each cycle and
gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 of each cycle.
DOUBLET IV: Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on
day 1 of each cycle.
After completion of study treatment, patients are followed up at 6 weeks, then every 3 months
for 2 years from randomization, every 6 months for years 2-4, and then annually for up to 10
years from randomization.
Inclusion Criteria:
- Previously registered to A151216 (NCT02194738)
- Central and/or local testing of EGFR with no EGFR exon 19 deletion or EGFR L858 R
mutation (applicable to non-squamous patients only)
- Central and/or local testing of ALK with no ALK rearrangement (failed testing is
considered negative) (applicable to non-squamous patients only)
- Central and/or local testing of PD-L1 immunohistochemistry (IHC) using one of the
following assays: DAKO 22C3, DAKO 28-8, EIL3N or SP263
- Note: Local testing results of EGFR and ALK by a local Clinical Laboratory
Improvement Act (CLIA) certified laboratory is acceptable. The report must
indicate the result as well as the CLIA number of the laboratory that performed
the assay. Local result of PD-L1 by DAKO 22C3, Dako 28-8, EIL3N or SP263 are
acceptable for enrollment on A081801. Patients with local results for EGFR, ALK
and PD-L1 still need to be registered to A151216 and follow all the submissions
requirements but do NOT need to wait for the results to proceed to A081801
registration
- Completely resected stage IIA, IIB IIIA or IIIB (T3-4N2) non-small cell lung cancer
(NSCLC) (squamous or non-squamous) with negative margins (complete R0 resection).
Patients will be staged according to the 8th edition of the American Joint Committee
on Cancer (AJCC) Staging Manual, 2017
- Note: Patients with pathologic N2 disease, completely resected, are eligible.
However, patients known to have N2 disease prior to surgery are not eligible;
guidelines do not recommend up-front surgery for this population
- Complete recovery from surgery. Registration to A081801 must be 30-77 days following
surgery
- No prior neoadjuvant or adjuvant therapy for current lung cancer diagnosis
- No prior allogeneic tissue/solid organ transplant
- No current pneumonitis or history of (non-infectious) pneumonitis that required
steroids
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1
- No active auto-immune disease that has required systemic treatment within the last 2
years (e.g., disease-modifying agents, corticosteroids, or immunosuppressive drugs).
Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid release
therapy for adrenal or pituitary insufficiency) is not considered a form of systemic
treatment
- Not pregnant and not nursing, because this study involves an agent that has known
genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing
potential only, a negative pregnancy test done =< 7 days prior to registration is
required
- No patients with a "currently active" second malignancy that is progressing or has
required active treatment within the last 3 years. Participants with non-melanoma skin
cancers or carcinoma in situ (e.g., breast carcinoma or cervical cancer in situ) that
have undergone potentially curative therapy are eligible
- No hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
- No live vaccine within 30 days prior to registration. Examples of live vaccines
include, but are not limited to, the following: measles, mumps, rubella,
varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG),
and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed
virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist)
are live attenuated vaccines and are not allowed
- No known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]
reactive) or known hepatitis C virus (defined as HCV ribonucleic acid [RNA]
[qualitative] is detected) infection
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Hemoglobin >= 8 gm/dl
- Calculated (Calc.) creatinine clearance >= 45 mL/min
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 x upper limit
of normal (ULN)
Exclusion Criteria:
- Patients must NOT have uncontrolled intercurrent illness including, but not limited
to, serious ongoing or active infection, symptomatic congestive heart failure,
uncontrolled cardiac arrhythmia, unstable angina pectoris, that would limit compliance
with study requirements
|
NCT0426xxxx/NCT04267861.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267861</url>
</required_header>
<id_info>
<org_study_id>999920055</org_study_id>
<secondary_id>20-C-N055</secondary_id>
<nct_id>NCT04267861</nct_id>
</id_info>
<brief_title>M7824 Related Adverse Effects in Adults With Cancer</brief_title>
<official_title>Retrospective Study of M7824 Related Adverse Effects in Adults With Cancer</official_title>
<sponsors>
<lead_sponsor>
<agency>National Cancer Institute (NCI)</agency>
<agency_class>NIH</agency_class>
</lead_sponsor>
</sponsors>
<source>National Institutes of Health Clinical Center (CC)</source>
<oversight_info>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Background:

Immunotherapy drugs use a person s own immune system to help fight cancer. These drugs work
better for some people than others. The drug M7824 has helped some people with cancer. But it
can cause side effects. Researchers want to learn all the side effects that M7824 can cause.
Once they do, they can prevent or reduce these side effects in future cancer treatments. This
will lead to better overall outcomes for people with cancer.

Objective:

To make a thorough list of adverse events in people with cancer being treated with systemic
therapies including M7824 at the National Cancer Institute (NCI).

Eligibility:

Participants previously enrolled in NCI protocols #15-C-0179 and #18-C-0056

Design:

All needed data have already been collected. These data are stored in existing records and
databases.

Researchers will review the medical records of adults with cancer who were enrolled in the
above protocols. The data collected will be relevant to the specific objectives being
addressed.

Data will be collected only if 2 conditions are met. One, the principal investigator gave
permission for use of the data gathered in the trial. Two, the participants of the trial did
not opt out of future use of the data.

Other protocols may be added. This will be done with an amendment.

...
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Immunotherapy agents utilize the immune system to help fight cancer. A number of
immunotherapy drugs have been approved for use in certain cancers. Despite being effective in
some patients, many of these promising drugs do not demonstrate efficacy in other patients.
M7824 (MSB0011359C), a bifunctional fusion protein that blocks both PD-L1 and transforming
growth factor beta (TGF-beta) signaling, is a promising novel drug that has proven
efficacious in a subset of cancer patients. However, we have observed side effects in
patients receiving M7824 that include both immune related adverse events and skin neoplasms.
It is imperative that these M7824 side effects be identified and characterized so that they
can be prevented or diminished during future cancer treatments. By thoroughly analyzing the
side effect profile of this drug, management of adverse effects and overall patient outcomes
can be better understood and optimized.

The primary goal of this protocol is to perform a retrospective chart review for the
investigation of the adverse events arising in cancer patients being treated with systemic
therapies including M7824 at the National Cancer Institute (NCI). This study will not involve
the use of specimens or participant contact. All data that are needed have already been
collected on the individual treatment protocols and are available in CRIS records or protocol
specific databases. Data will only be collected from treatment protocols where the PI has
given permission for use of the data on the trial the subjects were enrolled on and the
subjects did not opt out of future use of data. This protocol will be amended to incorporate
new research objectives and new protocols as necessary.
</textblock>
</detailed_description>
<overall_status>Active, not recruiting</overall_status>
<start_date type="Actual">January 28, 2020</start_date>
<completion_date type="Anticipated">November 1, 2023</completion_date>
<primary_completion_date type="Anticipated">November 1, 2023</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Retrospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>M7824 related adverse events</measure>
<time_frame>ongoing</time_frame>
<description>adverse event frequency and characterization</description>
</primary_outcome>
<number_of_groups>1</number_of_groups>
<enrollment type="Actual">232</enrollment>
<condition>Neoplasms</condition>
<condition>Skin Neoplasms</condition>
<arm_group>
<arm_group_label>1</arm_group_label>
<description>Medical records of subjects enrolled on NCI protocols 15-C-0179 and 18-C-0056</description>
</arm_group>
<eligibility>
<study_pop>
<textblock>
Subjects enrolled on CC protocols 15-C-0179 and 18-C-0056
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
- INCLUSION CRITERIA:

Adults with cancer enrolled on immunotherapy treatment protocols including M8724 in the
NCI.

EXCLUSION CRITERIA:

Patients who opted out of future use of data on their prior studies will be excluded from
this study.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Isaac F Brownell, M.D.</last_name>
<role>Principal Investigator</role>
<affiliation>National Cancer Institute (NCI)</affiliation>
</overall_official>
<location>
<facility>
<name>National Cancer Institute (NCI)</name>
<address>
<city>Bethesda</city>
<state>Maryland</state>
<zip>20892</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>August 28, 2023</verification_date>
<study_first_submitted>February 12, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>August 29, 2023</last_update_submitted>
<last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">August 30, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Skin Neoplasms</keyword>
<keyword>Immunotherapy</keyword>
<keyword>Anti-PD-1</keyword>
<keyword>Natural History</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Neoplasms</mesh_term>
<mesh_term>Skin Neoplasms</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Background:
Immunotherapy drugs use a person s own immune system to help fight cancer. These drugs work
better for some people than others. The drug M7824 has helped some people with cancer. But it
can cause side effects. Researchers want to learn all the side effects that M7824 can cause.
Once they do, they can prevent or reduce these side effects in future cancer treatments. This
will lead to better overall outcomes for people with cancer.
Objective:
To make a thorough list of adverse events in people with cancer being treated with systemic
therapies including M7824 at the National Cancer Institute (NCI).
Eligibility:
Participants previously enrolled in NCI protocols #15-C-0179 and #18-C-0056
Design:
All needed data have already been collected. These data are stored in existing records and
databases.
Researchers will review the medical records of adults with cancer who were enrolled in the
above protocols. The data collected will be relevant to the specific objectives being
addressed.
Data will be collected only if 2 conditions are met. One, the principal investigator gave
permission for use of the data gathered in the trial. Two, the participants of the trial did
not opt out of future use of the data.
Other protocols may be added. This will be done with an amendment.
...
Immunotherapy agents utilize the immune system to help fight cancer. A number of
immunotherapy drugs have been approved for use in certain cancers. Despite being effective in
some patients, many of these promising drugs do not demonstrate efficacy in other patients.
M7824 (MSB0011359C), a bifunctional fusion protein that blocks both PD-L1 and transforming
growth factor beta (TGF-beta) signaling, is a promising novel drug that has proven
efficacious in a subset of cancer patients. However, we have observed side effects in
patients receiving M7824 that include both immune related adverse events and skin neoplasms.
It is imperative that these M7824 side effects be identified and characterized so that they
can be prevented or diminished during future cancer treatments. By thoroughly analyzing the
side effect profile of this drug, management of adverse effects and overall patient outcomes
can be better understood and optimized.
The primary goal of this protocol is to perform a retrospective chart review for the
investigation of the adverse events arising in cancer patients being treated with systemic
therapies including M7824 at the National Cancer Institute (NCI). This study will not involve
the use of specimens or participant contact. All data that are needed have already been
collected on the individual treatment protocols and are available in CRIS records or protocol
specific databases. Data will only be collected from treatment protocols where the PI has
given permission for use of the data on the trial the subjects were enrolled on and the
subjects did not opt out of future use of data. This protocol will be amended to incorporate
new research objectives and new protocols as necessary.
Subjects enrolled on CC protocols 15-C-0179 and 18-C-0056
- INCLUSION CRITERIA:
Adults with cancer enrolled on immunotherapy treatment protocols including M8724 in the
NCI.
EXCLUSION CRITERIA:
Patients who opted out of future use of data on their prior studies will be excluded from
this study.
|
NCT0426xxxx/NCT04267874.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267874</url>
</required_header>
<id_info>
<org_study_id>OSU-19007</org_study_id>
<secondary_id>NCI-2020-00418</secondary_id>
<nct_id>NCT04267874</nct_id>
</id_info>
<brief_title>Black Raspberry Nectar for the Prevention of Lung Cancer, BE WELL Study</brief_title>
<official_title>The BE WELL Study: Black Raspberry Beverage Working to Prevent Lung Cancer</official_title>
<sponsors>
<lead_sponsor>
<agency>Ohio State University Comprehensive Cancer Center</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>National Cancer Institute (NCI)</agency>
<agency_class>NIH</agency_class>
</collaborator>
</sponsors>
<source>Ohio State University Comprehensive Cancer Center</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This trial studies how well black raspberry nectar works in changing the gut microbiome and
in reducing inflammatory processes that may lead to lung cancer. Studying the effects of
black raspberry beverage on inflammation may help doctors find strategies to reduce the risk
of developing lung cancer.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
PRIMARY FEASIBILITY OBJECTIVE:

I. To evaluate the feasibility of establishing a diet intervention trial with longitudinal
microbiome collection in Ohio State University Comprehensive Cancer Center (OSUCCC) Lung
Cancer Screening Clinic (OSUCCC-LCSC).

PRIMARY SCIENTIFIC OBJECTIVE:

I. To determine the impact of the black raspberry (BRB) nectar intervention on the microbiome
and inflammatory biomarkers.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive BRB nectar orally (PO) twice daily (BID) for weeks 0-4 and then
receive placebo PO BID for weeks 6-10 in the absence of unacceptable toxicity. Patients also
undergo collection of nasal swabs, blood, urine, and stool samples at weeks 0, 4, 6, and 10.

ARM II: Patients receive placebo PO BID for weeks 0-4 and then receive BRB nectar PO BID for
weeks 6-10 in the absence of unacceptable toxicity. Patients also undergo collection of nasal
swabs, blood, urine, and stool samples at weeks 0, 4, 6, and 10.
</textblock>
</detailed_description>
<overall_status>Active, not recruiting</overall_status>
<start_date type="Actual">October 25, 2019</start_date>
<completion_date type="Anticipated">December 31, 2022</completion_date>
<primary_completion_date type="Actual">May 13, 2021</primary_completion_date>
<phase>Early Phase 1</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Crossover Assignment</intervention_model>
<primary_purpose>Prevention</primary_purpose>
<masking>Single (Participant)</masking>
</study_design_info>
<primary_outcome>
<measure>Recruitment rates</measure>
<time_frame>Up to 3 years</time_frame>
<description>Recruitment rates will be defined as the proportion of screened accrued relative to those approached. Successful recruitment rates will be defined as >= 10% of participants approached agree to participate.</description>
</primary_outcome>
<primary_outcome>
<measure>Study adherence</measure>
<time_frame>Up to 3 years</time_frame>
<description>Study adherence will be defined as the percent of the biospecimens collected at the end of the study period, with a compliance goal of 60%. Will track the monthly collection of data and document reasons for missing any scheduled collection dates. The proportions of missing information at each time point will be calculated. Descriptive statistics will examine the distribution of all patient and treatment characteristics, overall and by patient and disease characteristics.</description>
</primary_outcome>
<primary_outcome>
<measure>Inflammatory markers found in nasal brushings</measure>
<time_frame>Up to 3 years</time_frame>
<description>Evaluated by ribonucleic acid sequencing.</description>
</primary_outcome>
<primary_outcome>
<measure>Changes in stool microbe relative abundances</measure>
<time_frame>Up to 3 years</time_frame>
<description>Evaluated by metagenomic whole sequencing.</description>
</primary_outcome>
<primary_outcome>
<measure>Biologic responses to the black raspberry (BRB) nectar</measure>
<time_frame>Up to 3 years</time_frame>
<description>Samples of urine, stool. and blood will be analyzed for BRB phytochemicals (ellagitannins, ellagic acid, quercetin glycosides, anthocyanins) and their metabolites (urolithins, quercetin glucuronides/sulfates, methylated anthocyanins).</description>
</primary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">96</enrollment>
<condition>Lung Carcinoma</condition>
<condition>Tobacco-Related Carcinoma</condition>
<arm_group>
<arm_group_label>Arm I (BRB nectar, placebo, biospecimen collection)</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Patients receive BRB nectar PO BID for weeks 0-4 and then receive placebo PO BID for weeks 6-10 in the absence of unacceptable toxicity. Patients also undergo collection of nasal swabs, blood, urine, and stool samples at weeks 0, 4, 6, and 10.</description>
</arm_group>
<arm_group>
<arm_group_label>Arm II (placebo, BRB nectar, biospecimen collection)</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Patients receive placebo PO BID for weeks 0-4 and then receive BRB nectar PO BID for weeks 6-10 in the absence of unacceptable toxicity. Patients also undergo collection of nasal swabs, blood, urine, and stool samples at weeks 0, 4, 6, and 10.</description>
</arm_group>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>Biospecimen Collection</intervention_name>
<description>Undergo collection of nasal swabs, blood, urine, and stool</description>
<arm_group_label>Arm I (BRB nectar, placebo, biospecimen collection)</arm_group_label>
<arm_group_label>Arm II (placebo, BRB nectar, biospecimen collection)</arm_group_label>
</intervention>
<intervention>
<intervention_type>Dietary Supplement</intervention_type>
<intervention_name>Nutritional Supplementation</intervention_name>
<description>Given black raspberry nectar PO</description>
<arm_group_label>Arm I (BRB nectar, placebo, biospecimen collection)</arm_group_label>
<arm_group_label>Arm II (placebo, BRB nectar, biospecimen collection)</arm_group_label>
<other_name>supplementation</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Placebo Administration</intervention_name>
<description>Given PO</description>
<arm_group_label>Arm I (BRB nectar, placebo, biospecimen collection)</arm_group_label>
<arm_group_label>Arm II (placebo, BRB nectar, biospecimen collection)</arm_group_label>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Questionnaire Administration</intervention_name>
<description>Ancillary studies</description>
<arm_group_label>Arm I (BRB nectar, placebo, biospecimen collection)</arm_group_label>
<arm_group_label>Arm II (placebo, BRB nectar, biospecimen collection)</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Have a 30 pack-year smoking history

- Be either a current smoker or a former smoker that quit in the last 15 years. Any
individual who is currently smoking and has smoked more than 100 cigarettes in their
lifetime will be identified as a current smoker

- Agree to consume a standardized vitamin / mineral supplement and avoid other
nutritional, dietary or alternative medications / supplements / probiotics for the
duration of the study

- Agree to follow a berry-free / controlled phenolic diet and to document consumption of
polyphenolic foods each day of the study using a simple daily form

Exclusion Criteria:

- Person has an allergy to any berries, pectin, or food colorants apples,as well as kiwi
fruit, strawberries, soy sauce, pine nuts, almonds, cherries, peaches, blackberries,
pears

- Person states that they are not a:

- Current smoker: active cigarette smoker who has smoked more than 30 pack-years in
the last 15 years OR

- Former smoker: not a current smoker active cigarette smoker who has smoked more
than 30 pack years in the last 15 years

- Person is unwilling to follow a berry-free/controlled polyphenol diet while on study

- Person has history of metabolic disorders (diabetes, hyper/hypo-thyroidism, etc.);
digestive illness which may result in nutrient malabsorption (Crohn's disease, Celiac,
renal/hepatic insufficiency, short bowel, etc.); disorders that affect connective
tissues; or blood clotting disorders

- Person has allergy or food intolerance to ingredients in study products (black
raspberries or other berries)

- Person is on a regimen of any of the following medications:

- Immunosuppressants, bisphosphonates, or steroids.

- Anticoagulants (warfarin, apixaban, dabigatran, and rivaroxaban)

- Probiotics

- Person is undergoing treatment for cancer in any form

- Person is currently pregnant or nursing or plans to become pregnant during this study

- Person plans to enter smoking cessation or change their smoking status during the
course of the study
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>55 Years</minimum_age>
<maximum_age>77 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Daniel Spakowicz, PhD, MS</last_name>
<role>Principal Investigator</role>
<affiliation>Ohio State University Comprehensive Cancer Center</affiliation>
</overall_official>
<location>
<facility>
<name>Ohio State University Comprehensive Cancer Center</name>
<address>
<city>Columbus</city>
<state>Ohio</state>
<zip>43210</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<link>
<url>http://cancer.osu.edu</url>
<description>The Jamesline</description>
</link>
<verification_date>July 2022</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>July 4, 2022</last_update_submitted>
<last_update_submitted_qc>July 4, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">July 7, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Ohio State University Comprehensive Cancer Center</investigator_affiliation>
<investigator_full_name>Daniel Spakowicz</investigator_full_name>
<investigator_title>Principal Investigator</investigator_title>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Carcinoma</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<provided_document_section>
<provided_document>
<document_type>Informed Consent Form</document_type>
<document_has_protocol>No</document_has_protocol>
<document_has_icf>Yes</document_has_icf>
<document_has_sap>No</document_has_sap>
<document_date>September 21, 2021</document_date>
<document_url>https://ClinicalTrials.gov/ProvidedDocs/74/NCT04267874/ICF_000.pdf</document_url>
</provided_document>
</provided_document_section>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This trial studies how well black raspberry nectar works in changing the gut microbiome and
in reducing inflammatory processes that may lead to lung cancer. Studying the effects of
black raspberry beverage on inflammation may help doctors find strategies to reduce the risk
of developing lung cancer.
PRIMARY FEASIBILITY OBJECTIVE:
I. To evaluate the feasibility of establishing a diet intervention trial with longitudinal
microbiome collection in Ohio State University Comprehensive Cancer Center (OSUCCC) Lung
Cancer Screening Clinic (OSUCCC-LCSC).
PRIMARY SCIENTIFIC OBJECTIVE:
I. To determine the impact of the black raspberry (BRB) nectar intervention on the microbiome
and inflammatory biomarkers.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive BRB nectar orally (PO) twice daily (BID) for weeks 0-4 and then
receive placebo PO BID for weeks 6-10 in the absence of unacceptable toxicity. Patients also
undergo collection of nasal swabs, blood, urine, and stool samples at weeks 0, 4, 6, and 10.
ARM II: Patients receive placebo PO BID for weeks 0-4 and then receive BRB nectar PO BID for
weeks 6-10 in the absence of unacceptable toxicity. Patients also undergo collection of nasal
swabs, blood, urine, and stool samples at weeks 0, 4, 6, and 10.
Inclusion Criteria:
- Have a 30 pack-year smoking history
- Be either a current smoker or a former smoker that quit in the last 15 years. Any
individual who is currently smoking and has smoked more than 100 cigarettes in their
lifetime will be identified as a current smoker
- Agree to consume a standardized vitamin / mineral supplement and avoid other
nutritional, dietary or alternative medications / supplements / probiotics for the
duration of the study
- Agree to follow a berry-free / controlled phenolic diet and to document consumption of
polyphenolic foods each day of the study using a simple daily form
Exclusion Criteria:
- Person has an allergy to any berries, pectin, or food colorants apples,as well as kiwi
fruit, strawberries, soy sauce, pine nuts, almonds, cherries, peaches, blackberries,
pears
- Person states that they are not a:
- Current smoker: active cigarette smoker who has smoked more than 30 pack-years in
the last 15 years OR
- Former smoker: not a current smoker active cigarette smoker who has smoked more
than 30 pack years in the last 15 years
- Person is unwilling to follow a berry-free/controlled polyphenol diet while on study
- Person has history of metabolic disorders (diabetes, hyper/hypo-thyroidism, etc.);
digestive illness which may result in nutrient malabsorption (Crohn's disease, Celiac,
renal/hepatic insufficiency, short bowel, etc.); disorders that affect connective
tissues; or blood clotting disorders
- Person has allergy or food intolerance to ingredients in study products (black
raspberries or other berries)
- Person is on a regimen of any of the following medications:
- Immunosuppressants, bisphosphonates, or steroids.
- Anticoagulants (warfarin, apixaban, dabigatran, and rivaroxaban)
- Probiotics
- Person is undergoing treatment for cancer in any form
- Person is currently pregnant or nursing or plans to become pregnant during this study
- Person plans to enter smoking cessation or change their smoking status during the
course of the study
|
NCT0426xxxx/NCT04267887.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267887</url>
</required_header>
<id_info>
<org_study_id>STUDY00016728</org_study_id>
<secondary_id>NCI-2020-00598</secondary_id>
<secondary_id>STUDY00016728</secondary_id>
<nct_id>NCT04267887</nct_id>
</id_info>
<brief_title>Advanced ChemoHormonal Therapy for Treatment Naive Metastatic Prostate Cancer</brief_title>
<official_title>Advanced ChemoHormonal Therapy for Treatment Naïve Metastatic Prostate Cancer: Apalutamide and Abiraterone Acetate With Prednisone and Androgen Deprivation Therapy After Treatment With Docetaxel and Androgen Deprivation Therapy</official_title>
<sponsors>
<lead_sponsor>
<agency>OHSU Knight Cancer Institute</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Janssen Scientific Affairs, LLC</agency>
<agency_class>Industry</agency_class>
</collaborator>
<collaborator>
<agency>Oregon Health and Science University</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>OHSU Knight Cancer Institute</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This phase II trial studies how well the combination of apalutamide, abiraterone acetate, and
prednisone after chemotherapy work in treating patients that have received no prior treatment
(treatment naive) for high risk prostate cancer that is sensitive to androgen deprivation
therapy (castration sensitive) and has spread to other parts of the body (metastatic). This
study also aims to understand the inheritance of prostate cancer. If a gene or genes that
cause prostate cancer can be found, the diagnosis and treatment of prostate cancer may be
improved. Testosterone (a male hormone) can cause the growth of prostate cancer cells.
Hormone therapy using apalutamide may fight prostate cancer by blocking the use of
testosterone by the tumor cells. Antihormone therapy, such as abiraterone acetate, may lessen
the amount of testosterone made by the body. Anti-inflammatory drugs such as prednisone lower
the body's immune response and are used with other drugs in the treatment of some types of
cancer. Apalutamide, abiraterone acetate, and prednisone after chemotherapy may work better
in treating patients with castration sensitive prostate cancer.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
PRIMARY OBJECTIVE:

I. Efficacy of apalutamide in combination with abiraterone acetate + prednisone following
docetaxel with ongoing androgen deprivation therapy in men with high risk metastatic
castration sensitive disease.

SECONDARY OBJECTIVES:

I. Safety and tolerability of apalutamide in combination with abiraterone acetate +
prednisone following docetaxel with ongoing androgen deprivation therapy.

II. Time to event.

III. Depth of prostate specific antigen (PSA) response.

EXPLORATORY OBJECTIVES:

I. Quality of life.

II. Falls.

III. Molecular changes from prostate cancer over time.

OUTLINE:

Patients receive apalutamide orally (PO) once daily (QD), abiraterone acetate PO QD, and
prednisone PO QD. Cycles repeat every 4 weeks in the absence of disease progression or
unacceptable toxicity. Patients also receive androgen deprivation therapy per standard of
care.

After completion of study treatment, patients are followed up every 6 months for up to 10
years.
</textblock>
</detailed_description>
<overall_status>Active, not recruiting</overall_status>
<start_date type="Actual">May 11, 2020</start_date>
<completion_date type="Anticipated">January 1, 2026</completion_date>
<primary_completion_date type="Anticipated">January 1, 2024</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Complete prostate specific antigen (PSA) response</measure>
<time_frame>At 12 months from the start of treatment</time_frame>
<description>The complete PSA response is defined as a PSA =< 0.2 ng/ml, confirmed with a 2nd measurement at least 3 weeks later. The estimated PSA response rate will be computed with 95% exact confidence interval. Binomial exact test will be used to determine whether the complete PSA response rate is significantly greater than 43%.</description>
</primary_outcome>
<secondary_outcome>
<measure>Overall survival</measure>
<time_frame>From day 1 of treatment, assessed up to 10 years</time_frame>
<description>Overall survival will be assessed with each patient visit. After the subject is off active follow up, survival will be assessed by phone.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Incidence of adverse events >= grade 2</measure>
<time_frame>Up to 10 years</time_frame>
<description>Determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Proportion of patients with PSA response >= 50% decrease</measure>
<time_frame>From baseline, assessed up to 12 months</time_frame>
<description>The proportion will be reported with 95% confidence interval.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Proportion of patients with PSA response >= 90% decrease</measure>
<time_frame>From baseline, assessed up to 12 months</time_frame>
<description>The proportion will be reported with 95% confidence interval.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Time to treatment failure</measure>
<time_frame>From start of treatment, assessed up to 10 years</time_frame>
<description>Kaplan-Meier plot will be used to describe the survival distributions.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Time to biochemical (PSA) progression</measure>
<time_frame>From start of treatment, assessed up to 10 years</time_frame>
<description>Kaplan-Meier plot will be used to describe the survival distributions.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Time to radiographic progression</measure>
<time_frame>From start of treatment, assessed up to 10 years</time_frame>
<description>Kaplan-Meier plot will be used to describe the survival distributions.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Time to symptomatic progressive disease</measure>
<time_frame>From start of treatment, assessed up to 10 years</time_frame>
<description>Kaplan-Meier plot will be used to describe the survival distributions.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Time to next therapy for metastatic castration resistant prostate cancer</measure>
<time_frame>From start of treatment, assessed up to 10 years</time_frame>
<description>Kaplan-Meier plot will be used to describe the survival distributions.</description>
</secondary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Actual">7</enrollment>
<condition>Castration-Sensitive Prostate Carcinoma</condition>
<condition>Metastatic Prostate Carcinoma</condition>
<condition>Stage IVB Prostate Cancer AJCC v8</condition>
<arm_group>
<arm_group_label>Treatment (apalutamide, abiraterone acetate, prednisone, ADT)</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Patients receive apalutamide PO QD, abiraterone acetate PO QD, and prednisone PO QD. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive androgen deprivation therapy per standard of care.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Abiraterone Acetate</intervention_name>
<description>Given PO</description>
<arm_group_label>Treatment (apalutamide, abiraterone acetate, prednisone, ADT)</arm_group_label>
<other_name>CB7630</other_name>
<other_name>Yonsa</other_name>
<other_name>Zytiga</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Antiandrogen Therapy</intervention_name>
<description>Given ADT per standard of care</description>
<arm_group_label>Treatment (apalutamide, abiraterone acetate, prednisone, ADT)</arm_group_label>
<other_name>ADT</other_name>
<other_name>Androgen Deprivation Therapy</other_name>
<other_name>Androgen Deprivation Therapy (ADT)</other_name>
<other_name>Anti-androgen Therapy</other_name>
<other_name>Anti-androgen Treatment</other_name>
<other_name>Antiandrogen Treatment</other_name>
<other_name>Hormone Deprivation Therapy</other_name>
<other_name>Hormone-Deprivation Therapy</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Apalutamide</intervention_name>
<description>Given PO</description>
<arm_group_label>Treatment (apalutamide, abiraterone acetate, prednisone, ADT)</arm_group_label>
<other_name>ARN 509</other_name>
<other_name>ARN-509</other_name>
<other_name>ARN509</other_name>
<other_name>Erleada</other_name>
<other_name>JNJ 56021927</other_name>
<other_name>JNJ-56021927</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Prednisone</intervention_name>
<description>Given PO</description>
<arm_group_label>Treatment (apalutamide, abiraterone acetate, prednisone, ADT)</arm_group_label>
<other_name>.delta.1-Cortisone</other_name>
<other_name>1, 2-Dehydrocortisone</other_name>
<other_name>Adasone</other_name>
<other_name>Cortancyl</other_name>
<other_name>Dacortin</other_name>
<other_name>DeCortin</other_name>
<other_name>Decortisyl</other_name>
<other_name>Decorton</other_name>
<other_name>Delta 1-Cortisone</other_name>
<other_name>Delta-Dome</other_name>
<other_name>Deltacortene</other_name>
<other_name>Deltacortisone</other_name>
<other_name>Deltadehydrocortisone</other_name>
<other_name>Deltasone</other_name>
<other_name>Deltison</other_name>
<other_name>Deltra</other_name>
<other_name>Econosone</other_name>
<other_name>Lisacort</other_name>
<other_name>Meprosona-F</other_name>
<other_name>Metacortandracin</other_name>
<other_name>Meticorten</other_name>
<other_name>Ofisolona</other_name>
<other_name>Orasone</other_name>
<other_name>Panafcort</other_name>
<other_name>Panasol-S</other_name>
<other_name>Paracort</other_name>
<other_name>Perrigo Prednisone</other_name>
<other_name>PRED</other_name>
<other_name>Predicor</other_name>
<other_name>Predicorten</other_name>
<other_name>Prednicen-M</other_name>
<other_name>Prednicort</other_name>
<other_name>Prednidib</other_name>
<other_name>Prednilonga</other_name>
<other_name>Predniment</other_name>
<other_name>Prednisone Intensol</other_name>
<other_name>Prednisonum</other_name>
<other_name>Prednitone</other_name>
<other_name>Promifen</other_name>
<other_name>Rayos</other_name>
<other_name>Servisone</other_name>
<other_name>SK-Prednisone</other_name>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Quality-of-Life Assessment</intervention_name>
<description>Ancillary studies</description>
<arm_group_label>Treatment (apalutamide, abiraterone acetate, prednisone, ADT)</arm_group_label>
<other_name>Quality of Life Assessment</other_name>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Questionnaire Administration</intervention_name>
<description>Ancillary studies</description>
<arm_group_label>Treatment (apalutamide, abiraterone acetate, prednisone, ADT)</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Patients must have histologically or cytologically confirmed prostate cancer OR a
strong suspicion of prostate cancer as evidenced by metastatic disease in a pattern
consistent with prostate cancer (such as blastic lesions on a nuclear medicine bone
scan or lymphadenopathy on the computed tomography [CT] scan) AND a PSA > 50 ng/mL

- Patients must meet either of the definitions for high risk disease as follows:

- Definition 1: Must have at least 2 of the following 3 at the time diagnosed
metastatic:

- visceral metastatic disease

- >=3 bone lesions

- Gleason 8-10 OR

- Definition 2: >=4 bone lesions, including >=1 outside of the vertebral column or
pelvis and/or visceral metastatic disease

- If a patient has received androgen deprivation therapy (ADT) for neoadjuvant or
adjuvant therapy at least 24 months MUST have elapsed since its use to day 1 of
restarting ADT for metastatic castration sensitive disease

- ADT sensitive disease- no evidence of PSA progression or new metastatic deposits since
starting ADT; PSA progression is defined as an increase in PSA greater than 25% above
nadir, and >2 ng/ml increase confirmed by a second value obtained at least 2 weeks
apart

- Have completed up to 6 cycles of docetaxel since developing metastatic castration
sensitive disease with no more than 16 weeks elapsed since day 21 of the final cycle

- All races and ethnic groups will be included

- Life expectancy of greater than 18 months

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Hemoglobin > 9.0 g/dL, independent of transfusion and/or growth factors

- Leukocytes > 3,000/uL

- Absolute neutrophil count > 1,500/uL

- Platelets >= 100,000 x 10^9/uL, independent of transfusion and/or growth factors

- Total bilirubin =< 1.5 x upper limit of normal (ULN) (Note: In subjects with Gilbert's
syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and
if direct bilirubin is =< 1.5 x ULN, subject may be eligible)

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) <
2.5 x institutional upper limit of normal

- Albumin > 3 g/dL

- Estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m^2; per Modification of
Diet in Renal Disease (MDRD) calculation or institutional standard

- Potassium >= 3.5 mmol/L

- Medications known to lower the seizure threshold must be discontinued or substituted
at least 4 weeks prior to day 1 of study

- Agrees to use a condom (even men with vasectomies) and another effective method of
birth control if he is having sex with a woman of childbearing potential or agrees to
use a condom if he is having sex with a woman who is pregnant while on study drug and
for 3 months following the last dose of study drug. Must also agree not to donate
sperm during the study and for 3 months after receiving the last dose of study drug

- Ability to understand, and the willingness to sign, a written informed consent
document, as well as comply with study requirements

Exclusion Criteria:

- Subjects who are unwilling to stop taking saw palmetto, PC-SPECs or other herbal
agents known to affect the PSA

- Patients may not have received any other investigational agents within 30 days prior
to day 1 of study

- Prior exposure to apalutamide, enzalutamide, abiraterone acetate, darolutamide, or any
other second-generation antiandrogen therapy

- Note: prior exposure to bicalutamide, flutamide, nilutamide, or any other
first-generation androgen receptor antagonist is permitted. No washout is
required. Subjects may be on one of these at the time of consent, but it must be
stopped prior to day 1 of study treatment. These drugs are frequently used in the
newly diagnosed metastatic setting to blunt the effect of the testosterone spike

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to apalutamide or other agents used in the study

- Subject has another active malignancy other than non-melanomatous skin cancer (unless
it is metastatic) or superficial bladder cancer

- Either of the following:

- Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke
within 1 year, brain arteriovenous malformation, Schwannoma, meningioma, or other
benign central nervous system [CNS] or meningeal disease which may require
treatment with surgery or radiation therapy)

- Severe or unstable angina, myocardial infarction, symptomatic congestive heart
failure or left ventricular ejection fraction < 50%, arterial or venous
thromboembolic events (e.g. pulmonary embolism, cerebrovascular accident
including transient ischemic attacks), or clinically significant ventricular
arrhythmias within 6 months prior to day 1 of study

- Current evidence of any of the following:

- Uncontrolled hypertension

- Gastrointestinal disorder affecting absorption

- Active infection (e.g. human immunodeficiency virus [HIV] or viral hepatitis)

- Any chronic medical condition requiring a higher dose of corticosteroid than a
total of 10 mg prednisone/prednisolone daily

- Any condition that in the opinion of the investigator, would preclude
participation in this study.

- Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment. If
a strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate
dosing frequency to twice a day only during the co-administration period (e.g.,
from 1,000 mg once daily to 1,000 mg twice a day).

- Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a
narrow therapeutic index. If an alternative treatment cannot be used, exercise
caution and consider a dose reduction of the concomitant CYP2D6 substrate

- Baseline moderate and severe hepatic impairment (Child Pugh Class B & C)

- Inability to stop a prohibited medication:

- Atypical antipsychotics (e.g. clozapine, olanzapine, risperidone, ziprasidone)

- Bupropion

- Lithium

- Meperidine and pethidine

- Phenothiazine antipsychotics (e.g. chlorpromazine, mesoridazine, thioridazine)

- Tricyclic antidepressants (e.g. amitriptyline, desipramine, doxepin, imipramine,
maprotiline, mirtazapine

- Tramadol
</textblock>
</criteria>
<gender>Male</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Julie Graff, MD</last_name>
<role>Principal Investigator</role>
<affiliation>OHSU Knight Cancer Institute</affiliation>
</overall_official>
<location>
<facility>
<name>OHSU Knight Cancer Institute</name>
<address>
<city>Portland</city>
<state>Oregon</state>
<zip>97239</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>May 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>May 19, 2023</last_update_submitted>
<last_update_submitted_qc>May 19, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">May 23, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>OHSU Knight Cancer Institute</investigator_affiliation>
<investigator_full_name>Julie Graff</investigator_full_name>
<investigator_title>Principal Investigator</investigator_title>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Carcinoma</mesh_term>
<mesh_term>Prostatic Neoplasms</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Ascorbic Acid</mesh_term>
<mesh_term>Prednisone</mesh_term>
<mesh_term>Cortisone</mesh_term>
<mesh_term>Methyltestosterone</mesh_term>
<mesh_term>Abiraterone Acetate</mesh_term>
<mesh_term>Hormones</mesh_term>
<mesh_term>Estrogens, Conjugated (USP)</mesh_term>
<mesh_term>Androgens</mesh_term>
<mesh_term>Androgen Antagonists</mesh_term>
</intervention_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This phase II trial studies how well the combination of apalutamide, abiraterone acetate, and
prednisone after chemotherapy work in treating patients that have received no prior treatment
(treatment naive) for high risk prostate cancer that is sensitive to androgen deprivation
therapy (castration sensitive) and has spread to other parts of the body (metastatic). This
study also aims to understand the inheritance of prostate cancer. If a gene or genes that
cause prostate cancer can be found, the diagnosis and treatment of prostate cancer may be
improved. Testosterone (a male hormone) can cause the growth of prostate cancer cells.
Hormone therapy using apalutamide may fight prostate cancer by blocking the use of
testosterone by the tumor cells. Antihormone therapy, such as abiraterone acetate, may lessen
the amount of testosterone made by the body. Anti-inflammatory drugs such as prednisone lower
the body's immune response and are used with other drugs in the treatment of some types of
cancer. Apalutamide, abiraterone acetate, and prednisone after chemotherapy may work better
in treating patients with castration sensitive prostate cancer.
PRIMARY OBJECTIVE:
I. Efficacy of apalutamide in combination with abiraterone acetate + prednisone following
docetaxel with ongoing androgen deprivation therapy in men with high risk metastatic
castration sensitive disease.
SECONDARY OBJECTIVES:
I. Safety and tolerability of apalutamide in combination with abiraterone acetate +
prednisone following docetaxel with ongoing androgen deprivation therapy.
II. Time to event.
III. Depth of prostate specific antigen (PSA) response.
EXPLORATORY OBJECTIVES:
I. Quality of life.
II. Falls.
III. Molecular changes from prostate cancer over time.
OUTLINE:
Patients receive apalutamide orally (PO) once daily (QD), abiraterone acetate PO QD, and
prednisone PO QD. Cycles repeat every 4 weeks in the absence of disease progression or
unacceptable toxicity. Patients also receive androgen deprivation therapy per standard of
care.
After completion of study treatment, patients are followed up every 6 months for up to 10
years.
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed prostate cancer OR a
strong suspicion of prostate cancer as evidenced by metastatic disease in a pattern
consistent with prostate cancer (such as blastic lesions on a nuclear medicine bone
scan or lymphadenopathy on the computed tomography [CT] scan) AND a PSA > 50 ng/mL
- Patients must meet either of the definitions for high risk disease as follows:
- Definition 1: Must have at least 2 of the following 3 at the time diagnosed
metastatic:
- visceral metastatic disease
- >=3 bone lesions
- Gleason 8-10 OR
- Definition 2: >=4 bone lesions, including >=1 outside of the vertebral column or
pelvis and/or visceral metastatic disease
- If a patient has received androgen deprivation therapy (ADT) for neoadjuvant or
adjuvant therapy at least 24 months MUST have elapsed since its use to day 1 of
restarting ADT for metastatic castration sensitive disease
- ADT sensitive disease- no evidence of PSA progression or new metastatic deposits since
starting ADT; PSA progression is defined as an increase in PSA greater than 25% above
nadir, and >2 ng/ml increase confirmed by a second value obtained at least 2 weeks
apart
- Have completed up to 6 cycles of docetaxel since developing metastatic castration
sensitive disease with no more than 16 weeks elapsed since day 21 of the final cycle
- All races and ethnic groups will be included
- Life expectancy of greater than 18 months
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Hemoglobin > 9.0 g/dL, independent of transfusion and/or growth factors
- Leukocytes > 3,000/uL
- Absolute neutrophil count > 1,500/uL
- Platelets >= 100,000 x 10^9/uL, independent of transfusion and/or growth factors
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (Note: In subjects with Gilbert's
syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and
if direct bilirubin is =< 1.5 x ULN, subject may be eligible)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) <
2.5 x institutional upper limit of normal
- Albumin > 3 g/dL
- Estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m^2; per Modification of
Diet in Renal Disease (MDRD) calculation or institutional standard
- Potassium >= 3.5 mmol/L
- Medications known to lower the seizure threshold must be discontinued or substituted
at least 4 weeks prior to day 1 of study
- Agrees to use a condom (even men with vasectomies) and another effective method of
birth control if he is having sex with a woman of childbearing potential or agrees to
use a condom if he is having sex with a woman who is pregnant while on study drug and
for 3 months following the last dose of study drug. Must also agree not to donate
sperm during the study and for 3 months after receiving the last dose of study drug
- Ability to understand, and the willingness to sign, a written informed consent
document, as well as comply with study requirements
Exclusion Criteria:
- Subjects who are unwilling to stop taking saw palmetto, PC-SPECs or other herbal
agents known to affect the PSA
- Patients may not have received any other investigational agents within 30 days prior
to day 1 of study
- Prior exposure to apalutamide, enzalutamide, abiraterone acetate, darolutamide, or any
other second-generation antiandrogen therapy
- Note: prior exposure to bicalutamide, flutamide, nilutamide, or any other
first-generation androgen receptor antagonist is permitted. No washout is
required. Subjects may be on one of these at the time of consent, but it must be
stopped prior to day 1 of study treatment. These drugs are frequently used in the
newly diagnosed metastatic setting to blunt the effect of the testosterone spike
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to apalutamide or other agents used in the study
- Subject has another active malignancy other than non-melanomatous skin cancer (unless
it is metastatic) or superficial bladder cancer
- Either of the following:
- Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke
within 1 year, brain arteriovenous malformation, Schwannoma, meningioma, or other
benign central nervous system [CNS] or meningeal disease which may require
treatment with surgery or radiation therapy)
- Severe or unstable angina, myocardial infarction, symptomatic congestive heart
failure or left ventricular ejection fraction < 50%, arterial or venous
thromboembolic events (e.g. pulmonary embolism, cerebrovascular accident
including transient ischemic attacks), or clinically significant ventricular
arrhythmias within 6 months prior to day 1 of study
- Current evidence of any of the following:
- Uncontrolled hypertension
- Gastrointestinal disorder affecting absorption
- Active infection (e.g. human immunodeficiency virus [HIV] or viral hepatitis)
- Any chronic medical condition requiring a higher dose of corticosteroid than a
total of 10 mg prednisone/prednisolone daily
- Any condition that in the opinion of the investigator, would preclude
participation in this study.
- Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment. If
a strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate
dosing frequency to twice a day only during the co-administration period (e.g.,
from 1,000 mg once daily to 1,000 mg twice a day).
- Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a
narrow therapeutic index. If an alternative treatment cannot be used, exercise
caution and consider a dose reduction of the concomitant CYP2D6 substrate
- Baseline moderate and severe hepatic impairment (Child Pugh Class B & C)
- Inability to stop a prohibited medication:
- Atypical antipsychotics (e.g. clozapine, olanzapine, risperidone, ziprasidone)
- Bupropion
- Lithium
- Meperidine and pethidine
- Phenothiazine antipsychotics (e.g. chlorpromazine, mesoridazine, thioridazine)
- Tricyclic antidepressants (e.g. amitriptyline, desipramine, doxepin, imipramine,
maprotiline, mirtazapine
- Tramadol
|
NCT0426xxxx/NCT04267900.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267900</url>
</required_header>
<id_info>
<org_study_id>PekingUMCH-NM25</org_study_id>
<nct_id>NCT04267900</nct_id>
</id_info>
<brief_title>99mTc-HPArk2 SPECT/CT for the Detection of HER2-positive Breast Cancer</brief_title>
<official_title>99mTc-HPArk2 SPECT/CT for the Detection of HER2-positive Breast Cancer</official_title>
<sponsors>
<lead_sponsor>
<agency>Peking Union Medical College Hospital</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Peking Union Medical College Hospital</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This is an open-label single photon emission tomography/computed tomography (SPECT/CT) study
to investigate the diagnostic performance and evaluation efficacy of 99mTc-HPArk2 in breast
cancer patients. A single dose of 11.1Mega-Becquerel (MBq) per kilogram body weight
99mTc-HPArk2 will be injected intravenously. Visual and semiquantitative method will be used
to assess the SPECT/CT images.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
99mTc-HPArk2 is an affibody probe targeting HER2. The investigators will determine the use of
99mTc-HPArk2 SPECT/CT in the detection of HER2-positive breast cancer, and to compare its
diagnostic value with routine immunohistochemistry (IHC) pathological staining. HER2 imaging,
specifically to HER2 receptor expressed on malignant breast cancer cell surface, might help
for targeted therapy with monoclonal antibody such as trastuzumab in breast cancer, and may
improve the treatment strategy of breast cancer. The investigator will determine the use of
99mTc-HPArk2 SPECT/CT in stratifying breast cancer.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">December 7, 2019</start_date>
<completion_date type="Actual">December 31, 2020</completion_date>
<primary_completion_date type="Actual">December 31, 2020</primary_completion_date>
<phase>Early Phase 1</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<primary_purpose>Diagnostic</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Standardized uptake value of 99mTc-HPArk2 in breast tumor</measure>
<time_frame>1 year</time_frame>
<description>The semiquantitative analysis will be performed by the same person for all the cases, and the standardized uptake value (SUV) of the tracer in breast tumor will be measured. SUV were obtained by a self-made software and referring to phantom study.</description>
</primary_outcome>
<secondary_outcome>
<measure>Adverse events collection</measure>
<time_frame>1 week</time_frame>
<description>Adverse events within 1 week after the injection and scanning of patients and patients will be followed and assessed</description>
</secondary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Actual">34</enrollment>
<condition>Breast Cancer</condition>
<arm_group>
<arm_group_label>99mTc-HPArk2 SPECT/CT</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>The patients were injected with 11.1 (MBq) per kilogram body weight of 99mTc-HPArk2 in one dose intravenously and underwent SPECT/CT scan 30-60 min later.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>99mTc-HPArk2</intervention_name>
<description>99mTc-HPArk2 were injected into the patients before the SPECT/CT scans</description>
<arm_group_label>99mTc-HPArk2 SPECT/CT</arm_group_label>
<other_name>99mTc labelled HER2 affibody</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- patients in suspicion of breast cancer by mammography or ultrasonography,and being
able to provide basic information and sign the written informed consent form

Exclusion Criteria:

- The exclusion criteria included claustrophobia, pregnancy, breastfeeding, kidney or
liver failure, inability to fulfill the study, and undergoing any preceding local or
systemic therapies that might interfere with HER2 binding.
</textblock>
</criteria>
<gender>Female</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>80 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Zhaohui Zhu, MD,PHD</last_name>
<role>Study Chair</role>
<affiliation>Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College</affiliation>
</overall_official>
<location>
<facility>
<name>Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College</name>
<address>
<city>Beijing</city>
<state>Beijing</state>
<zip>100730</zip>
<country>China</country>
</address>
</facility>
</location>
<location_countries>
<country>China</country>
</location_countries>
<verification_date>September 2022</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>September 13, 2022</last_update_submitted>
<last_update_submitted_qc>September 13, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">September 14, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>SPECT/CT</keyword>
<keyword>HER2 imaging</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Breast Neoplasms</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This is an open-label single photon emission tomography/computed tomography (SPECT/CT) study
to investigate the diagnostic performance and evaluation efficacy of 99mTc-HPArk2 in breast
cancer patients. A single dose of 11.1Mega-Becquerel (MBq) per kilogram body weight
99mTc-HPArk2 will be injected intravenously. Visual and semiquantitative method will be used
to assess the SPECT/CT images.
99mTc-HPArk2 is an affibody probe targeting HER2. The investigators will determine the use of
99mTc-HPArk2 SPECT/CT in the detection of HER2-positive breast cancer, and to compare its
diagnostic value with routine immunohistochemistry (IHC) pathological staining. HER2 imaging,
specifically to HER2 receptor expressed on malignant breast cancer cell surface, might help
for targeted therapy with monoclonal antibody such as trastuzumab in breast cancer, and may
improve the treatment strategy of breast cancer. The investigator will determine the use of
99mTc-HPArk2 SPECT/CT in stratifying breast cancer.
Inclusion Criteria:
- patients in suspicion of breast cancer by mammography or ultrasonography,and being
able to provide basic information and sign the written informed consent form
Exclusion Criteria:
- The exclusion criteria included claustrophobia, pregnancy, breastfeeding, kidney or
liver failure, inability to fulfill the study, and undergoing any preceding local or
systemic therapies that might interfere with HER2 binding.
|
NCT0426xxxx/NCT04267913.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267913</url>
</required_header>
<id_info>
<org_study_id>S1900D</org_study_id>
<secondary_id>NCI-2020-00171</secondary_id>
<secondary_id>S1900D</secondary_id>
<secondary_id>S1900D</secondary_id>
<secondary_id>U10CA180888</secondary_id>
<nct_id>NCT04267913</nct_id>
</id_info>
<brief_title>Testing of TAK228 (MLN0128, Sapanisertib) Plus Docetaxel to the Usual Standard of Care for Advanced Squamous Cell Lung Cancer (A Lung-MAP Treatment Trial)</brief_title>
<official_title>A Randomized Phase II Study of TAK228 (MLN0128, Sapanisertib) Plus Docetaxel Versus Standard of Care in Patients With Previously - Treated NFE2L2 or KEAP1-Positive Stage IV or Recurrent Squamous Cell Lung Cancer (ECOG-ACRIN LUNG-MAP Sub-Study)</official_title>
<sponsors>
<lead_sponsor>
<agency>SWOG Cancer Research Network</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>National Cancer Institute (NCI)</agency>
<agency_class>NIH</agency_class>
</collaborator>
</sponsors>
<source>SWOG Cancer Research Network</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This phase II LUNG-MAP treatment trial studies how well sapanisertib and docetaxel work for
the treatment for squamous cell lung cancer that is stage IV or has come back (recurrent).
Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for
cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop
the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by
stopping them from spreading. Giving sapanisertib and docetaxel may work better in treating
patients with squamous cell lung cancer compared to standard chemotherapy.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
PRIMARY OBJECTIVE:

I. To compare the investigator-assessed progression-free survival (IA-PFS) between patients
with NFE2L2 or KEAP1-positive stage IV or recurrent squamous cell lung cancer (SQCLC)
randomized to TAK228 (MLN0128, sapanisertib) + docetaxel versus standard of care therapy.

SECONDARY OBJECTIVES:

I. To compare overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1 between the treatment arms.

II. To compare overall survival (OS) between the treatment arms. III. To evaluate duration of
response (DOR) among responders within each treatment arm.

IV. To evaluate and compare the frequency and severity of toxicities associated within each
treatment arm.

V. To evaluate outcomes of IA-PFS, OS, and response in the subsets of patients eligible based
on the presence of NFE2L2 versus KEAP1 alterations.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To collect, process, and bank cell-free deoxyribonucleic acid (DNA) (cfDNA) at baseline,
cycle 2 day 1, and end of treatment for future development of a proposal to evaluate
comprehensive next-generation sequencing of circulating tumor DNA (ctDNA).

II. To establish a tissue/blood repository from patients with refractory non-small cell lung
cancer (NSCLC).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive docetaxel intravenously (IV) and dexamethasone IV over 30 minutes on
days 1 and 8 and sapanisertib orally (PO) once daily (QD) on days 2-4, 9-11, and 16-18.
Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
If docetaxel is discontinued, patients receive sapanisertib PO QD on days 1-21. Cycles repeat
every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive standard of care treatment comprising either docetaxel IV and
dexamethasone IV over 30 minutes on day 1 or docetaxel IV, dexamethasone IV over 30 minutes,
and ramucirumab IV over 60 minutes on day 1. Cycles repeat every 21 days in the absence of
disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years and
then at 3 years.
</textblock>
</detailed_description>
<overall_status>Withdrawn</overall_status>
<why_stopped>
The pharmaceutical company sold the compound and pulled out.
</why_stopped>
<start_date type="Anticipated">September 5, 2020</start_date>
<completion_date type="Anticipated">October 31, 2026</completion_date>
<primary_completion_date type="Anticipated">October 31, 2025</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Investigator-assessed progression-free survival (IA-PFS)</measure>
<time_frame>Up to 3 years</time_frame>
<description>IA-PFS will be compared between the arms using a stratified log-rank test.</description>
</primary_outcome>
<secondary_outcome>
<measure>Overall response rate (ORR)</measure>
<time_frame>Up to 3 years</time_frame>
<description>Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Duration of response</measure>
<time_frame>Up to 3 years</time_frame>
<description>Will be estimated using the Kaplan-Meier method. The Brookmeyer-Crowley method will be used to estimate 95% confidence intervals for the median. For point estimates at landmark times, the associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Hazard ratios for these outcomes will be estimated using a Cox Proportional Hazards regression model adjusting for the stratification factors.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Progression free survival</measure>
<time_frame>Up to 3 years</time_frame>
<description>Will be estimated using the Kaplan-Meier method. The Brookmeyer-Crowley method will be used to estimate 95% confidence intervals for the median. For point estimates at landmark times, the associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Hazard ratios for these outcomes will be estimated using a Cox Proportional Hazards regression model adjusting for the stratification factors.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Overall survival</measure>
<time_frame>Up to 3 years</time_frame>
<description>Will be estimated using the Kaplan-Meier method. The Brookmeyer-Crowley method will be used to estimate 95% confidence intervals for the median. For point estimates at landmark times, the associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Hazard ratios for these outcomes will be estimated using a Cox Proportional Hazards regression model adjusting for the stratification factors.</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">0</enrollment>
<condition>Lung Squamous Cell Carcinoma</condition>
<condition>Recurrent Lung Carcinoma</condition>
<condition>Stage IV Lung Cancer AJCC v8</condition>
<condition>Stage IVA Lung Cancer AJCC v8</condition>
<condition>Stage IVB Lung Cancer AJCC v8</condition>
<arm_group>
<arm_group_label>Arm A (docetaxel, dexamethasone, sapanisertib)</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Patients receive docetaxel IV and dexamethasone IV over 30 minutes on days 1 and 8 and sapanisertib PO QD on days 2-4, 9-11, and 16-18. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. If docetaxel is discontinued, patients receive sapanisertib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
</arm_group>
<arm_group>
<arm_group_label>Arm B (standard of care treatment)</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Patients receive standard of care treatment comprising either docetaxel IV and dexamethasone IV over 30 minutes on day 1 or docetaxel IV, dexamethasone IV over 30 minutes, and ramucirumab IV over 60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Dexamethasone</intervention_name>
<description>Given IV</description>
<arm_group_label>Arm A (docetaxel, dexamethasone, sapanisertib)</arm_group_label>
<arm_group_label>Arm B (standard of care treatment)</arm_group_label>
<other_name>Aacidexam</other_name>
<other_name>Adexone</other_name>
<other_name>Aknichthol Dexa</other_name>
<other_name>Alba-Dex</other_name>
<other_name>Alin</other_name>
<other_name>Alin Depot</other_name>
<other_name>Alin Oftalmico</other_name>
<other_name>Amplidermis</other_name>
<other_name>Anemul mono</other_name>
<other_name>Auricularum</other_name>
<other_name>Auxiloson</other_name>
<other_name>Baycadron</other_name>
<other_name>Baycuten</other_name>
<other_name>Baycuten N</other_name>
<other_name>Cortidexason</other_name>
<other_name>Cortisumman</other_name>
<other_name>Decacort</other_name>
<other_name>Decadrol</other_name>
<other_name>Decadron</other_name>
<other_name>Decadron DP</other_name>
<other_name>Decalix</other_name>
<other_name>Decameth</other_name>
<other_name>Decasone R.p.</other_name>
<other_name>Dectancyl</other_name>
<other_name>Dekacort</other_name>
<other_name>Deltafluorene</other_name>
<other_name>Deronil</other_name>
<other_name>Desamethasone</other_name>
<other_name>Desameton</other_name>
<other_name>Dexa-Mamallet</other_name>
<other_name>Dexa-Rhinosan</other_name>
<other_name>Dexa-Scheroson</other_name>
<other_name>Dexa-sine</other_name>
<other_name>Dexacortal</other_name>
<other_name>Dexacortin</other_name>
<other_name>Dexafarma</other_name>
<other_name>Dexafluorene</other_name>
<other_name>Dexalocal</other_name>
<other_name>Dexamecortin</other_name>
<other_name>Dexameth</other_name>
<other_name>Dexamethasone Intensol</other_name>
<other_name>Dexamethasonum</other_name>
<other_name>Dexamonozon</other_name>
<other_name>Dexapos</other_name>
<other_name>Dexinoral</other_name>
<other_name>Dexone</other_name>
<other_name>Dinormon</other_name>
<other_name>Fluorodelta</other_name>
<other_name>Fortecortin</other_name>
<other_name>Gammacorten</other_name>
<other_name>Hexadecadrol</other_name>
<other_name>Hexadrol</other_name>
<other_name>Lokalison-F</other_name>
<other_name>Loverine</other_name>
<other_name>Methylfluorprednisolone</other_name>
<other_name>Millicorten</other_name>
<other_name>Mymethasone</other_name>
<other_name>Orgadrone</other_name>
<other_name>Spersadex</other_name>
<other_name>TaperDex</other_name>
<other_name>Visumetazone</other_name>
<other_name>ZoDex</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Docetaxel</intervention_name>
<description>Given IV</description>
<arm_group_label>Arm A (docetaxel, dexamethasone, sapanisertib)</arm_group_label>
<arm_group_label>Arm B (standard of care treatment)</arm_group_label>
<other_name>Docecad</other_name>
<other_name>RP56976</other_name>
<other_name>Taxotere</other_name>
<other_name>Taxotere Injection Concentrate</other_name>
</intervention>
<intervention>
<intervention_type>Biological</intervention_type>
<intervention_name>Ramucirumab</intervention_name>
<description>Given IV</description>
<arm_group_label>Arm B (standard of care treatment)</arm_group_label>
<other_name>Anti-VEGFR-2 Fully Human Monoclonal Antibody IMC-1121B</other_name>
<other_name>Cyramza</other_name>
<other_name>IMC-1121B</other_name>
<other_name>LY3009806</other_name>
<other_name>Monoclonal Antibody HGS-ETR2</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Sapanisertib</intervention_name>
<description>Given PO</description>
<arm_group_label>Arm A (docetaxel, dexamethasone, sapanisertib)</arm_group_label>
<arm_group_label>Arm B (standard of care treatment)</arm_group_label>
<other_name>INK-128</other_name>
<other_name>INK128</other_name>
<other_name>MLN-0128</other_name>
<other_name>MLN0128</other_name>
<other_name>TAK-228</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Patients must be assigned to S1900D. Assignment to S1900D is determined by the S1400
or LUNGMAP protocol genomic profiling using the FoundationOne assay. Biomarker
eligibility for S1900D is based on the identification of an NFE2L2 mutation or KEAP1
alteration

- Patients must have a histologically or cytologically confirmed stage IV or recurrent
pure squamous cell lung cancer

- Patients must have measurable disease documented by computed tomography (CT) or
magnetic resonance imaging (MRI). The CT from a combined positron emission tomography
(PET)/CT may be used to document only non-measurable disease unless it is of
diagnostic quality. Measurable disease must be assessed within 28 days prior to
sub-study randomization. Pleural effusions, ascites and laboratory parameters are not
acceptable as the only evidence of disease. Non-measurable disease must be assessed
within 42 days prior to sub-study randomization. All disease must be assessed and
documented on the Baseline Tumor Assessment Form. Patients whose only measurable
disease is within a previous radiation therapy port must demonstrate clearly
progressive disease (in the opinion of the treating investigator) prior to
randomization. CT and MRI scans must be submitted for central review via transfer of
images and data (TRIAD)

- Patients must have a CT or MRI scan of the brain to evaluate for central nervous
system (CNS) disease within 42 days prior to sub-study randomization

- Patients with evidence of chronic hepatitis B virus (HBV) infection must have
undetectable HBV viral load on suppressive therapy within 28 days prior to sub-study
randomization

- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. Patients with HCV infection who are currently on treatment must have an
undetectable HCV viral load within 28 days prior to sub-study randomization

- Patients with a known history of human immunodeficiency virus (HIV) seropositivity:

- Must have undetectable viral load using standard HIV assays in clinical practice

- Must have CD4 count >= 400/mcL

- Must not require prophylaxis for any opportunistic infections (i.e., fungal,
mycobacterium avium complex [MAC], or pneumocystis pneumonia [PCP] prophylaxis)

- Must not be newly diagnosed within 12 months prior to sub-study randomization

- Patients must be able to swallow oral medications. Patients must not have any
impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of TAK228 (MLN0128, sapanisertib) (e.g. ulcerative
disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small
bowel resection, or enteric stomata)

- Patients must be able to safely receive at least one of the investigator's choice of
standard of care regimens

- Patients must have progressed (in the opinion of the treating physician) following the
most recent line of therapy

- Patients must have recovered (=< grade 1) from any side effects of prior therapy

- Absolute neutrophil count (ANC) >= 1,500/mcl (obtained within 28 days prior to
sub-study randomization)

- Platelet count >= 100,000 mcl (obtained within 28 days prior to sub-study
randomization)

- Hemoglobin >= 9 g/dL (obtained within 28 days prior to sub-study randomization).
Transfusion to obtain a hemoglobin (Hb) of >= 9 g/dl is acceptable

- Patients must have fasting triglycerides =< 300 mg/dL within 28 days prior to
sub-study randomization

- Serum bilirubin =< Institutional upper limit of normal (IULN) (within 28 days prior to
sub-study randomization. For patients with liver metastases, serum bilirubin must be
=< 2 x IULN

- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN (within
28 days prior to sub-study randomization) (if both ALT and AST are done, both must be
< 2 IULN). For patients with liver metastases, ALT or AST must be =< 5 x IULN (if both
ALT and AST are done, both must be =< 5 x IULN)

- Patients must have a serum creatinine =< the IULN or calculated creatinine clearance
>= 40 mL/min using the following Cockcroft-Gault formula. This specimen must have been
drawn and processed within 28 days prior to sub-study randomization

- Patients must have Zubrod performance status 0-1 documented within 28 days prior to
sub-study randomization

- Pre-study history and physical exam must be obtained within 28 days prior to
randomization

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
stage I or II cancer from which the patient is currently in complete remission, or any
other cancer from which the patient has been disease free for two years. In addition,
indolent or low-grade malignancies which are not expected to interfere with assessment
of the primary or toxicity endpoints are permissible (e.g. localized well
differentiated prostate cancer). These cases should be discussed with a study chair
prior to enrollment

- Patients must agree to have blood specimens submitted for circulating tumor DNA
(ctDNA)

- Patients must also be offered participation in banking and in the correlative studies
for collection and future use of specimens

- Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines

- As a part of the OPEN registration process the treating institution's identity is
provided in order to ensure that the current (within 365 days) date of institutional
review board approval for this study has been entered in the system

- Patients with impaired decision-making capacity are eligible as long as their
neurological or psychological condition does not preclude their safe participation in
the study (e.g., tracking pill consumption and reporting adverse events to the
investigator)

Exclusion Criteria:

- Patients must not have EGFR sensitizing mutations, EGFR T790M mutation, ALK gene
fusion, ROS 1 gene rearrangement, and BRAF V600E mutation unless they have progressed
following all standard of care targeted therapy

- Patient must not have leptomeningeal disease, spinal cord compression or brain
metastases unless: (1) metastases have been locally treated and have remained
clinically controlled and asymptomatic for at least 14 days following treatment, and
prior to sub-study randomization, AND (2) patient has no residual neurological
dysfunction and has been off corticosteroids for at least 14 days prior to sub-study
randomization. Patients with brain metastases that have not been treated may be
registered if the metastases are:

- < 2 mm OR deemed clinically equivocal, AND

- No evidence of shift, AND

- No focal or other neurologic deficits, AND

- No requirement for steroids, anti-seizure medications

- Patients must not have uncontrolled illnesses within 28 days prior to sub-study
randomization including:

- Uncontrolled asthma is defined as: oxygen (O2) saturation < 90% by arterial blood
gas analysis or pulse oximetry on room air

- Medically significant (symptomatic) bradycardia

- History of arrhythmia requiring an implantable cardiac defibrillator

- Symptomatic pulmonary hypertension

- Uncontrolled hypertension (use of anti-hypertensive agents to control
hypertension before cycle 1 day 1 [C1D1] is allowed)

- Clinically significant valvular disease

- Patients must not have received any radiation therapy within 14 days prior to
randomization

- Patients must not be planning to receive any concurrent chemotherapy, immunotherapy,
biologic or hormonal therapy for cancer treatment while receiving treatment on this
study. Concurrent use of hormones for non-cancer-related conditions (e.g. insulin for
diabetes and hormone replacement therapy) is acceptable

- Patient must not have had a major surgery within 14 days prior to sub-study
randomization. Patient must have fully recovered from the effects of prior surgery in
the opinion of the treating investigator

- Patients must not have previously received treatment with PI3K, AKT, PI3K/mTOR
inhibitors, TORC1/2 inhibitors or TORC1 inhibitors

- Patients must not have uncontrolled diabetes within 28 days prior to sub-study
randomization

- Definition of uncontrolled diabetes: Glycosylated hemoglobin (HbA1c) >= 8.0% and
fasting serum glucose (> 130 mg/dL) within 28 days prior to sub-study
randomization

- Patients must not have any grade III/IV cardiac disease as defined by the New York
Heart Association Criteria (i.e., patients with cardiac disease resulting in marked
limitation of physical activity or resulting in inability to carry on any physical
activity without discomfort), unstable angina pectoris, myocardial infarction within 6
months, or serious uncontrolled cardiac arrhythmia

- Patients must not have had an ischemic cerebrovascular event or pulmonary embolism
within 6 months

- Patients must not have a rate-corrected QT interval > 480 msec based on the 12-lead
electrocardiography (ECG) within 28 days prior to sub-study randomization (i.e.,
repeated demonstration of corrected QT [QTc] interval > 480 milliseconds, or history
of congenital long QT syndrome, or torsades de pointes). It is suggested that a local
cardiologist review the QTc intervals

- Patients must not have received any live attenuated vaccinations or been in close
contact with those who have received live vaccines within 28 days prior to sub-study
registration and throughout protocol treatment

- Patients must not be planning to use proton pump inhibitors (PPIs) at least one week
prior to sub-study randomization and throughout protocol treatment

- Patients must not be pregnant or nursing. Women of reproductive potential must have
agreed to use an effective contraceptive method and must not donate eggs during
protocol treatment and for 90 days after the last protocol treatment. Men of
reproductive potential must have agreed to use an effective contraceptive method and
must not donate sperm during protocol treatment and for 120 days after the last
protocol treatment. A woman is considered to be of "reproductive potential" if she has
had menses at any time in the preceding 12 consecutive months. In addition to routine
contraceptive methods, "effective contraception" also includes heterosexual celibacy
and surgery intended to prevent pregnancy (or with a side-effect of pregnancy
prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal
ligation. However, if at any point a previously celibate patient chooses to become
heterosexually active during the time period for use of contraceptive measures
outlined in the protocol, he/she is responsible for beginning contraceptive measures
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>N/A</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Paul K Paik</last_name>
<role>Principal Investigator</role>
<affiliation>SWOG Cancer Research Network</affiliation>
</overall_official>
<verification_date>November 2020</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>November 18, 2020</last_update_submitted>
<last_update_submitted_qc>November 18, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">November 20, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Carcinoma</mesh_term>
<mesh_term>Lung Neoplasms</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Dexamethasone</mesh_term>
<mesh_term>Dexamethasone acetate</mesh_term>
<mesh_term>Docetaxel</mesh_term>
<mesh_term>Ramucirumab</mesh_term>
<mesh_term>Antineoplastic Agents, Immunological</mesh_term>
<mesh_term>Antibodies</mesh_term>
<mesh_term>Immunoglobulins</mesh_term>
<mesh_term>Antibodies, Monoclonal</mesh_term>
<mesh_term>Lexatumumab</mesh_term>
<mesh_term>BB 1101</mesh_term>
</intervention_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This phase II LUNG-MAP treatment trial studies how well sapanisertib and docetaxel work for
the treatment for squamous cell lung cancer that is stage IV or has come back (recurrent).
Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for
cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop
the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by
stopping them from spreading. Giving sapanisertib and docetaxel may work better in treating
patients with squamous cell lung cancer compared to standard chemotherapy.
PRIMARY OBJECTIVE:
I. To compare the investigator-assessed progression-free survival (IA-PFS) between patients
with NFE2L2 or KEAP1-positive stage IV or recurrent squamous cell lung cancer (SQCLC)
randomized to TAK228 (MLN0128, sapanisertib) + docetaxel versus standard of care therapy.
SECONDARY OBJECTIVES:
I. To compare overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1 between the treatment arms.
II. To compare overall survival (OS) between the treatment arms. III. To evaluate duration of
response (DOR) among responders within each treatment arm.
IV. To evaluate and compare the frequency and severity of toxicities associated within each
treatment arm.
V. To evaluate outcomes of IA-PFS, OS, and response in the subsets of patients eligible based
on the presence of NFE2L2 versus KEAP1 alterations.
TRANSLATIONAL MEDICINE OBJECTIVES:
I. To collect, process, and bank cell-free deoxyribonucleic acid (DNA) (cfDNA) at baseline,
cycle 2 day 1, and end of treatment for future development of a proposal to evaluate
comprehensive next-generation sequencing of circulating tumor DNA (ctDNA).
II. To establish a tissue/blood repository from patients with refractory non-small cell lung
cancer (NSCLC).
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive docetaxel intravenously (IV) and dexamethasone IV over 30 minutes on
days 1 and 8 and sapanisertib orally (PO) once daily (QD) on days 2-4, 9-11, and 16-18.
Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
If docetaxel is discontinued, patients receive sapanisertib PO QD on days 1-21. Cycles repeat
every 21 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive standard of care treatment comprising either docetaxel IV and
dexamethasone IV over 30 minutes on day 1 or docetaxel IV, dexamethasone IV over 30 minutes,
and ramucirumab IV over 60 minutes on day 1. Cycles repeat every 21 days in the absence of
disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 2 years and
then at 3 years.
Inclusion Criteria:
- Patients must be assigned to S1900D. Assignment to S1900D is determined by the S1400
or LUNGMAP protocol genomic profiling using the FoundationOne assay. Biomarker
eligibility for S1900D is based on the identification of an NFE2L2 mutation or KEAP1
alteration
- Patients must have a histologically or cytologically confirmed stage IV or recurrent
pure squamous cell lung cancer
- Patients must have measurable disease documented by computed tomography (CT) or
magnetic resonance imaging (MRI). The CT from a combined positron emission tomography
(PET)/CT may be used to document only non-measurable disease unless it is of
diagnostic quality. Measurable disease must be assessed within 28 days prior to
sub-study randomization. Pleural effusions, ascites and laboratory parameters are not
acceptable as the only evidence of disease. Non-measurable disease must be assessed
within 42 days prior to sub-study randomization. All disease must be assessed and
documented on the Baseline Tumor Assessment Form. Patients whose only measurable
disease is within a previous radiation therapy port must demonstrate clearly
progressive disease (in the opinion of the treating investigator) prior to
randomization. CT and MRI scans must be submitted for central review via transfer of
images and data (TRIAD)
- Patients must have a CT or MRI scan of the brain to evaluate for central nervous
system (CNS) disease within 42 days prior to sub-study randomization
- Patients with evidence of chronic hepatitis B virus (HBV) infection must have
undetectable HBV viral load on suppressive therapy within 28 days prior to sub-study
randomization
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. Patients with HCV infection who are currently on treatment must have an
undetectable HCV viral load within 28 days prior to sub-study randomization
- Patients with a known history of human immunodeficiency virus (HIV) seropositivity:
- Must have undetectable viral load using standard HIV assays in clinical practice
- Must have CD4 count >= 400/mcL
- Must not require prophylaxis for any opportunistic infections (i.e., fungal,
mycobacterium avium complex [MAC], or pneumocystis pneumonia [PCP] prophylaxis)
- Must not be newly diagnosed within 12 months prior to sub-study randomization
- Patients must be able to swallow oral medications. Patients must not have any
impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of TAK228 (MLN0128, sapanisertib) (e.g. ulcerative
disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small
bowel resection, or enteric stomata)
- Patients must be able to safely receive at least one of the investigator's choice of
standard of care regimens
- Patients must have progressed (in the opinion of the treating physician) following the
most recent line of therapy
- Patients must have recovered (=< grade 1) from any side effects of prior therapy
- Absolute neutrophil count (ANC) >= 1,500/mcl (obtained within 28 days prior to
sub-study randomization)
- Platelet count >= 100,000 mcl (obtained within 28 days prior to sub-study
randomization)
- Hemoglobin >= 9 g/dL (obtained within 28 days prior to sub-study randomization).
Transfusion to obtain a hemoglobin (Hb) of >= 9 g/dl is acceptable
- Patients must have fasting triglycerides =< 300 mg/dL within 28 days prior to
sub-study randomization
- Serum bilirubin =< Institutional upper limit of normal (IULN) (within 28 days prior to
sub-study randomization. For patients with liver metastases, serum bilirubin must be
=< 2 x IULN
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN (within
28 days prior to sub-study randomization) (if both ALT and AST are done, both must be
< 2 IULN). For patients with liver metastases, ALT or AST must be =< 5 x IULN (if both
ALT and AST are done, both must be =< 5 x IULN)
- Patients must have a serum creatinine =< the IULN or calculated creatinine clearance
>= 40 mL/min using the following Cockcroft-Gault formula. This specimen must have been
drawn and processed within 28 days prior to sub-study randomization
- Patients must have Zubrod performance status 0-1 documented within 28 days prior to
sub-study randomization
- Pre-study history and physical exam must be obtained within 28 days prior to
randomization
- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
stage I or II cancer from which the patient is currently in complete remission, or any
other cancer from which the patient has been disease free for two years. In addition,
indolent or low-grade malignancies which are not expected to interfere with assessment
of the primary or toxicity endpoints are permissible (e.g. localized well
differentiated prostate cancer). These cases should be discussed with a study chair
prior to enrollment
- Patients must agree to have blood specimens submitted for circulating tumor DNA
(ctDNA)
- Patients must also be offered participation in banking and in the correlative studies
for collection and future use of specimens
- Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines
- As a part of the OPEN registration process the treating institution's identity is
provided in order to ensure that the current (within 365 days) date of institutional
review board approval for this study has been entered in the system
- Patients with impaired decision-making capacity are eligible as long as their
neurological or psychological condition does not preclude their safe participation in
the study (e.g., tracking pill consumption and reporting adverse events to the
investigator)
Exclusion Criteria:
- Patients must not have EGFR sensitizing mutations, EGFR T790M mutation, ALK gene
fusion, ROS 1 gene rearrangement, and BRAF V600E mutation unless they have progressed
following all standard of care targeted therapy
- Patient must not have leptomeningeal disease, spinal cord compression or brain
metastases unless: (1) metastases have been locally treated and have remained
clinically controlled and asymptomatic for at least 14 days following treatment, and
prior to sub-study randomization, AND (2) patient has no residual neurological
dysfunction and has been off corticosteroids for at least 14 days prior to sub-study
randomization. Patients with brain metastases that have not been treated may be
registered if the metastases are:
- < 2 mm OR deemed clinically equivocal, AND
- No evidence of shift, AND
- No focal or other neurologic deficits, AND
- No requirement for steroids, anti-seizure medications
- Patients must not have uncontrolled illnesses within 28 days prior to sub-study
randomization including:
- Uncontrolled asthma is defined as: oxygen (O2) saturation < 90% by arterial blood
gas analysis or pulse oximetry on room air
- Medically significant (symptomatic) bradycardia
- History of arrhythmia requiring an implantable cardiac defibrillator
- Symptomatic pulmonary hypertension
- Uncontrolled hypertension (use of anti-hypertensive agents to control
hypertension before cycle 1 day 1 [C1D1] is allowed)
- Clinically significant valvular disease
- Patients must not have received any radiation therapy within 14 days prior to
randomization
- Patients must not be planning to receive any concurrent chemotherapy, immunotherapy,
biologic or hormonal therapy for cancer treatment while receiving treatment on this
study. Concurrent use of hormones for non-cancer-related conditions (e.g. insulin for
diabetes and hormone replacement therapy) is acceptable
- Patient must not have had a major surgery within 14 days prior to sub-study
randomization. Patient must have fully recovered from the effects of prior surgery in
the opinion of the treating investigator
- Patients must not have previously received treatment with PI3K, AKT, PI3K/mTOR
inhibitors, TORC1/2 inhibitors or TORC1 inhibitors
- Patients must not have uncontrolled diabetes within 28 days prior to sub-study
randomization
- Definition of uncontrolled diabetes: Glycosylated hemoglobin (HbA1c) >= 8.0% and
fasting serum glucose (> 130 mg/dL) within 28 days prior to sub-study
randomization
- Patients must not have any grade III/IV cardiac disease as defined by the New York
Heart Association Criteria (i.e., patients with cardiac disease resulting in marked
limitation of physical activity or resulting in inability to carry on any physical
activity without discomfort), unstable angina pectoris, myocardial infarction within 6
months, or serious uncontrolled cardiac arrhythmia
- Patients must not have had an ischemic cerebrovascular event or pulmonary embolism
within 6 months
- Patients must not have a rate-corrected QT interval > 480 msec based on the 12-lead
electrocardiography (ECG) within 28 days prior to sub-study randomization (i.e.,
repeated demonstration of corrected QT [QTc] interval > 480 milliseconds, or history
of congenital long QT syndrome, or torsades de pointes). It is suggested that a local
cardiologist review the QTc intervals
- Patients must not have received any live attenuated vaccinations or been in close
contact with those who have received live vaccines within 28 days prior to sub-study
registration and throughout protocol treatment
- Patients must not be planning to use proton pump inhibitors (PPIs) at least one week
prior to sub-study randomization and throughout protocol treatment
- Patients must not be pregnant or nursing. Women of reproductive potential must have
agreed to use an effective contraceptive method and must not donate eggs during
protocol treatment and for 90 days after the last protocol treatment. Men of
reproductive potential must have agreed to use an effective contraceptive method and
must not donate sperm during protocol treatment and for 120 days after the last
protocol treatment. A woman is considered to be of "reproductive potential" if she has
had menses at any time in the preceding 12 consecutive months. In addition to routine
contraceptive methods, "effective contraception" also includes heterosexual celibacy
and surgery intended to prevent pregnancy (or with a side-effect of pregnancy
prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal
ligation. However, if at any point a previously celibate patient chooses to become
heterosexually active during the time period for use of contraceptive measures
outlined in the protocol, he/she is responsible for beginning contraceptive measures
|
NCT0426xxxx/NCT04267926.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267926</url>
</required_header>
<id_info>
<org_study_id>NURB-022-19S</org_study_id>
<secondary_id>4337</secondary_id>
<nct_id>NCT04267926</nct_id>
</id_info>
<brief_title>MitoQ for Fatigue in Multiple Sclerosis (MS)</brief_title>
<acronym>MitoQ</acronym>
<official_title>MitoQ for Fatigue in Multiple Sclerosis: A Placebo Controlled Trial</official_title>
<sponsors>
<lead_sponsor>
<agency>VA Office of Research and Development</agency>
<agency_class>U.S. Fed</agency_class>
</lead_sponsor>
</sponsors>
<source>VA Office of Research and Development</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
<is_us_export>No</is_us_export>
</oversight_info>
<brief_summary>
<textblock>
The purpose of this study is to determine whether MS patients who receive Oral mitoquinone
(MitoQ) have less fatigue than those receiving a placebo. A comparison between patient's
fatigue scored at baseline and fatigue scored 12 weeks after drug initiation will assess if
MitoQ has a significant change in fatigue.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Recruitment of subjects on hold due to COVID-19 pandemic

MitoQ is a potent antioxidant dietary supplement with potentially significant
immunomodulatory and anti-inflammatory properties. While the cause of MS related fatigue is
uncertain, the investigators believe that mitochondria dysfunction and resultant neuronal
energy depletion may be an important contributor to fatigue in MS.

This clinical trial will evaluate the potential beneficial effects of MitoQ on MS fatigue. It
will also explore the effects of MitoQ on cognitive function, quality of life and mood. If
enrolled in the study, patients will take two capsules of the study drug or placebo at the
same time every day for twelve weeks. There will be 4 study visits where the participant will
undergo medical and nervous system examinations, questionnaires, and blood draws. Because it
is a placebo-controlled trial, participants will have a 33% chance of receiving either
placebo (inactive), 20mg of MitoQ, or 40mg of MitoQ. This will be a blinded randomized study,
meaning neither the participant nor the investigator will know who received the placebo or
study drug.
</textblock>
</detailed_description>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">April 1, 2020</start_date>
<completion_date type="Anticipated">March 31, 2024</completion_date>
<primary_completion_date type="Anticipated">October 1, 2023</primary_completion_date>
<phase>Phase 1/Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>Double-blind, randomized trial</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>Double (Participant, Investigator)</masking>
<masking_description>The subject and investigator will be blinded.</masking_description>
</study_design_info>
<primary_outcome>
<measure>Modified Fatigue Inventory Scale (MFIS)</measure>
<time_frame>12 weeks</time_frame>
<description>MFIS is a self -reported fatigue survey. Scale 0 - 84</description>
</primary_outcome>
<secondary_outcome>
<measure>Symbol Digit Modalities Test (SDMT)</measure>
<time_frame>12 weeks</time_frame>
<description>SDMT measures cognitive function. Scale 0-110</description>
</secondary_outcome>
<secondary_outcome>
<measure>Expanded Disability Status Scale (EDSS)</measure>
<time_frame>12 weeks</time_frame>
<description>EDSS measures neurological function. Scale 0-10</description>
</secondary_outcome>
<secondary_outcome>
<measure>Beck's Depression Inventory (BDI)</measure>
<time_frame>12 weeks</time_frame>
<description>BDI is a self-reported questionnaire measuring depression. Scale 0-21</description>
</secondary_outcome>
<number_of_arms>3</number_of_arms>
<enrollment type="Anticipated">60</enrollment>
<condition>Multiple Sclerosis</condition>
<condition>Fatigue</condition>
<arm_group>
<arm_group_label>Placebo</arm_group_label>
<arm_group_type>Placebo Comparator</arm_group_type>
<description>Placebo</description>
</arm_group>
<arm_group>
<arm_group_label>20mg of MitoQ</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>20mg of oral mitoquinol</description>
</arm_group>
<arm_group>
<arm_group_label>40mg of MitoQ</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>40mg of Oral Mitoquinol</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>20 mg MitoQ</intervention_name>
<description>a third of subject will receive 20mg of oral MitoQ</description>
<arm_group_label>20mg of MitoQ</arm_group_label>
<other_name>Oral Mitoquinol</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Placebo</intervention_name>
<description>Subject will receive Placebo</description>
<arm_group_label>Placebo</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>40mg of MitoQ</intervention_name>
<description>a third of subjects will receive 40mg of MitoQ</description>
<arm_group_label>40mg of MitoQ</arm_group_label>
<other_name>Oral Mitoquinol</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- MS (any clinical subtype) as diagnosed by the 2017 McDonald criteria

- EDSS score of 2 to 8

- complaint of fatigue that has been persistent for at least two months

- Modified Fatigue Impact Scale (MFIS) score of 38 or greater

Exclusion Criteria:

- treatment with systemic glucocorticoids in the prior six weeks

- Beck Depression Inventory (BDI) >31 or BDI-FS>10 (severe depression)

- significant MS exacerbation in prior 30 days

- previous use of MitoQ or Coenzyme Q10 (CoQ10) within thirty days of screening
appointment

- other significant health problem that might increase risk of patient experiencing
Adverse Events (AEs), e.g.:

- active coronary heart disease

- liver disease

- pulmonary disease

- diabetes mellitus

- pregnancy or intending to become pregnant or breastfeeding

- unable to complete the self-report forms

- unable to give informed consent

- prisoners

- any condition which would make the patient in the opinion of the investigator
unsuitable for the study
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>70 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Vijayshree Yadav, MBBS</last_name>
<role>Principal Investigator</role>
<affiliation>VA Portland Health Care System, Portland, OR</affiliation>
</overall_official>
<overall_contact>
<last_name>Allison Fryman</last_name>
<phone>(503) 220-8262</phone>
<email>fryman@ohsu.edu</email>
</overall_contact>
<overall_contact_backup>
<last_name>Vijayshree Yadav, MBBS</last_name>
<phone>(503) 220-8262</phone>
<email>vijayshree.yadav@va.gov</email>
</overall_contact_backup>
<location>
<facility>
<name>VA Portland Health Care System, Portland, OR</name>
<address>
<city>Portland</city>
<state>Oregon</state>
<zip>97207-2964</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Allison Fryman</last_name>
<phone>503-220-8262</phone>
<email>fryman@ohsu.edu</email>
</contact>
<contact_backup>
<last_name>Vijayshree Yadav, MBBS</last_name>
<phone>(503) 220-8262</phone>
<email>vijayshree.yadav@va.gov</email>
</contact_backup>
<investigator>
<last_name>Vijayshree Yadav, MBBS</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>May 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>May 10, 2023</last_update_submitted>
<last_update_submitted_qc>May 10, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">May 11, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Multiple Sclerosis</keyword>
<keyword>Fatigue</keyword>
<keyword>Mitochondrial</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Multiple Sclerosis</mesh_term>
<mesh_term>Sclerosis</mesh_term>
<mesh_term>Fatigue</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Ubiquinone</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The purpose of this study is to determine whether MS patients who receive Oral mitoquinone
(MitoQ) have less fatigue than those receiving a placebo. A comparison between patient's
fatigue scored at baseline and fatigue scored 12 weeks after drug initiation will assess if
MitoQ has a significant change in fatigue.
Recruitment of subjects on hold due to COVID-19 pandemic
MitoQ is a potent antioxidant dietary supplement with potentially significant
immunomodulatory and anti-inflammatory properties. While the cause of MS related fatigue is
uncertain, the investigators believe that mitochondria dysfunction and resultant neuronal
energy depletion may be an important contributor to fatigue in MS.
This clinical trial will evaluate the potential beneficial effects of MitoQ on MS fatigue. It
will also explore the effects of MitoQ on cognitive function, quality of life and mood. If
enrolled in the study, patients will take two capsules of the study drug or placebo at the
same time every day for twelve weeks. There will be 4 study visits where the participant will
undergo medical and nervous system examinations, questionnaires, and blood draws. Because it
is a placebo-controlled trial, participants will have a 33% chance of receiving either
placebo (inactive), 20mg of MitoQ, or 40mg of MitoQ. This will be a blinded randomized study,
meaning neither the participant nor the investigator will know who received the placebo or
study drug.
Inclusion Criteria:
- MS (any clinical subtype) as diagnosed by the 2017 McDonald criteria
- EDSS score of 2 to 8
- complaint of fatigue that has been persistent for at least two months
- Modified Fatigue Impact Scale (MFIS) score of 38 or greater
Exclusion Criteria:
- treatment with systemic glucocorticoids in the prior six weeks
- Beck Depression Inventory (BDI) >31 or BDI-FS>10 (severe depression)
- significant MS exacerbation in prior 30 days
- previous use of MitoQ or Coenzyme Q10 (CoQ10) within thirty days of screening
appointment
- other significant health problem that might increase risk of patient experiencing
Adverse Events (AEs), e.g.:
- active coronary heart disease
- liver disease
- pulmonary disease
- diabetes mellitus
- pregnancy or intending to become pregnant or breastfeeding
- unable to complete the self-report forms
- unable to give informed consent
- prisoners
- any condition which would make the patient in the opinion of the investigator
unsuitable for the study
|
NCT0426xxxx/NCT04267939.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267939</url>
</required_header>
<id_info>
<org_study_id>18595</org_study_id>
<secondary_id>2018-003930-34</secondary_id>
<nct_id>NCT04267939</nct_id>
</id_info>
<brief_title>ATR Inhibitor Elimusertib (BAY1895344) Plus Niraparib Phase 1b Study in Advanced Solid Tumors and Ovarian Cancer</brief_title>
<official_title>An Open-label Phase 1b Study to Determine the Maximum Tolerated and/or Recommended Phase 2 Dose of the ATR Inhibitor Elimusertib (BAY 1895344) in Combination With PARP Inhibitor Niraparib, in Participants With Recurrent Advanced Solid Tumors and Ovarian Cancer</official_title>
<sponsors>
<lead_sponsor>
<agency>Bayer</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
<collaborator>
<agency>GlaxoSmithKline</agency>
<agency_class>Industry</agency_class>
</collaborator>
</sponsors>
<source>Bayer</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The purpose of the study is to test how well patients with advanced solid tumors and ovarian
cancer respond to treatment with elimusertib in combination with niraparib. In addition
researchers want to find for patients the optimal dose of elimusertib in combination with
niraparib, how the drug is tolerated and the way the body absorbs, distributes and discharges
the drug. The study medication elimusertib works by blocking a substance produced by the body
(ATR Kinase) which is important for the growth of tumor cells. Niraparib works by blocking a
substance produced by the body (PARP enzymes) in a way that tumor cells can be killed, or
made more susceptible to chemotherapy.
</textblock>
</brief_summary>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">February 26, 2020</start_date>
<completion_date type="Anticipated">March 3, 2025</completion_date>
<primary_completion_date type="Anticipated">March 3, 2025</primary_completion_date>
<phase>Phase 1</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Non-Randomized</allocation>
<intervention_model>Sequential Assignment</intervention_model>
<primary_purpose>Other</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Incidence of treatment emergent adverse events (TEAEs)</measure>
<time_frame>Up to 30 days after the last administration of study intervention</time_frame>
</primary_outcome>
<primary_outcome>
<measure>Severity of treatment emergent adverse events (TEAEs)</measure>
<time_frame>Up to 30 days after the last administration of study intervention</time_frame>
</primary_outcome>
<primary_outcome>
<measure>Incidence of treatment emergent serious adverse events (TESAEs)</measure>
<time_frame>Up to 30 days after the last administration of study intervention</time_frame>
</primary_outcome>
<primary_outcome>
<measure>Severity of treatment emergent serious adverse events (TESAEs)</measure>
<time_frame>Up to 30 days after the last administration of study intervention</time_frame>
</primary_outcome>
<primary_outcome>
<measure>Maximum tolerated dose (MTD): Frequency of Dose Limiting Toxicities (DLTs) at each dose level during the DLT observation period for Cycle 1</measure>
<time_frame>Cycle 1, 28 days after first administration of study intervention</time_frame>
</primary_outcome>
<primary_outcome>
<measure>Recommended Phase II dose (RP2D) of elimusertib</measure>
<time_frame>Up to 30 days after last administration of study Intervention</time_frame>
</primary_outcome>
<secondary_outcome>
<measure>Incidence of participants with complete response (CR)</measure>
<time_frame>At baseline and at the start of every 2nd cycle (each cycle is 28 days) starting with Cycle 3, and at the start of every 4th cycle after Cycle 11 up to 24 months.</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>Incidence of participants with partial response (PR)</measure>
<time_frame>At baseline and at the start of every 2nd cycle (each cycle is 28 days) starting with Cycle 3, and at the start of every 4th cycle after Cycle 11 up to 24 months.</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>Incidence of participants with stable disease (SD)</measure>
<time_frame>At baseline and at the start of every 2nd cycle (each cycle is 28 days) starting with Cycle 3, and at the start of every 4th cycle after Cycle 11 up to 24 months.</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>Incidence of participants with progressive disease (PD)</measure>
<time_frame>At baseline and at the start of every 2nd cycle (each cycle is 28 days) starting with Cycle 3, and at the start of every 4th cycle after Cycle 11 up to 24 months.</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>Objective response rate (ORR)</measure>
<time_frame>At baseline and at the start of every 2nd cycle (each cycle is 28 days) starting with Cycle 3, and at the start of every 4th cycle after Cycle 11 up to 24 months.</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>Disease control rate (DCR)</measure>
<time_frame>At baseline and at the start of every 2nd cycle (each cycle is 28 days) starting with Cycle 3, and at the start of every 4th cycle after Cycle 11 up to 24 months.</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>Cmax (Maximal plasma exposure) of elimusertib after single dose administration</measure>
<time_frame>Cycle 1 Day 5 and Cycle 1 Day 21, each cycle is 28 days.</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>AUC(0-8) of elimusertib after single dose administration</measure>
<time_frame>Cycle 1 Day 5 and Cycle 1 Day 21, each cycle is 28 days.</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>Cmax,md of elimusertib after multiple dose administration</measure>
<time_frame>Cycle 1 Day 5 and Cycle 1 Day 21, each cycle is 28 days.</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>AUC(0-8)md of elimusertib after multiple dose administration</measure>
<time_frame>Cycle 1 Day 5 and Cycle 1 Day 21, each cycle is 28 days.</time_frame>
<description>AUC: Area under the curve</description>
</secondary_outcome>
<number_of_arms>6</number_of_arms>
<enrollment type="Anticipated">89</enrollment>
<condition>Advanced Solid Tumors (Excluding Prostate Cancer)</condition>
<condition>Ovarian Cancer</condition>
<arm_group>
<arm_group_label>Dose escalation of elimusertib_Part A.1</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Dose escalation will initiate with Part A.1 in which niraparib is used at a lower fixed dose.</description>
</arm_group>
<arm_group>
<arm_group_label>Dose escalation of elimusertib_Part A.2</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>If the starting dose level in Part A.1 is tolerated, dose escalation in Part A.2 may be initiated on an optional basis. In Part A.2, niraparib is used at a higher fixed dose.</description>
</arm_group>
<arm_group>
<arm_group_label>Dose expansion_sub-population 1_lower dose of niraparib</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>MTDs and/or candidate RP2Ds for elimusertib used in combination with niraparib at a lower fixed dose.
MTD: Maximum tolerated dose. RP2D: Recommended phase 2 dose.</description>
</arm_group>
<arm_group>
<arm_group_label>Dose expansion_sub-population 2_lower dose of niraparib</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>MTDs and/or candidate RP2Ds for elimusertib used in combination with niraparib at a lower fixed dose.</description>
</arm_group>
<arm_group>
<arm_group_label>Dose expansion_sub-population 1_higher dose of niraparib</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>MTDs and/or candidate RP2Ds for elimusertib used in combination with niraparib at a higher fixed dose.</description>
</arm_group>
<arm_group>
<arm_group_label>Dose expansion_sub-population 2_higher dose of niraparib</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>MTDs and/or candidate RP2Ds for elimusertib used in combination with niraparib at a higher fixed dose.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Elimusertib (BAY1895344)</intervention_name>
<description>Elimusertib will be administered in 28-day cycles.</description>
<arm_group_label>Dose escalation of elimusertib_Part A.1</arm_group_label>
<arm_group_label>Dose escalation of elimusertib_Part A.2</arm_group_label>
<arm_group_label>Dose expansion_sub-population 1_higher dose of niraparib</arm_group_label>
<arm_group_label>Dose expansion_sub-population 1_lower dose of niraparib</arm_group_label>
<arm_group_label>Dose expansion_sub-population 2_higher dose of niraparib</arm_group_label>
<arm_group_label>Dose expansion_sub-population 2_lower dose of niraparib</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Niraparib</intervention_name>
<description>Niraparib will be administered in 28-day cycles.</description>
<arm_group_label>Dose escalation of elimusertib_Part A.1</arm_group_label>
<arm_group_label>Dose escalation of elimusertib_Part A.2</arm_group_label>
<arm_group_label>Dose expansion_sub-population 1_higher dose of niraparib</arm_group_label>
<arm_group_label>Dose expansion_sub-population 1_lower dose of niraparib</arm_group_label>
<arm_group_label>Dose expansion_sub-population 2_higher dose of niraparib</arm_group_label>
<arm_group_label>Dose expansion_sub-population 2_lower dose of niraparib</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Participant must be ≥ 18 years of age, at the time of signing the informed consent.

- Participants must have histologically confirmed diagnosis of the following indications
as described below:

- Dose escalation (Part A): recurrent advanced solid tumors, excluding prostate
cancer, who experienced disease progression after treatment with standard of care
therapy for metastatic disease.

- Dose expansion (Part B): recurrent EOC, fallopian tube or primary peritoneal
cancer

- Sub-population 1: participants PARPi naïve and with a
platinum-resistant/refractory disease (recurrence with a PFI < 6 months from
last platinum-based regimen). Participants may not have had more than 3
prior therapies since the development of platinum resistance.

- Sub-population 2: participants with disease progression on PARPi (including
niraparib), administered as maintenance as well active line of therapy.
Participants must have not received further line of therapy after disease
progression on PARPi.

- Participants in dose escalation (Part A) of the study will need to have
tumor-associated DDR deficiency and/or CCNE1 gene amplification.

-- A homozygous deletion and/or a deleterious mutation in a gene reported to be
involved in DNA repair and/or sensitive to ATRi's and/or PARPi's.

- Participants in dose expansion (Part B) of the study will need to have tumor
associated DDR deficiency (Sub-population 1). Participants in Part B (Sub-population
2) are not enrolled based on the presence or absence of a particular biomarker.

- Participants must have disease progression and measurable disease, as defined by
RECIST 1.1.

- Available archival tumor tissue ≤ 12 months old, otherwise a fresh baseline tumor
biopsy should be obtained.

- ECOG PS of 0 to 1

- Life expectancy of at least 12 weeks

- Adequate bone marrow function as assessed by the following laboratory tests to be
conducted within 7 (±2) days before the first dose of study intervention:

- Hemoglobin (Hb) ≥ 10 g/dL

- Platelet count ≥ 150 x 10^9/L

- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

- Participants must have adequate organ function.

- Participants must have adequate coagulation.

- Adequate cardiac function per institutional normal measured by echocardiography
(recommended) or cardiac MRI per institutional guidelines.

- A female participant is eligible to participate if she is not pregnant (confirmed by a
negative serum pregnancy test within 7 (±2) days of first study intervention), not
breastfeeding, or is not a woman of childbearing potential (WOCBP). WOCBP must agree
to use highly effective contraception during the intervention period and for at least
6 months (180 days) after the last dose of study intervention.

Exclusion Criteria:

- Inability to swallow oral medication

- Known hypersensitivity to elimusertib and/or niraparib or excipients of the
preparations or any agent given in association with this study

- History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis

- Ongoing or active uncontrolled infection (bacterial, fungal, or viral; e.g. hepatitis
viral) of CTCAE grade ≥ 2 that requires systemic treatment

- Participants with HIV may be be ineligible depending on various parameters, but are
not automatically excluded.

- Immunocompromised participants (e.g. diagnosis of immunodeficiency or ongoing
immunosuppressive therapy)

- Pleural effusion or ascites that causes respiratory compromise (CTCAE grade ≥ 2
dyspnea)

- Active HBV or HCV infection that requires treatment.

- Moderate or severe hepatic impairment, i.e. Child Pugh Class B or C

- Participants with significant cardiovascular disease and/or relevant findings meeting
the below criteria are excluded:

- History of cardiac disease: congestive heart failure NYHA class > II, unstable
angina (angina symptoms at rest), new-onset angina (within the past 6 months
before study entry), myocardial infarction within the past 6 months before study
entry, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers,
calcium channel blockers, and digoxin are permitted).

- Clinically relevant findings in the ECG such as a second- or third-degree
atrioventricular block, prolongation of the QRS complex ≥ 120 ms, or prolongation
of the of the QTc interval (Fridericia) over 450 ms unless agreed otherwise
between the investigator and the sponsor's medically responsible person. QTc >
450 ms detected in 2 or more time points within a 24-hour period are excluded.

- Clinically significant arterial hypertension despite optimal medical management
(per investigator´s opinion). Clinically significant hypertension defined as
systolic blood pressure above 150 mmHg and/or diastolic blood pressure above 90
mmHg, despite optimal medical management. For participants taking
antihypertensive medication, blood pressure should be stable/ controlled for more
than 7 days before first dose of study medication.

- Previous treatment with an ATR Inhibitor

- Participants in Part A and Part B (Sub-population 2): Previous treatment with known or
putative PARPi, if discontinued for CTCAE grade ≥ 3 AEs or CTCAE grade ≥ 3
hypersensitivity to PARPi. Participants in Part B Sub-population 1 must not have
received prior PARPi treatment.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Bayer Study Director</last_name>
<role>Study Director</role>
<affiliation>Bayer</affiliation>
</overall_official>
<overall_contact>
<last_name>Bayer Clinical Trials Contact</last_name>
<phone>(+) 1-888-8422937</phone>
<email>clinical-trials-contact@bayer.com</email>
</overall_contact>
<location>
<facility>
<name>Dana-Farber Cancer Institute</name>
<address>
<city>Boston</city>
<state>Massachusetts</state>
<zip>02215</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
</location>
<location>
<facility>
<name>Memorial Sloan-Kettering Cancer Center</name>
<address>
<city>New York</city>
<state>New York</state>
<zip>10065</zip>
<country>United States</country>
</address>
</facility>
<status>Completed</status>
</location>
<location>
<facility>
<name>Cleveland Clinic Foundation</name>
<address>
<city>Cleveland</city>
<state>Ohio</state>
<zip>44195</zip>
<country>United States</country>
</address>
</facility>
<status>Withdrawn</status>
</location>
<location>
<facility>
<name>University of Texas MD Anderson Cancer Center</name>
<address>
<city>Houston</city>
<state>Texas</state>
<zip>77030</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
</location>
<location>
<facility>
<name>Ospedale Regionale di Bellinzona e Valli</name>
<address>
<city>Bellinzona</city>
<state>Ticino</state>
<zip>6500</zip>
<country>Switzerland</country>
</address>
</facility>
<status>Not yet recruiting</status>
</location>
<location_countries>
<country>Switzerland</country>
<country>United States</country>
</location_countries>
<verification_date>September 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>September 8, 2023</last_update_submitted>
<last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">September 11, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Ovarian Neoplasms</mesh_term>
<mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Niraparib</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
<ipd_description>Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.
Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.</ipd_description>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The purpose of the study is to test how well patients with advanced solid tumors and ovarian
cancer respond to treatment with elimusertib in combination with niraparib. In addition
researchers want to find for patients the optimal dose of elimusertib in combination with
niraparib, how the drug is tolerated and the way the body absorbs, distributes and discharges
the drug. The study medication elimusertib works by blocking a substance produced by the body
(ATR Kinase) which is important for the growth of tumor cells. Niraparib works by blocking a
substance produced by the body (PARP enzymes) in a way that tumor cells can be killed, or
made more susceptible to chemotherapy.
Inclusion Criteria:
- Participant must be ≥ 18 years of age, at the time of signing the informed consent.
- Participants must have histologically confirmed diagnosis of the following indications
as described below:
- Dose escalation (Part A): recurrent advanced solid tumors, excluding prostate
cancer, who experienced disease progression after treatment with standard of care
therapy for metastatic disease.
- Dose expansion (Part B): recurrent EOC, fallopian tube or primary peritoneal
cancer
- Sub-population 1: participants PARPi naïve and with a
platinum-resistant/refractory disease (recurrence with a PFI < 6 months from
last platinum-based regimen). Participants may not have had more than 3
prior therapies since the development of platinum resistance.
- Sub-population 2: participants with disease progression on PARPi (including
niraparib), administered as maintenance as well active line of therapy.
Participants must have not received further line of therapy after disease
progression on PARPi.
- Participants in dose escalation (Part A) of the study will need to have
tumor-associated DDR deficiency and/or CCNE1 gene amplification.
-- A homozygous deletion and/or a deleterious mutation in a gene reported to be
involved in DNA repair and/or sensitive to ATRi's and/or PARPi's.
- Participants in dose expansion (Part B) of the study will need to have tumor
associated DDR deficiency (Sub-population 1). Participants in Part B (Sub-population
2) are not enrolled based on the presence or absence of a particular biomarker.
- Participants must have disease progression and measurable disease, as defined by
RECIST 1.1.
- Available archival tumor tissue ≤ 12 months old, otherwise a fresh baseline tumor
biopsy should be obtained.
- ECOG PS of 0 to 1
- Life expectancy of at least 12 weeks
- Adequate bone marrow function as assessed by the following laboratory tests to be
conducted within 7 (±2) days before the first dose of study intervention:
- Hemoglobin (Hb) ≥ 10 g/dL
- Platelet count ≥ 150 x 10^9/L
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
- Participants must have adequate organ function.
- Participants must have adequate coagulation.
- Adequate cardiac function per institutional normal measured by echocardiography
(recommended) or cardiac MRI per institutional guidelines.
- A female participant is eligible to participate if she is not pregnant (confirmed by a
negative serum pregnancy test within 7 (±2) days of first study intervention), not
breastfeeding, or is not a woman of childbearing potential (WOCBP). WOCBP must agree
to use highly effective contraception during the intervention period and for at least
6 months (180 days) after the last dose of study intervention.
Exclusion Criteria:
- Inability to swallow oral medication
- Known hypersensitivity to elimusertib and/or niraparib or excipients of the
preparations or any agent given in association with this study
- History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis
- Ongoing or active uncontrolled infection (bacterial, fungal, or viral; e.g. hepatitis
viral) of CTCAE grade ≥ 2 that requires systemic treatment
- Participants with HIV may be be ineligible depending on various parameters, but are
not automatically excluded.
- Immunocompromised participants (e.g. diagnosis of immunodeficiency or ongoing
immunosuppressive therapy)
- Pleural effusion or ascites that causes respiratory compromise (CTCAE grade ≥ 2
dyspnea)
- Active HBV or HCV infection that requires treatment.
- Moderate or severe hepatic impairment, i.e. Child Pugh Class B or C
- Participants with significant cardiovascular disease and/or relevant findings meeting
the below criteria are excluded:
- History of cardiac disease: congestive heart failure NYHA class > II, unstable
angina (angina symptoms at rest), new-onset angina (within the past 6 months
before study entry), myocardial infarction within the past 6 months before study
entry, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers,
calcium channel blockers, and digoxin are permitted).
- Clinically relevant findings in the ECG such as a second- or third-degree
atrioventricular block, prolongation of the QRS complex ≥ 120 ms, or prolongation
of the of the QTc interval (Fridericia) over 450 ms unless agreed otherwise
between the investigator and the sponsor's medically responsible person. QTc >
450 ms detected in 2 or more time points within a 24-hour period are excluded.
- Clinically significant arterial hypertension despite optimal medical management
(per investigator´s opinion). Clinically significant hypertension defined as
systolic blood pressure above 150 mmHg and/or diastolic blood pressure above 90
mmHg, despite optimal medical management. For participants taking
antihypertensive medication, blood pressure should be stable/ controlled for more
than 7 days before first dose of study medication.
- Previous treatment with an ATR Inhibitor
- Participants in Part A and Part B (Sub-population 2): Previous treatment with known or
putative PARPi, if discontinued for CTCAE grade ≥ 3 AEs or CTCAE grade ≥ 3
hypersensitivity to PARPi. Participants in Part B Sub-population 1 must not have
received prior PARPi treatment.
|
NCT0426xxxx/NCT04267952.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267952</url>
</required_header>
<id_info>
<org_study_id>509055</org_study_id>
<nct_id>NCT04267952</nct_id>
</id_info>
<brief_title>Hand Hygiene Intervention Program on Primary School Students' Health Outcomes and Absenteeism in School</brief_title>
<official_title>The Effect of the Theory of Planned Behaviour Based Hand Hygiene Intervention Program on Primary School Students' Health Outcomes and Absenteeism in School</official_title>
<sponsors>
<lead_sponsor>
<agency>Izmir Katip Celebi University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Izmir Katip Celebi University</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The most common infections in schools are acute respiratory infections (colds, pharyngitis,
influenza and others) and diarrheal diseases. The incidence of these infections may also be
an important cause of school absenteeism, leading to negative outcomes in both education and
health.

WHO states that handwashing a well-known primary infection control measure, is the most
important hygiene measure to prevent the spread of infection when handwashing is done with
soap and water. Since behavioral choices that determine lifestyle are made in childhood, it
is important that health education in hand hygiene be implemented as early as possible to
improve healthy behaviors. In this context, schools are important structures for information
and behavior change about water, sanitation and hygiene interventions.

Planned Behavior Theory (PBT) states that intention is the main precursor of behavior.
According to the theory, intention is guided by three independent variables (perceived
behavior control, attitudes and subjective norms), and intention formation leads to the
development of behavior. The theory has been used in a study to improve hand hygiene behavior
in health workers, but it has not been used in the literature to improve hygiene behaviors in
children.

Researches indicate that students who do not attend school frequently or for a long time have
difficulty in mastering the subject described in the lesson and that school absenteeism is an
issue that should be emphasized in education. Therefore, hand hygiene has a simultaneous
effect that improves both education and health and contributes to a safe and healthy learning
environment. The aim of this research is; To test the effect of hand hygiene intervention
program based on Planned Behavior Theory on students' health outcomes and school absenteeism.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
The most common infections in schools are acute respiratory infections (colds, pharyngitis,
influenza and others) and diarrheal diseases. Acute respiratory infections are a major cause
of morbidity and mortality in children and a major public health problem in both developed
and developing countries. The incidence of these infections may also be an important cause of
school absenteeism, leading to negative outcomes in both education and health.

Improving water, sanitation and hygiene in schools is an important intervention for the
healthy development of children. WHO states that handwashing a well-known primary infection
control measure, is the most important hygiene measure to prevent the spread of infection
when handwashing is done with soap and water. It was found that well-structured and applied
handwashing techniques were useful in reducing the incidence of gastro-intestinal and
respiratory infections in school children; handwashing with soap reduces respiratory
infections in children by 16% - 25%.

In children, unlike adults, it is more likely to give positive behavior because negative
hygiene habits are less established and do not have stereotyped and difficult to change
habits. Since behavioral choices that determine lifestyle are made in childhood, it is
important that health education in hand hygiene be implemented as early as possible to
improve healthy behaviors. In this context, schools are important structures for information
and behavior change about water, sanitation and hygiene interventions. Hand hygiene
initiatives in the school provide multiple gains by enabling children to become hygienic
ambassadors in their own homes and gaining the skills they can sustain during the adult
period.

Planned Behavior Theory (PBT) states that intention is the main precursor of behavior.

According to the theory, intention is guided by three independent variables (perceived
behavior control, attitudes and subjective norms), and intention formation leads to the
development of behavior. In a systematic review of 30 studies using PBT in various health
interventions, two thirds of studies reported effective behavior change. The theory has been
used in a study to improve hand hygiene behavior in health workers, but it has not been used
in the literature to improve hygiene behaviors in children.

Researches indicate that students who do not attend school frequently or for a long time have
difficulty in mastering the subject described in the lesson and that school absenteeism is an
issue that should be emphasized in education. Therefore, hand hygiene has a simultaneous
effect that improves both education and health and contributes to a safe and healthy learning
environment. The aim of this research is; To test the effect of hand hygiene intervention
program based on Planned Behavior Theory on students' health outcomes and school absenteeism.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">September 9, 2019</start_date>
<completion_date type="Actual">June 29, 2020</completion_date>
<primary_completion_date type="Actual">June 29, 2020</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Prevention</primary_purpose>
<masking>Single (Participant)</masking>
<masking_description>Participation will not know whether they are in the experimental or control group.</masking_description>
</study_design_info>
<primary_outcome>
<measure>Group A Streptekok infections in rapid antigen test</measure>
<time_frame>Total 20 weeks</time_frame>
<description>Children with symptoms of infection will be referred to the family physician to have a rapid antigen test and to report the result to the researcher.</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of symptoms of acute upper respiratory tract infection</measure>
<time_frame>Total 20 weeks</time_frame>
<description>Ten identified upper respiratory tract symptoms (fever, sore throat, runny nose, etc.) will be recorded weekly by family of children. The researcher will receive symptom information from the family via weekly sms</description>
</primary_outcome>
<primary_outcome>
<measure>school absenteeism</measure>
<time_frame>Total 20 weeks</time_frame>
<description>The number of days the child does not attend school due to illness and the percentage of absenteeism</description>
</primary_outcome>
<secondary_outcome>
<measure>Pollution rate of hands</measure>
<time_frame>From date of randomization until the date of first documented progression assessed up to 7 months</time_frame>
<description>Glogerm gel applied hands will shine areas containing microorganisms. Contamination rate will be calculated by taking the photo of the hands and performing brightness analysis in adobe photoshop program.</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">159</enrollment>
<condition>Respiratory Tract; Infection, Upper (Acute)</condition>
<condition>Hand Hygiene</condition>
<condition>Absenteeism</condition>
<arm_group>
<arm_group_label>first group</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Hand hygiene intervention program prepared by using planned behavior theory will be applied to the students in this group.</description>
</arm_group>
<arm_group>
<arm_group_label>second group</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Students in this group will be given classic hand hygiene training</description>
</arm_group>
<intervention>
<intervention_type>Behavioral</intervention_type>
<intervention_name>Hand hygiene intervention program developed according to planned behavior theory</intervention_name>
<description>The perception of the importance of hand hygiene with expression of damages of microorganisms (stories about illnesses etc.). Visually assisted hand hygiene training experiments to ensure the visibility of microorganisms in the environment. Demonstration and application of the correct hand washing technique with music. All applications will take place in three lessons (120-minute).</description>
<arm_group_label>first group</arm_group_label>
</intervention>
<intervention>
<intervention_type>Behavioral</intervention_type>
<intervention_name>Classical hand hygiene education</intervention_name>
<description>expression of hand hygiene with verbal presentation method in a 40-minute lecture</description>
<arm_group_label>second group</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- primary school student (especially third and fourth class student)

Exclusion Criteria:

- people with chronic disease
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>7 Years</minimum_age>
<maximum_age>11 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Şafak Dağhan</last_name>
<role>Study Director</role>
<affiliation>Ege University, Nursing Faculty</affiliation>
</overall_official>
<location>
<facility>
<name>Gülçin Uyanık</name>
<address>
<city>İzmir</city>
<state>Cigli</state>
<zip>35620</zip>
<country>Turkey</country>
</address>
</facility>
</location>
<location_countries>
<country>Turkey</country>
</location_countries>
<reference>
<citation>Tai JW, Mok ES, Ching PT, Seto WH, Pittet D. Nurses and physicians' perceptions of the importance and impact of healthcare-associated infections and hand hygiene: a multi-center exploratory study in Hong Kong. Infection. 2009 Aug;37(4):320-33. doi: 10.1007/s15010-009-8245-x. Epub 2009 Jul 27.</citation>
<PMID>19636497</PMID>
</reference>
<verification_date>July 2020</verification_date>
<study_first_submitted>December 21, 2019</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>July 28, 2020</last_update_submitted>
<last_update_submitted_qc>July 28, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">July 29, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Izmir Katip Celebi University</investigator_affiliation>
<investigator_full_name>Gulcin Uyanık</investigator_full_name>
<investigator_title>Research Assistant</investigator_title>
</responsible_party>
<keyword>Health education</keyword>
<keyword>Theory of planned behavior</keyword>
<keyword>Primary schools</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Respiratory Tract Infections</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The most common infections in schools are acute respiratory infections (colds, pharyngitis,
influenza and others) and diarrheal diseases. The incidence of these infections may also be
an important cause of school absenteeism, leading to negative outcomes in both education and
health.
WHO states that handwashing a well-known primary infection control measure, is the most
important hygiene measure to prevent the spread of infection when handwashing is done with
soap and water. Since behavioral choices that determine lifestyle are made in childhood, it
is important that health education in hand hygiene be implemented as early as possible to
improve healthy behaviors. In this context, schools are important structures for information
and behavior change about water, sanitation and hygiene interventions.
Planned Behavior Theory (PBT) states that intention is the main precursor of behavior.
According to the theory, intention is guided by three independent variables (perceived
behavior control, attitudes and subjective norms), and intention formation leads to the
development of behavior. The theory has been used in a study to improve hand hygiene behavior
in health workers, but it has not been used in the literature to improve hygiene behaviors in
children.
Researches indicate that students who do not attend school frequently or for a long time have
difficulty in mastering the subject described in the lesson and that school absenteeism is an
issue that should be emphasized in education. Therefore, hand hygiene has a simultaneous
effect that improves both education and health and contributes to a safe and healthy learning
environment. The aim of this research is; To test the effect of hand hygiene intervention
program based on Planned Behavior Theory on students' health outcomes and school absenteeism.
The most common infections in schools are acute respiratory infections (colds, pharyngitis,
influenza and others) and diarrheal diseases. Acute respiratory infections are a major cause
of morbidity and mortality in children and a major public health problem in both developed
and developing countries. The incidence of these infections may also be an important cause of
school absenteeism, leading to negative outcomes in both education and health.
Improving water, sanitation and hygiene in schools is an important intervention for the
healthy development of children. WHO states that handwashing a well-known primary infection
control measure, is the most important hygiene measure to prevent the spread of infection
when handwashing is done with soap and water. It was found that well-structured and applied
handwashing techniques were useful in reducing the incidence of gastro-intestinal and
respiratory infections in school children; handwashing with soap reduces respiratory
infections in children by 16% - 25%.
In children, unlike adults, it is more likely to give positive behavior because negative
hygiene habits are less established and do not have stereotyped and difficult to change
habits. Since behavioral choices that determine lifestyle are made in childhood, it is
important that health education in hand hygiene be implemented as early as possible to
improve healthy behaviors. In this context, schools are important structures for information
and behavior change about water, sanitation and hygiene interventions. Hand hygiene
initiatives in the school provide multiple gains by enabling children to become hygienic
ambassadors in their own homes and gaining the skills they can sustain during the adult
period.
Planned Behavior Theory (PBT) states that intention is the main precursor of behavior.
According to the theory, intention is guided by three independent variables (perceived
behavior control, attitudes and subjective norms), and intention formation leads to the
development of behavior. In a systematic review of 30 studies using PBT in various health
interventions, two thirds of studies reported effective behavior change. The theory has been
used in a study to improve hand hygiene behavior in health workers, but it has not been used
in the literature to improve hygiene behaviors in children.
Researches indicate that students who do not attend school frequently or for a long time have
difficulty in mastering the subject described in the lesson and that school absenteeism is an
issue that should be emphasized in education. Therefore, hand hygiene has a simultaneous
effect that improves both education and health and contributes to a safe and healthy learning
environment. The aim of this research is; To test the effect of hand hygiene intervention
program based on Planned Behavior Theory on students' health outcomes and school absenteeism.
Inclusion Criteria:
- primary school student (especially third and fourth class student)
Exclusion Criteria:
- people with chronic disease
|
NCT0426xxxx/NCT04267965.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267965</url>
</required_header>
<id_info>
<org_study_id>201601901B0</org_study_id>
<nct_id>NCT04267965</nct_id>
</id_info>
<brief_title>Pulmonary Function, Voice and Swallowing Symptoms After Parathyroidectomy</brief_title>
<official_title>Changes of Pulmonary Function, Voice and Swallowing Symptoms After Total Parathyroidectomy for Secondary Hyperparathyroidism in the Presence of Intact Recurrent Laryngeal Nerve</official_title>
<sponsors>
<lead_sponsor>
<agency>Chang Gung Memorial Hospital</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Chang Gung Memorial Hospital</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
In this study, investigators measure patient's voice frequency, swallowing function, and O2
desaturation of the 6 mins walking test before surgery and 4 months after surgery, to find
the increase of voice frequency, and swallowing function and the decrease of O2 desaturation.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
This was a prospective case-control study. From July 2017 to Dec. 2018, investigators
recruited 38 patients, who had undergone a successful operation of total parathyroidectomy
and bilateral thymectomy (TPxBT) plus autotransplantation for symptomatic secondary
hyperparathyroidism as the study group. In the same period 4 patients who had a surgical
failure were excluded from the study. Indications for surgery were patients who had undergone
long-term regular hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), with
serum levels of Ca > 10.1 mg/dL, P > 5.5 mg/dL, alkaline phosphatase (Alk-ptase) > 94 U/L and
intact parathyroid hormone(iPTH) > 800 pg/mL and with symptoms and signs such as skin
itching, bone pain, general weakness, insomnia and T-score of bone mineral density (BMD) (the
lowest T-score of lumbar spine 1-4, global femur, femoral neck, radial 1/3, and global
radius) < -2.5. During surgery, Total parathyroidectomy and bilateral thymectomy was
performed plus autotranplantation of 100 mg of hyperplastic parathyroid tissue to the
subcutaneous tissue of the forearm without harboring an arteriovenous fistula.

Ten patients with regular hemodialysis who had developed mild secondary hyperparathyroidism
(iPTH around 500 pg/mL) but did not undergo parathyroidectomy were recruited as the control
group.

Investigators recorded patients' age, symptoms, gender, body mass index (BMI) and measured
serum levels of Ca, P, Alk-ptase and iPTH, and BMD (T-score). The Investigators also recorded
patients' voice quality, airway invasion during swallowing and pulmonary functions before
surgery and 4 months after surgery to find the changes after surgery. In the control group,
investigators recorded and measured these items at baseline and 4 months later.

At 1 week after surgery, serum Ca, P, Alk-ptase and iPTH levels were measured again to make
sure that the operation was successful. A successful operation was defined as iPTH levels <
72 pg/mL within 1 week after surgery. Four patients were excluded from this study with a
surgical failure in the same period.

The perceptual evaluation of voice quality such as speech impairment and speech quality by
means of multidimensional clinical measurements based on auditory methods with grade,
hoarseness, roughness, breathiness, asthenia, and strain (GRBAS) on a scale (0-3)
(normal-high degree) were performed by the ear, nose, and throat specialist (Dr. Lai, C.C.).
Voice handicap index (VHI-10) (>11, abnormal) and eating assessment tool (EAT-10) (≥ 3,
abnormal) were evaluated by patients themselves.

Acoustic and aerodynamic measurements were applied to recordings of each subject producing
sustained vowel productions in a soundproof room. Acoustic variables including jitter (Jitt),
shimmer (ShdB), noise-to-harmonic ratio (NHR), fundamental frequency (Fo), and high pitch
were measured using computerized speech laboratory (Core Model SCL # 4300B, KayPENTAX
Elementries, Lincoln park, NJ).

The maximal phonation time and s/z ratio were measured with circumferentially vented
pneumotachography mask and differential transducers of the Aerophone system (Aerophone II,
Model 6800, KayPENTAX Elementrics). Vocal cord mobility, vocal cord closure (complete or
incomplete), airway invasion during swallowing were inspected with fiber-optic endoscopy to
show premature spillage, penetration-aspiration scale levels (1-8) (no entry of material into
the larynx or trachea-material enter the airway passes below vocal folds and no effort is
made to eject) (>1, abnormal). The Yale pharyngeal residue severity rating scale for
vallecula (0-4) (non-trace-mild-moderate-severe) and pyriform sinus (0-4) were also performed
by the ENT specialist.

The specialist of chest medicine (Dr. Chang, H.C.) performed pulmonary function tests
including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1),
bronchodilator test (BDT) (a positive response to BDT defined by the American Thoracic
Society as an increase in FEV1 or FVC ≥ 12% and 200 ml), total lung capacity (TLC), and
alveolar volume (VA) using MasterScope (Jaeger, VIASYS healthcare GmbH, Höchberg, Germany),
and diffusion capacity of the lung for carbon monoxide (DLCO) using Vmax Autobox
(SensorMedics, a subsidiary of VIASYS healthcare, California, USA). The 6 minutes walking
test (6MWT) was also performed to evaluate distance (meter) and O2 desaturation (differences
of O2 saturation between pre- and post-tests) (defined as positive if O2 desaturation ≧ 4%).
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">August 1, 2017</start_date>
<completion_date type="Actual">July 31, 2019</completion_date>
<primary_completion_date type="Actual">July 31, 2019</primary_completion_date>
<study_type>Observational [Patient Registry]</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<target_duration>4 Months</target_duration>
<primary_outcome>
<measure>Successful surgery is defined as iPTH levels less than 72 pg/dL within one week after surgery</measure>
<time_frame>one week after surgery</time_frame>
<description>After successful surgery, patients were recruited in the study, and we excluded patients with a surgical failure.</description>
</primary_outcome>
<primary_outcome>
<measure>Voice impairment(GRBAS)</measure>
<time_frame>4 months after surgery</time_frame>
<description>speech impairment and speech quality were evaluated with GRBAS on a scale (0-3), VHI-10 (>11, abnormal) and (EAT-10) (≥ 3, abnormal) .
*GRBAS (grade, roughness, breathiness, asthenia, strain) scale grades hoarseness, roughness, breathiness, aesthenia (weakness), and strain on a scale of 0-3 0 = normal, 1 = mild degree, 2 = moderate degree, and 3 = high degree</description>
</primary_outcome>
<primary_outcome>
<measure>Voice impairment(VH1-10)</measure>
<time_frame>4 months after surgery</time_frame>
<description>speech impairment and speech quality were evaluated with voice handicap index (VHI-10) (>11, abnormal) 0-4 Rating Scale 0 = Normal
= Almost Normal
= Sometimes
= Abnormal
= Always</description>
</primary_outcome>
<primary_outcome>
<measure>Voice impairment(EAT-10)</measure>
<time_frame>4 months after surgery</time_frame>
<description>speech impairment and speech quality were evaluated with EAT-10 (≥ 3, abnormal) .
*eating assessment tool (EAT-10) 0 - 4 Rating Scale 0 = No problem
= Mild Problem
= Mild to moderate
= Moderate problem
= Severe problem</description>
</primary_outcome>
<primary_outcome>
<measure>Acoustic voice analysis</measure>
<time_frame>4 months after surgery</time_frame>
<description>mean frequency (F0, Hz); Noise-to-Harmonic Ratio (NHR), jitter(%), and shimmer (%)</description>
</primary_outcome>
<primary_outcome>
<measure>Vocal cord examination</measure>
<time_frame>4 months later</time_frame>
<description>The maximal phonation time (sec) and s/z ratio were measured with circumferentially vented pneumotachography mask and differential transducers of the Aerophone system .</description>
</primary_outcome>
<primary_outcome>
<measure>Fiber optic endoscopic evaluation of swallowing (FEES)</measure>
<time_frame>4 months later.</time_frame>
<description>Vocal cord mobility, vocal cord closure (complete or incomplete), airway invasion during swallowing were inspected with fiber-optic endoscopy to show premature spillage, penetration-aspiration scale levels . The Yale pharyngeal residue severity rating scale for vallecula and pyriform sinus (0-4) (non-trace-mild-moderate-severe) and pyriform sinus (0-4) were also performed.</description>
</primary_outcome>
<primary_outcome>
<measure>Pulmonary function test</measure>
<time_frame>4 months later</time_frame>
<description>Forced vital capacity (FVC) (L), forced expiratory volume in 1 second (FEV1), bronchodilator test (BDT) (a positive response to BDT defined by the American Thoracic Society as an increase in FEV1 or FVC ≥ 12% and 200 ml), total lung capacity (TLC) (L), and alveolar volume (VA) using MasterScope (Jaeger, VIASYS healthcare GmbH, Höchberg, Germany), and diffusion capacity of the lung for carbon monoxide (DLCO) (%) using Vmax Autobox (SensorMedics, a subsidiary of VIASYS healthcare, California, USA).</description>
</primary_outcome>
<primary_outcome>
<measure>6MWT were performed.</measure>
<time_frame>4 months later</time_frame>
<description>The 6 minutes walking test (6MWT) was also performed to evaluate distance (meter) and O2 desaturation (differences of O2 saturation between pre- and post-tests) (defined as positive if O2 desaturation ≧ 4%).</description>
</primary_outcome>
<number_of_groups>2</number_of_groups>
<enrollment type="Actual">48</enrollment>
<condition>Secondary Hyperparathyroidism Due to Renal Causes</condition>
<arm_group>
<arm_group_label>Group A</arm_group_label>
<description>Patients who have been successfully operated on with total parathyroidectomy for symptomatic secondary hyperparathyroidism and their PTH levels are below 72 pg/dL within one week after surgery.</description>
</arm_group>
<arm_group>
<arm_group_label>Group B</arm_group_label>
<description>Patients who have had regular dialysis and their iPTH levels are around 500 pg/dL</description>
</arm_group>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>parathyroidectomy plus bilateral thymectomy and autotransplantation</intervention_name>
<description>Patients should receive total parathyroidectomy plus bilateral thymectomy and autotransplantation</description>
<arm_group_label>Group A</arm_group_label>
</intervention>
<eligibility>
<study_pop>
<textblock>
We included patients who had symptomatic secondary hyperparathyroidism and were
successfully operated during the two years period (Aug 1 2017 - July 31 2019).
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

1. age over 20 years

2. chronic renal failure with regular dialysis

3. iPTH> 800pg/mL, Ca > 10.1 mg/dL, and P > 5.5 mg/dL

4. symptoms of bone pain, skin itching, general weakness, insomnia and osteoporosis (T
score< -2.5)

Exclusion Criteria:

1. pregnancy women

2. patients after kidney transplantation

3. a failure in surgery
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>20 Years</minimum_age>
<maximum_age>80 Years</maximum_age>
</eligibility>
<overall_official>
<last_name>Chang Huang-Chih, MD</last_name>
<role>Study Director</role>
<affiliation>Co-host</affiliation>
</overall_official>
<overall_official>
<last_name>Chen Jib-Bor, MD</last_name>
<role>Study Director</role>
<affiliation>Co-host</affiliation>
</overall_official>
<overall_official>
<last_name>Lai Chi-Chih, MD</last_name>
<role>Study Director</role>
<affiliation>Co-host</affiliation>
</overall_official>
<location>
<facility>
<name>Fong-Fu Chou</name>
<address>
<city>Kaohsiung</city>
<zip>833</zip>
<country>Taiwan</country>
</address>
</facility>
</location>
<location_countries>
<country>Taiwan</country>
</location_countries>
<results_reference>
<citation>Okada M, Tominaga Y, Yamamoto T, Hiramitsu T, Narumi S, Watarai Y. Location Frequency of Missed Parathyroid Glands After Parathyroidectomy in Patients with Persistent or Recurrent Secondary Hyperparathyroidism. World J Surg. 2016 Mar;40(3):595-9. doi: 10.1007/s00268-015-3312-1.</citation>
<PMID>26563219</PMID>
</results_reference>
<results_reference>
<citation>Wood JM, Athanasiadis T, Allen J. Laryngitis. BMJ. 2014 Oct 9;349:g5827. doi: 10.1136/bmj.g5827. No abstract available.</citation>
<PMID>25300640</PMID>
</results_reference>
<results_reference>
<citation>Arffa RE, Krishna P, Gartner-Schmidt J, Rosen CA. Normative values for the Voice Handicap Index-10. J Voice. 2012 Jul;26(4):462-5. doi: 10.1016/j.jvoice.2011.04.006. Epub 2011 Aug 4.</citation>
<PMID>21816570</PMID>
</results_reference>
<results_reference>
<citation>Belafsky PC, Mouadeb DA, Rees CJ, Pryor JC, Postma GN, Allen J, Leonard RJ. Validity and reliability of the Eating Assessment Tool (EAT-10). Ann Otol Rhinol Laryngol. 2008 Dec;117(12):919-24. doi: 10.1177/000348940811701210.</citation>
<PMID>19140539</PMID>
</results_reference>
<results_reference>
<citation>Eckel FC, Boone DR. The S/Z ratio as an indicator of laryngeal pathology. J Speech Hear Disord. 1981 May;46(2):147-9. doi: 10.1044/jshd.4602.147.</citation>
<PMID>7253591</PMID>
</results_reference>
<results_reference>
<citation>Rosenbek JC, Robbins JA, Roecker EB, Coyle JL, Wood JL. A penetration-aspiration scale. Dysphagia. 1996 Spring;11(2):93-8. doi: 10.1007/BF00417897.</citation>
<PMID>8721066</PMID>
</results_reference>
<results_reference>
<citation>Neubauer PD, Rademaker AW, Leder SB. The Yale Pharyngeal Residue Severity Rating Scale: An Anatomically Defined and Image-Based Tool. Dysphagia. 2015 Oct;30(5):521-8. doi: 10.1007/s00455-015-9631-4. Epub 2015 Jun 7.</citation>
<PMID>26050238</PMID>
</results_reference>
<results_reference>
<citation>Richter DC, Joubert JR, Nell H, Schuurmans MM, Irusen EM. Diagnostic value of post-bronchodilator pulmonary function testing to distinguish between stable, moderate to severe COPD and asthma. Int J Chron Obstruct Pulmon Dis. 2008;3(4):693-9. doi: 10.2147/copd.s948.</citation>
<PMID>19281083</PMID>
</results_reference>
<results_reference>
<citation>Single breath carbon monoxide diffusing capacity (transfer factor). Recommendations for a standard technique. Statement of the American Thoracic Society. Am Rev Respir Dis. 1987 Nov;136(5):1299-307. doi: 10.1164/ajrccm/136.5.1299. No abstract available.</citation>
<PMID>3674590</PMID>
</results_reference>
<results_reference>
<citation>Waatevik M, Johannessen A, Gomez Real F, Aanerud M, Hardie JA, Bakke PS, Lind Eagan TM. Oxygen desaturation in 6-min walk test is a risk factor for adverse outcomes in COPD. Eur Respir J. 2016 Jul;48(1):82-91. doi: 10.1183/13993003.00975-2015. Epub 2016 Apr 13.</citation>
<PMID>27076586</PMID>
</results_reference>
<verification_date>February 2020</verification_date>
<study_first_submitted>January 22, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 11, 2020</last_update_submitted>
<last_update_submitted_qc>February 11, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Chang Gung Memorial Hospital</investigator_affiliation>
<investigator_full_name>Chou Fong-Fu</investigator_full_name>
<investigator_title>Consultant professor</investigator_title>
</responsible_party>
<keyword>Voice impairment</keyword>
<keyword>airway invasion</keyword>
<keyword>respiratory function</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Neoplasm Metastasis</mesh_term>
<mesh_term>Hyperparathyroidism</mesh_term>
<mesh_term>Hyperparathyroidism, Secondary</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
In this study, investigators measure patient's voice frequency, swallowing function, and O2
desaturation of the 6 mins walking test before surgery and 4 months after surgery, to find
the increase of voice frequency, and swallowing function and the decrease of O2 desaturation.
This was a prospective case-control study. From July 2017 to Dec. 2018, investigators
recruited 38 patients, who had undergone a successful operation of total parathyroidectomy
and bilateral thymectomy (TPxBT) plus autotransplantation for symptomatic secondary
hyperparathyroidism as the study group. In the same period 4 patients who had a surgical
failure were excluded from the study. Indications for surgery were patients who had undergone
long-term regular hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), with
serum levels of Ca > 10.1 mg/dL, P > 5.5 mg/dL, alkaline phosphatase (Alk-ptase) > 94 U/L and
intact parathyroid hormone(iPTH) > 800 pg/mL and with symptoms and signs such as skin
itching, bone pain, general weakness, insomnia and T-score of bone mineral density (BMD) (the
lowest T-score of lumbar spine 1-4, global femur, femoral neck, radial 1/3, and global
radius) < -2.5. During surgery, Total parathyroidectomy and bilateral thymectomy was
performed plus autotranplantation of 100 mg of hyperplastic parathyroid tissue to the
subcutaneous tissue of the forearm without harboring an arteriovenous fistula.
Ten patients with regular hemodialysis who had developed mild secondary hyperparathyroidism
(iPTH around 500 pg/mL) but did not undergo parathyroidectomy were recruited as the control
group.
Investigators recorded patients' age, symptoms, gender, body mass index (BMI) and measured
serum levels of Ca, P, Alk-ptase and iPTH, and BMD (T-score). The Investigators also recorded
patients' voice quality, airway invasion during swallowing and pulmonary functions before
surgery and 4 months after surgery to find the changes after surgery. In the control group,
investigators recorded and measured these items at baseline and 4 months later.
At 1 week after surgery, serum Ca, P, Alk-ptase and iPTH levels were measured again to make
sure that the operation was successful. A successful operation was defined as iPTH levels <
72 pg/mL within 1 week after surgery. Four patients were excluded from this study with a
surgical failure in the same period.
The perceptual evaluation of voice quality such as speech impairment and speech quality by
means of multidimensional clinical measurements based on auditory methods with grade,
hoarseness, roughness, breathiness, asthenia, and strain (GRBAS) on a scale (0-3)
(normal-high degree) were performed by the ear, nose, and throat specialist (Dr. Lai, C.C.).
Voice handicap index (VHI-10) (>11, abnormal) and eating assessment tool (EAT-10) (≥ 3,
abnormal) were evaluated by patients themselves.
Acoustic and aerodynamic measurements were applied to recordings of each subject producing
sustained vowel productions in a soundproof room. Acoustic variables including jitter (Jitt),
shimmer (ShdB), noise-to-harmonic ratio (NHR), fundamental frequency (Fo), and high pitch
were measured using computerized speech laboratory (Core Model SCL # 4300B, KayPENTAX
Elementries, Lincoln park, NJ).
The maximal phonation time and s/z ratio were measured with circumferentially vented
pneumotachography mask and differential transducers of the Aerophone system (Aerophone II,
Model 6800, KayPENTAX Elementrics). Vocal cord mobility, vocal cord closure (complete or
incomplete), airway invasion during swallowing were inspected with fiber-optic endoscopy to
show premature spillage, penetration-aspiration scale levels (1-8) (no entry of material into
the larynx or trachea-material enter the airway passes below vocal folds and no effort is
made to eject) (>1, abnormal). The Yale pharyngeal residue severity rating scale for
vallecula (0-4) (non-trace-mild-moderate-severe) and pyriform sinus (0-4) were also performed
by the ENT specialist.
The specialist of chest medicine (Dr. Chang, H.C.) performed pulmonary function tests
including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1),
bronchodilator test (BDT) (a positive response to BDT defined by the American Thoracic
Society as an increase in FEV1 or FVC ≥ 12% and 200 ml), total lung capacity (TLC), and
alveolar volume (VA) using MasterScope (Jaeger, VIASYS healthcare GmbH, Höchberg, Germany),
and diffusion capacity of the lung for carbon monoxide (DLCO) using Vmax Autobox
(SensorMedics, a subsidiary of VIASYS healthcare, California, USA). The 6 minutes walking
test (6MWT) was also performed to evaluate distance (meter) and O2 desaturation (differences
of O2 saturation between pre- and post-tests) (defined as positive if O2 desaturation ≧ 4%).
We included patients who had symptomatic secondary hyperparathyroidism and were
successfully operated during the two years period (Aug 1 2017 - July 31 2019).
Inclusion Criteria:
1. age over 20 years
2. chronic renal failure with regular dialysis
3. iPTH> 800pg/mL, Ca > 10.1 mg/dL, and P > 5.5 mg/dL
4. symptoms of bone pain, skin itching, general weakness, insomnia and osteoporosis (T
score< -2.5)
Exclusion Criteria:
1. pregnancy women
2. patients after kidney transplantation
3. a failure in surgery
|
NCT0426xxxx/NCT04267978.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267978</url>
</required_header>
<id_info>
<org_study_id>SBNK-YJ-2019-006-02</org_study_id>
<nct_id>NCT04267978</nct_id>
</id_info>
<brief_title>Study of Recombinant Human Endostatin Combined With Temozolomide and Irinotecan in Recurrent Gliomas</brief_title>
<official_title>Open-label Prospective Study of Recombinant Human Endostatin Combined With Cytotoxic Chemotherapy Regimen in the Treatment of Recurrent Gliomas</official_title>
<sponsors>
<lead_sponsor>
<agency>Beijing Sanbo Brain Hospital</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Beijing Sanbo Brain Hospital</source>
<oversight_info>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Almost all gliomas relapse. After temozolomide rechallenge or combination with irinotecan,
the progression-free survival rate at 6 months (PFS-6%) of recurrent glioblastoma was about
21%. After treatment with irinotecan-based chemotherapy regimen, the PFS-6% of recurrent
lower-grade gliomas was 40%. The optimal chemotherapeutics of recurrent gliomas has yet to be
determined.

Anti-angiogenesis is a promising therapeutic strategy. Vascular endothelial growth factor-A
(VEGF) is the primary driver of angiogenesis in tumors. Bevacizumab, a humanized monoclonal
antibody directed against VEGF, is the prototypical anti-angiogenic drug and received
accelerated approval of the United States Food and Drug Administration (FDA) for the
treatment of recurrent glioblastoma. Bevacizumab inproved the PFS-6% (36%), but had no effect
on the overall survival (OS) (9.2 months). Moreover, the effects of bevacizumab are transient
and most patients' tumors progress just after a median time of 3-5 months. Recombinant human
endostatin (rh-ES) is an endogenous broad-spectrum angiogenesis inhibitor that has been shown
to significantly improve therapeutic efficacy when combining with conventional chemotherapy
agents in non-small-cell lung cancer, breast cancer and melanoma.

In our previous study, we retrospectively analyzed the effect and toxicity of rh-ES when
combined with temozolomide and irinotecan on adult recurrent disseminated glioblastoma. After
combined treatment, PFS-6% was 23.3%; the median PFS and OS were 3.2 and 6.9 months,
respectively, which were promising compared with that in other studies. Once patients get
radiographic remission in a short time (4 months), they may get a long PFS.The combined
regimen did not reduce the sensitivity of tumor to bevacizumab. After tumor progression from
the combined chemotherapy, bevacizumab usage could help to prolong the survival time (5.1
months versus 2.4 months). Moreover, the toxicities of the combination therapy in this study
were manageable.

On the basis of prior clinical experience, we carry out this prospective trial to confirm the
efficacy and safety of the combination of rh-ES, temozolomide and irinotecan in patients with
recurrent gliomas.
</textblock>
</brief_summary>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">February 13, 2020</start_date>
<completion_date type="Anticipated">November 30, 2024</completion_date>
<primary_completion_date type="Anticipated">February 28, 2024</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Non-Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>glioblastoma, lower-grade glioma</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>progression-free survival rate at 6 months</measure>
<time_frame>up to 4 years</time_frame>
<description>the percentage of participants who remained progression free at 6 months after treatment initiation.</description>
</primary_outcome>
<secondary_outcome>
<measure>objective response rate</measure>
<time_frame>up to 4 years</time_frame>
<description>the percentage of patients who achieved confirmed complete response or partial response according to the Response Assessment in Neuro-Oncology (RANO) criteria.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Progression-free survival</measure>
<time_frame>up to 4 years</time_frame>
<description>the time interval from treatment initiation to disease progression or death, whichever occurs first.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Overall survival</measure>
<time_frame>up to 4 years</time_frame>
<description>the time interval from treatment initiation to death from any cause.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Safety data</measure>
<time_frame>up to 4 years</time_frame>
<description>Frequency and severity of adverse effects as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">109</enrollment>
<condition>Glioblastoma, Recurrent</condition>
<condition>Lower Grade Glioma, Recurrent</condition>
<arm_group>
<arm_group_label>glioblastoma</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
</arm_group>
<arm_group>
<arm_group_label>lower-grade glioma</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>recombinant human endostatin,temozolomide,irinotecan</intervention_name>
<description>Temozolomide was given orally 200mg/m2 for 5 days in each cycle. Day 1 TMZ was administered 3-6 hours prior to irinotecan.
Irinotecan was administrated 125mg/m2 on day 1 and day 15. Recombinant human endostatin was administrated 15mg/d, daily for 14 days. One treatment cycle was defined as 28 days (4 weeks), even if treatment is held mid-cycle for toxicity.
Treatment was continued until disease progression, patient withdrawal, or unacceptable toxicity.
The maximum number of treatment cycles was 12. After 12 cycles of treatment, if the investigator judges that the subject may continue to benefit from the regimen, the duration of treatment may be extended with the subject's consent.</description>
<arm_group_label>glioblastoma</arm_group_label>
<arm_group_label>lower-grade glioma</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Age ≥ 18 and ≤70;

2. Histopathologically-confirmed, supratentorial GBM or lower-grade gliomas (such as
oligodendroglioma, astrocytoma, oligoastrocytoma, anaplastic astrocytoma, anaplastic
oligodendroglioma or anaplastic oligoastrocytoma);

3. Recurrence is pathologically confirmed by another biopsy or surgery, which should have
been completed at least 2 weeks before enrollment, or confirmed by the MRI according
to RANO criteria, at least one bi-dimensionally measurable contrast-enhancing target
lesion, with one diameter at least 10 mm, visible on two or more axial slices 5mm
apart;

4. Received standard chemoradiotherapy and at least one cycle of chemotherapy after
primary diagnosis;

5. The time intervals between the last radiotherapy and enrollment are at least 3 months;

6. The interval form the last chemotherapy to the study enrollment was at least one
interval of chemotherapy with recover from the related toxic effects (except for hair
loss and pigmentation);

7. Karnofsky Performance Status ≥ 60;

8. If the patient is on glucocorticoid therapy, hormone dosage should be stable or
decreased at least 5 days before baseline MRI;

9. If the patient is receiving enzyme-inducing antiepileptic drugs (EIAEDs), the drugs
should be replaced with non-EIAEDs for at least 1 weeks away from enrollment;

10. Estimated survival of at least 12 weeks;

11. Participants must have adequate organ function as defined by the following criteria
(within 7 days before treatment):

1. Hematology (No transfusion within 14 days):

- Hemoglobin(HB)≥90g/L;

- Absolute neutrophil count (ANC)≥1.5×109/L;

- Platelet (PLT)≥80×109/L.

2. Chemistry:

- Serum bilirubin ≤ 1.5×upper limit of normal (ULN)

- ALT and AST≤2.5ULN；

- Serum creatinine ≤1.5ULN or creatinine clearance
rate(CCr)≥60ml/min；

3. ECG: heart rate in the normal range (55-100beats/min), normal or slightly
prolonged QT interval (QTc<480ms), normal or low T wave, normal or non-specific
ST segment changes.

12. Both men and women at the gestational age must agree to take adequate contraceptive
measures throughout the study period.

13. Participants volunteered to participate in the study and signed an informed consent
form (ICF)

Exclusion Criteria:

1. MRI examination is not available (such as pacemaker, metal denture);

2. Receiving any other investigational agent.

3. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to the drugs used in this study.

4. Patients who have received organ transplants.

5. Patients with HIV or Treponema pallidum infection.

6. Severe heart disease; ECG shows T wave inversion or elevation or ST segment specific
changes.

7. Having factors that affect oral drug absorption, such as vomiting, diarrhea and
intestinal obstruction

8. There were clinically significant bleeding symptoms or clear bleeding tendency in the
first 3 months before enrollment, such as gastrointestinal bleeding, hemorrhagic
gastric ulcer, gastrointestinal perforation, baseline fecal occult blood ++ and above,
intracranial or intracranial hemorrhage, or vasculitis;

9. Arteriovenous thrombosis events occurred within 6 months before enrollment, such as
cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage,
cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.;

10. Having bleeding disorder and are being treated with thrombolytic or anticoagulant
drugs.

11. Other conditions considered inappropriate by the researcher for inclusion.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>70 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Jun-ping Zhang</last_name>
<role>Principal Investigator</role>
<affiliation>Beijing Sanbo Brain Hospital</affiliation>
</overall_official>
<overall_contact>
<last_name>Jun-ping Zhang</last_name>
<phone>86-010-62856783</phone>
<email>doczhjp@hotmail.com</email>
</overall_contact>
<location>
<facility>
<name>Beijing Sanbo Brain Hospital</name>
<address>
<city>Beijing</city>
<country>China</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Jun-ping Zhang</last_name>
<phone>86-010-62856798</phone>
<email>doczhjp@hotmail.com</email>
</contact>
</location>
<location_countries>
<country>China</country>
</location_countries>
<verification_date>April 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>April 18, 2023</last_update_submitted>
<last_update_submitted_qc>April 18, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">April 19, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Beijing Sanbo Brain Hospital</investigator_affiliation>
<investigator_full_name>Junping Zhang</investigator_full_name>
<investigator_title>Chief physician</investigator_title>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Glioblastoma</mesh_term>
<mesh_term>Glioma</mesh_term>
<mesh_term>Recurrence</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Irinotecan</mesh_term>
<mesh_term>Temozolomide</mesh_term>
<mesh_term>Endostatins</mesh_term>
</intervention_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Almost all gliomas relapse. After temozolomide rechallenge or combination with irinotecan,
the progression-free survival rate at 6 months (PFS-6%) of recurrent glioblastoma was about
21%. After treatment with irinotecan-based chemotherapy regimen, the PFS-6% of recurrent
lower-grade gliomas was 40%. The optimal chemotherapeutics of recurrent gliomas has yet to be
determined.
Anti-angiogenesis is a promising therapeutic strategy. Vascular endothelial growth factor-A
(VEGF) is the primary driver of angiogenesis in tumors. Bevacizumab, a humanized monoclonal
antibody directed against VEGF, is the prototypical anti-angiogenic drug and received
accelerated approval of the United States Food and Drug Administration (FDA) for the
treatment of recurrent glioblastoma. Bevacizumab inproved the PFS-6% (36%), but had no effect
on the overall survival (OS) (9.2 months). Moreover, the effects of bevacizumab are transient
and most patients' tumors progress just after a median time of 3-5 months. Recombinant human
endostatin (rh-ES) is an endogenous broad-spectrum angiogenesis inhibitor that has been shown
to significantly improve therapeutic efficacy when combining with conventional chemotherapy
agents in non-small-cell lung cancer, breast cancer and melanoma.
In our previous study, we retrospectively analyzed the effect and toxicity of rh-ES when
combined with temozolomide and irinotecan on adult recurrent disseminated glioblastoma. After
combined treatment, PFS-6% was 23.3%; the median PFS and OS were 3.2 and 6.9 months,
respectively, which were promising compared with that in other studies. Once patients get
radiographic remission in a short time (4 months), they may get a long PFS.The combined
regimen did not reduce the sensitivity of tumor to bevacizumab. After tumor progression from
the combined chemotherapy, bevacizumab usage could help to prolong the survival time (5.1
months versus 2.4 months). Moreover, the toxicities of the combination therapy in this study
were manageable.
On the basis of prior clinical experience, we carry out this prospective trial to confirm the
efficacy and safety of the combination of rh-ES, temozolomide and irinotecan in patients with
recurrent gliomas.
Inclusion Criteria:
1. Age ≥ 18 and ≤70;
2. Histopathologically-confirmed, supratentorial GBM or lower-grade gliomas (such as
oligodendroglioma, astrocytoma, oligoastrocytoma, anaplastic astrocytoma, anaplastic
oligodendroglioma or anaplastic oligoastrocytoma);
3. Recurrence is pathologically confirmed by another biopsy or surgery, which should have
been completed at least 2 weeks before enrollment, or confirmed by the MRI according
to RANO criteria, at least one bi-dimensionally measurable contrast-enhancing target
lesion, with one diameter at least 10 mm, visible on two or more axial slices 5mm
apart;
4. Received standard chemoradiotherapy and at least one cycle of chemotherapy after
primary diagnosis;
5. The time intervals between the last radiotherapy and enrollment are at least 3 months;
6. The interval form the last chemotherapy to the study enrollment was at least one
interval of chemotherapy with recover from the related toxic effects (except for hair
loss and pigmentation);
7. Karnofsky Performance Status ≥ 60;
8. If the patient is on glucocorticoid therapy, hormone dosage should be stable or
decreased at least 5 days before baseline MRI;
9. If the patient is receiving enzyme-inducing antiepileptic drugs (EIAEDs), the drugs
should be replaced with non-EIAEDs for at least 1 weeks away from enrollment;
10. Estimated survival of at least 12 weeks;
11. Participants must have adequate organ function as defined by the following criteria
(within 7 days before treatment):
1. Hematology (No transfusion within 14 days):
- Hemoglobin(HB)≥90g/L;
- Absolute neutrophil count (ANC)≥1.5×109/L;
- Platelet (PLT)≥80×109/L.
2. Chemistry:
- Serum bilirubin ≤ 1.5×upper limit of normal (ULN)
- ALT and AST≤2.5ULN；
- Serum creatinine ≤1.5ULN or creatinine clearance
rate(CCr)≥60ml/min；
3. ECG: heart rate in the normal range (55-100beats/min), normal or slightly
prolonged QT interval (QTc<480ms), normal or low T wave, normal or non-specific
ST segment changes.
12. Both men and women at the gestational age must agree to take adequate contraceptive
measures throughout the study period.
13. Participants volunteered to participate in the study and signed an informed consent
form (ICF)
Exclusion Criteria:
1. MRI examination is not available (such as pacemaker, metal denture);
2. Receiving any other investigational agent.
3. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to the drugs used in this study.
4. Patients who have received organ transplants.
5. Patients with HIV or Treponema pallidum infection.
6. Severe heart disease; ECG shows T wave inversion or elevation or ST segment specific
changes.
7. Having factors that affect oral drug absorption, such as vomiting, diarrhea and
intestinal obstruction
8. There were clinically significant bleeding symptoms or clear bleeding tendency in the
first 3 months before enrollment, such as gastrointestinal bleeding, hemorrhagic
gastric ulcer, gastrointestinal perforation, baseline fecal occult blood ++ and above,
intracranial or intracranial hemorrhage, or vasculitis;
9. Arteriovenous thrombosis events occurred within 6 months before enrollment, such as
cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage,
cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.;
10. Having bleeding disorder and are being treated with thrombolytic or anticoagulant
drugs.
11. Other conditions considered inappropriate by the researcher for inclusion.
|
NCT0426xxxx/NCT04267991.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04267991</url>
</required_header>
<id_info>
<org_study_id>Hamaky5</org_study_id>
<nct_id>NCT04267991</nct_id>
</id_info>
<brief_title>Corneal Densitometry Changes With Adenoviral SEI</brief_title>
<official_title>Corneal Densitometry Changes With Adenoviral Keratoconjunctivitis Sub Epithelial Infiltrates</official_title>
<sponsors>
<lead_sponsor>
<agency>Benha University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Benha University</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
<is_us_export>No</is_us_export>
</oversight_info>
<brief_summary>
<textblock>
Adenoviral Sub epithelial infiltrates (SEI) affect ocular function.They lead to reduced
vision, photophobia, glare, halos, and foreign body sensation.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
first group of patients were treated with 0.03 % tacrolimus ointment twice daily for 6
months.S econd group underwent transepithelial PTK for subepithelial infiltrates. Baseline
and post-treatment full ophthalmic examination was done.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">April 1, 2018</start_date>
<completion_date type="Actual">April 15, 2020</completion_date>
<primary_completion_date type="Actual">April 1, 2020</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>changes of corneal densitometry</measure>
<time_frame>6 months</time_frame>
<description>Sub epithelial infiltrates was examined with the densitometry programme of the Pentacam (Fa. Oculus,Weimar, Germany)</description>
</primary_outcome>
<number_of_groups>3</number_of_groups>
<enrollment type="Actual">63</enrollment>
<condition>Corneal Disease</condition>
<arm_group>
<arm_group_label>Tacrolimus</arm_group_label>
<description>Patients were treated with 0.03 % tacrolimus ointment twice daily for 6 months.</description>
</arm_group>
<arm_group>
<arm_group_label>Phototherapeutic Keratectomy</arm_group_label>
<description>Patients underwent transepithelial PTK for subepithelial infiltrates.</description>
</arm_group>
<arm_group>
<arm_group_label>Control</arm_group_label>
<description>patients received only artificial tears eyedrop</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Tacrolimus ointment</intervention_name>
<description>Patients were treated with 0.03 % tacrolimus ointment twice daily for 6 months.</description>
<arm_group_label>Tacrolimus</arm_group_label>
<other_name>Protopic ointment</other_name>
</intervention>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>phototherapeutic keratectomy</intervention_name>
<description>Patients underwent transepithelial PTK for subepithelial infiltrates.</description>
<arm_group_label>Phototherapeutic Keratectomy</arm_group_label>
</intervention>
<eligibility>
<study_pop>
<textblock>
60 patients with adenoviral SEI
</textblock>
</study_pop>
<sampling_method>Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- adenoviral SEI

Exclusion Criteria:

- Other corneal diseases
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>75 Years</maximum_age>
</eligibility>
<overall_official>
<last_name>TAREK R ELHAMAKY</last_name>
<role>Principal Investigator</role>
<affiliation>Benha university faculty of medicine</affiliation>
</overall_official>
<location>
<facility>
<name>INMC</name>
<address>
<city>Abu Dhabi</city>
<zip>46266</zip>
<country>United Arab Emirates</country>
</address>
</facility>
</location>
<location_countries>
<country>United Arab Emirates</country>
</location_countries>
<verification_date>May 2020</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>May 28, 2020</last_update_submitted>
<last_update_submitted_qc>May 28, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">May 29, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Benha University</investigator_affiliation>
<investigator_full_name>Tarek Roshdy mohamed Mahgoub ELhamaky</investigator_full_name>
<investigator_title>Lecturer</investigator_title>
</responsible_party>
<keyword>adenoviral</keyword>
<keyword>infiltrates</keyword>
<keyword>PTK</keyword>
<keyword>tacrolimus</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Corneal Diseases</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Tacrolimus</mesh_term>
</intervention_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Adenoviral Sub epithelial infiltrates (SEI) affect ocular function.They lead to reduced
vision, photophobia, glare, halos, and foreign body sensation.
first group of patients were treated with 0.03 % tacrolimus ointment twice daily for 6
months.S econd group underwent transepithelial PTK for subepithelial infiltrates. Baseline
and post-treatment full ophthalmic examination was done.
60 patients with adenoviral SEI
Inclusion Criteria:
- adenoviral SEI
Exclusion Criteria:
- Other corneal diseases
|
NCT0426xxxx/NCT04268004.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268004</url>
</required_header>
<id_info>
<org_study_id>STUDY00000849</org_study_id>
<secondary_id>K08CA237338</secondary_id>
<nct_id>NCT04268004</nct_id>
</id_info>
<brief_title>Fertility Preservation in Male AYA With Cancer</brief_title>
<official_title>Optimizing Fertility Preservation and Decision Quality in Male AYA With Cancer: A Family-centered Intervention</official_title>
<sponsors>
<lead_sponsor>
<agency>Leena Nahata</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>National Cancer Institute (NCI)</agency>
<agency_class>NIH</agency_class>
</collaborator>
</sponsors>
<source>Nationwide Children's Hospital</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Very little is known about how medical providers can help adolescent and young adults (AYAs)
and their caregivers make decisions about fertility preservation (sperm banking) before
beginning cancer treatment. The purpose of this study is to see if having a guided
conversation about fertility preservation increases preservation rates and/or satisfaction
with the decision among AYA males with cancer. The primary hypothesis is that compared to
standard of care control group (routine fertility consult at diagnosis, n=20), AYAs in the
intervention arm (routine fertility consult at diagnosis + FP Decision Tool and Facilitated
Conversation by trained interventionist) will have higher rates of FP uptake. The secondary
hypothesis is that families in the intervention group will report better FP decision quality
compared to those in the control arm.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
A rapidly growing population of male childhood cancer survivors are at risk for infertility
and distress. As the number of male cancer survivors rises, it is essential to minimize
treatment late effects. One of the most prevalent and significant complications among males
is infertility, which can impair psychosocial development and reduce quality of life.
National guidelines emphasize offering fertility preservation (FP) prior to initiation of
cancer therapy, and sperm cryopreservation is an established and generally noninvasive FP
method for pubertal males. Early research suggested only males receiving high doses of
alkylating agents should bank sperm. However, variable sperm counts following equivalent
doses of cyclophosphamide and scenarios in which patients have to move quickly from "low
risk" treatments (which transiently impair sperm production) to "high risk" treatments,
support the premise that all males receiving chemotherapy and/or gonadal radiation should
consider FP at diagnosis. Despite studies showing ~50% of male childhood cancer survivors
have fertility impairment, reports from many centers show only ~25% of pubertal males bank
sperm prior to treatment. As survivors enter their reproductive years, many regret missed
opportunities for FP and experience distress about potential infertility. Thus, interventions
to improve FP uptake would have great potential for reproductive and psychological benefit.

Individual and family factors associated with sperm banking decisions remain poorly
understood. Young age, cost, inadequate knowledge, and urgency to start treatment are common
barriers to FP among AYA males with newly diagnosed cancer. As a result, most fertility
counseling and FP interventions have targeted healthcare providers and systems or
provider-patient interactions. While these are critical factors, less than half of male AYA
advised about FP in a recent study actually banked sperm, indicating knowledge is not
sufficient.

The purpose of this study is to test a decision tool and accompanying guided discussion as a
method of improving decision making regarding FP, compared to a standard of care fertility
consult.
</textblock>
</detailed_description>
<overall_status>Enrolling by invitation</overall_status>
<start_date type="Actual">January 1, 2021</start_date>
<completion_date type="Anticipated">December 1, 2025</completion_date>
<primary_completion_date type="Anticipated">December 1, 2024</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>Families will be randomly assigned to receive standard care or to receive standard care plus the investigator's study intervention. All families will then be followed for a year to assess outcomes.</intervention_model_description>
<primary_purpose>Other</primary_purpose>
<masking>Double (Investigator, Outcomes Assessor)</masking>
<masking_description>Participants and the interventionist will not be blinded. Research staff will be blinded.</masking_description>
</study_design_info>
<primary_outcome>
<measure>Fertility Preservation (FP) Uptake</measure>
<time_frame>Baseline to before AYA begins treatment (generally within one to two weeks from baseline)</time_frame>
<description>FP uptake</description>
</primary_outcome>
<secondary_outcome>
<measure>Brief Subjective Decision Quality (BSDQ) Questionnaire - AYA</measure>
<time_frame>1-month post randomization</time_frame>
<description>AYAs will complete the six-item Brief Subjective Decision Quality (BSDQ) Questionnaire with total scores ranging from 1-7; higher scores indicate more satisfaction with their decision.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Brief Subjective Decision Quality (BSDQ) Questionnaire - Caregiver</measure>
<time_frame>1-month post randomization</time_frame>
<description>Caregivers will complete the six-item Brief Subjective Decision Quality (BSDQ) Questionnaire with total scores ranging from 1-7; higher scores indicate more satisfaction with their decision.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Brief Subjective Decision Quality (BSDQ) Questionnaire - AYA</measure>
<time_frame>1-year post randomization</time_frame>
<description>AYAs will complete the six-item Brief Subjective Decision Quality (BSDQ) Questionnaire with total scores ranging from 1-7; higher scores indicate more satisfaction with their decision.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Brief Subjective Decision Quality (BSDQ) Questionnaire - Caregiver</measure>
<time_frame>1-year post randomization</time_frame>
<description>Caregivers will complete the six-item Brief Subjective Decision Quality (BSDQ) Questionnaire with total scores ranging from 1-7; higher scores indicate more satisfaction with their decision.</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">40</enrollment>
<condition>Infertility, Male</condition>
<arm_group>
<arm_group_label>Standard of Care (Control)</arm_group_label>
<arm_group_type>No Intervention</arm_group_type>
<description>Participants will receive a standard of care fertility consult.</description>
</arm_group>
<arm_group>
<arm_group_label>FP Decision Tool and Discussion (Treatment)</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Participants will receive a standard of care fertility consult and will participate in a family-centered psychoeducational intervention consisting of completing a FP Decision Tool and participating in a guided discussion about responses and discrepancies identified in the FP Decision Tool.</description>
</arm_group>
<intervention>
<intervention_type>Behavioral</intervention_type>
<intervention_name>FP Decision Tool and Discussion</intervention_name>
<description>The intervention will be administered by a trained interventionist. The interventionist will administer the digital FP Decision Tool to families in the intervention arm. The tool asks questions examining each AYA's thoughts or feelings regarding parenthood and fertility preservation. The parent version asks the same questions, plus additional questions asking the parent to rate their son's feelings on certain topics (i.e., whether their son wants to have a child, whether their son would be as happy with an adopted child versus a biological child). Items are coded based on the domains of the Health Belief Model (perceived benefits, perceived barriers, perceived threats, self-efficacy, and cues to action). Items are scored and the trained interventionist will facilitate a guided discussion based on the family's responses and discrepancies.</description>
<arm_group_label>FP Decision Tool and Discussion (Treatment)</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Male

- Aged 12-25 years

- Expected to have adjuvant therapy (chemotherapy and/or gonadal radiation) for newly
diagnosed cancer

- Pubertal (at least Tanner stage 2-3, eligible for sperm banking as determined in the
fertility consult)

- Proficient in English

Exclusion Criteria:

- Cognitive deficit that precludes completing measures

- Parents are non-English speaking
</textblock>
</criteria>
<gender>Male</gender>
<minimum_age>12 Years</minimum_age>
<maximum_age>25 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Leena Nahata, MD</last_name>
<role>Principal Investigator</role>
<affiliation>Nationwide Children's Hospital</affiliation>
</overall_official>
<location>
<facility>
<name>Nationwide Children's Hospital</name>
<address>
<city>Columbus</city>
<state>Ohio</state>
<zip>43205</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<reference>
<citation>Nahata L, Morgan TL, Lipak KG, Clark OE, Yeager ND, O'Brien SH, Whiteside S, Audino A, Quinn GP, Gerhardt CA. Perceptions of participating in family-centered fertility research among adolescent and young adult males newly diagnosed with cancer: A qualitative study. Pediatr Blood Cancer. 2019 Nov;66(11):e27966. doi: 10.1002/pbc.27966. Epub 2019 Aug 12.</citation>
<PMID>31407498</PMID>
</reference>
<reference>
<citation>Nahata L, Dattilo TM, Olsavsky AL, Lipak KG, Whiteside S, Yeager ND, Audino A, Klosky JL, Rausch J, Saraf A, O'Brien SH, Quinn GP, Gerhardt CA. Impact of a novel family-centered values clarification tool on adolescent sperm banking attempts at the time of a new cancer diagnosis. J Assist Reprod Genet. 2021 Jun;38(6):1561-1569. doi: 10.1007/s10815-021-02092-6. Epub 2021 Feb 10.</citation>
<PMID>33564937</PMID>
</reference>
<reference>
<citation>Theroux CI, Hill KN, Olsavsky AL, Klosky JL, Yeager ND, Audino A, O'Brien SH, Quinn GP, Gerhardt CA, Nahata L. Satisfaction with Fertility Preservation Decisions among Adolescent Males with Cancer: A Mixed Methods Study. Cancers (Basel). 2021 Jul 16;13(14):3559. doi: 10.3390/cancers13143559.</citation>
<PMID>34298773</PMID>
</reference>
<reference>
<citation>Nahata L, Olsavsky A, Dattilo TM, Lipak KG, Whiteside S, Yeager ND, Audino A, Rausch J, Klosky JL, O'Brien SH, Quinn GP, Gerhardt CA. Parent-Adolescent Concordance Regarding Fertility Perspectives and Sperm Banking Attempts in Adolescent Males With Cancer. J Pediatr Psychol. 2021 Oct 18;46(10):1149-1158. doi: 10.1093/jpepsy/jsab069.</citation>
<PMID>34333651</PMID>
</reference>
<reference>
<citation>Stanek C, Theroux CI, Olsavsky AL, Hill KN, Rausch JR, O'Brien SH, Quinn GP, Gerhardt CA, Nahata L. Study protocol for fertility preservation discussions and decisions: A family-centered psychoeducational intervention for male adolescents and emerging adults newly diagnosed with cancer and their families. PLoS One. 2022 Feb 16;17(2):e0263886. doi: 10.1371/journal.pone.0263886. eCollection 2022.</citation>
<PMID>35171948</PMID>
</reference>
<verification_date>February 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 1, 2023</last_update_submitted>
<last_update_submitted_qc>February 1, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">February 3, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor-Investigator</responsible_party_type>
<investigator_affiliation>Nationwide Children's Hospital</investigator_affiliation>
<investigator_full_name>Leena Nahata</investigator_full_name>
<investigator_title>Principal Investigator</investigator_title>
</responsible_party>
<keyword>Cancer</keyword>
<keyword>Fertility Preservation</keyword>
<keyword>Parenthood</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Infertility</mesh_term>
<mesh_term>Infertility, Male</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
<ipd_description>We do not plan on sharing individual participant data (IPD) with other researchers.</ipd_description>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Very little is known about how medical providers can help adolescent and young adults (AYAs)
and their caregivers make decisions about fertility preservation (sperm banking) before
beginning cancer treatment. The purpose of this study is to see if having a guided
conversation about fertility preservation increases preservation rates and/or satisfaction
with the decision among AYA males with cancer. The primary hypothesis is that compared to
standard of care control group (routine fertility consult at diagnosis, n=20), AYAs in the
intervention arm (routine fertility consult at diagnosis + FP Decision Tool and Facilitated
Conversation by trained interventionist) will have higher rates of FP uptake. The secondary
hypothesis is that families in the intervention group will report better FP decision quality
compared to those in the control arm.
A rapidly growing population of male childhood cancer survivors are at risk for infertility
and distress. As the number of male cancer survivors rises, it is essential to minimize
treatment late effects. One of the most prevalent and significant complications among males
is infertility, which can impair psychosocial development and reduce quality of life.
National guidelines emphasize offering fertility preservation (FP) prior to initiation of
cancer therapy, and sperm cryopreservation is an established and generally noninvasive FP
method for pubertal males. Early research suggested only males receiving high doses of
alkylating agents should bank sperm. However, variable sperm counts following equivalent
doses of cyclophosphamide and scenarios in which patients have to move quickly from "low
risk" treatments (which transiently impair sperm production) to "high risk" treatments,
support the premise that all males receiving chemotherapy and/or gonadal radiation should
consider FP at diagnosis. Despite studies showing ~50% of male childhood cancer survivors
have fertility impairment, reports from many centers show only ~25% of pubertal males bank
sperm prior to treatment. As survivors enter their reproductive years, many regret missed
opportunities for FP and experience distress about potential infertility. Thus, interventions
to improve FP uptake would have great potential for reproductive and psychological benefit.
Individual and family factors associated with sperm banking decisions remain poorly
understood. Young age, cost, inadequate knowledge, and urgency to start treatment are common
barriers to FP among AYA males with newly diagnosed cancer. As a result, most fertility
counseling and FP interventions have targeted healthcare providers and systems or
provider-patient interactions. While these are critical factors, less than half of male AYA
advised about FP in a recent study actually banked sperm, indicating knowledge is not
sufficient.
The purpose of this study is to test a decision tool and accompanying guided discussion as a
method of improving decision making regarding FP, compared to a standard of care fertility
consult.
Inclusion Criteria:
- Male
- Aged 12-25 years
- Expected to have adjuvant therapy (chemotherapy and/or gonadal radiation) for newly
diagnosed cancer
- Pubertal (at least Tanner stage 2-3, eligible for sperm banking as determined in the
fertility consult)
- Proficient in English
Exclusion Criteria:
- Cognitive deficit that precludes completing measures
- Parents are non-English speaking
|
NCT0426xxxx/NCT04268017.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268017</url>
</required_header>
<id_info>
<org_study_id>FTM_HEALTHY_01</org_study_id>
<nct_id>NCT04268017</nct_id>
</id_info>
<brief_title>Validation Study : FeetMe® Monitor Insoles for the Evaluation of Gait Speed</brief_title>
<official_title>Reliability and Competing Validity of the FeetMe Monitordevice® Measurement of the Spatial-temporal Parameters of the gaitRite System® in Healthy Subjects</official_title>
<sponsors>
<lead_sponsor>
<agency>FeetMe</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
</sponsors>
<source>FeetMe</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The aim of this study is to validate a smart insoles system in comparison to the
gold-standard GaitRite in a healthy population. The device evaluate gait parameters in real
time thanks to an embedded algorithm based on the processing of inertial measurement unit and
19 sensors signals.

At D0 and D7, the volunteer is evaluated by both the GaitRite® system and the FeetMe Monitor®
system simultaneously. Healthy volunteers have two measurements 7 days apart. The volunteer
repeats 5 trials at a comfortable speed on the GaitRite® mat while wearing the FeetMe®
insoles. Each measurement is repeated by 4 different operators. A total of 20 trials are made
by the volunteer.
</textblock>
</brief_summary>
<overall_status>Completed</overall_status>
<start_date type="Actual">September 17, 2018</start_date>
<completion_date type="Actual">October 2, 2018</completion_date>
<primary_completion_date type="Actual">October 2, 2018</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<primary_purpose>Basic Science</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Velocity measured through FeetMe Monitor device and GaitRit</measure>
<time_frame>1 day</time_frame>
</primary_outcome>
<secondary_outcome>
<measure>Stride length measured through FeetMe Monitor device and GaitRite</measure>
<time_frame>1 day</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>Cadence measured through FeetMe Monitor device and GaitRite</measure>
<time_frame>1 day</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>Stance phase measured through FeetMe Monitor device and GaitRite</measure>
<time_frame>1 day</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>Swing phase measured through FeetMe Monitor device and GaitRite</measure>
<time_frame>1 day</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>Stride duration measured through FeetMe Monitor device and GaitRite</measure>
<time_frame>1 day</time_frame>
</secondary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Actual">30</enrollment>
<condition>Healthy</condition>
<arm_group>
<arm_group_label>Healthy volunteer</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
</arm_group>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>FeetMe Monitor</intervention_name>
<description>For gait parameters' evaluation, the investigator asks the participant to move in a straight line over a 10-meter mat. The participant had to start the feet in line and then start walking at a comfortable speed. During this time, the investigator records the gait parameters from the FeetMe Monitor® and Gaitrite® system.
An operator asked the patient to repeat 3 trials. The same sequence was repeated by three other operators. The same measurement is done 7 days later.
A questionnaire is given to assess the ergonomics of the device</description>
<arm_group_label>Healthy volunteer</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Have more than 18 years old

- Don't be pregnant or breast feeding

Exclusion Criteria:

- Be part of another study

- Not be able to give consent

- Not have access to social security
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<location>
<facility>
<name>Fédération de Rééducation Neurolocomotrice, Laboratoire ARM - Hôpital Henri MONDOR, Assistance Publique - Hôpitaux de Paris</name>
<address>
<city>Créteil</city>
<zip>94000</zip>
<country>France</country>
</address>
</facility>
</location>
<location_countries>
<country>France</country>
</location_countries>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 11, 2020</last_update_submitted>
<last_update_submitted_qc>February 11, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Gait analysis</keyword>
<keyword>FeetMe®</keyword>
<keyword>GaitRite®</keyword>
<keyword>Healthy</keyword>
<keyword>Validation</keyword>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The aim of this study is to validate a smart insoles system in comparison to the
gold-standard GaitRite in a healthy population. The device evaluate gait parameters in real
time thanks to an embedded algorithm based on the processing of inertial measurement unit and
19 sensors signals.
At D0 and D7, the volunteer is evaluated by both the GaitRite® system and the FeetMe Monitor®
system simultaneously. Healthy volunteers have two measurements 7 days apart. The volunteer
repeats 5 trials at a comfortable speed on the GaitRite® mat while wearing the FeetMe®
insoles. Each measurement is repeated by 4 different operators. A total of 20 trials are made
by the volunteer.
Inclusion Criteria:
- Have more than 18 years old
- Don't be pregnant or breast feeding
Exclusion Criteria:
- Be part of another study
- Not be able to give consent
- Not have access to social security
|
NCT0426xxxx/NCT04268030.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268030</url>
</required_header>
<id_info>
<org_study_id>17112804-IRB02</org_study_id>
<nct_id>NCT04268030</nct_id>
</id_info>
<brief_title>High Order Spectral Analysis of Local Field Potential Data on a Subgroup of Parkinson's Disease Patients Who Are Carriers of Mutations in the Glucocerebrosidase (GBA) Gene Undergoing DBS Electrode Placement</brief_title>
<official_title>High Order Spectral Analysis of Local Field Potential Data on a Subgroup of Parkinson's Disease Patients Who Are Carriers of Mutations in the Glucocerebrosidase (GBA) Gene Undergoing DBS Electrode Placement</official_title>
<sponsors>
<lead_sponsor>
<agency>Rush University Medical Center</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Rush University Medical Center</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The aim is to study a specific group of PD patients, carriers of mutations in the
glucocerebrosidase (GBA) gene, which is the most common genetic risk factor for PD and is a
harbinger of aggressive cognitive and motor decline. Approximately 12-17% of PD patients
undergoing DBS are GBA mutation carriers. GBA mutation carriers with PD have a specific
phenotype characterized by more significant motor dysfunction and reduced short-term visual
memory function compared with their non-GBA counterparts. Thus as GBA mutation carriers have
a "signature" phenotype, the investigators hypothesize that these GBA mutation carriers have
a unique "signature" of oscillatory activity that can be distinguished from non-mutation
carriers during motor activation and during cognitive tasks. Identification of this
"signature" will provide critical information that is required to: 1) understand the
underlying neurophysiological mechanisms responsible for the aggressive disease course of GBA
associated PD, and 2) further develop customized adaptive DBS systems.
</textblock>
</brief_summary>
<overall_status>Completed</overall_status>
<start_date type="Actual">February 11, 2020</start_date>
<completion_date type="Actual">August 30, 2020</completion_date>
<primary_completion_date type="Actual">August 30, 2020</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Case-Only</observational_model>
<time_perspective>Cross-Sectional</time_perspective>
</study_design_info>
<primary_outcome>
<measure>change in beta symmetry</measure>
<time_frame>1 day</time_frame>
<description>LFP</description>
</primary_outcome>
<number_of_groups>1</number_of_groups>
<enrollment type="Actual">9</enrollment>
<condition>Parkinson Disease</condition>
<arm_group>
<arm_group_label>GBA mutation carriers with PD undergoing STN-DBS</arm_group_label>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>collection of LFPs</intervention_name>
<description>collection of local field potentials (LFPs) at rest and during hand opening and closing</description>
<arm_group_label>GBA mutation carriers with PD undergoing STN-DBS</arm_group_label>
</intervention>
<eligibility>
<study_pop>
<textblock>
Patients with Parkinson's disease (PD) with and without mutations in the GBA gene who
already have an implanted deep brain stimulator (DBS) device or those patients with PD-GBA
mutation carrier who will be undergoing placement of a DBS device using standard technique
with sedation and local anesthesia.
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- undergoing bilateral STN-DBS

- diagnosis of Parkinson's disease

Exclusion Criteria:

- no Parkinson's disease
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>30 Years</minimum_age>
<maximum_age>80 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<location>
<facility>
<name>Rush University Medical Center</name>
<address>
<city>Chicago</city>
<state>Illinois</state>
<zip>60612</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>July 2021</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>July 8, 2021</last_update_submitted>
<last_update_submitted_qc>July 8, 2021</last_update_submitted_qc>
<last_update_posted type="Actual">July 9, 2021</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Rush University Medical Center</investigator_affiliation>
<investigator_full_name>Gian Pal</investigator_full_name>
<investigator_title>Assistant Professor</investigator_title>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Parkinson Disease</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The aim is to study a specific group of PD patients, carriers of mutations in the
glucocerebrosidase (GBA) gene, which is the most common genetic risk factor for PD and is a
harbinger of aggressive cognitive and motor decline. Approximately 12-17% of PD patients
undergoing DBS are GBA mutation carriers. GBA mutation carriers with PD have a specific
phenotype characterized by more significant motor dysfunction and reduced short-term visual
memory function compared with their non-GBA counterparts. Thus as GBA mutation carriers have
a "signature" phenotype, the investigators hypothesize that these GBA mutation carriers have
a unique "signature" of oscillatory activity that can be distinguished from non-mutation
carriers during motor activation and during cognitive tasks. Identification of this
"signature" will provide critical information that is required to: 1) understand the
underlying neurophysiological mechanisms responsible for the aggressive disease course of GBA
associated PD, and 2) further develop customized adaptive DBS systems.
Patients with Parkinson's disease (PD) with and without mutations in the GBA gene who
already have an implanted deep brain stimulator (DBS) device or those patients with PD-GBA
mutation carrier who will be undergoing placement of a DBS device using standard technique
with sedation and local anesthesia.
Inclusion Criteria:
- undergoing bilateral STN-DBS
- diagnosis of Parkinson's disease
Exclusion Criteria:
- no Parkinson's disease
|
NCT0426xxxx/NCT04268043.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268043</url>
</required_header>
<id_info>
<org_study_id>2019041-2</org_study_id>
<nct_id>NCT04268043</nct_id>
</id_info>
<brief_title>Comparation of Proseal Laryngeal Mask Airway With Flexible Laryngeal Airway Mask</brief_title>
<official_title>Comparation of Efficacy and Safety of Proseal Laryngeal Mask Airway With Flexible Laryngeal Airway Mask in Otitis Media Surgery</official_title>
<sponsors>
<lead_sponsor>
<agency>Eye & ENT Hospital of Fudan University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Eye & ENT Hospital of Fudan University</source>
<oversight_info>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Objective To investigate the comparative effect of proseal laryngeal mask airway and flexible
laryngeal airway mask during otitis media surgery. Methods 200 patients of ASA I or II
classification, 18-65 years old, BMI<30 kg/m2 undergoing otitis media surgery are randomly
divided into two groups (Group P with proseal laryngeal mask airway and Group F with flexible
laryngeal airway mask, respectively). After induction, selecting a appropriate size of LMA to
patient,s weight, using the standard index finger-guided technique inserting the LMA, and
then the patients were ventilated mechanically. The success rate of inserting laryngeal mask,
the intubation time, surgery time and wake time were also recorded. Tidal volume and leakage
pressure in patients with supine and lateral positioning were assessed respectively. The
scale of fiberoptic bronchoscopy was also recorded to show airway exposure. Related
complications such as sore throat, hoarseness, cough, laryngospasm, bloating, nausea and
vomiting, soft tissue injury, blood residue after pulling out the LMA were
analyzed.Postoperative voice and laryngopharyngeal symptom are also recorded.
</textblock>
</brief_summary>
<overall_status>Not yet recruiting</overall_status>
<start_date type="Anticipated">October 1, 2021</start_date>
<completion_date type="Anticipated">December 1, 2023</completion_date>
<primary_completion_date type="Anticipated">June 1, 2023</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Other</primary_purpose>
<masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>successful insert rate</measure>
<time_frame>0 minute after insertion</time_frame>
<description>success rate of inserting laryngeal mask</description>
</primary_outcome>
<primary_outcome>
<measure>tidal volume</measure>
<time_frame>5 minute afer successful insertion</time_frame>
<description>tidal volume at 15cmH2O in patients with supine and lateral positioning</description>
</primary_outcome>
<primary_outcome>
<measure>leakage pressure</measure>
<time_frame>5 minute afer successful insertion</time_frame>
<description>leakage pressure in patients with supine and lateral positioning</description>
</primary_outcome>
<primary_outcome>
<measure>The scale of fiberoptic bronchoscopy</measure>
<time_frame>0 minute afer successful insertion</time_frame>
<description>1 = only vocal cords visible; 2 = vocal cords plus posterior epiglottis visible; 3 = vocal cords plus anterior epiglottis visible; and 4 = vocal cords invisible</description>
</primary_outcome>
<primary_outcome>
<measure>Number of Participants with cranial nerve injury</measure>
<time_frame>1hours after the surgery</time_frame>
<description>Number of Participants with cranial nerve injury</description>
</primary_outcome>
<secondary_outcome>
<measure>Number of Participants with sore throat</measure>
<time_frame>1hours after the surgery</time_frame>
<description>Number of Participants with sore throat</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of Participants with hoarseness</measure>
<time_frame>1hours after the surgery</time_frame>
<description>Number of Participants with hoarseness</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of Participants with cough</measure>
<time_frame>1hours after the surgery</time_frame>
<description>Number of Participants with cough</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of Participants with laryngospasm</measure>
<time_frame>1hours after the surgery</time_frame>
<description>Number of Participants with laryngospasm</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of Participants with soft tissue injury</measure>
<time_frame>1hours after the surgery</time_frame>
<description>Number of Participants with soft tissue injury</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">200</enrollment>
<condition>Anesthesia Intubation Complication</condition>
<arm_group>
<arm_group_label>flexible laryngeal airway</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
</arm_group>
<arm_group>
<arm_group_label>proseal laryngeal mask airway</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
</arm_group>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>flexible laryngeal airway mask</intervention_name>
<description>Ventilation with flexible laryngeal mask airway</description>
<arm_group_label>flexible laryngeal airway</arm_group_label>
</intervention>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>proseal laryngeal mask airway</intervention_name>
<description>Ventilation with proseal laryngeal mask airway</description>
<arm_group_label>proseal laryngeal mask airway</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

Clinical diagnosis of otitis media.

Exclusion Criteria:

Problems with the upper airway. Gastric carcinoma. Reflux esophagitis.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>65 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<verification_date>August 2021</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>August 18, 2021</last_update_submitted>
<last_update_submitted_qc>August 18, 2021</last_update_submitted_qc>
<last_update_posted type="Actual">August 19, 2021</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Objective To investigate the comparative effect of proseal laryngeal mask airway and flexible
laryngeal airway mask during otitis media surgery. Methods 200 patients of ASA I or II
classification, 18-65 years old, BMI<30 kg/m2 undergoing otitis media surgery are randomly
divided into two groups (Group P with proseal laryngeal mask airway and Group F with flexible
laryngeal airway mask, respectively). After induction, selecting a appropriate size of LMA to
patient,s weight, using the standard index finger-guided technique inserting the LMA, and
then the patients were ventilated mechanically. The success rate of inserting laryngeal mask,
the intubation time, surgery time and wake time were also recorded. Tidal volume and leakage
pressure in patients with supine and lateral positioning were assessed respectively. The
scale of fiberoptic bronchoscopy was also recorded to show airway exposure. Related
complications such as sore throat, hoarseness, cough, laryngospasm, bloating, nausea and
vomiting, soft tissue injury, blood residue after pulling out the LMA were
analyzed.Postoperative voice and laryngopharyngeal symptom are also recorded.
Inclusion Criteria:
Clinical diagnosis of otitis media.
Exclusion Criteria:
Problems with the upper airway. Gastric carcinoma. Reflux esophagitis.
|
NCT0426xxxx/NCT04268056.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268056</url>
</required_header>
<id_info>
<org_study_id>0141-19-RMB</org_study_id>
<nct_id>NCT04268056</nct_id>
</id_info>
<brief_title>Characterization of Skin Microbiome Profile and it's Correlation to Radiation Dermatitis</brief_title>
<official_title>Characterization of Skin Microbiome Profile Before and During Radiation Therapy and it's Correlation to the Occurrence and Severity of Radiation Dermatitis</official_title>
<sponsors>
<lead_sponsor>
<agency>AceTech</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
</sponsors>
<source>AceTech</source>
<oversight_info>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The purpose of this study is to characterize the skin microbiome profile of breast cancer
patients before and after receiving Radio Therapy treatments, and evaluate the relationship
between the microbiome profile and radiation dermatitis severity (grade) that the patient
will develop. Such characterizations can lead to potential biomarkers and/or therapeutic
targets that can be used for the prognosis, prevention and treatment of this condition.
</textblock>
</brief_summary>
<overall_status>Unknown status</overall_status>
<last_known_status>Active, not recruiting</last_known_status>
<start_date type="Actual">November 1, 2020</start_date>
<completion_date type="Anticipated">November 2021</completion_date>
<primary_completion_date type="Actual">July 20, 2021</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Cross-Sectional</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Radiation Dermatitis grade</measure>
<time_frame>through study completion, an average of 1 year</time_frame>
<description>Study participant will be evaluated by physician and nurse for the occurrence and the severity of RD. Skin condition (grade of RD) in the radiation area will be measured by the Radiation Therapy Oncology Group (RTOG) scoring.</description>
</primary_outcome>
<primary_outcome>
<measure>Microbiome composition</measure>
<time_frame>through study completion, an average of 1 year</time_frame>
<description>Collection of skin culture samples from body regions surrounding the RT treatment area and a control area</description>
</primary_outcome>
<secondary_outcome>
<measure>Validation Procedure of evaluation of Radiation Dermatitis grade by the our application (Radia-App)</measure>
<time_frame>through study completion, an average of 1 year</time_frame>
</secondary_outcome>
<number_of_groups>1</number_of_groups>
<enrollment type="Actual">100</enrollment>
<condition>Radiation Dermatitis</condition>
<arm_group>
<arm_group_label>RT patients</arm_group_label>
<description>100 patients with breast cancer undergoing radiation therapy</description>
</arm_group>
<intervention>
<intervention_type>Diagnostic Test</intervention_type>
<intervention_name>Collection of skin culture samples</intervention_name>
<description>Collection of skin culture samples using a sterile swab. the swab will gently rubbed on the skin on the 3 different skin areas. The target areas are i) regions surrounding the RT treatment area (if possible, not from the scar area or from skin folds areas), ii) a control site of the normal (healthy) breast , iii) a control area on the forehead.</description>
<arm_group_label>RT patients</arm_group_label>
</intervention>
<biospec_retention>Samples Without DNA</biospec_retention>
<biospec_descr>
<textblock>
Skin microbiome samples
</textblock>
</biospec_descr>
<eligibility>
<study_pop>
<textblock>
Patients with breast cancer undergoing radiation therapy.
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

1. Age ≥ 18 years

2. Histological confirmation of breast malignancy

3. Primary or recurrent disease eligible

4. Patients after breast lumpectomy and that scheduled to receive radiotherapy

5. Patients that receive minimum of 45 Gy

6. Ability to complete questionnaire(s) by themselves or with assistance

7. Provide informed written consent

Exclusion Criteria:

1. Patients with prior radiotherapy to any portion of the planned treatment site

2. Tumour involvement of the skin

3. Patients with active rash, pre-existing dermatitis, lupus, or scleroderma

4. Patient with other skin diseases/ skin disorders

5. Recent use of systemic or topical antibiotics or antifungal medications within 21 days
of first swab collection.

6. Recent use of any of the following within 21 days of first swab collection: o Systemic
or topical steroids o Use of systemic immunosuppressant drugs o Use of ultraviolet
light therapy

7. Prior usage of other topical and systemic medications within 21 days of first swab
collection

8. Prior usage of topical cosmetic products, creams, lotions, or gels within 14 days of
first swab collection in areas where samples are taken.

9. Clinical evidence of infection that in the judgement of the principle investigator
would interfere with proper assessment of the skin microbiome

10. Prior organ or bone marrow transplant

11. Any other reason that, in the opinion of the investigator, prevents the subject from
participating in the study or compromise the patient safety
</textblock>
</criteria>
<gender>Female</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Roxolyana Abdah-Borthnyak, MD</last_name>
<role>Principal Investigator</role>
<affiliation>Director, Radiation Service for Female Cancer</affiliation>
</overall_official>
<location>
<facility>
<name>Rambam Medical Center</name>
<address>
<city>Haifa</city>
<country>Israel</country>
</address>
</facility>
</location>
<location_countries>
<country>Israel</country>
</location_countries>
<verification_date>July 2021</verification_date>
<study_first_submitted>February 6, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>July 20, 2021</last_update_submitted>
<last_update_submitted_qc>July 20, 2021</last_update_submitted_qc>
<last_update_posted type="Actual">July 21, 2021</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Radiation dermatitis</keyword>
<keyword>Radio Therapy</keyword>
<keyword>Microbiome Profile</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Dermatitis</mesh_term>
<mesh_term>Radiodermatitis</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The purpose of this study is to characterize the skin microbiome profile of breast cancer
patients before and after receiving Radio Therapy treatments, and evaluate the relationship
between the microbiome profile and radiation dermatitis severity (grade) that the patient
will develop. Such characterizations can lead to potential biomarkers and/or therapeutic
targets that can be used for the prognosis, prevention and treatment of this condition.
Skin microbiome samples
Patients with breast cancer undergoing radiation therapy.
Inclusion Criteria:
1. Age ≥ 18 years
2. Histological confirmation of breast malignancy
3. Primary or recurrent disease eligible
4. Patients after breast lumpectomy and that scheduled to receive radiotherapy
5. Patients that receive minimum of 45 Gy
6. Ability to complete questionnaire(s) by themselves or with assistance
7. Provide informed written consent
Exclusion Criteria:
1. Patients with prior radiotherapy to any portion of the planned treatment site
2. Tumour involvement of the skin
3. Patients with active rash, pre-existing dermatitis, lupus, or scleroderma
4. Patient with other skin diseases/ skin disorders
5. Recent use of systemic or topical antibiotics or antifungal medications within 21 days
of first swab collection.
6. Recent use of any of the following within 21 days of first swab collection: o Systemic
or topical steroids o Use of systemic immunosuppressant drugs o Use of ultraviolet
light therapy
7. Prior usage of other topical and systemic medications within 21 days of first swab
collection
8. Prior usage of topical cosmetic products, creams, lotions, or gels within 14 days of
first swab collection in areas where samples are taken.
9. Clinical evidence of infection that in the judgement of the principle investigator
would interfere with proper assessment of the skin microbiome
10. Prior organ or bone marrow transplant
11. Any other reason that, in the opinion of the investigator, prevents the subject from
participating in the study or compromise the patient safety
|
NCT0426xxxx/NCT04268069.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268069</url>
</required_header>
<id_info>
<org_study_id>PL9643-201</org_study_id>
<nct_id>NCT04268069</nct_id>
</id_info>
<brief_title>Efficacy and Safety of PL9643 Ophthalmic Solution in Subjects With Dry Eye</brief_title>
<official_title>A Phase 2, Multi-center, Randomized, Double-Masked and Placebo-Controlled Study Evaluating the Efficacy and Safety of PL9643 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye</official_title>
<sponsors>
<lead_sponsor>
<agency>ORA, Inc.</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
<collaborator>
<agency>Palatin Technologies, Inc</agency>
<agency_class>Industry</agency_class>
</collaborator>
</sponsors>
<source>ORA, Inc.</source>
<oversight_info>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Evaluation of safety and efficacy of PL9643 Ophthalmic Solution compared to placebo for the
treatment of the signs and symptoms of dry eye.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
The clinical trial is a Phase 2, multi center, randomized, double masked and placebo
controlled study.

During a 14-day study run-in period (for the purpose of subject selection) prior to
randomization, all subjects will receive Placebo Ophthalmic Solution (vehicle) bilaterally.
During the screening period, exposure to the CAE® will be conducted to ascertain eligibility
to enter the study at Visit 1 and Visit 2. Those who qualify at Visit 2 will be randomized to
receive study drug in a double-masked fashion for 12 weeks. The CAE® exposure will occur at
all Visits.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">February 14, 2020</start_date>
<completion_date type="Actual">October 5, 2020</completion_date>
<primary_completion_date type="Actual">October 5, 2020</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>Inferior Corneal Fluorescein Staining Using The Ora Calibra Scale</measure>
<time_frame>Day 85</time_frame>
<description>An assessment of corneal fluorescein staining using the 0 [none] to 4 [worst] Ora Calibra Scale prior to and following exposure to a challenge in a controlled adverse environment (CAE)</description>
</primary_outcome>
<primary_outcome>
<measure>Ocular Discomfort Using The Ora Calibra Scale</measure>
<time_frame>Day 85</time_frame>
<description>A patient-reported subjective assessment of ocular discomfort using the 0 [none] to 4 [worst] Ora Calibra Scale recorded at each study visit throughout the treatment period</description>
</primary_outcome>
<secondary_outcome>
<measure>Corneal Fluorescein Staining Using The Ora Calibra Scale</measure>
<time_frame>12 weeks</time_frame>
<description>An assessment of corneal fluorescein staining using the 0 [none] to 4 [worst] Ora Calibra Scale prior to and following exposure to a challenge in a controlled adverse environment (CAE)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Conjunctival Lissamine Green Staining Using The Ora Calibra Scale</measure>
<time_frame>12 weeks</time_frame>
<description>An assessment of conjunctival lissamine green staining using the 0 [none] to 4 [worst] Ora Calibra Scale prior to and following exposure to a challenge in a controlled adverse environment (CAE)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Conjunctival Redness Using The Ora Calibra Scale</measure>
<time_frame>12 weeks</time_frame>
<description>An assessment of conjunctival redness using the 0 [none] to 4 [worst] Ora Calibra Scale prior to and following exposure to a challenge in a controlled adverse environment (CAE)</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">160</enrollment>
<condition>Dry Eye Disease</condition>
<arm_group>
<arm_group_label>Placebo Ophthalmic Solution (vehicle)</arm_group_label>
<arm_group_type>Placebo Comparator</arm_group_type>
<description>vehicle</description>
</arm_group>
<arm_group>
<arm_group_label>PL9643 Ophthalmic Solution</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>PL9643 Ophthalmic Solution</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>PL9643 Ophthalmic Solution</intervention_name>
<description>PL9643 Ophthalmic Solution as topical ophthalmic drops administered bilaterally for 12 weeks.</description>
<arm_group_label>PL9643 Ophthalmic Solution</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Placebo Ophthalmic Solution</intervention_name>
<description>Placebo solution as topical ophthalmic drops administered bilaterally for 12 weeks.</description>
<arm_group_label>Placebo Ophthalmic Solution (vehicle)</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Be at least 18 years of age.

- Provided written informed consent.

- Have a reported history of dry eye

- Have a history of use or desire to use eye drops for dry eye symptoms

- Have corrected visual acuity greater than or equal to +0.7 in both eyes

Exclusion Criteria:

- Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal)

- Have any planned ocular and/or lid surgeries over the study period.

- Have an uncontrolled systemic disease.

- Be a woman who is pregnant, nursing or planning a pregnancy.

- Be a woman of childbearing potential who is not using an acceptable means of birth
control

- Have a known allergy and/or sensitivity to the test article or its components.

- Have a condition or be in a situation which the investigator feels may put the subject
at significant risk, may confound the study results, or may interfere significantly
with the subject's participation in the study

- Have used an investigational drug or device within 30 days of Visit 1

- Be unable or unwilling to follow instructions, including participation in all study
assessments and visits
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<location>
<facility>
<name>Andover Eye Associates</name>
<address>
<city>Andover</city>
<state>Massachusetts</state>
<zip>01810</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Andover Eye Associates</name>
<address>
<city>Raynham</city>
<state>Massachusetts</state>
<zip>02767</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Vita Eye Clinc</name>
<address>
<city>Shelby</city>
<state>North Carolina</state>
<zip>28150</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Total Eye Care, P.A.</name>
<address>
<city>Memphis</city>
<state>Tennessee</state>
<zip>38119</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>November 2020</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>November 12, 2020</last_update_submitted>
<last_update_submitted_qc>November 12, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">November 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Dry Eye Syndromes</mesh_term>
<mesh_term>Keratoconjunctivitis Sicca</mesh_term>
<mesh_term>Eye Diseases</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Pharmaceutical Solutions</mesh_term>
<mesh_term>Ophthalmic Solutions</mesh_term>
</intervention_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Evaluation of safety and efficacy of PL9643 Ophthalmic Solution compared to placebo for the
treatment of the signs and symptoms of dry eye.
The clinical trial is a Phase 2, multi center, randomized, double masked and placebo
controlled study.
During a 14-day study run-in period (for the purpose of subject selection) prior to
randomization, all subjects will receive Placebo Ophthalmic Solution (vehicle) bilaterally.
During the screening period, exposure to the CAE® will be conducted to ascertain eligibility
to enter the study at Visit 1 and Visit 2. Those who qualify at Visit 2 will be randomized to
receive study drug in a double-masked fashion for 12 weeks. The CAE® exposure will occur at
all Visits.
Inclusion Criteria:
- Be at least 18 years of age.
- Provided written informed consent.
- Have a reported history of dry eye
- Have a history of use or desire to use eye drops for dry eye symptoms
- Have corrected visual acuity greater than or equal to +0.7 in both eyes
Exclusion Criteria:
- Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal)
- Have any planned ocular and/or lid surgeries over the study period.
- Have an uncontrolled systemic disease.
- Be a woman who is pregnant, nursing or planning a pregnancy.
- Be a woman of childbearing potential who is not using an acceptable means of birth
control
- Have a known allergy and/or sensitivity to the test article or its components.
- Have a condition or be in a situation which the investigator feels may put the subject
at significant risk, may confound the study results, or may interfere significantly
with the subject's participation in the study
- Have used an investigational drug or device within 30 days of Visit 1
- Be unable or unwilling to follow instructions, including participation in all study
assessments and visits
|
NCT0426xxxx/NCT04268082.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268082</url>
</required_header>
<id_info>
<org_study_id>20180036031</org_study_id>
<nct_id>NCT04268082</nct_id>
</id_info>
<brief_title>Insole-based Visual Biofeedback for Weight-bearing in Total Hip Replacement</brief_title>
<official_title>The Effects of Insole-based Visual Biofeedback on Weight-bearing in Patients Undergoing Total Hip Replacement. A Randomised Controlled Trial.</official_title>
<sponsors>
<lead_sponsor>
<agency>University of Pavia</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>University of Pavia</source>
<oversight_info>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The study investigates the effects of visual biofeedback, based on a sensorized system for
the dynamic evaluation of the plantar pressure versus rehabilitation with traditional verbal
instructions of the physiotherapist, on weight bearing distribution in patients who underwent
first total hip replacement. The study is a randomized controlled trial, with parallel
groups, without blinding.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Forty patients, who underwent first total hip replacement surgery were enrolled and divided
into two groups on second postoperative day. Experimental group followed the training wearing
sensorized insoles that provided plantar pressures and shift of foot center of pressure
images on three monitors. Control Group followed verbal instructions of physiotherapist
during training. From 4th to 10th postoperative day both groups followed the same
rehabilitation program including exercises to restore correct weight bearing.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">April 1, 2018</start_date>
<completion_date type="Actual">July 31, 2018</completion_date>
<primary_completion_date type="Actual">July 31, 2018</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>Single (Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>Weight Bearing Absolute difference between lower limbs (ΔWBA)</measure>
<time_frame>between the 4th and the 10th day post surgery</time_frame>
<description>Weight Bearing Absolute difference between lower limbs in kg as reported by the stabilometric platform</description>
</primary_outcome>
<primary_outcome>
<measure>Weight Bearing Percentage difference between lower limbs (ΔWBP)</measure>
<time_frame>between the 4th and the 10th day post surgery</time_frame>
<description>Weight Bearing Percentage difference between lower limbs in % as reported by the stabilometric platform</description>
</primary_outcome>
<primary_outcome>
<measure>Weight Bearing Percentage Healthy limb (WBPH)</measure>
<time_frame>between the 4th and the 10th day post surgery</time_frame>
<description>Weight Bearing Percentage Healthy limb in % as reported by the stabilometric platform</description>
</primary_outcome>
<primary_outcome>
<measure>Weight Bearing Percentage Surgical limb (WBPS)</measure>
<time_frame>between the 4th and the 10th day post surgery</time_frame>
<description>Weight Bearing Percentage Surgical limb in % as reported by the stabilometric platform</description>
</primary_outcome>
<primary_outcome>
<measure>Weight Bearing Absolute Healthy limb (WBAH)</measure>
<time_frame>between the 4th and the 10th day post surgery</time_frame>
<description>Weight Bearing Absolute Healthy limb in kg as reported by the stabilometric platform</description>
</primary_outcome>
<primary_outcome>
<measure>Weight Bearing Absolute Surgical limb (WBAS)</measure>
<time_frame>between the 4th and the 10th day post surgery</time_frame>
<description>Weight Bearing Absolute Surgical limb in kg as reported by the stabilometric platform</description>
</primary_outcome>
<secondary_outcome>
<measure>Mid Step Length Healthy limb (MSLH)</measure>
<time_frame>between the 4th and the 10th day post surgery</time_frame>
<description>Mid Step Length Healthy limb in mm as reported by the stabilometric platform</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mid Step Length Surgical limb (MSLS)</measure>
<time_frame>between the 4th and the 10th day post surgery</time_frame>
<description>Mid Step Length Surgical limb in mm as reported by the stabilometric platform</description>
</secondary_outcome>
<secondary_outcome>
<measure>Sway Healthy limb (SWH)</measure>
<time_frame>between the 4th and the 10th day post surgery</time_frame>
<description>Sway Healthy limb in mm as reported by the stabilometric platform</description>
</secondary_outcome>
<secondary_outcome>
<measure>Sway Surgical limb (SWS)</measure>
<time_frame>between the 4th and the 10th day post surgery</time_frame>
<description>Sway Surgical limb in mm as reported by the stabilometric platform</description>
</secondary_outcome>
<secondary_outcome>
<measure>Double Support Time (DST)</measure>
<time_frame>between the 4th and the 10th day post surgery</time_frame>
<description>Double Support Time in ms as reported by the stabilometric platform</description>
</secondary_outcome>
<secondary_outcome>
<measure>Numeric Rating Scale (NRS)</measure>
<time_frame>between the 4th and the 10th day post surgery</time_frame>
<description>Numeric Rating Scale</description>
</secondary_outcome>
<secondary_outcome>
<measure>Six Minutes Walking Test (6MWT)</measure>
<time_frame>between the 4th and the 10th day post surgery</time_frame>
<description>Six Minutes Walking Test in m</description>
</secondary_outcome>
<secondary_outcome>
<measure>World Health Organization Quality of Life Questionnaire (WHOQOL)</measure>
<time_frame>between the 4th and the 10th day post surgery</time_frame>
<description>World Health Organization Quality of Life Questionnaire</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">40</enrollment>
<condition>Total Hip Replacement</condition>
<condition>Visual Biofeedback</condition>
<condition>Weight Bearing</condition>
<arm_group>
<arm_group_label>Experimental Group</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>The Experimental Group followed the training wearing sensorized insoles that provided plantar pressures and shift of foot center of pressure images reported on monitors.</description>
</arm_group>
<arm_group>
<arm_group_label>Control Group</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>The Control Group followed verbal instructions of physiotherapist during training.</description>
</arm_group>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>Visual biofeedback with the use of sensorized insoles</intervention_name>
<description>Between the 4th and the 10th day post surgery, both groups performed the same rehabilitation protocol. The experimental group was re-educated to the correct gait dynamics by wearing the sensorized insoles and by using a specific software's graphical interface as a visual biofeedback.</description>
<arm_group_label>Experimental Group</arm_group_label>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Standard rehabilitation based on physiotherapist's verbal instructions</intervention_name>
<description>Between the 4th and the 10th day post surgery, both groups performed the same rehabilitation protocol.The Control group did not wear the insoles, but it carried out the rehabilitation programme under the physiotherapist supervision and with his verbal feedbacks.</description>
<arm_group_label>Control Group</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- 75 ≤ years of age,

- absence of conditions that could alter the gait cycle,

- absence of conditions that could reduce or alter visual ability,

- etherometry ≤ 0.5 mm

- Mini-Mental State Examination (MMSE) score ≥ 24.

Exclusion Criteria:

-
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>75 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Luca Marin, PhD</last_name>
<role>Principal Investigator</role>
<affiliation>University of Pavia, Pavia, Italy</affiliation>
</overall_official>
<location>
<facility>
<name>"Città di Pavia" University Hospital, Pavia, Italy</name>
<address>
<city>Pavia</city>
<zip>27100</zip>
<country>Italy</country>
</address>
</facility>
</location>
<location_countries>
<country>Italy</country>
</location_countries>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 6, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 12, 2020</last_update_submitted>
<last_update_submitted_qc>February 12, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>University of Pavia</investigator_affiliation>
<investigator_full_name>Luca Marin</investigator_full_name>
<investigator_title>Principal Investigator</investigator_title>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Body Weight</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The study investigates the effects of visual biofeedback, based on a sensorized system for
the dynamic evaluation of the plantar pressure versus rehabilitation with traditional verbal
instructions of the physiotherapist, on weight bearing distribution in patients who underwent
first total hip replacement. The study is a randomized controlled trial, with parallel
groups, without blinding.
Forty patients, who underwent first total hip replacement surgery were enrolled and divided
into two groups on second postoperative day. Experimental group followed the training wearing
sensorized insoles that provided plantar pressures and shift of foot center of pressure
images on three monitors. Control Group followed verbal instructions of physiotherapist
during training. From 4th to 10th postoperative day both groups followed the same
rehabilitation program including exercises to restore correct weight bearing.
Inclusion Criteria:
- 75 ≤ years of age,
- absence of conditions that could alter the gait cycle,
- absence of conditions that could reduce or alter visual ability,
- etherometry ≤ 0.5 mm
- Mini-Mental State Examination (MMSE) score ≥ 24.
Exclusion Criteria:
-
|
NCT0426xxxx/NCT04268095.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268095</url>
</required_header>
<id_info>
<org_study_id>0548-18-TLV</org_study_id>
<nct_id>NCT04268095</nct_id>
</id_info>
<brief_title>Post Operative Dressing After Clean Elective Hand Surgery</brief_title>
<official_title>Post Operative Dressing After Clean Elective Hand Surgery</official_title>
<sponsors>
<lead_sponsor>
<agency>Itay Ashkenazi</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Tel Aviv Medical Center</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Very little has been published about the optimal post operative dressing protocol, and no
practical conclusion has emerged from a meta-analysis published in 2013. Even fewer studies
focused on that topic specifically in hand surgery. Nevertheless, the functional impairment
due to a dressing in the hand is much greater than anywhere else, due to the constant use of
hands in daily life activities. Yet, habits differs widely following surgeon's preference,
from daily change with application of an antimicrobial unguent, to unchanged dressing until
the first follow up consultation after 2 weeks, to complete removal of the dressing and basic
soap and water cleaning at postoperative day (POD) 1. Those varying recommendations have
functional and logistical implication for the patients, especially the elderlies, for whom
autonomy is a fragile status that can be dramatically impaired by such protocols. The goal of
this study is to define which post operative dressing protocol is optimal in terms of wound
complications (disunion, infection)
</textblock>
</brief_summary>
<overall_status>Completed</overall_status>
<start_date type="Actual">December 31, 2019</start_date>
<completion_date type="Actual">February 1, 2021</completion_date>
<primary_completion_date type="Actual">December 31, 2020</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Prevention</primary_purpose>
<masking>Triple (Care Provider, Investigator, Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>Change in Instrumental activities of daily living questioner (IADL)</measure>
<time_frame>Baseline (Pre-op), 2 weeks, 6 weeks, 3 months</time_frame>
<description>Subjective function questioner. Scale 0-18. Higher score - better outcome.</description>
</primary_outcome>
<primary_outcome>
<measure>Change in Vancouver Scar Scale</measure>
<time_frame>2 weeks, 6 weeks, 3 months</time_frame>
<description>Evaluation of skin healing and scar formation. Scale 0-14. Higher score - inferior outcome.</description>
</primary_outcome>
<primary_outcome>
<measure>Change in quick Disability of the Arm, Shoulder and Hand questioner (DASH)</measure>
<time_frame>Baseline, 2 weeks, 6 weeks, 3 months</time_frame>
<description>Subjective function questioner. Scale 0-100. Higher score - inferior outcome.</description>
</primary_outcome>
<number_of_arms>3</number_of_arms>
<enrollment type="Actual">60</enrollment>
<condition>Trigger Finger Disorder</condition>
<condition>Carpal Tunnel Syndrome</condition>
<condition>Ganglion</condition>
<arm_group>
<arm_group_label>No dressing change</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Patients do not change dressing from procedure to first clinic followup after 14 days.</description>
</arm_group>
<arm_group>
<arm_group_label>Ambulatory dressing change</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Patients change dressing by an ambulatory nurse (not associated with the study) 2 times a week from surgery to first clinic followup after 14 days</description>
</arm_group>
<arm_group>
<arm_group_label>No dressing</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Patients take off dressing at post operative day 1 and clean it 3 times per day as instructed.</description>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Dressing protocol</intervention_name>
<description>Patients are assigned with different postoperative dressing protocols.</description>
<arm_group_label>Ambulatory dressing change</arm_group_label>
<arm_group_label>No dressing</arm_group_label>
<arm_group_label>No dressing change</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

* Elective hand surgery with clean wound (Type 1 in wound classification of american
college of surgeon 11) - (Carpal tunnel, trigger finger, cyst removal or foreign body
removal, tendon release).

Exclusion Criteria:

- Insertion of hardware

- Known skin condition disturbing normal healing,

- Immunodeficiency,

- Incapacity to understand or to observe the self cleaning protocol.

- Unexpected peroperative complication leading to a modification of the operative
technique.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<location>
<facility>
<name>Tel Aviv medical cemter</name>
<address>
<city>Tel Aviv</city>
<state>IL</state>
<zip>6423906</zip>
<country>Israel</country>
</address>
</facility>
</location>
<location_countries>
<country>Israel</country>
</location_countries>
<verification_date>April 2021</verification_date>
<study_first_submitted>February 5, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>April 3, 2021</last_update_submitted>
<last_update_submitted_qc>April 3, 2021</last_update_submitted_qc>
<last_update_posted type="Actual">April 6, 2021</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor-Investigator</responsible_party_type>
<investigator_affiliation>Tel Aviv Medical Center</investigator_affiliation>
<investigator_full_name>Itay Ashkenazi</investigator_full_name>
<investigator_title>Principal investigator</investigator_title>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Trigger Finger Disorder</mesh_term>
<mesh_term>Carpal Tunnel Syndrome</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>Yes</sharing_ipd>
<ipd_description>Data will be shared at the discretion of the Chief Investigator</ipd_description>
<ipd_info_type>Study Protocol</ipd_info_type>
<ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
<ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
<ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
<ipd_time_frame>30 days</ipd_time_frame>
<ipd_access_criteria>at the discretion of the Chief Investigator</ipd_access_criteria>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Very little has been published about the optimal post operative dressing protocol, and no
practical conclusion has emerged from a meta-analysis published in 2013. Even fewer studies
focused on that topic specifically in hand surgery. Nevertheless, the functional impairment
due to a dressing in the hand is much greater than anywhere else, due to the constant use of
hands in daily life activities. Yet, habits differs widely following surgeon's preference,
from daily change with application of an antimicrobial unguent, to unchanged dressing until
the first follow up consultation after 2 weeks, to complete removal of the dressing and basic
soap and water cleaning at postoperative day (POD) 1. Those varying recommendations have
functional and logistical implication for the patients, especially the elderlies, for whom
autonomy is a fragile status that can be dramatically impaired by such protocols. The goal of
this study is to define which post operative dressing protocol is optimal in terms of wound
complications (disunion, infection)
Inclusion Criteria:
* Elective hand surgery with clean wound (Type 1 in wound classification of american
college of surgeon 11) - (Carpal tunnel, trigger finger, cyst removal or foreign body
removal, tendon release).
Exclusion Criteria:
- Insertion of hardware
- Known skin condition disturbing normal healing,
- Immunodeficiency,
- Incapacity to understand or to observe the self cleaning protocol.
- Unexpected peroperative complication leading to a modification of the operative
technique.
|
NCT0426xxxx/NCT04268108.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268108</url>
</required_header>
<id_info>
<org_study_id>Liquid TIL</org_study_id>
<nct_id>NCT04268108</nct_id>
</id_info>
<brief_title>L-TIL in Patients With Malignancy Resistance to Anti-PD-1 Therapy</brief_title>
<official_title>Clinical Study of Liquid Tumor Infiltrating Lymphocytes in Patients With Advanced Malignancies Resistance to Anti-PD-1 Therapy</official_title>
<sponsors>
<lead_sponsor>
<agency>Henan Cancer Hospital</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Henan Cancer Hospital</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Safety and effectiveness of liquid tumor infiltrating lymphocytes in patients with advanced
malignant tumors who have failed to anti-PD-1 therapy
</textblock>
</brief_summary>
<overall_status>Unknown status</overall_status>
<last_known_status>Recruiting</last_known_status>
<start_date type="Actual">April 2, 2020</start_date>
<completion_date type="Anticipated">June 19, 2022</completion_date>
<primary_completion_date type="Anticipated">February 19, 2022</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>the rate of reverse events</measure>
<time_frame>three months</time_frame>
<description>the rate of reverse events</description>
</primary_outcome>
<secondary_outcome>
<measure>clinical benefit rate</measure>
<time_frame>three months</time_frame>
<description>the proportion of patients benefit from liquid tumor infiltrating lymphocytes</description>
</secondary_outcome>
<secondary_outcome>
<measure>time to progression</measure>
<time_frame>six months</time_frame>
<description>from the date of therapy to the first date of determined progressive disease</description>
</secondary_outcome>
<number_of_groups>1</number_of_groups>
<enrollment type="Anticipated">30</enrollment>
<condition>Advanced Solid Tumor</condition>
<arm_group>
<arm_group_label>group 1</arm_group_label>
<description>arm 1: secondary resistance to anti-PD-1 therapy: this patients group received liquid tumor infiltrating lymphocytes combined anti-PD-1 therapy.
arm 2: primary resistance to anti-PD-1 therapy: this patients group received FC preconditioning before received liquid tumor infiltrating lymphocytes</description>
</arm_group>
<intervention>
<intervention_type>Biological</intervention_type>
<intervention_name>liquid tumor infiltrating lymphocytes</intervention_name>
<description>Isolatation and amplification PD-1+ cells from peripheral blood lymphocytes under GMP conditions for clinical use.</description>
<arm_group_label>group 1</arm_group_label>
</intervention>
<eligibility>
<study_pop>
<textblock>
Eligible patients in our hospital
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- Expected lifespan is over 3 months

- malignant tumors diagnosed by pathological examination

- Imaging examination is at advanced stage with at least one measurable lesion

- Ineffective or resistant to previous anti-PD-1 therapy

- ECOG score 0-2

- Adequate organ function

- No other serious diseases that conflict with this protocol

- Women of childbearing age must check for a negative blood pregnancy test within 7
days, and subjects of childbearing age must use appropriate contraception during the
test and within 3 months

- witten informed consent from the patients

Exclusion Criteria:

- Severe infectious disease within 4 weeks before enrollment

- Active hepatitis B or C virus or HIV infection

- Severe autoimmune disease or immunodeficiency disease

- Severe allergies

- Severe mental disorder

- Systematically used a large amount of glucocorticoids within 4 weeks before enrollment

- With severe heart, liver, kidney insufficiency, diabetes and other diseases

- Participation in other clinical studies in the past 3 months or having been treated
with other gene products
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>70 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_contact>
<last_name>Quanli Gao, Dr.</last_name>
<phone>+86-371-65587795</phone>
<email>gaoquanli2015@126.com</email>
</overall_contact>
<overall_contact_backup>
<last_name>Tiepeng Li, Dr.</last_name>
<phone>+86-371-65587199</phone>
<email>claylee5405@163.com</email>
</overall_contact_backup>
<location>
<facility>
<name>Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital</name>
<address>
<city>Zhengzhou</city>
<state>Henan</state>
<zip>450008</zip>
<country>China</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Quanli Gao, M.D</last_name>
<phone>+86-371-65587795</phone>
<email>gaoquanli2015@126.com</email>
</contact>
<contact_backup>
<last_name>Lingdi Zhao, M.D.</last_name>
<phone>+86-371-65587483</phone>
<email>lingdizhao@126.com</email>
</contact_backup>
</location>
<location_countries>
<country>China</country>
</location_countries>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>June 10, 2020</last_update_submitted>
<last_update_submitted_qc>June 10, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">June 11, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>liquid tumor-infiltrating lymphocytes</keyword>
<keyword>anti-PD-1</keyword>
<keyword>resistance</keyword>
<keyword>solid tumor</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Neoplasms</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>Undecided</sharing_ipd>
<ipd_description>Need to solicit patients' consent whether to agree to share their information during the enrollment process,</ipd_description>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Safety and effectiveness of liquid tumor infiltrating lymphocytes in patients with advanced
malignant tumors who have failed to anti-PD-1 therapy
Eligible patients in our hospital
Inclusion Criteria:
- Expected lifespan is over 3 months
- malignant tumors diagnosed by pathological examination
- Imaging examination is at advanced stage with at least one measurable lesion
- Ineffective or resistant to previous anti-PD-1 therapy
- ECOG score 0-2
- Adequate organ function
- No other serious diseases that conflict with this protocol
- Women of childbearing age must check for a negative blood pregnancy test within 7
days, and subjects of childbearing age must use appropriate contraception during the
test and within 3 months
- witten informed consent from the patients
Exclusion Criteria:
- Severe infectious disease within 4 weeks before enrollment
- Active hepatitis B or C virus or HIV infection
- Severe autoimmune disease or immunodeficiency disease
- Severe allergies
- Severe mental disorder
- Systematically used a large amount of glucocorticoids within 4 weeks before enrollment
- With severe heart, liver, kidney insufficiency, diabetes and other diseases
- Participation in other clinical studies in the past 3 months or having been treated
with other gene products
|
NCT0426xxxx/NCT04268121.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268121</url>
</required_header>
<id_info>
<org_study_id>NEONEC D19-01</org_study_id>
<nct_id>NCT04268121</nct_id>
</id_info>
<brief_title>Efficacy of Neoadjuvant Chemotherapy in Terms of DFS in Patients With Localized Digestive Neuroendocrine Carcinomas</brief_title>
<acronym>NEONEC</acronym>
<official_title>Phase II Study to Evaluate the Efficacy of 12-month Neoadjuvant Chemotherapy in Terms of Disease-free Survival in Patients With Localized Digestive Neuroendocrine Carcinomas</official_title>
<sponsors>
<lead_sponsor>
<agency>GERCOR - Multidisciplinary Oncology Cooperative Group</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Fondation ARCAD</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>GERCOR - Multidisciplinary Oncology Cooperative Group</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
NEONEC is a single-phase, phase II study evaluating the efficacy of the 12-month neoadjuvant
chemotherapy in patients with locally differentiated digestive NEC. The recommended
chemotherapy is based on the current reference combination of platinum (cisplatin or
carboplatin) and etoposide (VP16). For anorectal locations, radiochemotherapy is proposed to
avoid the morbidity of conventional surgery.

The objective of the study is to improve relapse-free survival (RFS) in NEC patients treated
with neoadjuvant chemotherapy followed by surgery or chemoradiotherapy.

In parallel, we will perform a prospective cohort study with patients whose diagnosis is made
during surgery, who have not received neoadjuvant treatment, and who are offered an adjuvant
treatment of the same type (combination of platinum and platinum salts and etoposide).
</textblock>
</brief_summary>
<detailed_description>
<textblock>
A total of 48 patients is to be included in phase II and 30 patients in prospective cohort
during the inclusion period of phase II.

Phase II study treatment:

Neoadjuvant chemotherapy: Administration of 4 cycles of chemotherapy (3 months) with platinum
based chemotherapy (carboplatin or cisplatin, at the choice of the investigator) + etoposide.

Surgery or chemoradiotherapy depending on the tumor localization (the irradiation modalities
and associated chemotherapy treatment will be left to the discretion of the referring
radiotherapists according to current recommendations for each localization).

Prospective cohort:

- Surgery (prior to study entry)

- Adjuvant chemotherapy : Administration of 4 cycles of chemotherapy (3 months) with
platinum based chemotherapy (carboplatin or cisplatin, at the choice of the
investigator) + etoposide.
</textblock>
</detailed_description>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">January 5, 2021</start_date>
<completion_date type="Anticipated">June 2034</completion_date>
<primary_completion_date type="Anticipated">January 2034</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Non-Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>Phase II and prospective cohort</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Relapse-free survival (RFS) - phase II</measure>
<time_frame>At 12 months</time_frame>
<description>Interval between the date of the start of treatment (chemotherapy) and the date of first relapse or death (all causes). Relapse is defined according to RECIST version 1.1 criteria.</description>
</primary_outcome>
<primary_outcome>
<measure>Relapse-free survival (RFS) - prospective cohort</measure>
<time_frame>At 12 months</time_frame>
<description>Interval between the date of the start of treatment (chemotherapy) and the date of first relapse or death (all causes). Relapse is defined according to RECIST version 1.1 criteria.</description>
</primary_outcome>
<secondary_outcome>
<measure>Number of patient in response in pre-operative or prior radiochemotherapy (if applicable) - Phase II</measure>
<time_frame>At 3 months after the beginning of treatment (up to 36 months)</time_frame>
<description>according to RECIST 1.1</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of patients who do not benefit from surgery or radiochemotherapy (if applicable) - Phase II</measure>
<time_frame>Up to 39 months</time_frame>
<description>Number of patients who do not benefit from surgery or radiochemotherapy (if applicable) - Phase II</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of patients operated after neoadjuvant chemotherapy or receiving radiochemotherapy (if applicable) - Phase II</measure>
<time_frame>Up to 39 months</time_frame>
<description>Number of patients operated after neoadjuvant chemotherapy or receiving</description>
</secondary_outcome>
<secondary_outcome>
<measure>Overall survival (OS) - Phase II</measure>
<time_frame>up to 48 months</time_frame>
<description>Overall survival (OS) is defined as the time from study enrollment to death (from any cause) or to the last date the patients was known to be alive.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Overall survival (OS) - Prospective cohort</measure>
<time_frame>Up to 48 months</time_frame>
<description>Overall survival (OS) is defined as the time from study enrollment to death (from any cause) or to the last date the patients was known to be alive.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of participants with treatment-related adverse events grade 3-4 as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0 - Phase II</measure>
<time_frame>Up to 43 months</time_frame>
<description>Patients will be assessed for AEs throughout the study at every visit during treatment. Investigators using the NCI-CTCAE version 5.0 will grade the severity of AEs.
Institute Common Terminology Criteria for Adverse Toxicity Study (NCI-CTCAE) version 5.0</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of participants with treatment-related adverse events grade 3-4 as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0 - Prospective cohort</measure>
<time_frame>Up to 43 months</time_frame>
<description>Patients will be assessed for AEs throughout the study at every visit during treatment. Investigators using the NCI-CTCAE version 5.0 will grade the severity of AEs.
Institute Common Terminology Criteria for Adverse Toxicity Study (NCI-CTCAE) version 5.0</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">78</enrollment>
<condition>Neuroendocrine Carcinoma</condition>
<condition>Digestive Cancer</condition>
<arm_group>
<arm_group_label>Phase II</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Prospective, open, multi center, one-arm, national phase II study evaluating the benefits in terms of disease-free survival (DFS) at 12 months after the administration of neoadjuvant treatment in patients with localized digestive neuroendocrine carcinomas</description>
</arm_group>
<arm_group>
<arm_group_label>Prospective cohort</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Evaluation of DFS at 12 months in patients who underwent surgery and received adjuvant chemotherapy</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Neoadjuvant treatment</intervention_name>
<description>4 cycles of platinum-based chemotherapy (carboplatin or cisplatin) plus etoposide followed by surgery or chemoradiotherapy</description>
<arm_group_label>Phase II</arm_group_label>
<other_name>cisplatin / cisplatinum</other_name>
<other_name>etoposide / vepesid</other_name>
<other_name>carbopatin / paraplatin</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Adjuvant treatment</intervention_name>
<description>Surgery (before study entry) followed by 4 cycles of platinum-based chemotherapy (carboplatin or cisplatin) plus etoposide</description>
<arm_group_label>Prospective cohort</arm_group_label>
<other_name>cisplatin / cisplatinum</other_name>
<other_name>etoposide / vepesid</other_name>
<other_name>carbopatin / paraplatin</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

Phase II

1. Histologically proven digestive CNE, (the WHO 2017 classification: poorly
differentiated and Ki 67 > 20%),

2. Patients with localized CNE, without metastasis (computed tomography [CT],
thoraco-abdominopelvic CT scan [TAP] according to RECIST 1.1; examinations performed
no later than 21 days before starting the study treatment, possible locoregional lymph
node involvement defined according to the TNM classification),

3. Positron emission tomography (PET) and CT for lymph node status and elimination of
secondary visceral and/or bone disorders, 4. Resectable tumor, according to the
consensus decision made during local multidisciplinary surgical consultation meeting,

5. Age ≥ 18 years, 6. Written informed consent obtained from the patient, willing and able
to comply with the protocol, 7. Registration in a National Health Care System (Protection
Universelle Maladie [PUMa] included), 8. For female patients of childbearing potential,
negative pregnancy test within 7 days before starting the study treatment.

Men and women are required to use a reliable and adequate birth control during the study
(if applicable) during the period of treatment and during 6 months from the last treatment
administration.

Prospective cohort

1. Patients with localized digestive CNE histologically proven on the operative specimen
(the WHO 2017 classification: poorly differentiated and Ki 67> 20%),

2. Localized, without metastasis on computed tomography [CT], thoracoabdominopelvic CT
scan [TAP] RECIST 1.1, and/or locoregional lymph node involvement,

3. Age ≥ 18 years,

4. Written informed consent obtained from the patient, willing and able to comply with
the protocol,

5. Registration in a National Health Care System (PUMa - Protection Universelle Maladie
included),

6. For female patients of childbearing potential, negative pregnancy test within 7 days
before starting the study treatment.

Men and women are required to use a reliable and adequate birth control methods during the
study (if applicable) during the period of treatment and during 6 months from the last
treatment administration.

Exclusion Criteria:

Phase II

1. Well-differentiated NEC, whatever the grade,

2. Metastatic disease,

3. Cancer of unknown primary

4. Organ failure that does not allow chemotherapy treatment,

5. Previous malignancy within 5 years prior to the study except for cutaneous basal cell
carcinoma and uterine cancer in situ

6. Tumor with a mixed component (component accounts for ≥ 30%),

7. Patient impossible to follow-up,

8. Other than platinum-etoposide chemotherapy administrated,

9. Tutelage or guardianship or patient protected by law

Prospective cohort

1. Well-differentiated NEC, whatever the grade,

2. Metastatic disease,

3. Cancer of unknown primary

4. Organ failure that does not allow chemotherapy treatment,

5. Previous malignancy within 5 years prior to the study except for cutaneous basal cell
carcinoma and uterine cancer in situ

6. Tumor with a mixed component (component accounts for ≥ 30%),

7. Patient impossible to follow-up,

8. Other than platinum-etoposide chemotherapy administrated,

9. Tutelage or guardianship or patient protected by law.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Anna PELLAT</last_name>
<role>Principal Investigator</role>
<affiliation>Saint-Antoine Hospital</affiliation>
</overall_official>
<overall_contact>
<last_name>Anna PELLAT, MD</last_name>
<phone>+33 (0) 1 49 28 23 45</phone>
<email>anna.pellat@aphp.fr</email>
</overall_contact>
<overall_contact_backup>
<last_name>Marie-Line GARCIA-LARNICOL</last_name>
<email>marie-line.garcia-larnicol@gercor.com.fr</email>
</overall_contact_backup>
<location>
<facility>
<name>CHU Amiens - Hôpital Sud</name>
<address>
<city>Amiens</city>
<country>France</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Vincent HAUTEFEUILLE, MD</last_name>
<phone>+33(0)322088854</phone>
<email>hautefeuille.vincent@chu-amiens.fr</email>
</contact>
<investigator>
<last_name>Vincent HAUTEFEUILLE, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>CHU Jean Minjoz</name>
<address>
<city>Besançon</city>
<country>France</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Fabien CALCAGNO, MD</last_name>
<phone>+33(03)70632153</phone>
<email>fabien.calcagno@gmail.com</email>
</contact>
<investigator>
<last_name>Fabien CALCAGNO, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hôpital Beaujon</name>
<address>
<city>Clichy</city>
<country>France</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Olivia HENTIC, MD</last_name>
<phone>+ 33 (0)1 40 87 52 41</phone>
<email>olivia.hentic@aphp.fr</email>
</contact>
<investigator>
<last_name>Olivia HENTIC, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>CHU Dijon</name>
<address>
<city>Dijon</city>
<country>France</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Côme LEPAGE, MD</last_name>
<phone>+33 (0)3 80 39 33 40</phone>
<email>come.lepage@u-bourgogne.fr</email>
</contact>
<investigator>
<last_name>Côme LEPAGE, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hôpital Edouard Herriot</name>
<address>
<city>Lyon</city>
<country>France</country>
</address>
</facility>
<status>Not yet recruiting</status>
<contact>
<last_name>Thomas WALTER, MD</last_name>
</contact>
<investigator>
<last_name>Thomas WALTER, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Institut Paoli-Calmettes</name>
<address>
<city>Marseille</city>
<country>France</country>
</address>
</facility>
<status>Not yet recruiting</status>
<contact>
<last_name>Patricia NICCOLI, MD</last_name>
</contact>
<investigator>
<last_name>Patricia NICCOLI, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Saint Antoine Hospital</name>
<address>
<city>Paris</city>
<zip>75012</zip>
<country>France</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Anna PELLAT</last_name>
<phone>+33 (0) 1 49 28 23 45</phone>
<email>anna.pellat@aphp.fr</email>
</contact>
<contact_backup>
<last_name>Pauline AFCHAIN</last_name>
<phone>+33 (0) 1 49 28 23 45</phone>
<email>pauline.afchain@aphp.fr</email>
</contact_backup>
</location>
<location>
<facility>
<name>Groupe Hospitalier Diaconesses Croix Saint Simon</name>
<address>
<city>Paris</city>
<country>France</country>
</address>
</facility>
<status>Not yet recruiting</status>
<contact>
<last_name>Olivier DUBREUIL, MD</last_name>
</contact>
<investigator>
<last_name>Olivier DUBREUIL, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hôpital Cochin</name>
<address>
<city>Paris</city>
<country>France</country>
</address>
</facility>
<status>Not yet recruiting</status>
<contact>
<last_name>Romain CORIAT, md</last_name>
</contact>
<investigator>
<last_name>Romain CORIAT, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hôpital Saint Antoine</name>
<address>
<city>Paris</city>
<country>France</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Pauline AFCHAIN, MD</last_name>
<phone>+33 (0)1 49 28 23 29</phone>
<email>pauline.afchain@aphp.fr</email>
</contact>
<investigator>
<last_name>Pauline AFCHAIN, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Hôpital Haut Lévêque CHU Bordeaux</name>
<address>
<city>Pessac</city>
<country>France</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Denis SMITH, MD</last_name>
<phone>+ 33 (0)5 57 65 64 39</phone>
<email>denis.smith@chu-bordeaux.fr</email>
</contact>
<investigator>
<last_name>Denis SMITH, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>CHU Poitiers</name>
<address>
<city>Poitiers</city>
<country>France</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>David TOUGERON, MD</last_name>
<phone>+33(05)49443751</phone>
<email>David.TOUGERON@chu-poitiers.fr</email>
</contact>
<investigator>
<last_name>David TOUGERON, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>CHU Toulouse</name>
<address>
<city>Toulouse</city>
<country>France</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Rosine GUIMBAUD, MD</last_name>
<phone>+33 (0)561779649</phone>
<email>guimbaud.r@chu-toulouse.fr</email>
</contact>
<investigator>
<last_name>Rosine GUIMBAUD, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Institut Gustave Roussy</name>
<address>
<city>Villejuif</city>
<country>France</country>
</address>
</facility>
<status>Not yet recruiting</status>
<contact>
<last_name>Michel DUCREUX, MD</last_name>
</contact>
<investigator>
<last_name>Michel DUCREUX, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location_countries>
<country>France</country>
</location_countries>
<verification_date>June 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>June 28, 2023</last_update_submitted>
<last_update_submitted_qc>June 28, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">June 29, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Neoadjuvant treatment</keyword>
<keyword>Adjuvant treatment</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Carcinoma</mesh_term>
<mesh_term>Carcinoma, Neuroendocrine</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Cisplatin</mesh_term>
<mesh_term>Etoposide</mesh_term>
<mesh_term>Etoposide phosphate</mesh_term>
<mesh_term>Carboplatin</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
NEONEC is a single-phase, phase II study evaluating the efficacy of the 12-month neoadjuvant
chemotherapy in patients with locally differentiated digestive NEC. The recommended
chemotherapy is based on the current reference combination of platinum (cisplatin or
carboplatin) and etoposide (VP16). For anorectal locations, radiochemotherapy is proposed to
avoid the morbidity of conventional surgery.
The objective of the study is to improve relapse-free survival (RFS) in NEC patients treated
with neoadjuvant chemotherapy followed by surgery or chemoradiotherapy.
In parallel, we will perform a prospective cohort study with patients whose diagnosis is made
during surgery, who have not received neoadjuvant treatment, and who are offered an adjuvant
treatment of the same type (combination of platinum and platinum salts and etoposide).
A total of 48 patients is to be included in phase II and 30 patients in prospective cohort
during the inclusion period of phase II.
Phase II study treatment:
Neoadjuvant chemotherapy: Administration of 4 cycles of chemotherapy (3 months) with platinum
based chemotherapy (carboplatin or cisplatin, at the choice of the investigator) + etoposide.
Surgery or chemoradiotherapy depending on the tumor localization (the irradiation modalities
and associated chemotherapy treatment will be left to the discretion of the referring
radiotherapists according to current recommendations for each localization).
Prospective cohort:
- Surgery (prior to study entry)
- Adjuvant chemotherapy : Administration of 4 cycles of chemotherapy (3 months) with
platinum based chemotherapy (carboplatin or cisplatin, at the choice of the
investigator) + etoposide.
Inclusion Criteria:
Phase II
1. Histologically proven digestive CNE, (the WHO 2017 classification: poorly
differentiated and Ki 67 > 20%),
2. Patients with localized CNE, without metastasis (computed tomography [CT],
thoraco-abdominopelvic CT scan [TAP] according to RECIST 1.1; examinations performed
no later than 21 days before starting the study treatment, possible locoregional lymph
node involvement defined according to the TNM classification),
3. Positron emission tomography (PET) and CT for lymph node status and elimination of
secondary visceral and/or bone disorders, 4. Resectable tumor, according to the
consensus decision made during local multidisciplinary surgical consultation meeting,
5. Age ≥ 18 years, 6. Written informed consent obtained from the patient, willing and able
to comply with the protocol, 7. Registration in a National Health Care System (Protection
Universelle Maladie [PUMa] included), 8. For female patients of childbearing potential,
negative pregnancy test within 7 days before starting the study treatment.
Men and women are required to use a reliable and adequate birth control during the study
(if applicable) during the period of treatment and during 6 months from the last treatment
administration.
Prospective cohort
1. Patients with localized digestive CNE histologically proven on the operative specimen
(the WHO 2017 classification: poorly differentiated and Ki 67> 20%),
2. Localized, without metastasis on computed tomography [CT], thoracoabdominopelvic CT
scan [TAP] RECIST 1.1, and/or locoregional lymph node involvement,
3. Age ≥ 18 years,
4. Written informed consent obtained from the patient, willing and able to comply with
the protocol,
5. Registration in a National Health Care System (PUMa - Protection Universelle Maladie
included),
6. For female patients of childbearing potential, negative pregnancy test within 7 days
before starting the study treatment.
Men and women are required to use a reliable and adequate birth control methods during the
study (if applicable) during the period of treatment and during 6 months from the last
treatment administration.
Exclusion Criteria:
Phase II
1. Well-differentiated NEC, whatever the grade,
2. Metastatic disease,
3. Cancer of unknown primary
4. Organ failure that does not allow chemotherapy treatment,
5. Previous malignancy within 5 years prior to the study except for cutaneous basal cell
carcinoma and uterine cancer in situ
6. Tumor with a mixed component (component accounts for ≥ 30%),
7. Patient impossible to follow-up,
8. Other than platinum-etoposide chemotherapy administrated,
9. Tutelage or guardianship or patient protected by law
Prospective cohort
1. Well-differentiated NEC, whatever the grade,
2. Metastatic disease,
3. Cancer of unknown primary
4. Organ failure that does not allow chemotherapy treatment,
5. Previous malignancy within 5 years prior to the study except for cutaneous basal cell
carcinoma and uterine cancer in situ
6. Tumor with a mixed component (component accounts for ≥ 30%),
7. Patient impossible to follow-up,
8. Other than platinum-etoposide chemotherapy administrated,
9. Tutelage or guardianship or patient protected by law.
|
NCT0426xxxx/NCT04268134.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268134</url>
</required_header>
<id_info>
<org_study_id>UMCC 2019.125</org_study_id>
<secondary_id>HUM00171150</secondary_id>
<nct_id>NCT04268134</nct_id>
</id_info>
<brief_title>Altering Lipids for Tolerance of Aromatase Inhibitor Therapy</brief_title>
<acronym>ALTA</acronym>
<official_title>Omega-3 Fatty Acids, Oxylipins, and Tolerance of Aromatase Inhibitor Therapy</official_title>
<sponsors>
<lead_sponsor>
<agency>University of Michigan Rogel Cancer Center</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>University of Michigan Rogel Cancer Center</source>
<oversight_info>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Aromatase inhibitor medications have been approved by the U.S Food and Drug Administration
(FDA) for treatment of hormone receptor positive breast cancer. This treatment has been shown
to be very effective for treating breast cancer. However, some patients have difficulty
tolerating the treatment, and some even decide to stop treatment because of the side effects.
Research has shown that over half of patients who had joint pain and stiffness when taking an
aromatase inhibitor had an improvement in their symptoms when they took omega-3 fatty acid
supplements. This study is being conducted to test whether having patients start to take an
omega-3 fatty acid supplement soon after they starting taking an aromatase inhibitor medicine
will reduce the likelihood that they will have bothersome symptoms.
</textblock>
</brief_summary>
<overall_status>Completed</overall_status>
<start_date type="Actual">July 28, 2020</start_date>
<completion_date type="Actual">February 25, 2023</completion_date>
<primary_completion_date type="Actual">November 30, 2022</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<primary_purpose>Supportive Care</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Change in percentage of total fatty acids for each polyunsaturated fatty acid (PUFA) group from start of Omega-3 Fatty Acid (O3-FA) supplementation to 3 months of O3-FA</measure>
<time_frame>From start of Omega-3 Fatty Acid (O3-FA) supplementation to 3 months of O3-FA (at 6 months after start of AI therapy)</time_frame>
<description>Plasma oxylipins from blood samples collected at the start of O3-FA supplementation (3 months after start of Aromatase Inhibitor [AI] therapy alone) and after 3 months of AI therapy + O3-FA supplementation (6 months after start of AI therapy alone) will be quantified using solid phase extraction-liquid chromatography-electrospray ionization tandem mass spectroscopy. Oxylipins will be grouped according to PUFA substrate (linoleic acid [LA], arachidonic acid [AA], alpha-linoleic acid [ALA], eicosapentaenoid acid [EPA], and docosahexaenoic acid [DHA]). For each patient, the percentage of total fatty acids of each PUFA group will be calculated at both time points. The overall study percentage per PUFA group will be derived from the mean percentage of that PUFA group for all patients at each time point. The change in percentage between the two time points will be reported in tabular format for each PUFA group.</description>
</primary_outcome>
<secondary_outcome>
<measure>Change in percentage of total fatty acids for each PUFA group from baseline to 6 months of Aromatase Inhibitor (AI) (3 months of AI alone + 3 months of AI with O3-FA supplementation)</measure>
<time_frame>At 6 months after start of AI therapy</time_frame>
<description>Plasma oxylipins from blood samples collected at baseline (before AI therapy) and at 3 months of AI therapy + O3-FA supplementation (O3-FA supplementation starts 3 months after start of AI therapy) will be quantified using solid phase extraction-liquid chromatography-electrospray ionization tandem mass spectroscopy. Oxylipins will be grouped according to PUFA substrate (LA, AA, ALA, EPA and DHA). For each patient, the percentage of total fatty acids of each PUFA group will be calculated at both time points. The overall study percentage per PUFA group will be derived from the mean percentage of that PUFA group for all patients at each time point. The change in percentage between the two time points will be reported in tabular format for each PUFA group.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Change in percentage of total fatty acids for each PUFA group from baseline to 3 months of AI therapy alone</measure>
<time_frame>At 3 months after start of AI therapy</time_frame>
<description>Plasma oxylipins from blood samples collected at baseline and at 3 months after start of AI therapy alone will be quantified using solid phase extraction-liquid chromatography-electrospray ionization tandem mass spectroscopy. Oxylipins will be grouped according to PUFA substrate (LA, AA, ALA, EPA and DHA). For each patient, the percentage of total fatty acids of each PUFA group will be calculated at both time points. The overall study percentage per PUFA group will be derived from the mean percentage of that PUFA group for all patients at each time point. The change in percentage between the two time points will be reported in tabular format for each PUFA group.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of participants who develop AI-associated musculoskeletal symptoms (AIMSS)</measure>
<time_frame>Up to 9 months after start of AI therapy</time_frame>
<description>Patients will be considered to have developed AIMSS if any of the following apply: (1) a ≥0.22 increase in the Health Assessment Questionnaire (HAQ) score within 9 months, (2) a ≥2.0 increase in Brief Pain Inventory (BPI) average pain within 9 months, or (3) discontinuation of AI therapy within 9 months because of new or worsened musculoskeletal symptoms, assessed using a protocol-specific discontinuation form completed by the patient's provider. The HAQ assesses interference of pain with daily activities (range 0-3), with change of 0.22 defined as a clinically meaningful difference, as noted in the literature.* The BPI assesses average pain over 7 days (range 0-10), with a change of 2.0 defined as a clinically meaningful difference, as noted in the literature.* Patients whose providers specify pain as the first or second-ranked reason for discontinuation will be considered to have discontinued AI therapy because of new or worsened musculoskeletal symptoms. *See references.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of participants that discontinue AI therapy due to AIMSS</measure>
<time_frame>Up to 9 months after start of AI therapy</time_frame>
<description>Patients whose providers specify pain as the first or second-ranked reason for discontinuation (in a protocol-specific discontinuation form) will be considered to have discontinued AI therapy because of new or worsened musculoskeletal symptoms.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of participants that discontinue AI therapy due to toxicity.</measure>
<time_frame>Up to 9 months after start of AI therapy</time_frame>
<description>Patients whose providers specify toxicity as the first or second-ranked reason for discontinuation (in a protocol-specific discontinuation form) will be considered to have discontinued AI therapy due to toxicity.</description>
</secondary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Actual">77</enrollment>
<condition>Breast Cancer</condition>
<arm_group>
<arm_group_label>Omega 3 fatty acid supplement</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Omega-3 ethyl esters orally daily (containing 465 mg eicosapentaenoic acid [EPA] and 375 mg docosahexaenoic acid [DHA] per capsule,supplied as 4 x 1gm capsule)</description>
</arm_group>
<intervention>
<intervention_type>Dietary Supplement</intervention_type>
<intervention_name>Omega-3 fatty acid supplement</intervention_name>
<description>4 capsules taken by mouth each day for 24 weeks (starting at the week 12 visit).</description>
<arm_group_label>Omega 3 fatty acid supplement</arm_group_label>
<other_name>Lovaza</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria

- Female subject aged ≥ 18 years who are postmenopausal according to standard clinical
criteria or who will have been receiving LHRH agonist therapy for at least 28 days
prior to AI initiation.

- Stage 0-3 estrogen receptor positive (≥1%) and/or progesterone receptor positive (≥1%)
breast cancer, or patients at high risk of developing breast cancer who are planning
to initiate AI therapy for chemoprevention.

- Planned initiation of aromatase inhibitor therapy (anastrozole, exemestane, or
letrozole) for adjuvant treatment of breast cancer or for chemoprevention up to 30
days following baseline visit (ok to initiate screening up to 2 months before planned
baseline visit). Concurrent LHRH agonist, anti-HER2 directed therapy (e.g.,
trastuzumab, pertuzumab, ado-trastuzumab emtansine), and/or CDK4/6 inhibitor therapy
(e.g., palbociclib, ribociclib, abemaciclib) is permitted. Prior tamoxifen and/or
toremifene is permitted.

- Completion of surgery (mastectomy or lumpectomy/partial mastectomy) for treatment of
breast cancer. Completion of axillary surgery as indicated (not required). For
patients at high risk of breast cancer who have not been diagnosed with breast cancer,
no surgery is required.

- Completion of chemotherapy, if indicated. Concurrent use of radiation therapy, LHRHa
therapy, anti-HER2 therapy, PARP inhibitor, and CDK4/6 inhibitor therapy is permitted.
Prior tamoxifen is permitted.

- Agree to avoid taking omega-3 fatty acid supplements from sources outside the trial
during study participation.

- ECOG Performance Status ≤ 3.

- Able to complete questionnaires in English.

- Able to provide informed consent and willing to sign an approved consent form that
conforms to federal and institutional guidelines.

Exclusion Criteria

- Prior use of AI therapy for treatment or prevention of breast cancer.

- Use of omega-3 fatty acid supplementation during the 3 months prior to enrollment.
Consumption of O3-FA through diet is permitted.

- Use of warfarin, enoxaparin, or direct oral anticoagulants within 7 days prior to
registration.

- Known chronic liver disease (laboratory studies will not be assessed). Patients with
hepatosteatosis, viral hepatitis, or other liver disorders who have adequate liver
function according to the treating physician are permitted to enroll.

- Known symptomatic paroxysmal atrial fibrillation or persistent atrial fibrillation
(EKGs will not be performed).

- History of pancreatitis.

- Hypersensitivity to fish and/or shellfish.

- Unable to take oral medications.

- Any medical condition that would interfere with the absorption of study medication
capsules.

- Patients with a prior or concurrent malignancy whose natural history or treatment does
not, in the opinion of the treating investigator, have the potential to interfere with
the safety or efficacy assessment of the investigational regimen are eligible for this
trial.
</textblock>
</criteria>
<gender>Female</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Lynn Henry, MD, PhD</last_name>
<role>Principal Investigator</role>
<affiliation>University of Michigan Rogel Cancer Center</affiliation>
</overall_official>
<location>
<facility>
<name>University of Michigan Rogel Cancer Center</name>
<address>
<city>Ann Arbor</city>
<state>Michigan</state>
<zip>48109</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<reference>
<citation>Wolfe F, Michaud K, Strand V. Expanding the definition of clinical differences: from minimally clinically important differences to really important differences. Analyses in 8931 patients with rheumatoid arthritis. J Rheumatol. 2005 Apr;32(4):583-9.</citation>
<PMID>15801011</PMID>
</reference>
<reference>
<citation>Farrar JT, Pritchett YL, Robinson M, Prakash A, Chappell A. The clinical importance of changes in the 0 to 10 numeric rating scale for worst, least, and average pain intensity: analyses of data from clinical trials of duloxetine in pain disorders. J Pain. 2010 Feb;11(2):109-18. doi: 10.1016/j.jpain.2009.06.007. Epub 2009 Aug 8.</citation>
<PMID>19665938</PMID>
</reference>
<verification_date>August 2023</verification_date>
<study_first_submitted>January 29, 2020</study_first_submitted>
<study_first_submitted_qc>February 10, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>August 30, 2023</last_update_submitted>
<last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">August 31, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Aromatase inhibitor</keyword>
<keyword>Omega-3 fatty acid</keyword>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Aromatase inhibitor medications have been approved by the U.S Food and Drug Administration
(FDA) for treatment of hormone receptor positive breast cancer. This treatment has been shown
to be very effective for treating breast cancer. However, some patients have difficulty
tolerating the treatment, and some even decide to stop treatment because of the side effects.
Research has shown that over half of patients who had joint pain and stiffness when taking an
aromatase inhibitor had an improvement in their symptoms when they took omega-3 fatty acid
supplements. This study is being conducted to test whether having patients start to take an
omega-3 fatty acid supplement soon after they starting taking an aromatase inhibitor medicine
will reduce the likelihood that they will have bothersome symptoms.
Inclusion Criteria
- Female subject aged ≥ 18 years who are postmenopausal according to standard clinical
criteria or who will have been receiving LHRH agonist therapy for at least 28 days
prior to AI initiation.
- Stage 0-3 estrogen receptor positive (≥1%) and/or progesterone receptor positive (≥1%)
breast cancer, or patients at high risk of developing breast cancer who are planning
to initiate AI therapy for chemoprevention.
- Planned initiation of aromatase inhibitor therapy (anastrozole, exemestane, or
letrozole) for adjuvant treatment of breast cancer or for chemoprevention up to 30
days following baseline visit (ok to initiate screening up to 2 months before planned
baseline visit). Concurrent LHRH agonist, anti-HER2 directed therapy (e.g.,
trastuzumab, pertuzumab, ado-trastuzumab emtansine), and/or CDK4/6 inhibitor therapy
(e.g., palbociclib, ribociclib, abemaciclib) is permitted. Prior tamoxifen and/or
toremifene is permitted.
- Completion of surgery (mastectomy or lumpectomy/partial mastectomy) for treatment of
breast cancer. Completion of axillary surgery as indicated (not required). For
patients at high risk of breast cancer who have not been diagnosed with breast cancer,
no surgery is required.
- Completion of chemotherapy, if indicated. Concurrent use of radiation therapy, LHRHa
therapy, anti-HER2 therapy, PARP inhibitor, and CDK4/6 inhibitor therapy is permitted.
Prior tamoxifen is permitted.
- Agree to avoid taking omega-3 fatty acid supplements from sources outside the trial
during study participation.
- ECOG Performance Status ≤ 3.
- Able to complete questionnaires in English.
- Able to provide informed consent and willing to sign an approved consent form that
conforms to federal and institutional guidelines.
Exclusion Criteria
- Prior use of AI therapy for treatment or prevention of breast cancer.
- Use of omega-3 fatty acid supplementation during the 3 months prior to enrollment.
Consumption of O3-FA through diet is permitted.
- Use of warfarin, enoxaparin, or direct oral anticoagulants within 7 days prior to
registration.
- Known chronic liver disease (laboratory studies will not be assessed). Patients with
hepatosteatosis, viral hepatitis, or other liver disorders who have adequate liver
function according to the treating physician are permitted to enroll.
- Known symptomatic paroxysmal atrial fibrillation or persistent atrial fibrillation
(EKGs will not be performed).
- History of pancreatitis.
- Hypersensitivity to fish and/or shellfish.
- Unable to take oral medications.
- Any medical condition that would interfere with the absorption of study medication
capsules.
- Patients with a prior or concurrent malignancy whose natural history or treatment does
not, in the opinion of the treating investigator, have the potential to interfere with
the safety or efficacy assessment of the investigational regimen are eligible for this
trial.
|
NCT0426xxxx/NCT04268147.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268147</url>
</required_header>
<id_info>
<org_study_id>IRB18-1580</org_study_id>
<nct_id>NCT04268147</nct_id>
</id_info>
<brief_title>Instrumented Data Exchange for Ataxia Study</brief_title>
<acronym>IDEA</acronym>
<official_title>APDM Instrumented Data Exchange for Ataxia (IDEA) Study</official_title>
<sponsors>
<lead_sponsor>
<agency>University of Chicago</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Pfizer</agency>
<agency_class>Industry</agency_class>
</collaborator>
<collaborator>
<agency>Biogen</agency>
<agency_class>Industry</agency_class>
</collaborator>
<collaborator>
<agency>APDM Wearable Technologies</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>University of Chicago</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This research study is testing body-worn sensors to measure movement during simple tests of
coordination, in order to evaluate the progression and severity of ataxia.
</textblock>
</brief_summary>
<overall_status>Active, not recruiting</overall_status>
<start_date type="Actual">June 1, 2019</start_date>
<completion_date type="Anticipated">December 31, 2024</completion_date>
<primary_completion_date type="Anticipated">June 30, 2024</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Case-Control</observational_model>
<time_perspective>Cross-Sectional</time_perspective>
</study_design_info>
<primary_outcome>
<measure>iSARA</measure>
<time_frame>2 years</time_frame>
<description>measurements collected by wearable inertial sensors during instrumented Scale for the Assessment and Rating of Ataxia (iSARA)</description>
</primary_outcome>
<primary_outcome>
<measure>SARA</measure>
<time_frame>2 years</time_frame>
<description>Scale for the Assessment and Rating of Ataxia (SARA) measurements evaluated by clinician to measure severity of spinocerebellar ataxia through coordination, speech, stance, and gait</description>
</primary_outcome>
<primary_outcome>
<measure>mFARS</measure>
<time_frame>2 years</time_frame>
<description>modified Friedreich's Ataxia Rating Scale (mFARS) measurements evaluated by clinician compared to measure severity of Friedreich's ataxia through coordination, speech, stance, and gait</description>
</primary_outcome>
<primary_outcome>
<measure>Daily Life (UChicago site ONLY)</measure>
<time_frame>2 weeks</time_frame>
<description>APDM SmartSox technology used to measure daily life activity(movement, falls, etc.) of all University of Chicago subjects</description>
</primary_outcome>
<primary_outcome>
<measure>Ataxia App on Watch/iPhone</measure>
<time_frame>2 years</time_frame>
<description>Bi-weekly assessments completed on Ataxia Application for Apple Watches and iPhones. Data collected includes active monitoring of speech, stance, coordination, gait and patient-reported symptoms.</description>
</primary_outcome>
<primary_outcome>
<measure>Patient-Reported Questionnaires of Health</measure>
<time_frame>2 years</time_frame>
<description>Activities, Balance, and Confidence (ABC) Questionnaire; EQ-5D-5L Health Questionnaire; Modified Fatigue Impact Scale (MFIS-5); Activities of Daily Living (ADLs)</description>
</primary_outcome>
<primary_outcome>
<measure>Falls Questionnaire</measure>
<time_frame>2 years</time_frame>
<description>Automatic email sent out to subjects inquiring about any falls and near falls they have experienced during the past month</description>
</primary_outcome>
<primary_outcome>
<measure>Functional Staging</measure>
<time_frame>2 years</time_frame>
<description>Clinician evaluates severity of ataxia symptoms.</description>
</primary_outcome>
<primary_outcome>
<measure>Timed 25 Foot Walk</measure>
<time_frame>2 years</time_frame>
<description>Subjects walk for 25 feet, as quickly and safely as possible, while being timed</description>
</primary_outcome>
<number_of_groups>7</number_of_groups>
<enrollment type="Anticipated">144</enrollment>
<condition>Spinocerebellar Ataxia Type 1</condition>
<condition>Spinocerebellar Ataxia Type 2</condition>
<condition>Spinocerebellar Ataxia Type 3</condition>
<condition>Spinocerebellar Ataxia Type 6</condition>
<condition>Friedreich Ataxia</condition>
<arm_group>
<arm_group_label>Spinocerebellar Ataxia-1</arm_group_label>
<description>individuals with a genetically confirmed diagnosis of SCA-1</description>
</arm_group>
<arm_group>
<arm_group_label>Spinocerebellar Ataxia-2</arm_group_label>
<description>individuals with a genetically confirmed diagnosis of SCA-2</description>
</arm_group>
<arm_group>
<arm_group_label>Spinocerebellar Ataxia-3</arm_group_label>
<description>individuals with a genetically confirmed diagnosis of SCA-3</description>
</arm_group>
<arm_group>
<arm_group_label>Spinocerebellar Ataxia-6</arm_group_label>
<description>individuals with a genetically confirmed diagnosis of SCA-6</description>
</arm_group>
<arm_group>
<arm_group_label>Freidreich's Ataxia</arm_group_label>
<description>individuals with a genetically confirmed diagnosis of FA</description>
</arm_group>
<arm_group>
<arm_group_label>FA Controls</arm_group_label>
<description>Healthy, age-matched controls</description>
</arm_group>
<arm_group>
<arm_group_label>SCA Controls</arm_group_label>
<description>Healthy, age-matched controls</description>
</arm_group>
<eligibility>
<study_pop>
<textblock>
ataxia clinics
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- SCA 1, 2, 3, 6, and FA with mutations in the pathogenic range confirmed from genetic
testing

- SCA: aged 18-75 years

- FA: aged 12-30, diagnosed between ages 5-25

- community dwelling

- physically/cognitively capable of consenting/assenting and complying with the protocol
based on investigator's judgement

- able to walk independently 10 yards without an assistive device

- able to sit or stand unassisted for 30 seconds

- no other neurological or musculoskeletal disorder that could affect mobility

- no other history of head injury, vestibular function, stroke, or other disorders that
could affect mobility

- willing and able to participate in a 2-year study

- consent to be video recorded while performing study assessments

Exclusion Criteria:

- dementia that limits subjects' ability to follow directions

- pain that limits mobility

- SCA: enrolled in a clinical drug trial
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>12 Years</minimum_age>
<maximum_age>75 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<location>
<facility>
<name>University of California-Los Angeles</name>
<address>
<city>Los Angeles</city>
<state>California</state>
<zip>90095</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>The University of Chicago</name>
<address>
<city>Chicago</city>
<state>Illinois</state>
<zip>60637</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Johns Hopkins Medicine</name>
<address>
<city>Baltimore</city>
<state>Maryland</state>
<zip>21231</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Mass General Hospital</name>
<address>
<city>Boston</city>
<state>Massachusetts</state>
<zip>02114</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Oregon Health & Science University</name>
<address>
<city>Portland</city>
<state>Oregon</state>
<zip>97239</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>February 2023</verification_date>
<study_first_submitted>February 4, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 24, 2023</last_update_submitted>
<last_update_submitted_qc>February 24, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">February 27, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Ataxia</mesh_term>
<mesh_term>Cerebellar Ataxia</mesh_term>
<mesh_term>Spinocerebellar Ataxias</mesh_term>
<mesh_term>Spinocerebellar Degenerations</mesh_term>
<mesh_term>Friedreich Ataxia</mesh_term>
<mesh_term>Machado-Joseph Disease</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This research study is testing body-worn sensors to measure movement during simple tests of
coordination, in order to evaluate the progression and severity of ataxia.
ataxia clinics
Inclusion Criteria:
- SCA 1, 2, 3, 6, and FA with mutations in the pathogenic range confirmed from genetic
testing
- SCA: aged 18-75 years
- FA: aged 12-30, diagnosed between ages 5-25
- community dwelling
- physically/cognitively capable of consenting/assenting and complying with the protocol
based on investigator's judgement
- able to walk independently 10 yards without an assistive device
- able to sit or stand unassisted for 30 seconds
- no other neurological or musculoskeletal disorder that could affect mobility
- no other history of head injury, vestibular function, stroke, or other disorders that
could affect mobility
- willing and able to participate in a 2-year study
- consent to be video recorded while performing study assessments
Exclusion Criteria:
- dementia that limits subjects' ability to follow directions
- pain that limits mobility
- SCA: enrolled in a clinical drug trial
|
NCT0426xxxx/NCT04268160.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268160</url>
</required_header>
<id_info>
<org_study_id>IRB201902486</org_study_id>
<nct_id>NCT04268160</nct_id>
</id_info>
<brief_title>GPx Activity in Subjects With Aortic Stenosis Undergoing TAVR</brief_title>
<official_title>Glutathione Peroxidase Activity in Subjects With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement.</official_title>
<sponsors>
<lead_sponsor>
<agency>University of Florida</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>University of Florida</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The aim of this project is to investigate the association of glutathione peroxidase (GPx) and
severe aortic stenosis (AS), as well as the impact of transcatheter aortic valve replacement
(TAVR) on GPx activity post-procedure. The burden of oxidative stress will be determined by
the measurement of GPx, superoxide dismutase (SOD) and lipoprotein A (Lp(a)). We hypothesize
GPx activity is reduced in participants with severe AS vs control groups and GPx activity is
to increase after TAVR is performed.
</textblock>
</brief_summary>
<overall_status>Withdrawn</overall_status>
<why_stopped>
Funding issues and closed with the IRB
</why_stopped>
<start_date type="Anticipated">November 2020</start_date>
<completion_date type="Actual">June 15, 2021</completion_date>
<primary_completion_date type="Actual">June 15, 2021</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Level of GPx in blood samples</measure>
<time_frame>Baseline up to 6 months</time_frame>
<description>Glutathione peroxidase activity levels measured from whole blood in U/L units in participants with severe aortic stenosis after transcatheter valve replacement compared with the matched population</description>
</primary_outcome>
<number_of_groups>2</number_of_groups>
<enrollment type="Actual">0</enrollment>
<condition>Glutathione Peroxidase Activity</condition>
<condition>Aortic Stenosis</condition>
<condition>Transcatheter Aortic Valve Replacement</condition>
<arm_group>
<arm_group_label>Patients with severe aortic stenosis undergoing TAVR</arm_group_label>
<description>GPx activity levels will be measured on the day of TAVR procedure, the day of discharge, 1 month, and 6 months after the procedure</description>
</arm_group>
<arm_group>
<arm_group_label>Patients without aortic stenosis</arm_group_label>
<description>GPx activity levels will be measured on day of recruitment</description>
</arm_group>
<intervention>
<intervention_type>Diagnostic Test</intervention_type>
<intervention_name>Blood draw to measure GPx activity</intervention_name>
<description>Routine blood draw to measure levels of blood markers.</description>
<arm_group_label>Patients with severe aortic stenosis undergoing TAVR</arm_group_label>
<arm_group_label>Patients without aortic stenosis</arm_group_label>
</intervention>
<intervention>
<intervention_type>Diagnostic Test</intervention_type>
<intervention_name>Blood draw to measure SOD activity</intervention_name>
<description>Routine blood draw to measure levels of blood markers.</description>
<arm_group_label>Patients with severe aortic stenosis undergoing TAVR</arm_group_label>
<arm_group_label>Patients without aortic stenosis</arm_group_label>
</intervention>
<intervention>
<intervention_type>Diagnostic Test</intervention_type>
<intervention_name>Blood draw to measure Lp(a) levels</intervention_name>
<description>Routine blood draw to measure levels of blood markers.</description>
<arm_group_label>Patients with severe aortic stenosis undergoing TAVR</arm_group_label>
<arm_group_label>Patients without aortic stenosis</arm_group_label>
</intervention>
<eligibility>
<study_pop>
<textblock>
Study participants with severe aortic stenosis undergoing TAVR. They will be matched with
patients without aortic stenosis based on age, gender, race, and co-morbidities (including
stroke, history of coronary artery disease, heart failure, diabetes, hypertension, and
other valvular diseases).
</textblock>
</study_pop>
<sampling_method>Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- Age >18 years

- Patients with severe AS including participants with low flow, low gradient severe AS
and paradoxical severe AS

- Patients meeting criteria for TAVR procedure

Exclusion Criteria:

- Previous aortic valve replacement (surgical or TAVR)

- Participants undergoing chemotherapy

- End stage liver disease/cirrhosis (liver produces GSH)
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Chinelo Udemgba, MD</last_name>
<role>Principal Investigator</role>
<affiliation>University of Florida</affiliation>
</overall_official>
<location>
<facility>
<name>University of Florida</name>
<address>
<city>Jacksonville</city>
<state>Florida</state>
<zip>32209</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<reference>
<citation>Redfors, B. A. (2017). Biomarkers in Aortic Stenosis: A systematic Review. Structural Heart. The Journal of the Heart Team, 1-13.</citation>
</reference>
<reference>
<citation>Otto CM. Aortic stenosis and hyperlipidemia: establishing a cause-effect relationship. Am Heart J. 2004 May;147(5):761-3. doi: 10.1016/j.ahj.2003.12.014. No abstract available.</citation>
<PMID>15131528</PMID>
</reference>
<reference>
<citation>Memet C, Gerede DM, Ozenci M, Akbulut IM, Acibuca A, Kilickap M, Erol C. Evaluation of the Role of Oxidative Stress in Degenerative Aortic Stenosis. J Heart Valve Dis. 2015 Jul;24(4):445-50.</citation>
<PMID>26897814</PMID>
</reference>
<reference>
<citation>Nimse, S. B. (2015). Free radicals, natural antioxidants, and their reaction mechanism. Royal Society of Chemistry, 27986-28006.</citation>
</reference>
<reference>
<citation>Blankenberg S, Rupprecht HJ, Bickel C, Torzewski M, Hafner G, Tiret L, Smieja M, Cambien F, Meyer J, Lackner KJ; AtheroGene Investigators. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med. 2003 Oct 23;349(17):1605-13. doi: 10.1056/NEJMoa030535.</citation>
<PMID>14573732</PMID>
</reference>
<reference>
<citation>Bolzan AD, Bianchi MS, Bianchi NO. Superoxide dismutase, catalase and glutathione peroxidase activities in human blood: influence of sex, age and cigarette smoking. Clin Biochem. 1997 Aug;30(6):449-54. doi: 10.1016/s0009-9120(97)00047-7.</citation>
<PMID>9316738</PMID>
</reference>
<reference>
<citation>Zheng KH, Tsimikas S, Pawade T, Kroon J, Jenkins WSA, Doris MK, White AC, Timmers NKLM, Hjortnaes J, Rogers MA, Aikawa E, Arsenault BJ, Witztum JL, Newby DE, Koschinsky ML, Fayad ZA, Stroes ESG, Boekholdt SM, Dweck MR. Lipoprotein(a) and Oxidized Phospholipids Promote Valve Calcification in Patients With Aortic Stenosis. J Am Coll Cardiol. 2019 May 7;73(17):2150-2162. doi: 10.1016/j.jacc.2019.01.070.</citation>
<PMID>31047003</PMID>
</reference>
<reference>
<citation>Arsenault BJ, Boekholdt SM, Dube MP, Rheaume E, Wareham NJ, Khaw KT, Sandhu MS, Tardif JC. Lipoprotein(a) levels, genotype, and incident aortic valve stenosis: a prospective Mendelian randomization study and replication in a case-control cohort. Circ Cardiovasc Genet. 2014 Jun;7(3):304-10. doi: 10.1161/CIRCGENETICS.113.000400. Epub 2014 Apr 5.</citation>
<PMID>24704946</PMID>
</reference>
<reference>
<citation>Mahmaljy H, Tawney A, Young M. Transcatheter Aortic Valve Replacement (TAVR/TAVI, Percutaneous Replacement) [Updated 2019 Dec 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-.</citation>
</reference>
<verification_date>June 2021</verification_date>
<study_first_submitted>February 5, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>June 28, 2021</last_update_submitted>
<last_update_submitted_qc>June 28, 2021</last_update_submitted_qc>
<last_update_posted type="Actual">June 30, 2021</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>glutathione peroxidase, GPx, aortic stenosis, transcatheter aortic valve replacement, TAVR</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Aortic Valve Stenosis</mesh_term>
<mesh_term>Constriction, Pathologic</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The aim of this project is to investigate the association of glutathione peroxidase (GPx) and
severe aortic stenosis (AS), as well as the impact of transcatheter aortic valve replacement
(TAVR) on GPx activity post-procedure. The burden of oxidative stress will be determined by
the measurement of GPx, superoxide dismutase (SOD) and lipoprotein A (Lp(a)). We hypothesize
GPx activity is reduced in participants with severe AS vs control groups and GPx activity is
to increase after TAVR is performed.
Study participants with severe aortic stenosis undergoing TAVR. They will be matched with
patients without aortic stenosis based on age, gender, race, and co-morbidities (including
stroke, history of coronary artery disease, heart failure, diabetes, hypertension, and
other valvular diseases).
Inclusion Criteria:
- Age >18 years
- Patients with severe AS including participants with low flow, low gradient severe AS
and paradoxical severe AS
- Patients meeting criteria for TAVR procedure
Exclusion Criteria:
- Previous aortic valve replacement (surgical or TAVR)
- Participants undergoing chemotherapy
- End stage liver disease/cirrhosis (liver produces GSH)
|
NCT0426xxxx/NCT04268173.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268173</url>
</required_header>
<id_info>
<org_study_id>2017-0866</org_study_id>
<secondary_id>UH3DA044826</secondary_id>
<secondary_id>A534265</secondary_id>
<secondary_id>SMPH/MEDICINE/INFECT DIS</secondary_id>
<secondary_id>Protocol Version 2/1/2023</secondary_id>
<nct_id>NCT04268173</nct_id>
</id_info>
<brief_title>Community-Based, Client-Centered Prevention Homes to Address the Rural Opioid Epidemic- Aim 3</brief_title>
<official_title>Community-Based, Client-Centered Prevention Homes to Address the Rural Opioid Epidemic- Aim 3</official_title>
<sponsors>
<lead_sponsor>
<agency>University of Wisconsin, Madison</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Tulane University</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>National Institute on Drug Abuse (NIDA)</agency>
<agency_class>NIH</agency_class>
</collaborator>
</sponsors>
<source>University of Wisconsin, Madison</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The goal of this study is to effectively use a client-centered community-based intervention
to engage people who inject drugs (PWIDs) in healthcare that helps reduce risky behaviors and
lower infectious disease risks. Participants in the intervention group of this study will
undergo a 12-week intensive multilevel harm reduction case-management intervention at three
rural Vivent Health offices geared towards reducing human immunodeficiency virus (HIV),
hepatitis C virus (HCV), and overdose risks in PWIDs. Prevention Navigators (PNs) at each
office will help coordinate referrals to reduce substance use disorder and increase
engagement in the substance use disorder care cascades. PNs will also engage participants in
HIV, HCV, and sexually transmitted infections(STIs) care cascades.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
This project will be conducted by an experienced, interdisciplinary team working across
academic, public health, and non-government sectors. The main community partner Vivent
Health, formerly known as the AIDS Resource Center of Wisconsin (ARCW), is a unique,
state-wide organization that provides harm reduction services, including syringe services and
confidential HIV and HCV testing, to clients at 10 fixed sites and numerous mobile units
reaching all 72 Wisconsin counties. Based on investigator's preliminary studies and prior
collaborations, investigator has selected 6 counties in rural Wisconsin, three of which
investigator will deploy and evaluate the Client-Centered Prevention Home intervention model
at Vivent Health field offices located within these service areas. Participants in the
intervention will undergo a 12-week intensive multilevel harm reduction case-management
intervention geared towards coordinating referrals to reduce substance use disorder and
increase engagement in the substance use disorder care cascades, and reduce vulnerability to
HIV, STIs, and HCV and increase in engagement in the HIV, STI, and HCV care cascades.
Participants in the intervention arm will work with Prevention Navigators to undergo a risk
assessment and identify problems and create goals that they want to achieve. Each session
after that will be used to review the needs assessment and goals. During their last meeting,
participants and prevention navigators will develop a discharge plan that will enable the
participants to work on their goals on their own. Participants at all six sites will undergo
rapid testing for HIV, HCV, and STIs, and fill out survey questionnaires to evaluate risk
behaviors, intervention effectiveness, and general needs of the communities. There are three
groups in this study which consist of intervention, delayed intervention (3 month wait-list
period before intervention begins), and a nonintervention control group.

Per the protocol amendment approved on 9/3/2021, no additional participants will be recruited
into the delayed intervention arm and therefore the anticipated enrollment has change to 405.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">March 12, 2020</start_date>
<completion_date type="Actual">July 31, 2023</completion_date>
<primary_completion_date type="Actual">July 31, 2023</primary_completion_date>
<phase>Phase 3</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Non-Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>Participants will be enrolled using a parallel crossover and cross-site study design. At three sites, participants will be enrolled in immediate intervention, or a 3 month wait list intervention, serving as a control for three months before engaging in the intervention. At three other sites, participants will serve as controls, receiving treatment as usual.</intervention_model_description>
<primary_purpose>Health Services Research</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Change in the addiction treatment accessibility and utilization as assessed by change in Likert scale</measure>
<time_frame>Baseline, 3 months, and 6 months</time_frame>
<description>Following questions will be asked on a scale of 1 to 5, where 1=strongly disagree and 5=strongly agree:
If I wanted to start a medical treatment for opioid or heroine addiction, I could easily get into a methadone program
If I wanted to start medical treatment for opioid or heroin addiction, I could easily get buprenorphine or Suboxone or Subutex.
An increase in the Likert scale among intervention participants is associated with increased access to addiction treatment programs compared to the controls.</description>
</primary_outcome>
<primary_outcome>
<measure>Change in the addiction treatment accessibility and utilization as assessed by change in frequency of "Yes" answers</measure>
<time_frame>Baseline, 3 months, and 6 months</time_frame>
<description>Following questions will be asked with yes or no answers.
In the last 3 months, have you gone to a self-help group like Narcotics Anonymous, Alcoholics Anonymous, Celebrate Recovery, or Rational Recovery?
In the past 3 months, have you received outpatient counseling from a provider or program?
In the past 3 months, have you stayed overnight at a residential or inpatient drug treatment facility?
In the past 3 months, have you been in detox?
In the past 3 months, have you stayed overnight at a sober house?
In the past 3 months, have you gotten buprenorphine maintenance medication-like Suboxone or Subutex-from a doctor or program?
In the past 3 months, have you gotten methadone maintenance from a clinic?
In the past 3 months, have you gotten buprenorphine shots - like Sublocade - from a doctor or program?
Among the intervention group, an increase number of "yes" answers over time will show an improvement in this outcome, compared to the control group.</description>
</primary_outcome>
<primary_outcome>
<measure>Change in the risk of viral hepatitis as assessed by change in Likert scale</measure>
<time_frame>Baseline, 3 months, and 6 months</time_frame>
<description>Following question will be asked on a scale of 1 to 5, where 1=strongly disagree and 5=strongly agree.
a. I am certain that I got all 3 recommended shots for Hepatitis B.
A shift to a total score of 5 would show improvement in this outcome. In combination of viral hepatitis prevalence, investigators are interested to know the change in hepatitis risk. This question will ask about Hepatitis B vaccination specifically.</description>
</primary_outcome>
<primary_outcome>
<measure>Change in the risk of HIV as assessed by change in Likert scale</measure>
<time_frame>Baseline, 3 months, and 6 months</time_frame>
<description>Following questions will be asked to gauge ease of accessing condoms and clean injecting equipment to assess how risky the participants behaviors are in relation to HIV transmission.
It's easy for me to get new, clean syringes or needles.
It's easy for me and my sex partners to get condoms.
Questions will be answered on a scale of 1 to 5, with 1=strongly disagree and 5=strongly agree. An increase in the Likert scale among intervention participants is associated with increased access to HIV prevention compared to the controls.</description>
</primary_outcome>
<primary_outcome>
<measure>Change in the risk of HIV as assessed by risky behavior frequencies</measure>
<time_frame>Baseline, 3 months, and 6 months</time_frame>
<description>Six questions will be asked to gauge frequency of safe injection and sex behaviors that reduce the risk of HIV. Participants will be asked how many times in the last 30 days they have practiced these behaviors. An increase in frequency in any of the following six behaviors will be considered a success for this outcome in the intervention group.
Have you ever heard of medicine people can take to prevent HIV?
Have you had sex without a condom?
Were you diagnosed with an STD in the past?
Have you had sex with more than one person in the past 6 months?
In the last 3 months, where have you gotten most of your syringes?
In the last 3 months, how often have you shared needles with someone else, used a syringe more than once, used equipment you knew wasn't clean, or received equipment from a potentially unsafe source?</description>
</primary_outcome>
<primary_outcome>
<measure>Change in the risk of drug overdose as assessed by change in Likert scale</measure>
<time_frame>Baseline, 3 months, and 6 months</time_frame>
<description>Following question will be asked on a scale of 1 to 5, where 1=strongly disagree and 5=strongly agree
a. If I wanted the overdose reversal drug naloxone or Narcan, I could easily get it.
An increase in the Likert scale among intervention participants is associated with a decreased risk of overdose death compared to the controls.</description>
</primary_outcome>
<primary_outcome>
<measure>Change in smoking frequency as assessed by self-reported behaviors</measure>
<time_frame>Baseline, 3 months, and 6 months</time_frame>
<description>A change in smoking behavior frequency will be assessed by asking participants how often they are smoking cigarettes. A decrease in frequency is considered a success in this outcome. Following questions will be asked
Do you smoke cigarettes?
On average, how many cigarettes do you smoke a day?</description>
</primary_outcome>
<primary_outcome>
<measure>Change in Self-stigma as assessed by change in Likert scale</measure>
<time_frame>Baseline, 3 months, and 6 months</time_frame>
<description>Five questions will be asked to gauge feelings of shame, fear, and other negative emotions surrounding drug use. Following questions will be answered on a scale of 1 to 5, with 1=strongly disagree and 5=strongly agree.
How much do you feel ashamed of using drugs?
How much do you feel people avoid you because you use drugs?
How much do you fear you will lose your friends because you use drugs?
How much do you fear family will reject you because you use drugs?
How much do you think other people are uncomfortable being around you because you use drugs?
A decrease in the Likert scale among intervention participants is associated with decreased self-stigma compared to the controls.</description>
</primary_outcome>
<secondary_outcome>
<measure>Change in the risk of drug overdose as assessed by change in frequency of narcan distribution</measure>
<time_frame>Baseline, 3 months, and 6 months</time_frame>
<description>ServicePoint data from Vivent Health will be used to understand the frequency of Narcan distribution over the time of the study. Any increase in study participants receiving Narcan would be considered a success for this outcome.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Change in the treatment frequency of viral hepatitis as assessed by Wisconsin(WI) surveillance databases and Medicaid data.</measure>
<time_frame>Baseline, 3 months, and 6 months</time_frame>
<description>Frequency of viral hepatitis treatment in participants will be assessed by accessing the WI disease surveillance database known as Wisconsin Electronic Disease Surveillance System (WEDSS). An increase in number of participants receiving treatment will be a success for this outcome. Medicaid data will be monitored to evaluate frequency of treatment.</description>
</secondary_outcome>
<other_outcome>
<measure>Addiction treatment accessibility and utilization frequency assessment from long term Medicaid data.</measure>
<time_frame>Year 2</time_frame>
<description>Long term changes in frequency of addiction treatment services will be assessed by reviewing Medicaid data over time.</description>
</other_outcome>
<other_outcome>
<measure>Hepatitis C treatment frequency from long term Medicaid data.</measure>
<time_frame>Year 2</time_frame>
<description>Long term changes in frequency of HCV treatment services will be assesses by reviewing Medicaid data over time.</description>
</other_outcome>
<number_of_arms>3</number_of_arms>
<enrollment type="Actual">341</enrollment>
<condition>Drug Use Disorders</condition>
<condition>Hepatitis C</condition>
<condition>Harm Reduction</condition>
<condition>Opioid-use Disorder</condition>
<arm_group>
<arm_group_label>Immediate Intervention</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Participants enrolled in this arm will receive a 12-week community-based, client-centered, prevention intervention.</description>
</arm_group>
<arm_group>
<arm_group_label>Delayed Intervention</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Participants enrolled in this arm will receive a 12-week community-based, client-centered, prevention intervention after being put on a wait-list for three months.
Per the protocol amendment approved on 9/3/2021, no additional participants will be recruited into the delayed intervention arm.</description>
</arm_group>
<arm_group>
<arm_group_label>Nonintervention</arm_group_label>
<arm_group_type>No Intervention</arm_group_type>
<description>Participants enrolled in this arm will receive services as usual from Vivent Health and will not engage in the intervention.</description>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Community-Based, Client-Centered Prevention Home</intervention_name>
<description>Prevention Navigators at Vivent Helath offices will engage participants in risk assessments, goal planning, and treatment referrals based on their needs and desires.</description>
<arm_group_label>Delayed Intervention</arm_group_label>
<arm_group_label>Immediate Intervention</arm_group_label>
<other_name>Prevention Navigation</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- has injected drugs in the past 30 days, resides in Wisconsin, over 18 years of age

- able to read and write in English

Exclusion Criteria:

-
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Ryan Westergaard, MD, PhD, MPH</last_name>
<role>Principal Investigator</role>
<affiliation>University of Wisconsin, Madison</affiliation>
</overall_official>
<location>
<facility>
<name>Vivent Health</name>
<address>
<city>Appleton</city>
<state>Wisconsin</state>
<zip>54911</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Vivent Health</name>
<address>
<city>Eau Claire</city>
<state>Wisconsin</state>
<zip>54701</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Vivent Health</name>
<address>
<city>Green Bay</city>
<state>Wisconsin</state>
<zip>54301</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Vivent Health</name>
<address>
<city>La Crosse</city>
<state>Wisconsin</state>
<zip>54603</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Wisconsin, Madison</name>
<address>
<city>Madison</city>
<state>Wisconsin</state>
<zip>53706</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Vivent Health</name>
<address>
<city>Schofield</city>
<state>Wisconsin</state>
<zip>54476</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Vivent Health</name>
<address>
<city>Superior</city>
<state>Wisconsin</state>
<zip>54880</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>August 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>August 31, 2023</last_update_submitted>
<last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">September 1, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Hepatitis C</mesh_term>
<mesh_term>Opioid-Related Disorders</mesh_term>
<mesh_term>Substance-Related Disorders</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>Yes</sharing_ipd>
<ipd_description>Individual participant data collected during the trial, after deidentification. Proposals should be directed to the Data coordinating center at University of Washington. If approved after review, requestors will enter into a formal data sharing agreement. Data will be shared via encrypted single-user file transmission protocol.</ipd_description>
<ipd_info_type>Study Protocol</ipd_info_type>
<ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
<ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
<ipd_info_type>Analytic Code</ipd_info_type>
<ipd_time_frame>Data will be available after upload to the data coordinating center at University of Washington and will remain for the time records must be held for, according to our data use agreement.</ipd_time_frame>
<ipd_access_criteria>Data will only be shared among researchers in the cooperative agreement.</ipd_access_criteria>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The goal of this study is to effectively use a client-centered community-based intervention
to engage people who inject drugs (PWIDs) in healthcare that helps reduce risky behaviors and
lower infectious disease risks. Participants in the intervention group of this study will
undergo a 12-week intensive multilevel harm reduction case-management intervention at three
rural Vivent Health offices geared towards reducing human immunodeficiency virus (HIV),
hepatitis C virus (HCV), and overdose risks in PWIDs. Prevention Navigators (PNs) at each
office will help coordinate referrals to reduce substance use disorder and increase
engagement in the substance use disorder care cascades. PNs will also engage participants in
HIV, HCV, and sexually transmitted infections(STIs) care cascades.
This project will be conducted by an experienced, interdisciplinary team working across
academic, public health, and non-government sectors. The main community partner Vivent
Health, formerly known as the AIDS Resource Center of Wisconsin (ARCW), is a unique,
state-wide organization that provides harm reduction services, including syringe services and
confidential HIV and HCV testing, to clients at 10 fixed sites and numerous mobile units
reaching all 72 Wisconsin counties. Based on investigator's preliminary studies and prior
collaborations, investigator has selected 6 counties in rural Wisconsin, three of which
investigator will deploy and evaluate the Client-Centered Prevention Home intervention model
at Vivent Health field offices located within these service areas. Participants in the
intervention will undergo a 12-week intensive multilevel harm reduction case-management
intervention geared towards coordinating referrals to reduce substance use disorder and
increase engagement in the substance use disorder care cascades, and reduce vulnerability to
HIV, STIs, and HCV and increase in engagement in the HIV, STI, and HCV care cascades.
Participants in the intervention arm will work with Prevention Navigators to undergo a risk
assessment and identify problems and create goals that they want to achieve. Each session
after that will be used to review the needs assessment and goals. During their last meeting,
participants and prevention navigators will develop a discharge plan that will enable the
participants to work on their goals on their own. Participants at all six sites will undergo
rapid testing for HIV, HCV, and STIs, and fill out survey questionnaires to evaluate risk
behaviors, intervention effectiveness, and general needs of the communities. There are three
groups in this study which consist of intervention, delayed intervention (3 month wait-list
period before intervention begins), and a nonintervention control group.
Per the protocol amendment approved on 9/3/2021, no additional participants will be recruited
into the delayed intervention arm and therefore the anticipated enrollment has change to 405.
Inclusion Criteria:
- has injected drugs in the past 30 days, resides in Wisconsin, over 18 years of age
- able to read and write in English
Exclusion Criteria:
-
|
NCT0426xxxx/NCT04268186.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268186</url>
</required_header>
<id_info>
<org_study_id>18-07-20</org_study_id>
<secondary_id>R21AG061743</secondary_id>
<nct_id>NCT04268186</nct_id>
</id_info>
<brief_title>TDCS to Improve Motivation and Memory in Elderly (TIME)</brief_title>
<official_title>Noninvasive Brain Stimulation as a Tool to Study the Role of Motivation in Age-related Cognitive Abilities</official_title>
<sponsors>
<lead_sponsor>
<agency>Northeastern University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Massachusetts General Hospital</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>National Institute on Aging (NIA)</agency>
<agency_class>NIH</agency_class>
</collaborator>
</sponsors>
<source>Northeastern University</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
<is_us_export>Yes</is_us_export>
</oversight_info>
<brief_summary>
<textblock>
Fundamental advancements in understanding successful aging are limited by the lack of causal,
rather than just correlational methods to connect age-related changes in memory ability to
changes in brain structure and function. In this study, non-invasive electric brain
stimulation will be used as a tool to create causal links between successful memory function
in aging and brain structures associated with motivation. Recently, it was shown that a group
of elderly, dubbed "superagers", are indistinguishable from young adults in memory
performance and the structure of cortical limbic regions. A key superaging region is
mid-cingulate cortex (MCC), a brain structure associated with motivation and tenacity. The
MCC is a hub region that synchronizes information flow between three core brain networks. The
goal of the research is to explore the contribution of motivation to memory performance by
modulating MCC connectivity with transcranial direct current stimulation (tDCS) to provide
the first causal evidence that experimentally induced motivation can improve memory
performance. Since MCC has not been stimulated with tDCS before, we will test three different
stimulation protocols and compare against a placebo. The stimulation protocols were
computationally optimized for this project. The primary aim is to find the stimulation
protocol most successful at improving memory performance. In order to elucidate the
mechanisms behind these changes, effects of stimulation on motivation and network
connectivity will be investigated. If indeed memory can be improved by increasing motivation
and effort via stimulating MCC, this study will generate new insights into the motivational
mechanisms of successful aging.
</textblock>
</brief_summary>
<overall_status>Unknown status</overall_status>
<last_known_status>Recruiting</last_known_status>
<start_date type="Actual">January 22, 2020</start_date>
<completion_date type="Anticipated">September 2020</completion_date>
<primary_completion_date type="Anticipated">September 2020</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Basic Science</primary_purpose>
<masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>Change in "Feeling of difficulty" from baseline</measure>
<time_frame>1 week</time_frame>
<description>Self-reports of difficulty will be queried during a memory task. Feeling of difficulty asks "How easy or difficult do you think the task will be (did you find the task)?" Answer is reported on a 7 point-scale.</description>
</primary_outcome>
<primary_outcome>
<measure>Change in "Estimates of effort" from baseline</measure>
<time_frame>1 week</time_frame>
<description>Self-reports of effort will be queried during a memory task. Estimates of Effort asks "How much effort do you think it will take you (did it take you) to complete the task?" Answer is reported on a 7 point-scale.</description>
</primary_outcome>
<primary_outcome>
<measure>Change in "NASA Task Load Index" from baseline</measure>
<time_frame>1 week</time_frame>
<description>NASA Task Load Index will be queried during a memory task. It includes self-report scales that provide state markers of cognitive effort.</description>
</primary_outcome>
<primary_outcome>
<measure>Change in "Time to complete unsolvable anagrams" from baseline</measure>
<time_frame>1 week</time_frame>
<description>Time in seconds participants spend on unsolvable anagram task before quitting.</description>
</primary_outcome>
<secondary_outcome>
<measure>Change in "Memory recognition discriminability (d')" from baseline</measure>
<time_frame>1 week</time_frame>
<description>A standard measure of memory recognition performance in an associative memory task.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Change in "Intrinsic functional connectivity strength" from baseline</measure>
<time_frame>1 week</time_frame>
<description>A measure of the strength with which mid-cingulate cortex and other brain regions are functionally connected, as measured with resting-state fMRI.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Change in "California Verbal Learning Test" score from baseline</measure>
<time_frame>1 week</time_frame>
<description>California Verbal Learning Test (CVLT-II) is a comprehensive, detailed assessment of verbal learning and memory deficits in older adolescents and adults. The task asks participants to remember a list of 16 words. Higher scores mean better outcomes.</description>
</secondary_outcome>
<number_of_arms>4</number_of_arms>
<enrollment type="Anticipated">72</enrollment>
<condition>Motivation</condition>
<arm_group>
<arm_group_label>Direct tDCS</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Transcranial direct current stimulation (tDCS) was computationally optimized to target mid-cingulate cortex directly.</description>
</arm_group>
<arm_group>
<arm_group_label>Indirect tDCS</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Transcranial direct current stimulation (tDCS) was computationally optimized to target the middle frontal gyrus, a brain area connected to mid-cingulate cortex.</description>
</arm_group>
<arm_group>
<arm_group_label>Personalized tDCS</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Transcranial direct current stimulation (tDCS) will be individually optimized to simultaneously stimulate key nodes connected to mid-cingulate cortex, including anterior insula, MFG and supramarginal gyrus.</description>
</arm_group>
<arm_group>
<arm_group_label>Sham tDCS</arm_group_label>
<arm_group_type>Sham Comparator</arm_group_type>
<description>Placebo transcranial direct current stimulation (tDCS) will be applied.</description>
</arm_group>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>Direct tDCS</intervention_name>
<description>Transcranial direct current stimulation (tDCS) will be applied. Stimulation amplitude is 2 mA. Stimulation duration is 20 minutes. The configuration used is two electrodes at AFz and CPz of the 10-10 electrode system.</description>
<arm_group_label>Direct tDCS</arm_group_label>
</intervention>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>Indirect tDCS</intervention_name>
<description>Transcranial direct current stimulation (tDCS) will be applied. Stimulation amplitude is 2 mA. Stimulation duration is 20 minutes. The configuration used is two electrodes at AF3 and AF4 of the 10-10 electrode system.</description>
<arm_group_label>Indirect tDCS</arm_group_label>
</intervention>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>Personalized tDCS</intervention_name>
<description>Transcranial direct current stimulation (tDCS) will be applied. Stimulation amplitude is 2 mA. Stimulation duration is 20 minutes. The configuration used will be optimized to stimulate key nodes connected to MCC, including anterior insula, MFG and supramarginal gyrus, and designed using an individual head model that will be combined with each subject's measured connectivity map. The number of electrodes will be minimally 2 and maximally 32.</description>
<arm_group_label>Personalized tDCS</arm_group_label>
</intervention>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>Sham tDCS</intervention_name>
<description>Transcranial direct current stimulation (tDCS) will be applied. Stimulation amplitude is 2 mA. Stimulation duration is 20 minutes. Placebo stimulation will be applied by ramping the current up and immediately down over 30 seconds. The configuration used is two electrodes at AF3 and AF4 of the 10-10 electrode system.</description>
<arm_group_label>Sham tDCS</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- between the ages of 65 and 80

- normal or corrected to normal vision

- fluent in speaking, reading and understanding English

- right-handed

Exclusion Criteria:

- any metal implants that may cause harm through MRI scanning

- other metals that may interfere with obtaining MRI signals

- claustrophobic

- pregnancy

- history of neurological or psychiatric illnesses

- history of fainting, seizures or epilepsy

- history of migraines

- history of drug abuse

- learning disability

- intracranial lesion

- any prescription or regular medication except for birth control

- any uncontrolled medical condition

- skin disease or damage on scalp

- hair style or head dress that prevents electrode contact with the scalp

- any condition affecting agility of hands (e.g. acute or chronic tenosynovitis, active
joint deformity of arthritic origin)
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>65 Years</minimum_age>
<maximum_age>80 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Sumientra M Rampersad, PhD</last_name>
<role>Principal Investigator</role>
<affiliation>Northeastern University</affiliation>
</overall_official>
<overall_contact>
<last_name>Sumientra M Rampersad, PhD</last_name>
<phone>6173733880</phone>
<email>s.rampersad@northeastern.edu</email>
</overall_contact>
<overall_contact_backup>
<last_name>Alexandra Touroutoglou, PhD</last_name>
<email>atourout@nmr.mgh.harvard.edu</email>
</overall_contact_backup>
<location>
<facility>
<name>Northeastern University</name>
<address>
<city>Boston</city>
<state>Massachusetts</state>
<zip>02115</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Sumientra M Rampersad, PhD</last_name>
<phone>617-373-3880</phone>
<email>s.rampersad@northeastern.edu</email>
</contact>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 11, 2020</last_update_submitted>
<last_update_submitted_qc>February 11, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Northeastern University</investigator_affiliation>
<investigator_full_name>Sumientra Rampersad</investigator_full_name>
<investigator_title>Research Assistant Professor</investigator_title>
</responsible_party>
<keyword>cognitive functioning</keyword>
<keyword>elderly</keyword>
<keyword>healthy</keyword>
<keyword>tDCS</keyword>
<keyword>motivation</keyword>
<keyword>memory</keyword>
<keyword>structural MRI</keyword>
<keyword>resting-state fMRI</keyword>
<patient_data>
<sharing_ipd>Yes</sharing_ipd>
<ipd_description>De-identified connectivity maps and motivation and memory task data will be made available via our lab website.</ipd_description>
<ipd_time_frame>Data will be made available within 6 months after publication.</ipd_time_frame>
<ipd_access_criteria>Data will be freely available on our lab website.</ipd_access_criteria>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Fundamental advancements in understanding successful aging are limited by the lack of causal,
rather than just correlational methods to connect age-related changes in memory ability to
changes in brain structure and function. In this study, non-invasive electric brain
stimulation will be used as a tool to create causal links between successful memory function
in aging and brain structures associated with motivation. Recently, it was shown that a group
of elderly, dubbed "superagers", are indistinguishable from young adults in memory
performance and the structure of cortical limbic regions. A key superaging region is
mid-cingulate cortex (MCC), a brain structure associated with motivation and tenacity. The
MCC is a hub region that synchronizes information flow between three core brain networks. The
goal of the research is to explore the contribution of motivation to memory performance by
modulating MCC connectivity with transcranial direct current stimulation (tDCS) to provide
the first causal evidence that experimentally induced motivation can improve memory
performance. Since MCC has not been stimulated with tDCS before, we will test three different
stimulation protocols and compare against a placebo. The stimulation protocols were
computationally optimized for this project. The primary aim is to find the stimulation
protocol most successful at improving memory performance. In order to elucidate the
mechanisms behind these changes, effects of stimulation on motivation and network
connectivity will be investigated. If indeed memory can be improved by increasing motivation
and effort via stimulating MCC, this study will generate new insights into the motivational
mechanisms of successful aging.
Inclusion Criteria:
- between the ages of 65 and 80
- normal or corrected to normal vision
- fluent in speaking, reading and understanding English
- right-handed
Exclusion Criteria:
- any metal implants that may cause harm through MRI scanning
- other metals that may interfere with obtaining MRI signals
- claustrophobic
- pregnancy
- history of neurological or psychiatric illnesses
- history of fainting, seizures or epilepsy
- history of migraines
- history of drug abuse
- learning disability
- intracranial lesion
- any prescription or regular medication except for birth control
- any uncontrolled medical condition
- skin disease or damage on scalp
- hair style or head dress that prevents electrode contact with the scalp
- any condition affecting agility of hands (e.g. acute or chronic tenosynovitis, active
joint deformity of arthritic origin)
|
NCT0426xxxx/NCT04268199.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268199</url>
</required_header>
<id_info>
<org_study_id>EASE</org_study_id>
<nct_id>NCT04268199</nct_id>
</id_info>
<brief_title>A Multicentre, Non-Blinded Study Exploring Self-Administration of Chemotherapy in the Home Environment</brief_title>
<acronym>EASE</acronym>
<official_title>A Multicentre, Non-Blinded Study Exploring Self-Administration of Chemotherapy in the Home Environment</official_title>
<sponsors>
<lead_sponsor>
<agency>AHS Cancer Control Alberta</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Tom Baker Cancer Centre</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>AHS Cancer Control Alberta</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This study is to see if the standard of care subcutaneous injection of bortezomib can safely
be administered at home by the patient or caregiver. All tests and assessments are based on
standard of care procedures.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Chemotherapy for malignancies is predominantly prescribed and delivered in a tertiary
hospital and/or cancer centre setting. However, with modern chemotherapy, with a reduced side
effect profile, this paradigm should be challenged. Indeed, the use of methotrexate and other
biologics (a form of chemotherapy) in the Rheumatologic setting is commonly delivered
effectively and safely in the community.

Taken together, a hospital-based model of chemotherapy delivery may not be warranted in all
circumstances. Moreover, the use of this current model invariably discounts the time
commitments, needs of patients and caregivers, as well as while not addressing the emerging
concerns regarding system capacity, efficiency and effectiveness of safe chemotherapy
delivery.
</textblock>
</detailed_description>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">May 29, 2020</start_date>
<completion_date type="Anticipated">May 2026</completion_date>
<primary_completion_date type="Anticipated">May 2024</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Number of patients able to self-administer</measure>
<time_frame>2 years from study start</time_frame>
<description>Number of eligible patients availing of self-administration</description>
</primary_outcome>
<primary_outcome>
<measure>Myeloma response outcomes</measure>
<time_frame>2 years from study start</time_frame>
<description>Myeloma outcomes as per International Myeloma Foundation Response (IMWG) Criteria</description>
</primary_outcome>
<primary_outcome>
<measure>Adverse events great than grade 3</measure>
<time_frame>2 years from study start</time_frame>
<description>Adverse event documentation as per CTCAE version 5.0 scales of greater than grade 3</description>
</primary_outcome>
<primary_outcome>
<measure>Number of patients with missed doses</measure>
<time_frame>2 years from study start</time_frame>
<description>Proportion of missed doses</description>
</primary_outcome>
<primary_outcome>
<measure>Patient Satisfaction and Quality of Life Survey 1</measure>
<time_frame>2 years from study start</time_frame>
<description>Patient Satisfaction Surveys - FACIT-TS-PS (Functional Assessment of Chronic Illness Therapy)</description>
</primary_outcome>
<primary_outcome>
<measure>Patient Satisfaction and Quality of Life Survey 2</measure>
<time_frame>2 years from study start</time_frame>
<description>Patient Satisfaction Surveys - CQOLC (Caregiver Quality of Life - Cancer)</description>
</primary_outcome>
<primary_outcome>
<measure>Patient Satisfaction and Quality of Life Survey 3</measure>
<time_frame>2 years from study start</time_frame>
<description>Patient Satisfaction Surveys - EORTC QLQ-MY20 (European Organization of Research and Treatment of Cancer - Quality of Life)</description>
</primary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Anticipated">100</enrollment>
<condition>Myeloma</condition>
<condition>Myeloma Multiple</condition>
<arm_group>
<arm_group_label>Self Injection of Bortezomib</arm_group_label>
<arm_group_type>Other</arm_group_type>
<description>Subcutaneous self administration of bortezomib</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Bortezomib Injection</intervention_name>
<description>Subcutaneous injection</description>
<arm_group_label>Self Injection of Bortezomib</arm_group_label>
<other_name>Velcade</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Patients are aged 18 years old or older with a diagnosis of symptomatic myeloma,

- Stable clinical status as deemed by responsible investigator,

- Personally (or caregiver) willing and deemed capable to self-administer with teaching,

- Previously received more than 4 injections of bortezomib within the hospital and/or
cancer centre environment,

- Signed informed consent.

Exclusion Criteria:

- Currently participating in clinical trials that includes the use of bortezomib,

- History of allergic reactions to bortezomib,

- History of bleeding attributable to bortezomib,

- History of greater than or equal to grade 3 side effects attributable to bortezomib,

- Clinically deemed unlikely to be compliant with therapy by responsible investigator,

- Life expectancy anticipated to be less than 6 months,

- Deemed geographically inaccessible to receive care.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Jason Tay, MD</last_name>
<role>Principal Investigator</role>
<affiliation>Tom Baker Cancer Centre</affiliation>
</overall_official>
<overall_contact>
<last_name>Jason Tay, MD</last_name>
<phone>403-944-3265</phone>
<email>Jason.Tay@ahs.ca</email>
</overall_contact>
<overall_contact_backup>
<last_name>Amy Abel</last_name>
<email>Amy.Abel@ahs.ca</email>
</overall_contact_backup>
<location>
<facility>
<name>Tom Baker Cancer Centre</name>
<address>
<city>Calgary</city>
<state>Alberta</state>
<zip>T2N 4N2</zip>
<country>Canada</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Jason Tay, MD</last_name>
<phone>403-944-3265</phone>
<email>Jason.Tay@ahs.ca</email>
</contact>
<contact_backup>
<last_name>Amy Abel</last_name>
<email>Amy.Abel@ahs.ca</email>
</contact_backup>
</location>
<location_countries>
<country>Canada</country>
</location_countries>
<verification_date>May 2022</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>May 4, 2022</last_update_submitted>
<last_update_submitted_qc>May 4, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">May 5, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Multiple Myeloma</mesh_term>
<mesh_term>Neoplasms, Plasma Cell</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Bortezomib</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This study is to see if the standard of care subcutaneous injection of bortezomib can safely
be administered at home by the patient or caregiver. All tests and assessments are based on
standard of care procedures.
Chemotherapy for malignancies is predominantly prescribed and delivered in a tertiary
hospital and/or cancer centre setting. However, with modern chemotherapy, with a reduced side
effect profile, this paradigm should be challenged. Indeed, the use of methotrexate and other
biologics (a form of chemotherapy) in the Rheumatologic setting is commonly delivered
effectively and safely in the community.
Taken together, a hospital-based model of chemotherapy delivery may not be warranted in all
circumstances. Moreover, the use of this current model invariably discounts the time
commitments, needs of patients and caregivers, as well as while not addressing the emerging
concerns regarding system capacity, efficiency and effectiveness of safe chemotherapy
delivery.
Inclusion Criteria:
- Patients are aged 18 years old or older with a diagnosis of symptomatic myeloma,
- Stable clinical status as deemed by responsible investigator,
- Personally (or caregiver) willing and deemed capable to self-administer with teaching,
- Previously received more than 4 injections of bortezomib within the hospital and/or
cancer centre environment,
- Signed informed consent.
Exclusion Criteria:
- Currently participating in clinical trials that includes the use of bortezomib,
- History of allergic reactions to bortezomib,
- History of bleeding attributable to bortezomib,
- History of greater than or equal to grade 3 side effects attributable to bortezomib,
- Clinically deemed unlikely to be compliant with therapy by responsible investigator,
- Life expectancy anticipated to be less than 6 months,
- Deemed geographically inaccessible to receive care.
|
NCT0426xxxx/NCT04268212.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268212</url>
</required_header>
<id_info>
<org_study_id>STUDY00004172</org_study_id>
<nct_id>NCT04268212</nct_id>
</id_info>
<brief_title>An Alternative Approach to Improve Hyperglycemia Among Type 2 Diabetes Patients</brief_title>
<official_title>Effects of Bitter Melon Intake and Moderate-Intensity Physical Activity on Postprandial Glucose Responses in Type 2 Diabetic Patients</official_title>
<sponsors>
<lead_sponsor>
<agency>Arizona State University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Arizona State University</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The study compared the effect of bitter melon intake and moderate exercise on postprandial
glucose levels as measured by incremental area under the curve (iAUC) in eight patients with
type 2 diabetes.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Background: This study compared the effects of bitter melon intake and moderate-intensity
physical activity on postprandial glucose responses in type 2 diabetic patients.

Methods: A total of 8 patients with type 2 diabetes were randomly assigned to two sequences
(AB, BA) with two treatments (A or B) using a 2 x 2 randomized cross-over design: A) 100 ml
of bitter melon juice administered 15 minutes prior to the 75-g oral glucose load; B) 30
minutes walking at moderate-intensity performed 15 minutes after the oral glucose load.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">April 15, 2016</start_date>
<completion_date type="Actual">September 20, 2016</completion_date>
<primary_completion_date type="Actual">August 20, 2016</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Crossover Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>Double (Investigator, Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>mean glucose</measure>
<time_frame>2-hour postprandial period</time_frame>
<description>mean glucose values</description>
</primary_outcome>
<primary_outcome>
<measure>incremental area under the curve</measure>
<time_frame>2-hour postprandial period</time_frame>
<description>2-hour postprandial glucose incremental area under the curve</description>
</primary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">8</enrollment>
<condition>Type2 Diabetes</condition>
<arm_group>
<arm_group_label>Bitter Melon</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>The participants were asked to consume 100 ml of bitter melon juice 15 minutes prior to the 75-g oral glucose intake. Participants drank the juice within 5 minutes. Participants remained seated throughout the following 2 hours.</description>
</arm_group>
<arm_group>
<arm_group_label>Exercise</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Participants performed 30 minutes of treadmill walking at 65% of the age-predicted maximum heart rate. The exercise started 15 minutes after the 75-g oral glucose intake.</description>
</arm_group>
<intervention>
<intervention_type>Dietary Supplement</intervention_type>
<intervention_name>Bitter melon juice (100 ml)</intervention_name>
<description>Fresh bitter melon fruits were purchased from certified local groceries. The seeds of bitter melon were removed, and the juice was obtained from the raw fruit using a blender. Every 140 g of bitter melon fruit produced approximately 100 ml bitter melon juice.</description>
<arm_group_label>Bitter Melon</arm_group_label>
</intervention>
<intervention>
<intervention_type>Behavioral</intervention_type>
<intervention_name>Exercise</intervention_name>
<description>The walking exercise was started 15 minutes after the glucose load. Walking speed was determined to elicit 65% of the maximum heart rate (HRmax) during exercise for each participant. HRmax was estimated using the America College of Cardiology prediction model, HRmax=208 - 0.7 × age. All participants wore a heart rate monitor (Polar, Vantage, XL) around the chest to assess exercise intensity. A rate of perceived exertion was assessed every 2 minutes based on the Borg's scale.</description>
<arm_group_label>Exercise</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- An age of 20 to 79 years

- Physician-diagnosed type 2 diabetes

- Medical clearance for physical activity from their healthcare provider

Exclusion Criteria:

- Pregnant or were receiving insulin treatment

- An allergy to bitter melon

- Medical conditions that impacted the normal the functioning of the gastrointestinal
tract

- Contraindications to physical activity
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>20 Years</minimum_age>
<maximum_age>79 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Chong Lee, Ph.D.</last_name>
<role>Principal Investigator</role>
<affiliation>Arizona State University</affiliation>
</overall_official>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 13, 2020</last_update_submitted>
<last_update_submitted_qc>February 13, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 17, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Diabetes Mellitus, Type 2</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The study compared the effect of bitter melon intake and moderate exercise on postprandial
glucose levels as measured by incremental area under the curve (iAUC) in eight patients with
type 2 diabetes.
Background: This study compared the effects of bitter melon intake and moderate-intensity
physical activity on postprandial glucose responses in type 2 diabetic patients.
Methods: A total of 8 patients with type 2 diabetes were randomly assigned to two sequences
(AB, BA) with two treatments (A or B) using a 2 x 2 randomized cross-over design: A) 100 ml
of bitter melon juice administered 15 minutes prior to the 75-g oral glucose load; B) 30
minutes walking at moderate-intensity performed 15 minutes after the oral glucose load.
Inclusion Criteria:
- An age of 20 to 79 years
- Physician-diagnosed type 2 diabetes
- Medical clearance for physical activity from their healthcare provider
Exclusion Criteria:
- Pregnant or were receiving insulin treatment
- An allergy to bitter melon
- Medical conditions that impacted the normal the functioning of the gastrointestinal
tract
- Contraindications to physical activity
|
NCT0426xxxx/NCT04268225.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268225</url>
</required_header>
<id_info>
<org_study_id>0044-20-RMC</org_study_id>
<nct_id>NCT04268225</nct_id>
</id_info>
<brief_title>Ultrasound Guided Peripheral Intravenous Catheterization in the Pediatric Intensive Care Unit.</brief_title>
<official_title>Ultrasound Guided Peripheral Intravenous Catheterization in Children Hospitalized in the Pediatric Intensive Care Unit: a Randomized Controlled Prospective Trial.</official_title>
<sponsors>
<lead_sponsor>
<agency>Rabin Medical Center</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Rabin Medical Center</source>
<oversight_info>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This is a randomized controlled prospective study. The purpose of this study is to compare a
recently described technique of ultrasound (US) guided, dynamic needle tip positioning
(DNTP), to the traditional technique of vein visualization and palpation for peripheral
venous cannulation in intubated, sedated, and mechanically ventilated pediatric intensive
care unit (PICU) patients. First attempt success rate, overall success rate within 3 attempts
or 10 minutes (whichever comes first), number of attempts to success, time to success and
cannula sizes will be compared between the 2 techniques. The study will include intubated,
sedated and mechanically ventilated children, aged 0-18 years, hospitalized in the PICU who
require peripheral intravenous (PIV) access for their management.
</textblock>
</brief_summary>
<overall_status>Unknown status</overall_status>
<last_known_status>Not yet recruiting</last_known_status>
<start_date type="Anticipated">March 2020</start_date>
<completion_date type="Anticipated">March 2022</completion_date>
<primary_completion_date type="Anticipated">March 2022</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Supportive Care</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Success of peripheral IV cannulation on first attempt</measure>
<time_frame>10 minutes</time_frame>
<description>Assessment of peripheral IV cannulation success on first attempt (Yes vs No)</description>
</primary_outcome>
<secondary_outcome>
<measure>Overall peripheral IV cannulation success rate</measure>
<time_frame>10 minutes</time_frame>
<description>The overall success rate of peripheral intravenous cannulation within 3 attempts.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Time to successful peripheral IV cannulation</measure>
<time_frame>up to 10 minutes</time_frame>
<description>Defined as the time from first skin puncture to successful cannulation (minutes).</description>
</secondary_outcome>
<secondary_outcome>
<measure>Number of attempts to success</measure>
<time_frame>up to 10 minutes</time_frame>
<description>Number of puncture attempts (1,2 or 3) needed for achieving a a successful cannulation</description>
</secondary_outcome>
<secondary_outcome>
<measure>Inserted cannula diameter</measure>
<time_frame>up to 10 minutes</time_frame>
<description>Cannula diameter (in GA) successfully inserted</description>
</secondary_outcome>
<other_outcome>
<measure>Patient age</measure>
<time_frame>1 day (At the time of peripheral IV cannulation)</time_frame>
<description>Age in years</description>
</other_outcome>
<other_outcome>
<measure>Patient sex</measure>
<time_frame>1 day (At the time of peripheral IV cannulation)</time_frame>
<description>Female vs Male</description>
</other_outcome>
<other_outcome>
<measure>Patient body mass index (BMI)</measure>
<time_frame>1 day (At the time of peripheral IV cannulation)</time_frame>
<description>BMI (in kg/m^2) for age percentile</description>
</other_outcome>
<other_outcome>
<measure>Patient inotropic and vasoactive support</measure>
<time_frame>1 day (At the time of peripheral IV cannulation)</time_frame>
<description>Vasoactive-Inotropic Score (VIS score)</description>
</other_outcome>
<other_outcome>
<measure>Admission-cannulation time</measure>
<time_frame>1 day (At the time of peripheral IV cannulation)</time_frame>
<description>Time from hospital admission to first attempt of cannulation</description>
</other_outcome>
<other_outcome>
<measure>Reason for admission</measure>
<time_frame>1 day (At the time of peripheral IV cannulation)</time_frame>
<description>Medical vs Surgical</description>
</other_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">90</enrollment>
<condition>Peripheral Venous Cannulation</condition>
<arm_group>
<arm_group_label>Ultrasound Guided Dynamic Needle Tip Positioning Technique</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>In this arm the US transducer, protected with a sterile cover and sterile gel will be placed in the short axis above the distal end of the selected vein, moving the probe to place the vein in the center of the ultrasound screen under the middle mark of the image. The catheter needle will be inserted close to the transducer. The needle tip will be visualized as a white dot on the ultrasound screen. Then, the transducer will be shifted slightly proximally until the white dot disappears from the screen. The needle and the transducer will be moved alternately toward the patient several times to visualize the needle tip in real time. After penetrating the anterior wall of the vein, these steps will be repeated a few more times with a smaller insertion angle to visualize the white dot in the vein. Finally, the outer catheter will be fully advanced and the needle core will be extracted.</description>
</arm_group>
<arm_group>
<arm_group_label>Traditional insertion group</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>For traditional insertion technique insertion attempt will be blind or tactile. Otherwise, the same protocol and measurements as elaborated for the US guided group will be applied.</description>
</arm_group>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>US guided dynamic needle tip positioning peripheral intravenous cannulation</intervention_name>
<description>Catheterizations will be performed by one of three pediatric intensivists with vast experience in both traditional and US guided DNTP techniques for peripheral intravenous access. The operator will be allowed to independently choose which peripheral vein to cannulate. If necessary, patients will be given supplemental dose of sedation and analgesia in addition to the already given continuous infusions for invasive mechanical ventilation. Before puncture, the limb will be taped and maintained in an optimal position. A tourniquet will be placed proximal to the planned cannulation site. The site of puncture will be disinfected with Chlorhexidine gluconate 0.5% w/v, Alcohol 70% v/v. The choice of catheter will be left to the discretion of the operator. Available PIV cannulas include : 14 GA, 2X45 mm; 17 GA, 1.4X45 mm; 18 GA 1.2X45 mm; 20 GA 1X32mm BD Venflon™ and 24 GA, 0.7X19 mm; 26 GA 0.6X19 mm BD Neoflon™ (Becton Dickinson Infusion Therapy AB, Helsingborg, Sweden).</description>
<arm_group_label>Ultrasound Guided Dynamic Needle Tip Positioning Technique</arm_group_label>
</intervention>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>Traditional peripheral intravenous cannulation</intervention_name>
<description>For traditional insertion technique insertion attempt will be blind or tactile.</description>
<arm_group_label>Traditional insertion group</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Invasively ventilated

2. Younger than 18 years

3. Peripheral venous access required

4. Difficult intravenous access (DIVA) score of 4 or greater (on a scale of 0-10 with
higher scores implying more difficult access)

Exclusion Criteria:

1. Refusal to consent

2. Research staff not available
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>N/A</minimum_age>
<maximum_age>18 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Avichai Weissbach, MD</last_name>
<role>Principal Investigator</role>
<affiliation>Rabin Medical Center</affiliation>
</overall_official>
<overall_contact>
<last_name>Avichai Weissbach, MD</last_name>
<phone>+97239253686</phone>
<email>weissbac@gmail.com</email>
</overall_contact>
<reference>
<citation>Costantino TG, Parikh AK, Satz WA, Fojtik JP. Ultrasonography-guided peripheral intravenous access versus traditional approaches in patients with difficult intravenous access. Ann Emerg Med. 2005 Nov;46(5):456-61. doi: 10.1016/j.annemergmed.2004.12.026.</citation>
<PMID>16271677</PMID>
</reference>
<reference>
<citation>Doniger SJ, Ishimine P, Fox JC, Kanegaye JT. Randomized controlled trial of ultrasound-guided peripheral intravenous catheter placement versus traditional techniques in difficult-access pediatric patients. Pediatr Emerg Care. 2009 Mar;25(3):154-9. doi: 10.1097/PEC.0b013e31819a8946.</citation>
<PMID>19262420</PMID>
</reference>
<reference>
<citation>Otani T, Morikawa Y, Hayakawa I, Atsumi Y, Tomari K, Tomobe Y, Uda K, Funakoshi Y, Sakaguchi C, Nishimoto S, Hataya H. Ultrasound-guided peripheral intravenous access placement for children in the emergency department. Eur J Pediatr. 2018 Oct;177(10):1443-1449. doi: 10.1007/s00431-018-3201-3. Epub 2018 Jun 30.</citation>
<PMID>29961178</PMID>
</reference>
<reference>
<citation>Vinograd AM, Zorc JJ, Dean AJ, Abbadessa MKF, Chen AE. First-Attempt Success, Longevity, and Complication Rates of Ultrasound-Guided Peripheral Intravenous Catheters in Children. Pediatr Emerg Care. 2018 Jun;34(6):376-380. doi: 10.1097/PEC.0000000000001063.</citation>
<PMID>28221281</PMID>
</reference>
<reference>
<citation>Elkhunovich M, Barreras J, Bock Pinero V, Ziv N, Vaiyani A, Mailhot T. The use of ultrasound for peripheral IV placement by vascular access team nurses at a tertiary children's hospital. J Vasc Access. 2017 Jan 18;18(1):57-63. doi: 10.5301/jva.5000615. Epub 2016 Nov 15.</citation>
<PMID>27886365</PMID>
</reference>
<reference>
<citation>Benkhadra M, Collignon M, Fournel I, Oeuvrard C, Rollin P, Perrin M, Volot F, Girard C. Ultrasound guidance allows faster peripheral IV cannulation in children under 3 years of age with difficult venous access: a prospective randomized study. Paediatr Anaesth. 2012 May;22(5):449-54. doi: 10.1111/j.1460-9592.2012.03830.x. Epub 2012 Mar 12.</citation>
<PMID>22409596</PMID>
</reference>
<reference>
<citation>Kiberenge RK, Ueda K, Rosauer B. Ultrasound-Guided Dynamic Needle Tip Positioning Technique Versus Palpation Technique for Radial Arterial Cannulation in Adult Surgical Patients: A Randomized Controlled Trial. Anesth Analg. 2018 Jan;126(1):120-126. doi: 10.1213/ANE.0000000000002261.</citation>
<PMID>29135593</PMID>
</reference>
<reference>
<citation>Liu L, Tan Y, Li S, Tian J. "Modified Dynamic Needle Tip Positioning" Short-Axis, Out-of-Plane, Ultrasound-Guided Radial Artery Cannulation in Neonates: A Randomized Controlled Trial. Anesth Analg. 2019 Jul;129(1):178-183. doi: 10.1213/ANE.0000000000003445.</citation>
<PMID>29787409</PMID>
</reference>
<reference>
<citation>Takeshita J, Inata Y, Ito Y, Nishiyama K, Shimizu Y, Takeuchi M, Shime N. Dynamic Needle Tip Positioning for Ultrasound-Guided Placement of a Peripherally Inserted Central Catheter in Pediatric Patients. J Cardiothorac Vasc Anesth. 2020 Jan;34(1):114-118. doi: 10.1053/j.jvca.2019.04.029. Epub 2019 May 2.</citation>
<PMID>31129072</PMID>
</reference>
<reference>
<citation>Takeshita J, Yoshida T, Nakajima Y, Nakayama Y, Nishiyama K, Ito Y, Shimizu Y, Takeuchi M, Shime N. Dynamic Needle Tip Positioning for Ultrasound-Guided Arterial Catheterization in Infants and Small Children With Deep Arteries: A Randomized Controlled Trial. J Cardiothorac Vasc Anesth. 2019 Jul;33(7):1919-1925. doi: 10.1053/j.jvca.2018.12.002. Epub 2018 Dec 4.</citation>
<PMID>30638922</PMID>
</reference>
<reference>
<citation>Takeshita J, Yoshida T, Nakajima Y, Nakayama Y, Nishiyama K, Ito Y, Shimizu Y, Takeuchi M, Shime N. Superiority of Dynamic Needle Tip Positioning for Ultrasound-Guided Peripheral Venous Catheterization in Patients Younger Than 2 Years Old: A Randomized Controlled Trial. Pediatr Crit Care Med. 2019 Sep;20(9):e410-e414. doi: 10.1097/PCC.0000000000002034.</citation>
<PMID>31232853</PMID>
</reference>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 9, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>March 12, 2020</last_update_submitted>
<last_update_submitted_qc>March 12, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">March 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This is a randomized controlled prospective study. The purpose of this study is to compare a
recently described technique of ultrasound (US) guided, dynamic needle tip positioning
(DNTP), to the traditional technique of vein visualization and palpation for peripheral
venous cannulation in intubated, sedated, and mechanically ventilated pediatric intensive
care unit (PICU) patients. First attempt success rate, overall success rate within 3 attempts
or 10 minutes (whichever comes first), number of attempts to success, time to success and
cannula sizes will be compared between the 2 techniques. The study will include intubated,
sedated and mechanically ventilated children, aged 0-18 years, hospitalized in the PICU who
require peripheral intravenous (PIV) access for their management.
Inclusion Criteria:
1. Invasively ventilated
2. Younger than 18 years
3. Peripheral venous access required
4. Difficult intravenous access (DIVA) score of 4 or greater (on a scale of 0-10 with
higher scores implying more difficult access)
Exclusion Criteria:
1. Refusal to consent
2. Research staff not available
|
NCT0426xxxx/NCT04268238.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268238</url>
</required_header>
<id_info>
<org_study_id>HMI</org_study_id>
<nct_id>NCT04268238</nct_id>
</id_info>
<brief_title>Pain Control in Dentin Hypersensitivity in Patients With MIH</brief_title>
<official_title>Pain Control in Dentin Hypersensitivity in Patients With MIH: Study Protocol for a Randomized, Controlled, Clinical Trial</official_title>
<sponsors>
<lead_sponsor>
<agency>University of Nove de Julho</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>University of Nove de Julho</source>
<oversight_info>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This study aims to evaluate the effectiveness of different protocols in controlling dentin
hypersensitivity in patients with teeth affected by MIH. The subjects will be randomly
designated in four experimental groups, according to different treatments. Pain will be
assessed with the visual analog scale (Visual Analogue Scale - VAS), after stimulation with
air from the triple syringe and and an exploratory probe at the time of (initial)
recruitment, immediately after treatment, after 1 week and 1 month, 3 and 6 months after
treatment.
</textblock>
</brief_summary>
<overall_status>Unknown status</overall_status>
<last_known_status>Not yet recruiting</last_known_status>
<start_date type="Anticipated">March 20, 2020</start_date>
<completion_date type="Anticipated">December 20, 2020</completion_date>
<primary_completion_date type="Anticipated">November 20, 2020</primary_completion_date>
<phase>Phase 1/Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>Double (Participant, Outcomes Assessor)</masking>
<masking_description>Study participants and the outcome assessor of sensitivity will be blind to the procedure. However, the researcher who will apply the products is not blind, due to the different forms of clinical manipulation of products.</masking_description>
</study_design_info>
<primary_outcome>
<measure>Change in Pain Evaluated by a Visual Analog Scale (VAS)</measure>
<time_frame>Baseline, immediately after treatment, 1 week, 1, 3 and 6 months after treatment.</time_frame>
<description>Pain will be assessed with the visual analogue scale (Visual Analogue Scale - VAS), after stimulation with air from the triple syringe and an explorer probe.</description>
</primary_outcome>
<number_of_arms>4</number_of_arms>
<enrollment type="Anticipated">140</enrollment>
<condition>Hypersensitivity Dentin</condition>
<arm_group>
<arm_group_label>Control group</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Two weeks before the start of the study, the volunteers will go through a wash out period, where they should only use oral care products donated by the researchers, which should be used until the end of the study. The oral hygiene kit will contain 1 toothbrush (Professional Lab Series, Colgate Palmolive), 1 toothpaste without desensitizing agent, but with fluorine (Elmex) and 1 dental floss (Colgate). Afterwards, this group will receive no treatment. Instead of the sealant, water will be used and the laser will remain with power 0W, that is, there will be no light emission, giving the group the characteristic of the control group, no treatment.</description>
</arm_group>
<arm_group>
<arm_group_label>Sealant group</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>In this group, besides the instructions described in the control group, the teeth that will be sealed will be isolated. 35% phosphoric acid will be applied for 20 seconds and then it will be necessary to wash and dry the tooth surface. Apply a thin layer of PermaSeal (sealant) for 5 seconds to the tooth surface and light curing for 20 seconds.</description>
</arm_group>
<arm_group>
<arm_group_label>Low Level Laser Group</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>In this group, besides the instructions described in the control group, volunteers will receive irradiation with AsGaAl laser, wavelength of 780 nm (Laser XT Therapy, DMC, São Carlos, SP) with fixed power of 100mW, energy density of 35 J/cm2 (considering a spot size of 0.028 cm2 of this equipment), the dose will be 1 J per point. The irradiation will be performed at a cervical, an apical point and another point exactly on the injury, totaling a dose of 3J. Treatment should be performed in 3 sessions with an ideal 72-hour interval between them.</description>
</arm_group>
<arm_group>
<arm_group_label>Low Level Laser + Sealant Group</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>In this group, patients will receive the treatments described in Control group, Sealant group and Low Level Laser Group.</description>
</arm_group>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>Hygiene Guidance</intervention_name>
<description>Two weeks before the start of the study, the volunteers will go through a wash out period, where they should only use oral care products donated by the researchers, which should be used until the end of the study. The oral hygiene kit will contain 1 toothbrush (Professional Lab Series, Colgate Palmolive), 1 toothpaste without desensitizing agent, but with fluorine (Elmex) and 1 dental floss (Colgate).</description>
<arm_group_label>Control group</arm_group_label>
<arm_group_label>Low Level Laser + Sealant Group</arm_group_label>
<arm_group_label>Low Level Laser Group</arm_group_label>
<arm_group_label>Sealant group</arm_group_label>
</intervention>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>Sealant Application</intervention_name>
<description>Permaseal (Ultradent) is an unloaded resin based on methacrylate and photopolymerizable. The teeth that will be sealed will be isolated. 35% phosphoric acid will be applied for 20 seconds and then it will be necessary to wash and dry the tooth surface. Apply a thin layer of PermaSeal for 5 seconds to the tooth surface and light curing for 20 seconds. After that, it is necessary to evaluate occlusion.</description>
<arm_group_label>Low Level Laser + Sealant Group</arm_group_label>
<arm_group_label>Sealant group</arm_group_label>
</intervention>
<intervention>
<intervention_type>Radiation</intervention_type>
<intervention_name>Low Level Laser Application</intervention_name>
<description>Volunteers will receive irradiation with AsGaAl laser, wavelength of 780nm (Laser XT Therapy, DMC, São Carlos, SP) with fixed power of 100mW, density of energy of 35 J/cm2 (considering a spot size of 0.028cm2 of this equipment), the dose will be 1 J per point. Irradiation will be performed at a cervical, an apical point, and another point exactly on the injury, totaling a dose of 3J. Treatment should be performed in 3 sessions with an ideal 72-hour interval between them.</description>
<arm_group_label>Low Level Laser + Sealant Group</arm_group_label>
<arm_group_label>Low Level Laser Group</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Be between 18 and 35 years old;

- Present good general health;

- Present at least one tooth with dentin hypersensitivity reported in the cervical
region, which must have a graduated sensitivity equal to or greater than 4 in the VAS
scale.

Exclusion Criteria:

- Present active caries lesions or restoration defects in the tooth to be analyzed;

- Present sufficient dentin loss that requires restorative treatment or periodontal
surgery;

- Volunteers who underwent any professional desensitizer treatment in the last 6 months;

- Volunteers who used desensitizing pastes in the 3 months;

- Volunteers who were using anti-inflammatory or analgesic drugs at the time of
recruitment;

- Volunteers who are pregnant or breastfeeding.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>35 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 11, 2020</last_update_submitted>
<last_update_submitted_qc>February 11, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>University of Nove de Julho</investigator_affiliation>
<investigator_full_name>Sandra Kalil Bussadori</investigator_full_name>
<investigator_title>Principal Investigator</investigator_title>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Dentin Sensitivity</mesh_term>
<mesh_term>Hypersensitivity</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This study aims to evaluate the effectiveness of different protocols in controlling dentin
hypersensitivity in patients with teeth affected by MIH. The subjects will be randomly
designated in four experimental groups, according to different treatments. Pain will be
assessed with the visual analog scale (Visual Analogue Scale - VAS), after stimulation with
air from the triple syringe and and an exploratory probe at the time of (initial)
recruitment, immediately after treatment, after 1 week and 1 month, 3 and 6 months after
treatment.
Inclusion Criteria:
- Be between 18 and 35 years old;
- Present good general health;
- Present at least one tooth with dentin hypersensitivity reported in the cervical
region, which must have a graduated sensitivity equal to or greater than 4 in the VAS
scale.
Exclusion Criteria:
- Present active caries lesions or restoration defects in the tooth to be analyzed;
- Present sufficient dentin loss that requires restorative treatment or periodontal
surgery;
- Volunteers who underwent any professional desensitizer treatment in the last 6 months;
- Volunteers who used desensitizing pastes in the 3 months;
- Volunteers who were using anti-inflammatory or analgesic drugs at the time of
recruitment;
- Volunteers who are pregnant or breastfeeding.
|
NCT0426xxxx/NCT04268251.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268251</url>
</required_header>
<id_info>
<org_study_id>AsanMCHSKim_06</org_study_id>
<nct_id>NCT04268251</nct_id>
</id_info>
<brief_title>Evaluation of Cavernous Sinus Invasion by Pituitary Adenoma Using Deep Learning Based Denoising MR</brief_title>
<official_title>Prospective MRI Evaluation of Cavernous Sinus Invasion by Pituitary Adenoma Using Deep Learning Based Denoising</official_title>
<sponsors>
<lead_sponsor>
<agency>Asan Medical Center</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Asan Medical Center</source>
<oversight_info>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Preoperative evaluation of cavernous sinus invasion by pituitary adenoma is critical for
performing safe operation and deciding on surgical extent as well as for treatment success.
Because of the small size of the pituitary gland and sellar fossa, determining the exact
relationship between the pituitary adenoma and cavernous sinus can be challenging. Performing
thin slice thickness MRI may be beneficial but is inevitably associated with increased noise
level. By applying deep learning based denoising algorithm, diagnosis of cavernous sinus
invasion by pituitary adenoma may be improved.
</textblock>
</brief_summary>
<overall_status>Unknown status</overall_status>
<last_known_status>Recruiting</last_known_status>
<start_date type="Actual">January 12, 2020</start_date>
<completion_date type="Anticipated">February 28, 2021</completion_date>
<primary_completion_date type="Anticipated">February 28, 2021</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<primary_purpose>Diagnostic</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Cavernous sinus invasion</measure>
<time_frame>Within 1 week</time_frame>
<description>Presence or absence of cavernous sinus invasion determined surgically</description>
</primary_outcome>
<secondary_outcome>
<measure>Size of pituitary adenoma (in mm), laterality of pituitary adenoma (unilateral or bilateral) on the MRI</measure>
<time_frame>Within 1 week</time_frame>
<description>Size of the tumor (in mm), laterality of the tumor (unilateral or bilateral) on the MRI</description>
</secondary_outcome>
<secondary_outcome>
<measure>Margin of pituitary adenoma (well-delineated, poorly delineated) on the MRI</measure>
<time_frame>Within 1 week</time_frame>
<description>Margin of pituitary adenoma (well-delineated, poorly delineated) on the MRI</description>
</secondary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Anticipated">76</enrollment>
<condition>Cavernous Sinus Invasion by Pituitary Adenoma</condition>
<arm_group>
<arm_group_label>Deep learning based denoising MR</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>1 mm slice thickness coronal contrast-enhanced T1 weighted imaging with deep learning based denoising vs. 3 mm slice thickness coronal contrast-enhanced T1 weighted imaging</description>
</arm_group>
<intervention>
<intervention_type>Diagnostic Test</intervention_type>
<intervention_name>MRI with deep learning based denoising</intervention_name>
<description>1-mm coronal contrast-enhanced T1 weighted image with deep learning based denoising</description>
<arm_group_label>Deep learning based denoising MR</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Patients undergoing preoperative brain MR for pituitary adenoma

Exclusion Criteria:

- Patients who have any type of bioimplant activated by mechanical, electronic, or
magnetic means (e.g., cochlear implants, pacemakers, neurostimulators, biostimulates,
electronic infusion pumps, etc), because such devices may be displaced or malfunction

- Patients who are pregnant or breast feeding; urine pregnancy test will be performed on
women of child bearing potential

- Poor MRI image quality due to artifacts
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Ho Sung Kim, MD PhD</last_name>
<role>Principal Investigator</role>
<affiliation>Asan Medical Center</affiliation>
</overall_official>
<overall_contact>
<last_name>Ho Sung Kim, MD PhD</last_name>
<phone>+82 2 3010 5682</phone>
<email>radhskim@gmail.com</email>
</overall_contact>
<overall_contact_backup>
<last_name>Minjae Kim, MD</last_name>
<phone>+82 2 3010 0187</phone>
<email>manzae.kim@gmail.com</email>
</overall_contact_backup>
<location>
<facility>
<name>Asan Medical Center</name>
<address>
<city>Seoul</city>
<country>Korea, Republic of</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Minjae Kim, MD</last_name>
<phone>+82 2 3010 0187</phone>
<email>manzae.kim@gmail.com</email>
</contact>
</location>
<location_countries>
<country>Korea, Republic of</country>
</location_countries>
<verification_date>February 2020</verification_date>
<study_first_submitted>January 13, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 19, 2020</last_update_submitted>
<last_update_submitted_qc>February 19, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 20, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Asan Medical Center</investigator_affiliation>
<investigator_full_name>Ho Sung Kim</investigator_full_name>
<investigator_title>Professor</investigator_title>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Adenoma</mesh_term>
<mesh_term>Pituitary Neoplasms</mesh_term>
<mesh_term>Pituitary Diseases</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Preoperative evaluation of cavernous sinus invasion by pituitary adenoma is critical for
performing safe operation and deciding on surgical extent as well as for treatment success.
Because of the small size of the pituitary gland and sellar fossa, determining the exact
relationship between the pituitary adenoma and cavernous sinus can be challenging. Performing
thin slice thickness MRI may be beneficial but is inevitably associated with increased noise
level. By applying deep learning based denoising algorithm, diagnosis of cavernous sinus
invasion by pituitary adenoma may be improved.
Inclusion Criteria:
- Patients undergoing preoperative brain MR for pituitary adenoma
Exclusion Criteria:
- Patients who have any type of bioimplant activated by mechanical, electronic, or
magnetic means (e.g., cochlear implants, pacemakers, neurostimulators, biostimulates,
electronic infusion pumps, etc), because such devices may be displaced or malfunction
- Patients who are pregnant or breast feeding; urine pregnancy test will be performed on
women of child bearing potential
- Poor MRI image quality due to artifacts
|
NCT0426xxxx/NCT04268264.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268264</url>
</required_header>
<id_info>
<org_study_id>R2338</org_study_id>
<nct_id>NCT04268264</nct_id>
</id_info>
<brief_title>A Feasibility Study to Test the Acceptability, Tolerance and Safety of Incremental Haemodialysis</brief_title>
<acronym>ENDURE</acronym>
<official_title>Effect of Incremental Introduction of Dialysis Versus Standard Care in Patients With End-stage Renal Disease: a Feasibility Study</official_title>
<sponsors>
<lead_sponsor>
<agency>Hull University Teaching Hospitals NHS Trust</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Hull University Teaching Hospitals NHS Trust</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This feasibility study tests if patients find incremental HD acceptable, whether they
tolerate the treatment as planned and to evaluate its safety. Over a period of 18-months, 20
participants will be recruited in to the study who are about to start HD therapy for ESRD.
The participants will start HD incrementally (incremental HD group) reaching full dose HD
over a period of approximately 15 weeks. The outcomes will be compared to a cohort of 40
matched patients who previously started HD in the conventional manner (historical controls,
conventional HD group).

All patients will be followed-up for 6 months after first dialysis. Participants will be
reviewed regularly during this time, and will undergo laboratory and bed-site monitoring
tests. Acceptability and tolerance will be tested by documenting the numbers and percentages
of patients who agree to participate and continue in the study. Patients who decline the
invitation to join the study will be given the opportunity to express their reasons for
declining to go on incremental HD (they will not play further part in the study). The safety
of incremental HD will be tested by comparing the rates of pre-defined safety events in the
incremental HD vs. conventional HD groups.

The impact of incremental HD on patients' residual renal function will be monitored using
serial 24-hour urine collections, bio-impedance testing will be conducted to estimate changes
in fluid load, measurements of quality-of-life will be undertaken by using patient KDQOL-SF
v1.3 questionnaires. These tests will be repeated at regular intervals. Blood tests for
estimation of residual renal function and markers of renal anemia, bone disease and cardiac
load will be performed at regular intervals and will be compared between the two groups
(incremental HD vs. conventional HD groups). These measurements will help in the evaluation
of impact of incremental HD on patients' health and well-being. The completion rates of these
tests will provide important information about whether they should be included in a future
larger trial of incremental HD. Participants undergoing incremental HD will be invited to
take part in semi-structured interviews aimed at exploring patients' experiences of receiving
incremental HD and their participation in the study.

Data from this study will be used to test if it is feasible to use deaths (or a combination
of deaths and cardiovascular events) as the main outcome measure in a future definitive trial
on incremental HD. The data should enable a sample-size calculation for a future full-scale
trial.
</textblock>
</brief_summary>
<overall_status>Completed</overall_status>
<start_date type="Actual">May 1, 2019</start_date>
<completion_date type="Actual">February 28, 2022</completion_date>
<primary_completion_date type="Actual">February 28, 2022</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Non-Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Acceptability: Recruitment rate</measure>
<time_frame>6 months</time_frame>
<description>What proportion of eligible patients were recruited in to the trial?</description>
</primary_outcome>
<primary_outcome>
<measure>Tolerance: Retention rate</measure>
<time_frame>6 months</time_frame>
<description>What proportion of participants completed treatment as planned</description>
</primary_outcome>
<primary_outcome>
<measure>Completion rates of non-routine tests</measure>
<time_frame>6 months</time_frame>
<description>Completion rates of the non-routine tests a) the 24-hour urine collections, b) six-minute walk test, c) bio-impedance testing and d) quality of life questionnaires</description>
</primary_outcome>
<secondary_outcome>
<measure>Mortality and cardiovascular event rates</measure>
<time_frame>6 months</time_frame>
<description>Differences in mortality, and the composite of mortality and major cardiovascular events, between the interventional and control groups.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mechanistic 1: Rate of loss of residual renal function in the interventional group</measure>
<time_frame>6 months</time_frame>
<description>Differences in renal urea clearance (in millilitres/min) from baseline</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mechanistic 2:Changes in fluid load</measure>
<time_frame>6 months</time_frame>
<description>Differences in overhydration volume (as measured through bio-impedance testing)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mechanistic 3:Quality of life</measure>
<time_frame>6 months</time_frame>
<description>Changes in quality of life scores (using KDQOL-SF v 1.3) from baseline</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mechanistic 4: Anaemia control</measure>
<time_frame>6 months</time_frame>
<description>Changes in haemoglobin levels from baseline</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mechanistic 5: Parathyroid hormone control</measure>
<time_frame>6 months</time_frame>
<description>Changes in serum Parathyroid hormone, calcium and phosphate levels from baseline</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mechanistic 6: Cardiac load</measure>
<time_frame>6 months</time_frame>
<description>Changes in serum NT-proBNP measurements from baseline</description>
</secondary_outcome>
<secondary_outcome>
<measure>Safety 1: pre dialysis hyperkalaemia</measure>
<time_frame>6 months</time_frame>
<description>Number of events: pre-dialysis hyperkalaemia (6.5 mmol/l or above)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Safety 2: severe hypertension</measure>
<time_frame>6 months</time_frame>
<description>Number of events: severe pre-dialysis hypertension (systolic BP > 180 and/or diastolic BP > 110 mmHg)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Safety 3: Inter-dialytic weight gain</measure>
<time_frame>6 months</time_frame>
<description>Number of events: interdialytic weight gain of greater than 4 kg</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">54</enrollment>
<condition>Renal Failure</condition>
<condition>Hemodialysis Complication</condition>
<condition>Morality</condition>
<arm_group>
<arm_group_label>Treatment arm</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Will receive trial intervention, Incremental haemodialysis (n=20)</description>
</arm_group>
<arm_group>
<arm_group_label>Control arm</arm_group_label>
<arm_group_type>Other</arm_group_type>
<description>Historical controls. Matched controls from database of historical patients receiving conventional, three times weekly haemodialysis treatment (n=40)</description>
</arm_group>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>Incremental haemodialysis</intervention_name>
<description>twice weekly haemodilysis at the start, gradually building up to full dose dialysis over a period of 15 weeks</description>
<arm_group_label>Treatment arm</arm_group_label>
</intervention>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>Conventional haemodialysis</intervention_name>
<description>three times weekly 4-hour long haemodialysis sessions from the start</description>
<arm_group_label>Control arm</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Age > 18

- patients with CKD-5 who are about to start planned HD

- At least 3 months of prior specialist renal follow-up at the time of starting HD

- Able to meet all the study requirements

- Written signed informed consent.

Exclusion Criteria:

- Age < 18

- No prior contact with nephrologists for > 3 months

- Cross-over in to HD from peritoneal dialysis

- Currently undergoing HD therapy

- Any condition which in the opinion of the investigator makes the participant
unsuitable for entry in to the study

- Participation in an interventional study in the preceding 6 weeks

- History of myocardial infarction in the preceding 3 months

- Inability to provide informed consent

- Inability to comply with the study schedule and follow-up.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<location>
<facility>
<name>Hull University Teaching Hospitals NHS Trust</name>
<address>
<city>Hull</city>
<state>East Yorkshire</state>
<zip>HU3 2JZ</zip>
<country>United Kingdom</country>
</address>
</facility>
</location>
<location_countries>
<country>United Kingdom</country>
</location_countries>
<verification_date>April 2022</verification_date>
<study_first_submitted>November 14, 2019</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>April 11, 2022</last_update_submitted>
<last_update_submitted_qc>April 11, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">April 18, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Renal Insufficiency</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>Undecided</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This feasibility study tests if patients find incremental HD acceptable, whether they
tolerate the treatment as planned and to evaluate its safety. Over a period of 18-months, 20
participants will be recruited in to the study who are about to start HD therapy for ESRD.
The participants will start HD incrementally (incremental HD group) reaching full dose HD
over a period of approximately 15 weeks. The outcomes will be compared to a cohort of 40
matched patients who previously started HD in the conventional manner (historical controls,
conventional HD group).
All patients will be followed-up for 6 months after first dialysis. Participants will be
reviewed regularly during this time, and will undergo laboratory and bed-site monitoring
tests. Acceptability and tolerance will be tested by documenting the numbers and percentages
of patients who agree to participate and continue in the study. Patients who decline the
invitation to join the study will be given the opportunity to express their reasons for
declining to go on incremental HD (they will not play further part in the study). The safety
of incremental HD will be tested by comparing the rates of pre-defined safety events in the
incremental HD vs. conventional HD groups.
The impact of incremental HD on patients' residual renal function will be monitored using
serial 24-hour urine collections, bio-impedance testing will be conducted to estimate changes
in fluid load, measurements of quality-of-life will be undertaken by using patient KDQOL-SF
v1.3 questionnaires. These tests will be repeated at regular intervals. Blood tests for
estimation of residual renal function and markers of renal anemia, bone disease and cardiac
load will be performed at regular intervals and will be compared between the two groups
(incremental HD vs. conventional HD groups). These measurements will help in the evaluation
of impact of incremental HD on patients' health and well-being. The completion rates of these
tests will provide important information about whether they should be included in a future
larger trial of incremental HD. Participants undergoing incremental HD will be invited to
take part in semi-structured interviews aimed at exploring patients' experiences of receiving
incremental HD and their participation in the study.
Data from this study will be used to test if it is feasible to use deaths (or a combination
of deaths and cardiovascular events) as the main outcome measure in a future definitive trial
on incremental HD. The data should enable a sample-size calculation for a future full-scale
trial.
Inclusion Criteria:
- Age > 18
- patients with CKD-5 who are about to start planned HD
- At least 3 months of prior specialist renal follow-up at the time of starting HD
- Able to meet all the study requirements
- Written signed informed consent.
Exclusion Criteria:
- Age < 18
- No prior contact with nephrologists for > 3 months
- Cross-over in to HD from peritoneal dialysis
- Currently undergoing HD therapy
- Any condition which in the opinion of the investigator makes the participant
unsuitable for entry in to the study
- Participation in an interventional study in the preceding 6 weeks
- History of myocardial infarction in the preceding 3 months
- Inability to provide informed consent
- Inability to comply with the study schedule and follow-up.
|
NCT0426xxxx/NCT04268277.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268277</url>
</required_header>
<id_info>
<org_study_id>POLE-1</org_study_id>
<nct_id>NCT04268277</nct_id>
</id_info>
<brief_title>Pembrolizumab in MarginalzoneLymphoma A MULTICENTER OPEN LABEL SINGLE-ARM PHASE II STUDY</brief_title>
<official_title>Pembrolizumab in Marginalzone Lymphoma A MULTICENTER OPEN LABEL SINGLE-ARM PHASE II STUDY</official_title>
<sponsors>
<lead_sponsor>
<agency>University of Ulm</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>X-act Cologne Clinical Research GmbH</agency>
<agency_class>Industry</agency_class>
</collaborator>
<collaborator>
<agency>Zentrum für Klinische Studien Ulm</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>Merck Sharp & Dohme LLC</agency>
<agency_class>Industry</agency_class>
</collaborator>
<collaborator>
<agency>Celltrion Healthcare Co., LTD</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>University of Ulm</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
For marginal zone lymphoma (MZL) Rituximab in combination with conventional chemotherapy is
widely used for those patients who fail local therapy or do not qualify for such. Depending
on the MZL subtype Rituximab/chemotherapy is able to induce in part long remissions, but does
not prevent relapse later on. In addition, chemotherapy associated toxicity is often
problematic in MZL patients, who are mostly of advanced age. Thus, chemotherapy-free
approaches are highly attractive for this patient group. Rituximab single agent is a widely
used chemotherapy-free approach in MZL, but was significantly inferior compared to
Rituximab/chlorambucil in a large randomized prospective clinical trial in treatment naïve
MZL with a CR rate of 55.8% vs. 78.8%, respectively (P < 0.001). Thus, it is the major aim to
develop chemotherapy-free approaches for MZL, which approach or surpass efficacy of
rituximab/chemotherapy combinations, but avoid chemotherapy associated toxicities.

Checkpoint inhibitors such as Pembrolizumab have revolutionized cancer treatment and have
also shown first encouraging results in Non-Hodgkin lymphomas. Based on these observations it
is the aim of this study to test the toxicity and efficacy of Pembrolizumab in combination
with the anti-CD20 antibody Rituximab in patients with newly diagnosed or relapsed MZL in
need of treatment, who are not eligible or failed local therapy, following the assumption
that this novel chemotherapy-free combination is significantly more efficient than Rituximab
single agent therapy and at least as efficient as rituximab/chemotherapy, but avoids
chemotherapy-related toxicity.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
For marginal zone lymphoma (MZL) Rituximab in combination with conventional chemotherapy is
widely used for those patients who fail local therapy or do not qualify for such. Depending
on the MZL subtype Rituximab/chemotherapy is able to induce in part long remissions, but does
not prevent relapse later on. In addition, chemotherapy associated toxicity is often
problematic in MZL patients, who are mostly of advanced age. Thus, chemotherapy-free
approaches are highly attractive for this patient group. Rituximab single agent is a widely
used chemotherapy-free approach in MZL, but was significantly inferior compared to
Rituximab/chlorambucil in a large randomized prospective clinical trial in treatment naïve
MZL with a CR rate of 55.8% vs. 78.8%, respectively (P < 0.001). Thus, it is the major aim to
develop chemotherapy-free approaches for MZL, which approach or surpass efficacy of
rituximab/chemotherapy combinations, but avoid chemotherapy associated toxicities.

Checkpoint inhibitors such as Pembrolizumab have revolutionized cancer treatment and have
also shown first encouraging results in Non-Hodgkin lymphomas. Based on these observations it
is the aim of this study to test the toxicity and efficacy of Pembrolizumab in combination
with the anti-CD20 antibody Rituximab in patients with newly diagnosed or relapsed MZL in
need of treatment, who are not eligible or failed local therapy, following the assumption
that this novel chemotherapy-free combination is significantly more efficient than Rituximab
single agent therapy and at least as efficient as rituximab/chemotherapy, but avoids
chemotherapy-related toxicity.

The objective of the trial is to test the efficacy and toxicity of treatment with
Pembrolizumab and Rituximab in patients with MZL in need of treatment, who have failed or are
not eligible for local therapy or relapsed. For efficacy the rate of complete remissions
(according to the GELA criteria for gastric MALT or to the Cheson 2007 criteria for nodal and
splenic MZL) after end of treatment (18 cycles) will be primarily analyzed. For toxicity
assessment treatment associated adverse events, quality of life and cumulative incidence of
secondary malignancies will be documented.

This study is a European multicenter, single-arm, open-label, phase II trial of 18 cycles of
Pembrolizumab and Rituximab in patients aged ≥ 18 years with previously untreated or relapsed
MZL in need of treatment.

Primary endpoint is the complete response (CR rate (CRR) determined after end of treatment
(18 cycles).

The study flow will be as follows:

- Previously untreated or relapsed patients will be screened for eligibility for the
trial. If the patient is eligible for the study, the patient will be registered before
the first cycle of treatment.

- Patients who progress at any time point during treatment are considered as treatment
failure. They will be followed up for overall survival until end of follow up period or
death.

- Patients, who achieve at least a SD after treatment will be followed up for response
until progression/relapse and for overall survival until death.

It is expected that a total of 56 patients at approximately 15 investigator sites in Germany
and 3 centers in Austria will be registered. Every patient will receive treatment over a time
period of 18 cycles (each cycle lasts 3 weeks). Subsequently, patients will be monitored
every 3 months for 2 additional years, subsequently every 6 months for three additional
years. The follow-up phase will be shorter than 5 years if End of Study is reached before
this time period.
</textblock>
</detailed_description>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">March 1, 2022</start_date>
<completion_date type="Anticipated">April 2029</completion_date>
<primary_completion_date type="Anticipated">April 2029</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>CR rate</measure>
<time_frame>12 months</time_frame>
<description>CR rate (CRR) after end of treatment (18 cycles)</description>
</primary_outcome>
<secondary_outcome>
<measure>Response rate</measure>
<time_frame>58 weeks</time_frame>
<description>The response rates are evaluated 4 weeks after the end of treatment</description>
</secondary_outcome>
<secondary_outcome>
<measure>Best response</measure>
<time_frame>54 weeks</time_frame>
<description>Best response is determined in the time interval from the start of induction therapy to end of follow-up.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Time to best response</measure>
<time_frame>54 weeks</time_frame>
<description>Time to best response is defined as the time from the start of induction to best response the patient achieves (CR, PR)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Time to first response</measure>
<time_frame>54 weeks</time_frame>
<description>Time to first response is defined as the time from the start of induction to first response (CR, PR)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Progression free survival (PFS)</measure>
<time_frame>54 weeks</time_frame>
<description>Progression free survival (PFS) is defined as the time from registration to the first occurrence of progression or relapse as assessed by the investigator, or death from any cause. PFS for patients without disease progression, relapse, or death will be censored at the time of the last tumor assessment.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Time to treatment failure (TTF)</measure>
<time_frame>54 weeks</time_frame>
<description>Time to treatment failure is defined as the time of registration to discontinuation of therapy for any reason including death from any cause, progression, toxicity or add-on of new anti-cancer therapy. Patients alive without treatment failure are censored at the latest tumor assessment date.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Duration of Response (DR)</measure>
<time_frame>54 weeks</time_frame>
<description>Duration of response will be calculated in patients with response (CR, PR) to induction from end of induction to the date of progression, relapse or death from any cause. Patients alive without progression and relapse will be censored at the latest tumor assessment date or the stopping date.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Cause specific survival (CSS)</measure>
<time_frame>54 weeks</time_frame>
<description>Cause specific survivial is defined as the period from the induction registration to death from lymphoma or lymphoma related cause; death unrelated to MZL is considered as a competing event.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Overall survival (OS)</measure>
<time_frame>54 weeks</time_frame>
<description>Overall survival is defined as the period from the induction registration to death from any cause. Patients who have not died until the time of the analysis will be censored at their last contact date.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Quality of life during trial</measure>
<time_frame>54 weeks</time_frame>
<description>Quality of life will be measured by the FACT Lym before start of treatment and during trial participation.</description>
</secondary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Anticipated">56</enrollment>
<condition>Marginal Zone Lymphoma</condition>
<arm_group>
<arm_group_label>Rituximab & Pembrolizumab</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Cycle 1 (21 days cycle):
Rituximab: 375 mg/m2 day 1, 8, 15 Pembrolizumab: 200 mg IV fixed dose day 2
Cycle 2-18 (21 days cycle) or until progression or non-tolerable toxicity:
Rituximab: 375 mg/m2 day 1 every second cycle Pembrolizumab: 200 mg IV fixed dose day 1</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Rituximab</intervention_name>
<description>100 mg concentrate for solution for infusion</description>
<arm_group_label>Rituximab & Pembrolizumab</arm_group_label>
<other_name>Truxima</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Pembrolizumab</intervention_name>
<description>100 mg/ 4mL concentrate for solution for infusion</description>
<arm_group_label>Rituximab & Pembrolizumab</arm_group_label>
<other_name>Keytruda</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

Patients must have a proven pathological diagnosis of MZL, diagnosed by a reference
pathology center.

Patients must meet the following inclusion criteria to be eligible for participation in
this study:

- Confirmed CD20 positive de novo or relapsed MALT Lymphoma in need of treatment
following or being not eligible for local therapy (including surgery, radiotherapy and
antibiotics e.g. for H. pylori-positive gastric lymphoma arisen at any extranodal
site) OR

- Confirmed CD20 positive de novo or relapsed splenic MZL in need of treatment following
or not being eligible for local therapy (including surgery and antiviral therapy for
Hepatitis C Virus) OR

- Confirmed CD20 positive de novo or relapsed nodal MZL in need of treatment following
or not being eligible for local therapy (radiotherapy). The need of treatment is
applicable in the case of B symptoms, deterioration of peripheral blood counts due to
lymphoma infiltration of the bone marrow, rapid enlargement of lymph nodes or
compression of vital organs by bulky disease.

For nodal MZL and extragastric MALT lymphoma:

• At least one bi-dimensionally measurable lesion (>=1.5 cm in its largest dimension by
CT/PET-CT scan or MRI)

For splenic MZL (SMZL):

In patients with splenic MZL, an enlarged spleen on CT scan and lymphoma cell infiltration
has to be seen in bone marrow and/or peripheral blood.

At least one of the following criteria must be fulfilled:

- Bulky progressive or painful splenomegaly

- one of the following symptomatic/progressive cytopenias: Hb < 10 g/dL, or Platelet
count < 80.000 /µL, or neutropenia < 1000 /µL, whatever the reason (autoimmune or
hypersplenism or bone marrow infiltration)

- splenectomised patients with rapidly raising lymphocyte counts, development of
lymphadenopathy or involvement of extranodal sites if not being eligible for local
therapy

- SMZL with concomitant hepatitis C infection which has not responded to or has relapsed
after Interferon and/or Ribavirin and/or direct antiviral agents (patients positive
for HCV antibody are eligible only if PCR is negative for HCV RNA)

For gastric MALT Lymphoma:

For gastric MALT lymphoma, the clinical evidence of the MZL as seen by gastroendoscopy is
sufficient. There is no need to show a measurable lesion by CT scan or MRI.

Inclusion is possible for patients with:

- H. pylori-negative cases following or being not eligible for local therapy (i.e.,
surgery, radiotherapy or antibiotics) or after systemic therapy

- H. pylori-positive disease that has remained stable, progressed, or relapsed following
antibiotic therapy

Others:

- Age ≥ 18 years

- Life expectancy > 3 months

- Meet the following pretreatment laboratory criteria at the Screening visit conducted
within 28 days of study enrollment (unless due to underlying lymphoma):

- Baseline platelet count ≥ 75 x 109/L (if not due to BM infiltration by the
lymphoma), absolute neutrophil count ≥ 1.5 x 109/L.

- Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (Criteria must be met without
erythropoietin dependency and without packed red blood cell (pRBC) transfusion
within last 2 weeks)

- International Normalized Ratio (INR) or Prothrombin Time (PT): ≤ 1.5 × ULN unless
subject is receiving anticoagulant therapy as long as PT or PTT is within
therapeutic range of intended use of anticoagulants

- Activated Partial Thromboplastin Time (aPTT): ≤ 1.5 × ULN unless subject is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
of intended use of anticoagulants

- ASAT (SGOT): ≤ 2.5 times the upper limit of institutional laboratory normal value
or ≤ 5 times the upper limit of institutional laboratory normal value in subjects
with lymphoma in the liver.

- ALAT (SGPT): ≤ 2,5 times the upper limit of institutional laboratory normal value
or ≤ 5 times the upper limit of institutional laboratory normal value in subjects
with lymphoma in the liver

- Serum total bilirubin: ≤ 1.5 × ULN OR Direct bilirubin ≤ ULN for subjects with
total bilirubin levels > 1.5 ULN (unless clearly related to the disease)

- Serum creatinine ≤ 1.5 × ULN OR ≥ 60 mL/min GFR or CrCl for subjects with
creatinine levels > 1.5 × institutional ULN

- Negative HIV antibody

- Patients with occult or prior HBV infection (defined as negative HBsAg and
positive total HBcAb) may be included if HBV DNA is undetectable, provided that
they are willing to undergo monthly DNA testing. Patients who have protective
titers of HBSAb after vaccination or prior but cured hepatitis B are eligible.

- Patients positive for HCV antibody are eligible only if PCR is negative for HCV
RNA.

- For women of child-bearing potential only: Pregnancy β-HCG negative. Serum or
urine β-HCG must be negative during screening and at study enrolment visit.

- Premenopausal fertile females must agree to use a highly effective method of birth
control for the duration of the therapy up to 12 months after the last dose of
Rituximab and through 4 months after the last dose of Pembrolizumab. A highly
effective method of birth control is defined as those which results in a low failure
rate (i.e. less than 1% per year) when used consistently and correctly such as
combined (estrogen and progestogen containing) hormonal contraception associated with
inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal
contraception associated with inhibition of ovulation (oral, injectable or
implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS),
bilateral tubal occlusion, vasectomised partner or sexual abstinence. Contraception
and pregnancy testing are required according the CTFG recommendations
(http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/
2014_09_HMA_CTFG_Contraception.pdf)

- Men must agree not to father a child for the duration of therapy and 6 months after
and must agree to advice a female partner to use a highly effective method of birth
control. According to CTFG recommendations, men must use condoms.

- Willingness and ability to comply with scheduled visits, drug administration plan,
imaging studies, laboratory tests, other study procedures, and study restrictions

- Evidence of a personally signed informed consent indicating that the subject is aware
of the neoplastic nature of the disease and has been informed of the procedures to be
followed, the experimental nature of the therapy, alternatives, potential benefits,
possible side effects, potential risks and discomforts, and other pertinent aspects of
study participation

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrolment:

- ECOG performance status ≥ 2

- History of a malignancy except for the following: adequately treated local basal cell
or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial
bladder cancer, asymptomatic prostate cancer without known metastatic disease and with
no requirement for therapy or requiring only hormonal therapy and with normal prostate
specific antigen for ≥ 1 year prior to study enrolment visit, other malignancy treated
with a curative intent and currently in complete remission, for ≥ 3 years

- Central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence of
transformation to a high-grade or diffuse large B-cell lymphoma

- Has had prior chemotherapy (systemic anti-cancer therapy), targeted small molecule
therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not
recovered (i.e., ≤ Grade 1 or baseline value) from AEs due to a previously
administered agent

- Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and
may qualify for the study

- Note: If a subject received major surgery, they must have recovered adequately
from complications from the intervention prior to starting therapy

- Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of
study enrolment visit

- Ongoing drug-induced liver injury, chronic active hepatitis B (HBV), alcoholic liver
disease, non-alcoholic steatohepatitis, primary biliary cholangitis, extrahepatic
obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension

- Treatment with any other investigational agent or participating in another clinical
trial with an investigational product within 4 weeks prior to entering this study or
within 5 x the half-life (t1/2) of the investigational product, whichever is longer

- Breastfeeding or Pregnancy

- Congestive heart failure > New York Heart Association (NYHA) class 2

- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3
months)

- Myocardial infarction less than 6 months before start of study medication

- Uncontrolled arterial hypertension despite optimal medical management

- Prior or ongoing clinically significant illness, medical condition, surgical history,
physical finding, electrocardiogram (ECG) finding, or laboratory abnormality that, in
the investigator's opinion, could adversely affect the safety of the subject or impair
the assessment of study results

- Vaccination with a live vaccine within 30 days prior to start of therapy

- Arterial or venous thrombotic or embolic events such as cerebrovascular accident
(including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
within 3 months before the start of study medication

- Non-healing wound, ulcer, or bone fracture

- History or concurrent interstitial lung disease of any severity and/or severely
impaired lung function (as judged by the investigator)

- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
CTLA-4, OX 40, CD137)

- Has received prior radiotherapy within 2 weeks of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease

- Has known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days prior to
first dose of study treatment

- Has a history of non-infectious pneumonitis that required steroids, or current
pneumonitis

- History of anaphylaxis in association with previous administration of monoclonal
antibodies or severe hypersensitivity (≥Grade 3) to the investigational medicinal
products and/or any of its excipients

- Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment

- Has a known history of active TB (Bacillus Tuberculosis)

- Medical history of allogeneic stem cell transplant

- Ongoing alcohol or drug addiction or known psychiatric or substance abuse disorders
that would interfere with cooperation with the requirements of the trial

- Diagnosis of Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Christian Buske, Prof. Dr.</last_name>
<role>Principal Investigator</role>
<affiliation>University Hospital of Ulm Department of Internal Medicine III</affiliation>
</overall_official>
<overall_contact>
<last_name>Ivonne Kriebisch</last_name>
<phone>+4973150065834</phone>
<email>studien.gla@uniklinik-ulm.de</email>
</overall_contact>
<location>
<facility>
<name>Medizinische Universität Graz, Hämatologie</name>
<address>
<city>Graz</city>
<zip>8036</zip>
<country>Austria</country>
</address>
</facility>
<status>Not yet recruiting</status>
<contact>
<last_name>Peter Neumeister, Univ. Prof.</last_name>
</contact>
</location>
<location>
<facility>
<name>Medizinische Universität Wien, Innere Medizin I, Abteilung Onkologie</name>
<address>
<city>Wien</city>
<zip>1090</zip>
<country>Austria</country>
</address>
</facility>
<status>Not yet recruiting</status>
<contact>
<last_name>Markus Raderer, Prof. Dr.</last_name>
</contact>
</location>
<location>
<facility>
<name>Universitätsklinikum Ulm; Klinik für Innere Medizin Innere Medizin III</name>
<address>
<city>Ulm</city>
<state>Baden- Württemberg</state>
<zip>89081</zip>
<country>Germany</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Christian Buske, Prof.Dr.</last_name>
<email>christian.buske@uniklinik-ulm.de</email>
</contact>
</location>
<location>
<facility>
<name>Charité Universitätsmedizin Berlin; Hämatologie - Onkologie - Tumorimmunologie</name>
<address>
<city>Berlin</city>
<zip>12200</zip>
<country>Germany</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Corinna Leng, Dr.</last_name>
</contact>
</location>
<location>
<facility>
<name>Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III</name>
<address>
<city>Chemnitz</city>
<zip>09116</zip>
<country>Germany</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Mathias Hänel, PD Dr.</last_name>
</contact>
</location>
<location>
<facility>
<name>Gemeinschaftspraxis Dr. med. Johannes Mohm, Dr. med. Gabriele Prange-Krex</name>
<address>
<city>Dresden</city>
<zip>01307</zip>
<country>Germany</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Gabriele Prange-Krex, Dr. med.</last_name>
</contact>
</location>
<location>
<facility>
<name>Kliniken Maria Hilf GmbH; Klinik für Hämatologie, Onkologie und Gastroenterologie</name>
<address>
<city>Mönchengladbach</city>
<zip>41063</zip>
<country>Germany</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Ullrich Graeven, Prof. Dr.</last_name>
</contact>
</location>
<location>
<facility>
<name>Klinikum rechts der Isar der TU München, Klinik und Poliklinik für Innere Medizin III</name>
<address>
<city>München</city>
<zip>81675</zip>
<country>Germany</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Simon Heidegger, PD Dr.</last_name>
</contact>
</location>
<location>
<facility>
<name>Gemeinschaftspraxis für Hämatologie und Onkologie</name>
<address>
<city>Münster</city>
<zip>48149</zip>
<country>Germany</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Rüdiger Liersch, PD Dr.</last_name>
</contact>
</location>
<location>
<facility>
<name>Klinikum Oldenburg AöR, Universitätsklinik für Innere Medizin, Onkologie und Hämatologie</name>
<address>
<city>Oldenburg</city>
<zip>26133</zip>
<country>Germany</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Andreas Voss</last_name>
</contact>
</location>
<location>
<facility>
<name>Brüderkrankenhaus St. Josef, Klinik für Hämatologie und Onkologie</name>
<address>
<city>Paderborn</city>
<zip>33098</zip>
<country>Germany</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Tobias Gaska, Dr. med.</last_name>
</contact>
</location>
<location>
<facility>
<name>Klinikum Passau, II. Medizinische Klinik - Hämatologie, Onkologie und Palliativmedizin</name>
<address>
<city>Passau</city>
<zip>94032</zip>
<country>Germany</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Thomas Südhoff, Prof. Dr.</last_name>
</contact>
</location>
<location>
<facility>
<name>RoMed Klinikum Rosenheim, Med. Klinik II / OTK</name>
<address>
<city>Rosenheim</city>
<zip>83002</zip>
<country>Germany</country>
</address>
</facility>
<status>Not yet recruiting</status>
<contact>
<last_name>Gerhard Puchtler, Dr.</last_name>
</contact>
</location>
<location>
<facility>
<name>Robert-Bosch-Krankenhaus; Hämatologie, Onkologie und Palliativmedizin</name>
<address>
<city>Stuttgart</city>
<zip>70376</zip>
<country>Germany</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Alexander Stehle, Dr.</last_name>
</contact>
</location>
<location_countries>
<country>Austria</country>
<country>Germany</country>
</location_countries>
<verification_date>June 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>June 29, 2023</last_update_submitted>
<last_update_submitted_qc>June 29, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">July 3, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>University of Ulm</investigator_affiliation>
<investigator_full_name>Christian Buske</investigator_full_name>
<investigator_title>Prof. Dr.</investigator_title>
</responsible_party>
<keyword>Hematology</keyword>
<keyword>Oncology</keyword>
<keyword>Relapse</keyword>
<keyword>MALT</keyword>
<keyword>Pembrolizumab</keyword>
<keyword>Rituximab</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Lymphoma</mesh_term>
<mesh_term>Lymphoma, B-Cell, Marginal Zone</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Rituximab</mesh_term>
<mesh_term>Pembrolizumab</mesh_term>
</intervention_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
For marginal zone lymphoma (MZL) Rituximab in combination with conventional chemotherapy is
widely used for those patients who fail local therapy or do not qualify for such. Depending
on the MZL subtype Rituximab/chemotherapy is able to induce in part long remissions, but does
not prevent relapse later on. In addition, chemotherapy associated toxicity is often
problematic in MZL patients, who are mostly of advanced age. Thus, chemotherapy-free
approaches are highly attractive for this patient group. Rituximab single agent is a widely
used chemotherapy-free approach in MZL, but was significantly inferior compared to
Rituximab/chlorambucil in a large randomized prospective clinical trial in treatment naïve
MZL with a CR rate of 55.8% vs. 78.8%, respectively (P < 0.001). Thus, it is the major aim to
develop chemotherapy-free approaches for MZL, which approach or surpass efficacy of
rituximab/chemotherapy combinations, but avoid chemotherapy associated toxicities.
Checkpoint inhibitors such as Pembrolizumab have revolutionized cancer treatment and have
also shown first encouraging results in Non-Hodgkin lymphomas. Based on these observations it
is the aim of this study to test the toxicity and efficacy of Pembrolizumab in combination
with the anti-CD20 antibody Rituximab in patients with newly diagnosed or relapsed MZL in
need of treatment, who are not eligible or failed local therapy, following the assumption
that this novel chemotherapy-free combination is significantly more efficient than Rituximab
single agent therapy and at least as efficient as rituximab/chemotherapy, but avoids
chemotherapy-related toxicity.
For marginal zone lymphoma (MZL) Rituximab in combination with conventional chemotherapy is
widely used for those patients who fail local therapy or do not qualify for such. Depending
on the MZL subtype Rituximab/chemotherapy is able to induce in part long remissions, but does
not prevent relapse later on. In addition, chemotherapy associated toxicity is often
problematic in MZL patients, who are mostly of advanced age. Thus, chemotherapy-free
approaches are highly attractive for this patient group. Rituximab single agent is a widely
used chemotherapy-free approach in MZL, but was significantly inferior compared to
Rituximab/chlorambucil in a large randomized prospective clinical trial in treatment naïve
MZL with a CR rate of 55.8% vs. 78.8%, respectively (P < 0.001). Thus, it is the major aim to
develop chemotherapy-free approaches for MZL, which approach or surpass efficacy of
rituximab/chemotherapy combinations, but avoid chemotherapy associated toxicities.
Checkpoint inhibitors such as Pembrolizumab have revolutionized cancer treatment and have
also shown first encouraging results in Non-Hodgkin lymphomas. Based on these observations it
is the aim of this study to test the toxicity and efficacy of Pembrolizumab in combination
with the anti-CD20 antibody Rituximab in patients with newly diagnosed or relapsed MZL in
need of treatment, who are not eligible or failed local therapy, following the assumption
that this novel chemotherapy-free combination is significantly more efficient than Rituximab
single agent therapy and at least as efficient as rituximab/chemotherapy, but avoids
chemotherapy-related toxicity.
The objective of the trial is to test the efficacy and toxicity of treatment with
Pembrolizumab and Rituximab in patients with MZL in need of treatment, who have failed or are
not eligible for local therapy or relapsed. For efficacy the rate of complete remissions
(according to the GELA criteria for gastric MALT or to the Cheson 2007 criteria for nodal and
splenic MZL) after end of treatment (18 cycles) will be primarily analyzed. For toxicity
assessment treatment associated adverse events, quality of life and cumulative incidence of
secondary malignancies will be documented.
This study is a European multicenter, single-arm, open-label, phase II trial of 18 cycles of
Pembrolizumab and Rituximab in patients aged ≥ 18 years with previously untreated or relapsed
MZL in need of treatment.
Primary endpoint is the complete response (CR rate (CRR) determined after end of treatment
(18 cycles).
The study flow will be as follows:
- Previously untreated or relapsed patients will be screened for eligibility for the
trial. If the patient is eligible for the study, the patient will be registered before
the first cycle of treatment.
- Patients who progress at any time point during treatment are considered as treatment
failure. They will be followed up for overall survival until end of follow up period or
death.
- Patients, who achieve at least a SD after treatment will be followed up for response
until progression/relapse and for overall survival until death.
It is expected that a total of 56 patients at approximately 15 investigator sites in Germany
and 3 centers in Austria will be registered. Every patient will receive treatment over a time
period of 18 cycles (each cycle lasts 3 weeks). Subsequently, patients will be monitored
every 3 months for 2 additional years, subsequently every 6 months for three additional
years. The follow-up phase will be shorter than 5 years if End of Study is reached before
this time period.
Inclusion Criteria:
Patients must have a proven pathological diagnosis of MZL, diagnosed by a reference
pathology center.
Patients must meet the following inclusion criteria to be eligible for participation in
this study:
- Confirmed CD20 positive de novo or relapsed MALT Lymphoma in need of treatment
following or being not eligible for local therapy (including surgery, radiotherapy and
antibiotics e.g. for H. pylori-positive gastric lymphoma arisen at any extranodal
site) OR
- Confirmed CD20 positive de novo or relapsed splenic MZL in need of treatment following
or not being eligible for local therapy (including surgery and antiviral therapy for
Hepatitis C Virus) OR
- Confirmed CD20 positive de novo or relapsed nodal MZL in need of treatment following
or not being eligible for local therapy (radiotherapy). The need of treatment is
applicable in the case of B symptoms, deterioration of peripheral blood counts due to
lymphoma infiltration of the bone marrow, rapid enlargement of lymph nodes or
compression of vital organs by bulky disease.
For nodal MZL and extragastric MALT lymphoma:
• At least one bi-dimensionally measurable lesion (>=1.5 cm in its largest dimension by
CT/PET-CT scan or MRI)
For splenic MZL (SMZL):
In patients with splenic MZL, an enlarged spleen on CT scan and lymphoma cell infiltration
has to be seen in bone marrow and/or peripheral blood.
At least one of the following criteria must be fulfilled:
- Bulky progressive or painful splenomegaly
- one of the following symptomatic/progressive cytopenias: Hb < 10 g/dL, or Platelet
count < 80.000 /µL, or neutropenia < 1000 /µL, whatever the reason (autoimmune or
hypersplenism or bone marrow infiltration)
- splenectomised patients with rapidly raising lymphocyte counts, development of
lymphadenopathy or involvement of extranodal sites if not being eligible for local
therapy
- SMZL with concomitant hepatitis C infection which has not responded to or has relapsed
after Interferon and/or Ribavirin and/or direct antiviral agents (patients positive
for HCV antibody are eligible only if PCR is negative for HCV RNA)
For gastric MALT Lymphoma:
For gastric MALT lymphoma, the clinical evidence of the MZL as seen by gastroendoscopy is
sufficient. There is no need to show a measurable lesion by CT scan or MRI.
Inclusion is possible for patients with:
- H. pylori-negative cases following or being not eligible for local therapy (i.e.,
surgery, radiotherapy or antibiotics) or after systemic therapy
- H. pylori-positive disease that has remained stable, progressed, or relapsed following
antibiotic therapy
Others:
- Age ≥ 18 years
- Life expectancy > 3 months
- Meet the following pretreatment laboratory criteria at the Screening visit conducted
within 28 days of study enrollment (unless due to underlying lymphoma):
- Baseline platelet count ≥ 75 x 109/L (if not due to BM infiltration by the
lymphoma), absolute neutrophil count ≥ 1.5 x 109/L.
- Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (Criteria must be met without
erythropoietin dependency and without packed red blood cell (pRBC) transfusion
within last 2 weeks)
- International Normalized Ratio (INR) or Prothrombin Time (PT): ≤ 1.5 × ULN unless
subject is receiving anticoagulant therapy as long as PT or PTT is within
therapeutic range of intended use of anticoagulants
- Activated Partial Thromboplastin Time (aPTT): ≤ 1.5 × ULN unless subject is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
of intended use of anticoagulants
- ASAT (SGOT): ≤ 2.5 times the upper limit of institutional laboratory normal value
or ≤ 5 times the upper limit of institutional laboratory normal value in subjects
with lymphoma in the liver.
- ALAT (SGPT): ≤ 2,5 times the upper limit of institutional laboratory normal value
or ≤ 5 times the upper limit of institutional laboratory normal value in subjects
with lymphoma in the liver
- Serum total bilirubin: ≤ 1.5 × ULN OR Direct bilirubin ≤ ULN for subjects with
total bilirubin levels > 1.5 ULN (unless clearly related to the disease)
- Serum creatinine ≤ 1.5 × ULN OR ≥ 60 mL/min GFR or CrCl for subjects with
creatinine levels > 1.5 × institutional ULN
- Negative HIV antibody
- Patients with occult or prior HBV infection (defined as negative HBsAg and
positive total HBcAb) may be included if HBV DNA is undetectable, provided that
they are willing to undergo monthly DNA testing. Patients who have protective
titers of HBSAb after vaccination or prior but cured hepatitis B are eligible.
- Patients positive for HCV antibody are eligible only if PCR is negative for HCV
RNA.
- For women of child-bearing potential only: Pregnancy β-HCG negative. Serum or
urine β-HCG must be negative during screening and at study enrolment visit.
- Premenopausal fertile females must agree to use a highly effective method of birth
control for the duration of the therapy up to 12 months after the last dose of
Rituximab and through 4 months after the last dose of Pembrolizumab. A highly
effective method of birth control is defined as those which results in a low failure
rate (i.e. less than 1% per year) when used consistently and correctly such as
combined (estrogen and progestogen containing) hormonal contraception associated with
inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal
contraception associated with inhibition of ovulation (oral, injectable or
implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS),
bilateral tubal occlusion, vasectomised partner or sexual abstinence. Contraception
and pregnancy testing are required according the CTFG recommendations
(http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/
2014_09_HMA_CTFG_Contraception.pdf)
- Men must agree not to father a child for the duration of therapy and 6 months after
and must agree to advice a female partner to use a highly effective method of birth
control. According to CTFG recommendations, men must use condoms.
- Willingness and ability to comply with scheduled visits, drug administration plan,
imaging studies, laboratory tests, other study procedures, and study restrictions
- Evidence of a personally signed informed consent indicating that the subject is aware
of the neoplastic nature of the disease and has been informed of the procedures to be
followed, the experimental nature of the therapy, alternatives, potential benefits,
possible side effects, potential risks and discomforts, and other pertinent aspects of
study participation
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrolment:
- ECOG performance status ≥ 2
- History of a malignancy except for the following: adequately treated local basal cell
or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial
bladder cancer, asymptomatic prostate cancer without known metastatic disease and with
no requirement for therapy or requiring only hormonal therapy and with normal prostate
specific antigen for ≥ 1 year prior to study enrolment visit, other malignancy treated
with a curative intent and currently in complete remission, for ≥ 3 years
- Central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence of
transformation to a high-grade or diffuse large B-cell lymphoma
- Has had prior chemotherapy (systemic anti-cancer therapy), targeted small molecule
therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not
recovered (i.e., ≤ Grade 1 or baseline value) from AEs due to a previously
administered agent
- Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and
may qualify for the study
- Note: If a subject received major surgery, they must have recovered adequately
from complications from the intervention prior to starting therapy
- Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of
study enrolment visit
- Ongoing drug-induced liver injury, chronic active hepatitis B (HBV), alcoholic liver
disease, non-alcoholic steatohepatitis, primary biliary cholangitis, extrahepatic
obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension
- Treatment with any other investigational agent or participating in another clinical
trial with an investigational product within 4 weeks prior to entering this study or
within 5 x the half-life (t1/2) of the investigational product, whichever is longer
- Breastfeeding or Pregnancy
- Congestive heart failure > New York Heart Association (NYHA) class 2
- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3
months)
- Myocardial infarction less than 6 months before start of study medication
- Uncontrolled arterial hypertension despite optimal medical management
- Prior or ongoing clinically significant illness, medical condition, surgical history,
physical finding, electrocardiogram (ECG) finding, or laboratory abnormality that, in
the investigator's opinion, could adversely affect the safety of the subject or impair
the assessment of study results
- Vaccination with a live vaccine within 30 days prior to start of therapy
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident
(including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
within 3 months before the start of study medication
- Non-healing wound, ulcer, or bone fracture
- History or concurrent interstitial lung disease of any severity and/or severely
impaired lung function (as judged by the investigator)
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
CTLA-4, OX 40, CD137)
- Has received prior radiotherapy within 2 weeks of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days prior to
first dose of study treatment
- Has a history of non-infectious pneumonitis that required steroids, or current
pneumonitis
- History of anaphylaxis in association with previous administration of monoclonal
antibodies or severe hypersensitivity (≥Grade 3) to the investigational medicinal
products and/or any of its excipients
- Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment
- Has a known history of active TB (Bacillus Tuberculosis)
- Medical history of allogeneic stem cell transplant
- Ongoing alcohol or drug addiction or known psychiatric or substance abuse disorders
that would interfere with cooperation with the requirements of the trial
- Diagnosis of Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)
|
NCT0426xxxx/NCT04268290.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268290</url>
</required_header>
<id_info>
<org_study_id>NFEC-2019-156</org_study_id>
<nct_id>NCT04268290</nct_id>
</id_info>
<brief_title>Single Incision Plus One Port Laparoscopic Surgery Assistant Enhanced Recovery After Surgery on Colorectal Cancer</brief_title>
<official_title>Effect of Single Incision Plus One Port Laparoscopic Surgery Assistant Enhanced Recovery After Surgery on Colorectal Cancer : A Single Arm Trial</official_title>
<sponsors>
<lead_sponsor>
<agency>Nanfang Hospital, Southern Medical University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Nanfang Hospital, Southern Medical University</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Conventional laparoscopic surgery (CLS) for colorectal cancer has been demonstrated to be
safe and feasible and present minimally invasive benefits including faster recovery, reduced
postoperative pain and shorter hospital stay, also acquiring comparable oncologic outcomes
with open surgery. To achieve further minimally invasive outcomes, SILS plus one port surgery
was attempted by some surgeons. Preliminary results showed that SILS+1 could achieve better
minimally invasive benefits than CLS while preserving oncologic feasibility.

Till now, ERAS has been practiced in colorectal cancer surgery for approximately 20 years.
Studies have proven that ERAS is safe and significantly improved the recovery course of
patients during perioperative period, meanwhile, the expense could be greatly reduced.

Based on ERAS studies protocols and SILS+1 trials, investigators tried to combine SILS+1 with
ERAS, hopefully to provide patients with more safe, economic, feasible and rapid surgery and
perioperative strategies.
</textblock>
</brief_summary>
<overall_status>Unknown status</overall_status>
<last_known_status>Not yet recruiting</last_known_status>
<start_date type="Anticipated">February 15, 2020</start_date>
<completion_date type="Anticipated">February 15, 2022</completion_date>
<primary_completion_date type="Anticipated">February 15, 2022</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Rehabilitative rate</measure>
<time_frame>4 days</time_frame>
<description>The percentage of patients who met discharge criteria in the fourth day after surgery</description>
</primary_outcome>
<primary_outcome>
<measure>Postoperative hospital stays</measure>
<time_frame>1 month</time_frame>
<description>Days from surgery to discharge</description>
</primary_outcome>
<secondary_outcome>
<measure>Medical cost</measure>
<time_frame>1 month</time_frame>
<description>The patient's expenses from surgery to discharge are recorded in RMB "yuan"</description>
</secondary_outcome>
<secondary_outcome>
<measure>Postoperative pain score</measure>
<time_frame>Once a day from 6 hours to the fourth day after surgery</time_frame>
<description>Postoperative pain is recorded using the visual analog scale (VAS) pain score tool on postoperative day . On a scale of 1 to 10, the higher the score, the greater the pain.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Postoperative recovery index</measure>
<time_frame>1 month</time_frame>
<description>The first Time to early mobilization(hour), flatus(hour), liquid diet(hour), soft diet(hour), removal of the Nasogastric tubes(hour) , removal of the peritoneal drainage(hour) are used to assess the postoperative recovery</description>
</secondary_outcome>
<secondary_outcome>
<measure>Postoperative inflammatory immune response</measure>
<time_frame>3 days</time_frame>
<description>It includes the number of white blood cells and lymphocytes,CRP, IL-6</description>
</secondary_outcome>
<secondary_outcome>
<measure>compliance with ERAS measures</measure>
<time_frame>perioperative</time_frame>
<description>It is defined as if the patients complete every ERAS measure or not. We can defined it "yes " or "not".</description>
</secondary_outcome>
<secondary_outcome>
<measure>6 min postoperative walking test(6MWT)</measure>
<time_frame>Once a day from the frist to the fourth day after surgery</time_frame>
<description>Study site, subject preparation, trial procedures, and medical monitoring refer to the 6MWT guidelines issued by the American thoracic society in 2002.</description>
</secondary_outcome>
<secondary_outcome>
<measure>hospital readmissions</measure>
<time_frame>30days</time_frame>
<description>It can be defined as the number of patients readmitted within 30 days because of postoperative complications.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Morbidity and mortality rates</measure>
<time_frame>30 days</time_frame>
<description>Morbidity and mortality rates are defined as postoperative complications graded according to Clavien-Dindo within 30 days.</description>
</secondary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Anticipated">120</enrollment>
<condition>Colorectal Cancer</condition>
<arm_group>
<arm_group_label>SILS plus one assistant ERAS</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Preoperative:
preadmission information, education, counseling, optimization ( breathing training), shortening fasting time and carbohydrate load
Intraoperative:
The intravenous fluid therapy is restricted. All patients undergo single incision plus one port laparoscopic surgery(SILS plus one).
A suitable warming device (such as forced-air heating blankets) and warmed intravenous fluids are been adopted routinely to keep body temperature
Postoperative:
multimodal analgesia (surgical site infiltration, a nonsteroidal anti-inflammatory drug, epidural analgesia) early oral intake and move. nasogastric tubes should not be used routinely. Nasogastric tubes inserted during surgery are been removed before reversal of an aesthesia.</description>
</arm_group>
<intervention>
<intervention_type>Combination Product</intervention_type>
<intervention_name>Single incision plus one port laparoscopic surgery</intervention_name>
<description>SILS plus one port surgery and enhanced recovery after surgery protocol both are methods taking the minimally invasive benefits for the patients including faster recovery, reduced postoperative pain and shorter hospital stay.</description>
<arm_group_label>SILS plus one assistant ERAS</arm_group_label>
<other_name>The program of enhanced recovery After Surgery</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Primary tumor diagnosed as adenocarcinoma confirmed pathologically by endoscopic
biopsy

- cT1-4a, N0-3, M0 at preoperative evaluation according to the AJCC Cancer Staging
Manual Seventh Edition

- Located in the cecum, ascending colon, transverse colon, descending colon, sigmoid
colon, the upper segment of the rectum.

- Diameter ≦ 5cm

- No severe organ dysfunction

- Performance status of 0 or 1 on ECOG (Eastern Cooperative Oncology Group) scale

- ASA (American Society of Anesthesiology) score class I or II

- Written informed consent

Exclusion Criteria:

- Unsuitable for patients undergoing single incision plus one port laparoscopic surgery

- Patients with Complications caused by colorectal cancer ( bleeding , perforation,
obstruction or incomplete obstruction )

- Previous abdominal surgery

- Malignant diseases within the past 5years

- Requirements of simultaneous surgery for another diseases
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>75 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Wang Yannan, M.D</last_name>
<role>Principal Investigator</role>
<affiliation>Nanfang Hospital, Southern Medical University</affiliation>
</overall_official>
<overall_contact>
<last_name>Wang Yanan, M.D</last_name>
<phone>+86-131-8909-6629</phone>
<email>wyn8116@163.com</email>
</overall_contact>
<verification_date>November 2019</verification_date>
<study_first_submitted>December 25, 2019</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 12, 2020</last_update_submitted>
<last_update_submitted_qc>February 12, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Colorectal Cancer</keyword>
<keyword>ERAS</keyword>
<keyword>Single Incision plus one</keyword>
<keyword>Laparoscopic surgery</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Colorectal Neoplasms</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Conventional laparoscopic surgery (CLS) for colorectal cancer has been demonstrated to be
safe and feasible and present minimally invasive benefits including faster recovery, reduced
postoperative pain and shorter hospital stay, also acquiring comparable oncologic outcomes
with open surgery. To achieve further minimally invasive outcomes, SILS plus one port surgery
was attempted by some surgeons. Preliminary results showed that SILS+1 could achieve better
minimally invasive benefits than CLS while preserving oncologic feasibility.
Till now, ERAS has been practiced in colorectal cancer surgery for approximately 20 years.
Studies have proven that ERAS is safe and significantly improved the recovery course of
patients during perioperative period, meanwhile, the expense could be greatly reduced.
Based on ERAS studies protocols and SILS+1 trials, investigators tried to combine SILS+1 with
ERAS, hopefully to provide patients with more safe, economic, feasible and rapid surgery and
perioperative strategies.
Inclusion Criteria:
- Primary tumor diagnosed as adenocarcinoma confirmed pathologically by endoscopic
biopsy
- cT1-4a, N0-3, M0 at preoperative evaluation according to the AJCC Cancer Staging
Manual Seventh Edition
- Located in the cecum, ascending colon, transverse colon, descending colon, sigmoid
colon, the upper segment of the rectum.
- Diameter ≦ 5cm
- No severe organ dysfunction
- Performance status of 0 or 1 on ECOG (Eastern Cooperative Oncology Group) scale
- ASA (American Society of Anesthesiology) score class I or II
- Written informed consent
Exclusion Criteria:
- Unsuitable for patients undergoing single incision plus one port laparoscopic surgery
- Patients with Complications caused by colorectal cancer ( bleeding , perforation,
obstruction or incomplete obstruction )
- Previous abdominal surgery
- Malignant diseases within the past 5years
- Requirements of simultaneous surgery for another diseases
|
NCT0426xxxx/NCT04268303.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268303</url>
</required_header>
<id_info>
<org_study_id>BXCL501-301</org_study_id>
<nct_id>NCT04268303</nct_id>
</id_info>
<brief_title>Dexmedetomidine in the Treatment of Agitation Associated With Schizophrenia</brief_title>
<acronym>SERENITY I</acronym>
<official_title>A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Study To Determine Efficacy and Safety of BXCL501 In Agitation Associated With Schizophrenia</official_title>
<sponsors>
<lead_sponsor>
<agency>BioXcel Therapeutics Inc</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
<collaborator>
<agency>Cognitive Research Corporation</agency>
<agency_class>Industry</agency_class>
</collaborator>
</sponsors>
<source>BioXcel Therapeutics Inc</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This is a definitive study to support the safety and efficacy evaluation of BXCL501 for the
acute treatment of agitation in schizophrenia. The BXCL501-301 study is designed to
characterize the efficacy, safety and tolerability of BXCL501 (sublingual film formulation of
DEX, HCl) in agitation associated with schizophrenia, schizoaffective disorder or
schizophreniform disorder.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
The study will enroll approximately 375 subjects randomized 1:1:1 to dose regimens of 180µg,
120µg BXCL501, or placebo. Male and female adults with acute agitation associated with
schizophrenia, schizoaffective disorder, or schizophreniform disorder will be enrolled.
Eligible subjects may be identified in outpatient clinics, mental health, psychiatric or
medical emergency services including medical/psychiatric observation units, or as newly
admitted to a hospital setting for acute agitation or already in hospital for chronic
underlying conditions. Subjects will be domiciled in a clinical research setting or
hospitalized to remain under medical supervision while undergoing screening procedures to
assess eligibility. Efficacy and safety assessments will be conducted periodically before and
after dosing.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">January 24, 2020</start_date>
<completion_date type="Actual">May 6, 2020</completion_date>
<primary_completion_date type="Actual">May 6, 2020</primary_completion_date>
<phase>Phase 3</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>Phase III, Randomized, Double-Blind, Placebo-Controlled</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
<masking_description>Double-Blind, Placebo-Controlled</masking_description>
</study_design_info>
<primary_outcome>
<measure>Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score</measure>
<time_frame>Baseline and 2 hours</time_frame>
<description>The Positive and Negative Syndrome Scale-Excited Component (PEC) includes 5 items-poor impulse control, tension, hostility, uncooperativeness, and excitement-each of which is rated from 1 (minimum) to 7 (maximum); the sum of these 5 items, the PEC total score, ranges from 5 (absence of agitation) to 35 (extremely severe).</description>
</primary_outcome>
<secondary_outcome>
<measure>Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time</measure>
<time_frame>Baseline and 10, 20, 30, 45, 60, 90 minutes post-dose</time_frame>
<description>Effect on agitation onset was measured by change from baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) total score. The Positive and Negative Syndrome Scale-Excited Component (PEC) includes 5 items-poor impulse control, tension, hostility, uncooperativeness, and excitement-each of which is rated from 1 (minimum) to 7 (maximum); the sum of these 5 items, the PEC total score, ranges from 5 (absence of agitation) to 35 (extremely severe).</description>
</secondary_outcome>
<number_of_arms>3</number_of_arms>
<enrollment type="Actual">380</enrollment>
<condition>Agitation</condition>
<condition>Schizophrenia</condition>
<condition>Schizo Affective Disorder</condition>
<condition>Schizoaffective Disorder</condition>
<condition>Schizophreniform Disorders</condition>
<arm_group>
<arm_group_label>120 Micrograms</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Sublingual film containing 120 Micrograms dexmedetomidine</description>
</arm_group>
<arm_group>
<arm_group_label>180 Micrograms</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Sublingual film containing 180 Micrograms dexmedetomidine</description>
</arm_group>
<arm_group>
<arm_group_label>Placebo</arm_group_label>
<arm_group_type>Placebo Comparator</arm_group_type>
<description>Sublingual placebo film</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Sublingual film containing dexmedetomidine (BXCL501)</intervention_name>
<description>Sublingual film containing dexmedetomidine (BXCL501)</description>
<arm_group_label>120 Micrograms</arm_group_label>
<arm_group_label>180 Micrograms</arm_group_label>
<other_name>Dexmedetomidine</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Placebo Film</intervention_name>
<description>Placebo Film for BXCL501</description>
<arm_group_label>Placebo</arm_group_label>
<other_name>Placebo</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

A subject will be eligible for inclusion in the study if he or she meets the following
criteria:

1. Male and female patients between the ages of 18 to 75 years, inclusive.

2. Patients who have met DSM-5 criteria for schizophrenia, schizoaffective, or
schizophreniform disorder.

3. Patients who are judged to be clinically agitated at Screening and Baseline with a
total score of ≥ 14 on the 5 items (poor impulse control, tension, hostility,
uncooperativeness, and excitement) comprising the PANSS Excited Component (PEC).

4. Patients who have a score of ≥ 4 on at least 1 of the 5 items on the PEC at Baseline.

5. Patients who read, understand, and provide written informed consent.

6. Patients who are in good general health prior to study participation as determined by
a detailed medical history, physical examination, 12-lead ECG with rhythm strip, blood
chemistry profile, hematology, urinalysis, and in the opinion of the Principal
Investigator.

7. Participants who agree to use a medically acceptable and effective birth control
method

Exclusion Criteria:

A subject will be excluded from the study if he or she meets the following criteria:

1. Patients with agitation caused by acute intoxication, including positive
identification of alcohol by breathalyzer or drugs of abuse (with the exception of
THC) during urine screening.

2. Use of benzodiazepines, hypnotics and anti-psychotic drugs in the 4 hours before study
treatment.

3. Treatment with alpha-1 noradrenergic blockers (terazosin, doxazosin, tamsulosin,
alfuzosin, or prazosin) or other prohibited medications.

4. Patients who are judged to be at significant risk of suicide

5. Female patients who have a positive pregnancy test at screening or are breastfeeding.

6. Patients who have hydrocephalus, seizure disorder, or history of significant head
trauma, stroke, transient ischemic attack, subarachnoid bleeding, brain tumor,
encephalopathy, meningitis, Parkinson's disease or focal neurological findings.

7. History of syncope or other syncopal attacks, current evidence of hypovolemia,
orthostatic hypotension.

8. Patients with laboratory or ECG abnormalities considered clinically significant by the
investigator.

9. Patients with serious or unstable medical illnesses.

10. Patients who have received an investigational drug within 30 days prior to the current
agitation episode.

11. Patients who are considered by the investigator, for any reason, to be an unsuitable
candidate for receiving DEX.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>75 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Robert Risinger, MD</last_name>
<role>Study Chair</role>
<affiliation>BioXcel Therapeutics</affiliation>
</overall_official>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>Little Rock</city>
<state>Arkansas</state>
<zip>72211</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>Cerritos</city>
<state>California</state>
<zip>78754</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>Culver City</city>
<state>California</state>
<zip>90230</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>Long Beach</city>
<state>California</state>
<zip>90806</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>Orange</city>
<state>California</state>
<zip>92868</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>Miami Lakes</city>
<state>Florida</state>
<zip>33016</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>Chicago</city>
<state>Illinois</state>
<zip>60640</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>Gaithersburg</city>
<state>Maryland</state>
<zip>20877</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89102</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>Berlin</city>
<state>New Jersey</state>
<zip>08009</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>Marlton</city>
<state>New Jersey</state>
<zip>08053</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>Charleston</city>
<state>South Carolina</state>
<zip>29407</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>Austin</city>
<state>Texas</state>
<zip>78754</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>DeSoto</city>
<state>Texas</state>
<zip>75115</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>BioXcel Clinical Research Site</name>
<address>
<city>Richardson</city>
<state>Texas</state>
<zip>75080</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<link>
<url>https://www.psychiatrist.com/jcp/schizophrenia/sublingual-dexmedetomidine-for-agitation-schizophrenia/</url>
<description>Journal Article</description>
</link>
<verification_date>May 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<results_first_submitted>April 26, 2023</results_first_submitted>
<results_first_submitted_qc>May 25, 2023</results_first_submitted_qc>
<results_first_posted type="Actual">June 18, 2023</results_first_posted>
<last_update_submitted>May 25, 2023</last_update_submitted>
<last_update_submitted_qc>May 25, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">June 18, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Psychomotor Agitation</mesh_term>
<mesh_term>Schizophrenia</mesh_term>
<mesh_term>Psychotic Disorders</mesh_term>
<mesh_term>Mood Disorders</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Dexmedetomidine</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<provided_document_section>
<provided_document>
<document_type>Study Protocol</document_type>
<document_has_protocol>Yes</document_has_protocol>
<document_has_icf>No</document_has_icf>
<document_has_sap>No</document_has_sap>
<document_date>January 31, 2020</document_date>
<document_url>https://ClinicalTrials.gov/ProvidedDocs/03/NCT04268303/Prot_000.pdf</document_url>
</provided_document>
<provided_document>
<document_type>Statistical Analysis Plan</document_type>
<document_has_protocol>No</document_has_protocol>
<document_has_icf>No</document_has_icf>
<document_has_sap>Yes</document_has_sap>
<document_date>April 1, 2020</document_date>
<document_url>https://ClinicalTrials.gov/ProvidedDocs/03/NCT04268303/SAP_001.pdf</document_url>
</provided_document>
</provided_document_section>
<clinical_results>
<participant_flow>
<group_list>
<group group_id="P1">
<title>120 Micrograms</title>
<description>Sublingual film containing 120 Micrograms dexmedetomidine
Sublingual film containing dexmedetomidine (BXCL501): Sublingual film containing dexmedetomidine (BXCL501)</description>
</group>
<group group_id="P2">
<title>180 Micrograms</title>
<description>Sublingual film containing 180 Micrograms dexmedetomidine
Sublingual film containing dexmedetomidine (BXCL501): Sublingual film containing dexmedetomidine (BXCL501)</description>
</group>
<group group_id="P3">
<title>Placebo</title>
<description>Sublingual placebo film
Placebo Film: Placebo Film for BXCL501</description>
</group>
</group_list>
<period_list>
<period>
<title>Overall Study</title>
<milestone_list>
<milestone>
<title>STARTED</title>
<participants_list>
<participants group_id="P1" count="129"/>
<participants group_id="P2" count="125">One participant enrolled in both the 120 microgram treatment group and subsequently the 180 microgram treatment group (at a second site) completed both courses of treatments, but is included only in the 120 microgram group for the randomized population.</participants>
<participants group_id="P3" count="126"/>
</participants_list>
</milestone>
<milestone>
<title>COMPLETED</title>
<participants_list>
<participants group_id="P1" count="126"/>
<participants group_id="P2" count="123"/>
<participants group_id="P3" count="123"/>
</participants_list>
</milestone>
<milestone>
<title>NOT COMPLETED</title>
<participants_list>
<participants group_id="P1" count="3"/>
<participants group_id="P2" count="2"/>
<participants group_id="P3" count="3"/>
</participants_list>
</milestone>
</milestone_list>
<drop_withdraw_reason_list>
<drop_withdraw_reason>
<title>Lost to Follow-up</title>
<participants_list>
<participants group_id="P1" count="1"/>
<participants group_id="P2" count="1"/>
<participants group_id="P3" count="2"/>
</participants_list>
</drop_withdraw_reason>
<drop_withdraw_reason>
<title>Withdrawal by Subject</title>
<participants_list>
<participants group_id="P1" count="0"/>
<participants group_id="P2" count="1"/>
<participants group_id="P3" count="1"/>
</participants_list>
</drop_withdraw_reason>
<drop_withdraw_reason>
<title>Adverse Event</title>
<participants_list>
<participants group_id="P1" count="2"/>
<participants group_id="P2" count="0"/>
<participants group_id="P3" count="0"/>
</participants_list>
</drop_withdraw_reason>
</drop_withdraw_reason_list>
</period>
</period_list>
</participant_flow>
<baseline>
<population>Safety population (all participants who received study drug). One participant enrolled and randomized to the 120 μg group was enrolled a second time at a different site and randomized to the 180 μg group. The data from the first enrollment and treatment (120 μg) were included in the efficacy analyses. The data from both enrollments (120 μg and 180 μg) were included in the safety analyses and counted separately for each treatment group.</population>
<group_list>
<group group_id="B1">
<title>120 Micrograms</title>
<description>Sublingual film containing 120 Micrograms dexmedetomidine
Sublingual film containing dexmedetomidine (BXCL501): Sublingual film containing dexmedetomidine (BXCL501)</description>
</group>
<group group_id="B2">
<title>180 Micrograms</title>
<description>Sublingual film containing 180 Micrograms dexmedetomidine
Sublingual film containing dexmedetomidine (BXCL501): Sublingual film containing dexmedetomidine (BXCL501)</description>
</group>
<group group_id="B3">
<title>Placebo</title>
<description>Sublingual placebo film
Placebo Film: Placebo Film for BXCL501</description>
</group>
<group group_id="B4">
<title>Total</title>
<description>Total of all reporting groups</description>
</group>
</group_list>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Overall</scope>
<count_list>
<count group_id="B1" value="129"/>
<count group_id="B2" value="125"/>
<count group_id="B3" value="126"/>
<count group_id="B4" value="380"/>
</count_list>
</analyzed>
</analyzed_list>
<measure_list>
<measure>
<title>Age</title>
<units>years</units>
<param>Mean</param>
<dispersion>Standard Deviation</dispersion>
<class_list>
<class>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="45.7" spread="11.3"/>
<measurement group_id="B2" value="46.0" spread="11.9"/>
<measurement group_id="B3" value="45.1" spread="11.1"/>
<measurement group_id="B4" value="45.6" spread="11.4"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
<measure>
<title>Sex: Female, Male</title>
<units>Participants</units>
<param>Count of Participants</param>
<class_list>
<class>
<category_list>
<category>
<title>Female</title>
<measurement_list>
<measurement group_id="B1" value="52"/>
<measurement group_id="B2" value="43"/>
<measurement group_id="B3" value="44"/>
<measurement group_id="B4" value="139"/>
</measurement_list>
</category>
<category>
<title>Male</title>
<measurement_list>
<measurement group_id="B1" value="77"/>
<measurement group_id="B2" value="82"/>
<measurement group_id="B3" value="82"/>
<measurement group_id="B4" value="241"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
<measure>
<title>Ethnicity (NIH/OMB)</title>
<units>Participants</units>
<param>Count of Participants</param>
<class_list>
<class>
<category_list>
<category>
<title>Hispanic or Latino</title>
<measurement_list>
<measurement group_id="B1" value="17"/>
<measurement group_id="B2" value="13"/>
<measurement group_id="B3" value="7"/>
<measurement group_id="B4" value="37"/>
</measurement_list>
</category>
<category>
<title>Not Hispanic or Latino</title>
<measurement_list>
<measurement group_id="B1" value="112"/>
<measurement group_id="B2" value="112"/>
<measurement group_id="B3" value="119"/>
<measurement group_id="B4" value="343"/>
</measurement_list>
</category>
<category>
<title>Unknown or Not Reported</title>
<measurement_list>
<measurement group_id="B1" value="0"/>
<measurement group_id="B2" value="0"/>
<measurement group_id="B3" value="0"/>
<measurement group_id="B4" value="0"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
<measure>
<title>Race/Ethnicity, Customized</title>
<units>Participants</units>
<param>Count of Participants</param>
<class_list>
<class>
<title>Black or African American</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="92"/>
<measurement group_id="B2" value="102"/>
<measurement group_id="B3" value="102"/>
<measurement group_id="B4" value="296"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>White</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="33"/>
<measurement group_id="B2" value="21"/>
<measurement group_id="B3" value="21"/>
<measurement group_id="B4" value="75"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>Other</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="4"/>
<measurement group_id="B2" value="2"/>
<measurement group_id="B3" value="3"/>
<measurement group_id="B4" value="9"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>Hispanic or Latino</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="17"/>
<measurement group_id="B2" value="13"/>
<measurement group_id="B3" value="7"/>
<measurement group_id="B4" value="37"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
<measure>
<title>Positive and Negative Syndrome Scale-Excited Component</title>
<population>One participant enrolled and randomized to the 120 μg group was enrolled a second time at a different site and randomized to the 180 μg group. The data from the first enrollment and treatment (120 μg) were included in the efficacy analyses. The data from both enrollments (120 μg and 180 μg) were included in the safety analyses and counted separately in each treatment group; they were counted once when dose groups were combined.</population>
<units>units on a scale</units>
<param>Mean</param>
<dispersion>Standard Deviation</dispersion>
<class_list>
<class>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="17.5" spread="2.5"/>
<measurement group_id="B2" value="17.6" spread="2.7"/>
<measurement group_id="B3" value="17.6" spread="2.3"/>
<measurement group_id="B4" value="17.6" spread="2.5"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
</measure_list>
</baseline>
<outcome_list>
<outcome>
<type>Primary</type>
<title>Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score</title>
<description>The Positive and Negative Syndrome Scale-Excited Component (PEC) includes 5 items-poor impulse control, tension, hostility, uncooperativeness, and excitement-each of which is rated from 1 (minimum) to 7 (maximum); the sum of these 5 items, the PEC total score, ranges from 5 (absence of agitation) to 35 (extremely severe).</description>
<time_frame>Baseline and 2 hours</time_frame>
<population>Intent-to-Treat population, defined as all participants in the safety population who have a PEC score post-dose.</population>
<group_list>
<group group_id="O1">
<title>120 Micrograms</title>
<description>Sublingual film containing 120 Micrograms dexmedetomidine
Sublingual film containing dexmedetomidine (BXCL501): Sublingual film containing dexmedetomidine (BXCL501)</description>
</group>
<group group_id="O2">
<title>180 Micrograms</title>
<description>Sublingual film containing 180 Micrograms dexmedetomidine
Sublingual film containing dexmedetomidine (BXCL501): Sublingual film containing dexmedetomidine (BXCL501)</description>
</group>
<group group_id="O3">
<title>Placebo</title>
<description>Sublingual placebo film
Placebo Film: Placebo Film for BXCL501</description>
</group>
</group_list>
<measure>
<title>Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score</title>
<description>The Positive and Negative Syndrome Scale-Excited Component (PEC) includes 5 items-poor impulse control, tension, hostility, uncooperativeness, and excitement-each of which is rated from 1 (minimum) to 7 (maximum); the sum of these 5 items, the PEC total score, ranges from 5 (absence of agitation) to 35 (extremely severe).</description>
<population>Intent-to-Treat population, defined as all participants in the safety population who have a PEC score post-dose.</population>
<units>score on a scale</units>
<param>Mean</param>
<dispersion>Standard Deviation</dispersion>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Measure</scope>
<count_list>
<count group_id="O1" value="129"/>
<count group_id="O2" value="125"/>
<count group_id="O3" value="126"/>
</count_list>
</analyzed>
</analyzed_list>
<class_list>
<class>
<title>Baseline</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="17.5" spread="2.46"/>
<measurement group_id="O2" value="17.6" spread="2.69"/>
<measurement group_id="O3" value="17.6" spread="2.26"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>2 Hours</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="-8.4" spread="4.83"/>
<measurement group_id="O2" value="-10.4" spread="4.34"/>
<measurement group_id="O3" value="-4.7" spread="4.69"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
<analysis_list>
<analysis>
<group_id_list>
<group_id>O2</group_id>
<group_id>O3</group_id>
</group_id_list>
<non_inferiority_type>Superiority</non_inferiority_type>
<p_value><0.0001</p_value>
<method>Mixed Models Analysis</method>
</analysis>
<analysis>
<group_id_list>
<group_id>O1</group_id>
<group_id>O3</group_id>
</group_id_list>
<non_inferiority_type>Superiority</non_inferiority_type>
<p_value><0.0001</p_value>
<method>Mixed Models Analysis</method>
</analysis>
</analysis_list>
</outcome>
<outcome>
<type>Secondary</type>
<title>Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time</title>
<description>Effect on agitation onset was measured by change from baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) total score. The Positive and Negative Syndrome Scale-Excited Component (PEC) includes 5 items-poor impulse control, tension, hostility, uncooperativeness, and excitement-each of which is rated from 1 (minimum) to 7 (maximum); the sum of these 5 items, the PEC total score, ranges from 5 (absence of agitation) to 35 (extremely severe).</description>
<time_frame>Baseline and 10, 20, 30, 45, 60, 90 minutes post-dose</time_frame>
<population>Intent-to-Treat population, defined as all participants in the safety population who have a PEC score post-dose.</population>
<group_list>
<group group_id="O1">
<title>120 Micrograms</title>
<description>Sublingual film containing 120 Micrograms dexmedetomidine
Sublingual film containing dexmedetomidine (BXCL501): Sublingual film containing dexmedetomidine (BXCL501)</description>
</group>
<group group_id="O2">
<title>180 Micrograms</title>
<description>Sublingual film containing 180 Micrograms dexmedetomidine
Sublingual film containing dexmedetomidine (BXCL501): Sublingual film containing dexmedetomidine (BXCL501)</description>
</group>
<group group_id="O3">
<title>Placebo</title>
<description>Sublingual placebo film
Placebo Film: Placebo Film for BXCL501</description>
</group>
</group_list>
<measure>
<title>Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time</title>
<description>Effect on agitation onset was measured by change from baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) total score. The Positive and Negative Syndrome Scale-Excited Component (PEC) includes 5 items-poor impulse control, tension, hostility, uncooperativeness, and excitement-each of which is rated from 1 (minimum) to 7 (maximum); the sum of these 5 items, the PEC total score, ranges from 5 (absence of agitation) to 35 (extremely severe).</description>
<population>Intent-to-Treat population, defined as all participants in the safety population who have a PEC score post-dose.</population>
<units>score on a scale</units>
<param>Mean</param>
<dispersion>Standard Deviation</dispersion>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Measure</scope>
<count_list>
<count group_id="O1" value="129"/>
<count group_id="O2" value="125"/>
<count group_id="O3" value="126"/>
</count_list>
</analyzed>
</analyzed_list>
<class_list>
<class>
<title>Baseline</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="17.5" spread="2.46"/>
<measurement group_id="O2" value="17.6" spread="2.69"/>
<measurement group_id="O3" value="17.6" spread="2.26"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>10 minutes</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="-1.3" spread="2.50"/>
<measurement group_id="O2" value="-2.0" spread="3.19"/>
<measurement group_id="O3" value="-1.3" spread="2.17"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>20 minutes</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="-2.8" spread="4.03"/>
<measurement group_id="O2" value="-3.9" spread="4.54"/>
<measurement group_id="O3" value="-2.5" spread="3.20"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>30 minutes</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="-4.4" spread="4.90"/>
<measurement group_id="O2" value="-5.7" spread="5.27"/>
<measurement group_id="O3" value="-3.1" spread="3.56"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>45 minutes</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="-5.7" spread="5.18"/>
<measurement group_id="O2" value="-7.6" spread="5.32"/>
<measurement group_id="O3" value="-3.6" spread="3.78"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>60 minutes</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="-6.9" spread="5.06"/>
<measurement group_id="O2" value="-8.8" spread="4.96"/>
<measurement group_id="O3" value="-4.1" spread="4.16"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>90 minutes</title>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="-8.0" spread="5.00"/>
<measurement group_id="O2" value="-9.8" spread="4.60"/>
<measurement group_id="O3" value="-4.6" spread="4.38"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
<analysis_list>
<analysis>
<group_id_list>
<group_id>O2</group_id>
<group_id>O3</group_id>
</group_id_list>
<groups_desc>180 Micrograms versus placebo; 90 minutes post-dose</groups_desc>
<non_inferiority_type>Superiority</non_inferiority_type>
<p_value><0.0001</p_value>
<method>Mixed Models Analysis</method>
</analysis>
<analysis>
<group_id_list>
<group_id>O1</group_id>
<group_id>O3</group_id>
</group_id_list>
<groups_desc>120 Micrograms versus placebo; 90 minutes post-dose</groups_desc>
<non_inferiority_type>Superiority</non_inferiority_type>
<p_value><0.0001</p_value>
<method>Mixed Models Analysis</method>
</analysis>
<analysis>
<group_id_list>
<group_id>O2</group_id>
<group_id>O3</group_id>
</group_id_list>
<groups_desc>180 Micrograms versus placebo; 60 minutes post-dose</groups_desc>
<non_inferiority_type>Superiority</non_inferiority_type>
<p_value><0.0001</p_value>
<method>Mixed Models Analysis</method>
</analysis>
<analysis>
<group_id_list>
<group_id>O1</group_id>
<group_id>O3</group_id>
</group_id_list>
<groups_desc>120 Micrograms versus placebo; 60 minutes post-dose</groups_desc>
<non_inferiority_type>Superiority</non_inferiority_type>
<p_value><0.0001</p_value>
<method>Mixed Models Analysis</method>
</analysis>
<analysis>
<group_id_list>
<group_id>O2</group_id>
<group_id>O3</group_id>
</group_id_list>
<groups_desc>180 Micrograms versus placebo; 45 minutes post-dose</groups_desc>
<non_inferiority_type>Superiority</non_inferiority_type>
<p_value><0.0001</p_value>
<method>Mixed Models Analysis</method>
</analysis>
<analysis>
<group_id_list>
<group_id>O1</group_id>
<group_id>O3</group_id>
</group_id_list>
<groups_desc>120 Micrograms versus placebo; 45 minutes post-dose</groups_desc>
<non_inferiority_type>Superiority</non_inferiority_type>
<p_value><0.0001</p_value>
<method>Mixed Models Analysis</method>
</analysis>
<analysis>
<group_id_list>
<group_id>O2</group_id>
<group_id>O3</group_id>
</group_id_list>
<groups_desc>180 Micrograms versus placebo; 30 minutes post-dose</groups_desc>
<non_inferiority_type>Superiority</non_inferiority_type>
<p_value><0.0001</p_value>
<method>Mixed Models Analysis</method>
</analysis>
<analysis>
<group_id_list>
<group_id>O1</group_id>
<group_id>O3</group_id>
</group_id_list>
<groups_desc>120 Micrograms versus placebo; 30 minutes post-dose</groups_desc>
<non_inferiority_type>Superiority</non_inferiority_type>
<p_value>0.0075</p_value>
<method>Mixed Models Analysis</method>
</analysis>
<analysis>
<group_id_list>
<group_id>O2</group_id>
<group_id>O3</group_id>
</group_id_list>
<groups_desc>180 Micrograms versus placebo; 20 minutes post-dose</groups_desc>
<non_inferiority_type>Superiority</non_inferiority_type>
<p_value>0.0032</p_value>
<method>Mixed Models Analysis</method>
</analysis>
<analysis>
<group_id_list>
<group_id>O1</group_id>
<group_id>O3</group_id>
</group_id_list>
<groups_desc>120 Micrograms versus placebo; 20 minutes post-dose</groups_desc>
<non_inferiority_type>Superiority</non_inferiority_type>
<p_value>0.4097</p_value>
<method>Mixed Models Analysis</method>
</analysis>
<analysis>
<group_id_list>
<group_id>O2</group_id>
<group_id>O3</group_id>
</group_id_list>
<groups_desc>180 Micrograms versus placebo; 10 minutes post-dose</groups_desc>
<non_inferiority_type>Superiority</non_inferiority_type>
<p_value>0.0457</p_value>
<method>Mixed Models Analysis</method>
</analysis>
<analysis>
<group_id_list>
<group_id>O1</group_id>
<group_id>O3</group_id>
</group_id_list>
<groups_desc>120 Micrograms versus placebo; 10 minutes post-dose</groups_desc>
<non_inferiority_type>Superiority</non_inferiority_type>
<p_value>0.9720</p_value>
<method>Mixed Models Analysis</method>
</analysis>
</analysis_list>
</outcome>
</outcome_list>
<reported_events>
<time_frame>30 days</time_frame>
<desc>Adverse Events: The Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. One participant enrolled and randomized to the 120 μg group was enrolled a second time at a different site and randomized to the 180 μg group. The data from both enrollments (120 μg and 180 μg) were included in the safety analyses and counted separately in each treatment group; they were counted once when dose groups were combined.</desc>
<group_list>
<group group_id="E1">
<title>120 Micrograms</title>
<description>Sublingual film containing 120 Micrograms dexmedetomidine
Sublingual film containing dexmedetomidine (BXCL501): Sublingual film containing dexmedetomidine (BXCL501)</description>
</group>
<group group_id="E2">
<title>180 Micrograms</title>
<description>Sublingual film containing 180 Micrograms dexmedetomidine
Sublingual film containing dexmedetomidine (BXCL501): Sublingual film containing dexmedetomidine (BXCL501)</description>
</group>
<group group_id="E3">
<title>Placebo</title>
<description>Sublingual placebo film
Placebo Film: Placebo Film for BXCL501</description>
</group>
</group_list>
<serious_events>
<category_list>
<category>
<title>Total</title>
<event_list>
<event>
<sub_title>Total, all-cause mortality</sub_title>
<counts group_id="E1" subjects_affected="0" subjects_at_risk="129"/>
<counts group_id="E2" subjects_affected="0" subjects_at_risk="126"/>
<counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
</event>
<event>
<sub_title>Total, serious adverse events</sub_title>
<counts group_id="E1" subjects_affected="0" subjects_at_risk="129"/>
<counts group_id="E2" subjects_affected="0" subjects_at_risk="126"/>
<counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
</event>
</event_list>
</category>
</category_list>
</serious_events>
<other_events>
<frequency_threshold>3</frequency_threshold>
<default_assessment>Non-systematic Assessment</default_assessment>
<category_list>
<category>
<title>Total</title>
<event_list>
<event>
<sub_title>Total, other adverse events</sub_title>
<counts group_id="E1" subjects_affected="51" subjects_at_risk="129"/>
<counts group_id="E2" subjects_affected="47" subjects_at_risk="126"/>
<counts group_id="E3" subjects_affected="19" subjects_at_risk="126"/>
</event>
</event_list>
</category>
<category>
<title>Gastrointestinal disorders</title>
<event_list>
<event>
<sub_title>Dry mouth</sub_title>
<counts group_id="E1" subjects_affected="10" subjects_at_risk="129"/>
<counts group_id="E2" subjects_affected="5" subjects_at_risk="126"/>
<counts group_id="E3" subjects_affected="2" subjects_at_risk="126"/>
</event>
</event_list>
</category>
<category>
<title>Nervous system disorders</title>
<event_list>
<event>
<sub_title>Dizziness</sub_title>
<counts group_id="E1" subjects_affected="3" subjects_at_risk="129"/>
<counts group_id="E2" subjects_affected="8" subjects_at_risk="126"/>
<counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
</event>
<event>
<sub_title>Headache</sub_title>
<counts group_id="E1" subjects_affected="6" subjects_at_risk="129"/>
<counts group_id="E2" subjects_affected="4" subjects_at_risk="126"/>
<counts group_id="E3" subjects_affected="6" subjects_at_risk="126"/>
</event>
<event>
<sub_title>Hypoesthesia oral</sub_title>
<counts group_id="E1" subjects_affected="5" subjects_at_risk="129"/>
<counts group_id="E2" subjects_affected="7" subjects_at_risk="126"/>
<counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
</event>
<event>
<sub_title>Paresthesia oral</sub_title>
<counts group_id="E1" subjects_affected="5" subjects_at_risk="129"/>
<counts group_id="E2" subjects_affected="3" subjects_at_risk="126"/>
<counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
</event>
<event>
<sub_title>Somnolence</sub_title>
<counts group_id="E1" subjects_affected="28" subjects_at_risk="129"/>
<counts group_id="E2" subjects_affected="29" subjects_at_risk="126"/>
<counts group_id="E3" subjects_affected="10" subjects_at_risk="126"/>
</event>
</event_list>
</category>
<category>
<title>Vascular disorders</title>
<event_list>
<event>
<sub_title>Hypotension</sub_title>
<counts group_id="E1" subjects_affected="8" subjects_at_risk="129"/>
<counts group_id="E2" subjects_affected="5" subjects_at_risk="126"/>
<counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
</event>
<event>
<sub_title>Orthostatic hypotension</sub_title>
<counts group_id="E1" subjects_affected="2" subjects_at_risk="129"/>
<counts group_id="E2" subjects_affected="7" subjects_at_risk="126"/>
<counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
</event>
</event_list>
</category>
</category_list>
</other_events>
</reported_events>
<certain_agreements>
<pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
<restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
</certain_agreements>
<point_of_contact>
<name_or_title>Vice President Head of Clinical Operations</name_or_title>
<organization>BioXcel Therapeutics</organization>
<phone>(475) 355 5177</phone>
<email>cgommoll@bioxceltherapeutics.com</email>
</point_of_contact>
</clinical_results>
</clinical_study>
|
This is a definitive study to support the safety and efficacy evaluation of BXCL501 for the
acute treatment of agitation in schizophrenia. The BXCL501-301 study is designed to
characterize the efficacy, safety and tolerability of BXCL501 (sublingual film formulation of
DEX, HCl) in agitation associated with schizophrenia, schizoaffective disorder or
schizophreniform disorder.
The study will enroll approximately 375 subjects randomized 1:1:1 to dose regimens of 180µg,
120µg BXCL501, or placebo. Male and female adults with acute agitation associated with
schizophrenia, schizoaffective disorder, or schizophreniform disorder will be enrolled.
Eligible subjects may be identified in outpatient clinics, mental health, psychiatric or
medical emergency services including medical/psychiatric observation units, or as newly
admitted to a hospital setting for acute agitation or already in hospital for chronic
underlying conditions. Subjects will be domiciled in a clinical research setting or
hospitalized to remain under medical supervision while undergoing screening procedures to
assess eligibility. Efficacy and safety assessments will be conducted periodically before and
after dosing.
Inclusion Criteria:
A subject will be eligible for inclusion in the study if he or she meets the following
criteria:
1. Male and female patients between the ages of 18 to 75 years, inclusive.
2. Patients who have met DSM-5 criteria for schizophrenia, schizoaffective, or
schizophreniform disorder.
3. Patients who are judged to be clinically agitated at Screening and Baseline with a
total score of ≥ 14 on the 5 items (poor impulse control, tension, hostility,
uncooperativeness, and excitement) comprising the PANSS Excited Component (PEC).
4. Patients who have a score of ≥ 4 on at least 1 of the 5 items on the PEC at Baseline.
5. Patients who read, understand, and provide written informed consent.
6. Patients who are in good general health prior to study participation as determined by
a detailed medical history, physical examination, 12-lead ECG with rhythm strip, blood
chemistry profile, hematology, urinalysis, and in the opinion of the Principal
Investigator.
7. Participants who agree to use a medically acceptable and effective birth control
method
Exclusion Criteria:
A subject will be excluded from the study if he or she meets the following criteria:
1. Patients with agitation caused by acute intoxication, including positive
identification of alcohol by breathalyzer or drugs of abuse (with the exception of
THC) during urine screening.
2. Use of benzodiazepines, hypnotics and anti-psychotic drugs in the 4 hours before study
treatment.
3. Treatment with alpha-1 noradrenergic blockers (terazosin, doxazosin, tamsulosin,
alfuzosin, or prazosin) or other prohibited medications.
4. Patients who are judged to be at significant risk of suicide
5. Female patients who have a positive pregnancy test at screening or are breastfeeding.
6. Patients who have hydrocephalus, seizure disorder, or history of significant head
trauma, stroke, transient ischemic attack, subarachnoid bleeding, brain tumor,
encephalopathy, meningitis, Parkinson's disease or focal neurological findings.
7. History of syncope or other syncopal attacks, current evidence of hypovolemia,
orthostatic hypotension.
8. Patients with laboratory or ECG abnormalities considered clinically significant by the
investigator.
9. Patients with serious or unstable medical illnesses.
10. Patients who have received an investigational drug within 30 days prior to the current
agitation episode.
11. Patients who are considered by the investigator, for any reason, to be an unsuitable
candidate for receiving DEX.
|
NCT0426xxxx/NCT04268316.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268316</url>
</required_header>
<id_info>
<org_study_id>53483</org_study_id>
<nct_id>NCT04268316</nct_id>
</id_info>
<brief_title>Virtual Reality Behavioral Activation: An Intervention for Major Depressive Disorder</brief_title>
<official_title>Virtual Reality Behavioral Activation: An Intervention for Major Depressive Disorder</official_title>
<sponsors>
<lead_sponsor>
<agency>Stanford University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Stanford University</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>Yes</is_fda_regulated_device>
<is_unapproved_device>Yes</is_unapproved_device>
<is_us_export>Yes</is_us_export>
</oversight_info>
<brief_summary>
<textblock>
The primary purpose of this study is to test the safety and feasibility of virtual reality
(VR) technology in the use of behavioral activation (BA) as a treatment for major depressive
disorder (MDD). The secondary purpose of this study is to examine whether any evidence of
clinical efficacy exists for VR delivered BA.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
This is a treatment development trial. Participants will be randomly assigned to BA in VR, BA
in real-life, or a waitlist control group. The former two groups will follow a BA protocol
developed for primary care settings over a four-week treatment period. This study is taking
place over Zoom, due to COVID-19.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">May 18, 2020</start_date>
<completion_date type="Actual">January 15, 2021</completion_date>
<primary_completion_date type="Actual">January 15, 2021</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>Participants will be randomized to either BA in VR, BA in real-life, or a waitlist control group.</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Participant's Desire to Continue Using VR After the Study Ends</measure>
<time_frame>Assessed at the end of week 3, after session 4</time_frame>
<description>This outcome was measured using the "Intention to use Technology " questions of the Technology Acceptance Model questionnaire. These are questions 11, 12, and 13 and allow participants the option of circling Strongly Disagree (0), Disagree (1), Neutral (2), Agree (3), or Strongly Agree (4). With 3 questions, the total range was 0-12 (higher scores indicate greater acceptance).</description>
</primary_outcome>
<primary_outcome>
<measure>Number of Participants Who Dropped Out of Each Study Arm</measure>
<time_frame>3-weeks</time_frame>
<description>Participant treatment dropout was compared across each study arm. This was reported as the count of participants who discontinued the study for any reason.</description>
</primary_outcome>
<primary_outcome>
<measure>Participant's Satisfaction With the VR-BA Treatment</measure>
<time_frame>Assessed at the end of week 3, after session 4</time_frame>
<description>This outcome was measured using the "Attitudes Toward Use " questions of the Technology Acceptance Model questionnaire. These are questions 7, 8, 9, and 10 and allow participants the option of circling Strongly Disagree (0), Disagree (1), Neutral (2), Agree (3), or Strongly Agree (4). With 4 questions, the total range was 0-16 (higher scores indicate greater acceptance).</description>
</primary_outcome>
<primary_outcome>
<measure>Participant's Use of the VR Headset</measure>
<time_frame>Assessed at the end of week 3, after session 4</time_frame>
<description>This was measured by noting the amount of times the VR headset is used during the 3-week study period.</description>
</primary_outcome>
<primary_outcome>
<measure>Participant's Acceptance of VR-BA Treatment</measure>
<time_frame>Assessed at the end of week 3, after session 4</time_frame>
<description>This was measured using the overall Technology Acceptance Model questionnaire, which encompasses 13 questions and allows participants the option of circling Strongly Disagree (0), Disagree (1), Neutral (2), Agree (3), or Strongly Agree (4), yielding a range of 0-52 (higher scores indicate greater acceptance).</description>
</primary_outcome>
<primary_outcome>
<measure>How Well Can Participants Tolerate the VR-BA Treatment?</measure>
<time_frame>Assessed at the end of week 3, after session 4</time_frame>
<description>This was determined by the Simulator Sickness Questionnaire, which names 16 adverse symptoms and asks participants to circle as compared to baseline: No more than usual (0), Slightly more than usual (1), Moderately more than usual (2), or Severely more than usual (3), yielding a range of 0-48 (lower scores indicate greater tolerability).</description>
</primary_outcome>
<primary_outcome>
<measure>How Present Did Individuals in the VR-BA Treatment Feel?</measure>
<time_frame>Assessed at the end of week 3, after session 4</time_frame>
<description>This was measured using the Presence Questionnaire, which asks three questions and asks the participants to circle either Not at all (0), Slightly (1), Moderately (2), Strongly (3), or Very Strongly (4), yielding a range of 0-12 (higher scores indicate greater presence).</description>
</primary_outcome>
<secondary_outcome>
<measure>Change in Depression Scores on the PHQ-9 From Baseline to Session 4, Compared Across Three Study Arms</measure>
<time_frame>Assessed at baseline and session 4.</time_frame>
<description>How participants' depression scores on the Patient Health Questionnaire (PHQ-9) change over time using VR-BA compared to BA in real life and a waitlist control. The PHQ-9 is a 9-question screener with a score range of 0-29, with 29 indicating the most severe depression and 0 indicating a lack of depression symptoms. The greater the change over time, the greater the symptom reduction.</description>
</secondary_outcome>
<number_of_arms>3</number_of_arms>
<enrollment type="Actual">20</enrollment>
<condition>Major Depressive Disorder</condition>
<condition>MDD</condition>
<condition>Depression</condition>
<arm_group>
<arm_group_label>Virtual Reality Behavioral Activation</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Participants randomized to this arm will perform all of their behavioral activation in virtual reality. Participants will meet with the clinician once a week for three weeks (4 sessions). In between weekly therapy sessions, participants will pick four pleasurable activities to enjoy in virtual reality.</description>
</arm_group>
<arm_group>
<arm_group_label>Behavioral Activation in real-life</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Participants randomized to this arm will perform all of their behavioral activation in real life. Participants will meet with the clinician once a week for three weeks (4 sessions). In between weekly therapy sessions, participants will pick four pleasurable or mastery activities to perform in real life.</description>
</arm_group>
<arm_group>
<arm_group_label>Waitlist Control</arm_group_label>
<arm_group_type>No Intervention</arm_group_type>
<description>Participants randomized to this arm will not receive any type of intervention and will be asked to complete the PHQ-9 once a week for three weeks (4 sessions) to track symptoms. Participants will be offered to engage in behavioral activation in real life or with virtual reality when the four weeks are complete. Their data will only be used from the time they were on the waitlist.</description>
</arm_group>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>Virtual Reality Behavioral Activation</intervention_name>
<description>Participants will choose four "activities" to complete in virtual reality over the course of the week. These activities are video 360 and range from viewing animals, to viewing nature scenes, to traveling to a different location in the world, to viewing adrenaline-pumping activities.</description>
<arm_group_label>Virtual Reality Behavioral Activation</arm_group_label>
</intervention>
<intervention>
<intervention_type>Behavioral</intervention_type>
<intervention_name>Behavioral Activation in real-life</intervention_name>
<description>Participants will choose four pleasurable and/or mastery activities to complete over the course of the week in real life.</description>
<arm_group_label>Behavioral Activation in real-life</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Patient must meet DSM V criteria for MDD

- Patient must be at least 18 years of age

- Patient must be English speaking

Exclusion Criteria:

- Substance Use Disorders in past year

- Any psychosis or bipolar I disorder

- Any seizure in the last 6 months or untreated epilepsy

- Current nonsuicidal self-injury or parasuicidal behavior

- Current suicidal urges and intent
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Kim Bullock, MD</last_name>
<role>Study Director</role>
<affiliation>Stanford University</affiliation>
</overall_official>
<overall_official>
<last_name>Margot Paul, MS</last_name>
<role>Principal Investigator</role>
<affiliation>Stanford University</affiliation>
</overall_official>
<location>
<facility>
<name>Stanford University</name>
<address>
<city>Palo Alto</city>
<state>California</state>
<zip>94304</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<results_reference>
<citation>Paul M, Bullock K, Bailenson J. Virtual Reality Behavioral Activation as an Intervention for Major Depressive Disorder: Case Report. JMIR Ment Health. 2020 Nov 3;7(11):e24331. doi: 10.2196/24331.</citation>
<PMID>33031046</PMID>
</results_reference>
<verification_date>May 2021</verification_date>
<study_first_submitted>February 5, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<results_first_submitted>April 13, 2021</results_first_submitted>
<results_first_submitted_qc>April 13, 2021</results_first_submitted_qc>
<results_first_posted type="Actual">May 10, 2021</results_first_posted>
<last_update_submitted>May 8, 2021</last_update_submitted>
<last_update_submitted_qc>May 8, 2021</last_update_submitted_qc>
<last_update_posted type="Actual">June 2, 2021</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Stanford University</investigator_affiliation>
<investigator_full_name>Margot Paul</investigator_full_name>
<investigator_title>Principle Investigator</investigator_title>
</responsible_party>
<keyword>virtual reality</keyword>
<keyword>behavioral activation</keyword>
<keyword>depression</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Depression</mesh_term>
<mesh_term>Depressive Disorder</mesh_term>
<mesh_term>Depressive Disorder, Major</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
<ipd_description>No current plan to share data.</ipd_description>
</patient_data>
<provided_document_section>
<provided_document>
<document_type>Study Protocol</document_type>
<document_has_protocol>Yes</document_has_protocol>
<document_has_icf>No</document_has_icf>
<document_has_sap>No</document_has_sap>
<document_date>February 25, 2020</document_date>
<document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT04268316/Prot_000.pdf</document_url>
</provided_document>
<provided_document>
<document_type>Statistical Analysis Plan</document_type>
<document_has_protocol>No</document_has_protocol>
<document_has_icf>No</document_has_icf>
<document_has_sap>Yes</document_has_sap>
<document_date>April 13, 2021</document_date>
<document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT04268316/SAP_001.pdf</document_url>
</provided_document>
</provided_document_section>
<clinical_results>
<participant_flow>
<pre_assignment_details>20 participants signed consent, but only 13 participants were randomized to a study arm.</pre_assignment_details>
<group_list>
<group group_id="P1">
<title>Virtual Reality Behavioral Activation</title>
<description>Participants engage in VR activities over the week for three weeks.</description>
</group>
<group group_id="P2">
<title>Behavioral Activation in Real-life</title>
<description>Participants engage in real life pleasurable activities over the week for three weeks.</description>
</group>
<group group_id="P3">
<title>Waitlist Control</title>
<description>Participants answer the PHQ-9 weekly for four sessions.</description>
</group>
</group_list>
<period_list>
<period>
<title>Overall Study</title>
<milestone_list>
<milestone>
<title>STARTED</title>
<participants_list>
<participants group_id="P1" count="5"/>
<participants group_id="P2" count="4"/>
<participants group_id="P3" count="4"/>
</participants_list>
</milestone>
<milestone>
<title>COMPLETED</title>
<participants_list>
<participants group_id="P1" count="3"/>
<participants group_id="P2" count="3"/>
<participants group_id="P3" count="4"/>
</participants_list>
</milestone>
<milestone>
<title>NOT COMPLETED</title>
<participants_list>
<participants group_id="P1" count="2"/>
<participants group_id="P2" count="1"/>
<participants group_id="P3" count="0"/>
</participants_list>
</milestone>
</milestone_list>
<drop_withdraw_reason_list>
<drop_withdraw_reason>
<title>Withdrawal by Subject</title>
<participants_list>
<participants group_id="P1" count="2"/>
<participants group_id="P2" count="1"/>
<participants group_id="P3" count="0"/>
</participants_list>
</drop_withdraw_reason>
</drop_withdraw_reason_list>
</period>
</period_list>
</participant_flow>
<baseline>
<group_list>
<group group_id="B1">
<title>Virtual Reality Behavioral Activation</title>
<description>Participants engage in VR activities over the week for three weeks.</description>
</group>
<group group_id="B2">
<title>Behavioral Activation in Real-life</title>
<description>Participants engage in real life pleasurable activities over the week for three weeks.</description>
</group>
<group group_id="B3">
<title>Waitlist Control</title>
<description>Participants answer the PHQ-9 weekly for four sessions.</description>
</group>
<group group_id="B4">
<title>Total</title>
<description>Total of all reporting groups</description>
</group>
</group_list>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Overall</scope>
<count_list>
<count group_id="B1" value="5"/>
<count group_id="B2" value="4"/>
<count group_id="B3" value="4"/>
<count group_id="B4" value="13"/>
</count_list>
</analyzed>
</analyzed_list>
<measure_list>
<measure>
<title>Age</title>
<units>years</units>
<param>Mean</param>
<dispersion>Standard Deviation</dispersion>
<class_list>
<class>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="5"/>
<count group_id="B2" value="4"/>
<count group_id="B3" value="4"/>
<count group_id="B4" value="13"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="31.6" spread="9.2"/>
<measurement group_id="B2" value="46" spread="15.7"/>
<measurement group_id="B3" value="29.5" spread="5.2"/>
<measurement group_id="B4" value="35.4" spread="12.3"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
<measure>
<title>Sex/Gender, Customized</title>
<units>Participants</units>
<param>Count of Participants</param>
<class_list>
<class>
<title>male</title>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="5"/>
<count group_id="B2" value="4"/>
<count group_id="B3" value="4"/>
<count group_id="B4" value="13"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="1"/>
<measurement group_id="B2" value="3"/>
<measurement group_id="B3" value="1"/>
<measurement group_id="B4" value="5"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>female</title>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="5"/>
<count group_id="B2" value="4"/>
<count group_id="B3" value="4"/>
<count group_id="B4" value="13"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="4"/>
<measurement group_id="B2" value="1"/>
<measurement group_id="B3" value="2"/>
<measurement group_id="B4" value="7"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>non-binary/third gender</title>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="5"/>
<count group_id="B2" value="4"/>
<count group_id="B3" value="4"/>
<count group_id="B4" value="13"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="0"/>
<measurement group_id="B2" value="0"/>
<measurement group_id="B3" value="1"/>
<measurement group_id="B4" value="1"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
<measure>
<title>Race/Ethnicity, Customized</title>
<units>Participants</units>
<param>Count of Participants</param>
<class_list>
<class>
<title>Non-Hispanic Caucasian</title>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="5"/>
<count group_id="B2" value="4"/>
<count group_id="B3" value="4"/>
<count group_id="B4" value="13"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="3"/>
<measurement group_id="B2" value="3"/>
<measurement group_id="B3" value="1"/>
<measurement group_id="B4" value="7"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>Chinese</title>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="5"/>
<count group_id="B2" value="4"/>
<count group_id="B3" value="4"/>
<count group_id="B4" value="13"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="1"/>
<measurement group_id="B2" value="1"/>
<measurement group_id="B3" value="0"/>
<measurement group_id="B4" value="2"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>Indian</title>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="5"/>
<count group_id="B2" value="4"/>
<count group_id="B3" value="4"/>
<count group_id="B4" value="13"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="1"/>
<measurement group_id="B2" value="0"/>
<measurement group_id="B3" value="0"/>
<measurement group_id="B4" value="1"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>African American</title>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="5"/>
<count group_id="B2" value="4"/>
<count group_id="B3" value="4"/>
<count group_id="B4" value="13"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="0"/>
<measurement group_id="B2" value="0"/>
<measurement group_id="B3" value="1"/>
<measurement group_id="B4" value="1"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>Mexican</title>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="5"/>
<count group_id="B2" value="4"/>
<count group_id="B3" value="4"/>
<count group_id="B4" value="13"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="0"/>
<measurement group_id="B2" value="0"/>
<measurement group_id="B3" value="1"/>
<measurement group_id="B4" value="1"/>
</measurement_list>
</category>
</category_list>
</class>
<class>
<title>Hispanic/Latino</title>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="5"/>
<count group_id="B2" value="4"/>
<count group_id="B3" value="4"/>
<count group_id="B4" value="13"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="0"/>
<measurement group_id="B2" value="0"/>
<measurement group_id="B3" value="1"/>
<measurement group_id="B4" value="1"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
<measure>
<title>Region of Enrollment</title>
<units>Participants</units>
<param>Count of Participants</param>
<class_list>
<class>
<title>United States</title>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="5"/>
<count group_id="B2" value="4"/>
<count group_id="B3" value="4"/>
<count group_id="B4" value="13"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="5"/>
<measurement group_id="B2" value="4"/>
<measurement group_id="B3" value="4"/>
<measurement group_id="B4" value="13"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
<measure>
<title>Patient Health Questionnaire-9 (PHQ-9)</title>
<description>Total Score Depression Severity
0 Lack of depression symptoms
1-4 Minimal depression
5-9 Mild depression
10-14 Moderate depression
15-19 Moderately severe depression
20-27 Severe depression</description>
<population>Participants that completed the protocol are included in the analysis.</population>
<units>score on a scale</units>
<param>Mean</param>
<dispersion>Standard Deviation</dispersion>
<class_list>
<class>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Class</scope>
<count_list>
<count group_id="B1" value="3"/>
<count group_id="B2" value="3"/>
<count group_id="B3" value="4"/>
<count group_id="B4" value="10"/>
</count_list>
</analyzed>
</analyzed_list>
<category_list>
<category>
<measurement_list>
<measurement group_id="B1" value="14.3" spread="5.7"/>
<measurement group_id="B2" value="15.3" spread="4.9"/>
<measurement group_id="B3" value="14" spread="4.1"/>
<measurement group_id="B4" value="14.5" spread="4.3"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
</measure_list>
</baseline>
<outcome_list>
<outcome>
<type>Primary</type>
<title>Participant's Desire to Continue Using VR After the Study Ends</title>
<description>This outcome was measured using the "Intention to use Technology " questions of the Technology Acceptance Model questionnaire. These are questions 11, 12, and 13 and allow participants the option of circling Strongly Disagree (0), Disagree (1), Neutral (2), Agree (3), or Strongly Agree (4). With 3 questions, the total range was 0-12 (higher scores indicate greater acceptance).</description>
<time_frame>Assessed at the end of week 3, after session 4</time_frame>
<population>This outcome measure was assessed in the Virtual Reality Behavioral Activation group only.</population>
<group_list>
<group group_id="O1">
<title>Virtual Reality Behavioral Activation</title>
<description>Participants engage in VR activities over the week for three weeks.</description>
</group>
</group_list>
<measure>
<title>Participant's Desire to Continue Using VR After the Study Ends</title>
<description>This outcome was measured using the "Intention to use Technology " questions of the Technology Acceptance Model questionnaire. These are questions 11, 12, and 13 and allow participants the option of circling Strongly Disagree (0), Disagree (1), Neutral (2), Agree (3), or Strongly Agree (4). With 3 questions, the total range was 0-12 (higher scores indicate greater acceptance).</description>
<population>This outcome measure was assessed in the Virtual Reality Behavioral Activation group only.</population>
<units>score on a scale</units>
<param>Mean</param>
<dispersion>Standard Deviation</dispersion>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Measure</scope>
<count_list>
<count group_id="O1" value="5"/>
</count_list>
</analyzed>
</analyzed_list>
<class_list>
<class>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="9.54" spread="2.5"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
</outcome>
<outcome>
<type>Primary</type>
<title>Number of Participants Who Dropped Out of Each Study Arm</title>
<description>Participant treatment dropout was compared across each study arm. This was reported as the count of participants who discontinued the study for any reason.</description>
<time_frame>3-weeks</time_frame>
<group_list>
<group group_id="O1">
<title>Virtual Reality Behavioral Activation</title>
<description>Participants engage in VR activities over the week for three weeks.</description>
</group>
<group group_id="O2">
<title>Behavioral Activation in Real-life</title>
<description>Participants engage in real life pleasurable activities over the week for three weeks.</description>
</group>
<group group_id="O3">
<title>Waitlist Control</title>
<description>Participants answer the PHQ-9 weekly for four sessions.</description>
</group>
</group_list>
<measure>
<title>Number of Participants Who Dropped Out of Each Study Arm</title>
<description>Participant treatment dropout was compared across each study arm. This was reported as the count of participants who discontinued the study for any reason.</description>
<units>Participants</units>
<param>Count of Participants</param>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Measure</scope>
<count_list>
<count group_id="O1" value="5"/>
<count group_id="O2" value="4"/>
<count group_id="O3" value="4"/>
</count_list>
</analyzed>
</analyzed_list>
<class_list>
<class>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="2"/>
<measurement group_id="O2" value="1"/>
<measurement group_id="O3" value="0"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
</outcome>
<outcome>
<type>Primary</type>
<title>Participant's Satisfaction With the VR-BA Treatment</title>
<description>This outcome was measured using the "Attitudes Toward Use " questions of the Technology Acceptance Model questionnaire. These are questions 7, 8, 9, and 10 and allow participants the option of circling Strongly Disagree (0), Disagree (1), Neutral (2), Agree (3), or Strongly Agree (4). With 4 questions, the total range was 0-16 (higher scores indicate greater acceptance).</description>
<time_frame>Assessed at the end of week 3, after session 4</time_frame>
<population>This outcome measure was assessed in the Virtual Reality Behavioral Activation group only.</population>
<group_list>
<group group_id="O1">
<title>Virtual Reality Behavioral Activation</title>
<description>Participants engage in VR activities over the week for three weeks.</description>
</group>
</group_list>
<measure>
<title>Participant's Satisfaction With the VR-BA Treatment</title>
<description>This outcome was measured using the "Attitudes Toward Use " questions of the Technology Acceptance Model questionnaire. These are questions 7, 8, 9, and 10 and allow participants the option of circling Strongly Disagree (0), Disagree (1), Neutral (2), Agree (3), or Strongly Agree (4). With 4 questions, the total range was 0-16 (higher scores indicate greater acceptance).</description>
<population>This outcome measure was assessed in the Virtual Reality Behavioral Activation group only.</population>
<units>score on a scale</units>
<param>Mean</param>
<dispersion>Standard Deviation</dispersion>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Measure</scope>
<count_list>
<count group_id="O1" value="5"/>
</count_list>
</analyzed>
</analyzed_list>
<class_list>
<class>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="12.5" spread="3.5"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
</outcome>
<outcome>
<type>Primary</type>
<title>Participant's Use of the VR Headset</title>
<description>This was measured by noting the amount of times the VR headset is used during the 3-week study period.</description>
<time_frame>Assessed at the end of week 3, after session 4</time_frame>
<population>This outcome measure was assessed in the Virtual Reality Behavioral Activation group of protocol completers only.</population>
<group_list>
<group group_id="O1">
<title>Virtual Reality Behavioral Activation</title>
<description>Participants engage in VR activities over the week for three weeks.</description>
</group>
</group_list>
<measure>
<title>Participant's Use of the VR Headset</title>
<description>This was measured by noting the amount of times the VR headset is used during the 3-week study period.</description>
<population>This outcome measure was assessed in the Virtual Reality Behavioral Activation group of protocol completers only.</population>
<units>times used</units>
<param>Mean</param>
<dispersion>Standard Deviation</dispersion>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Measure</scope>
<count_list>
<count group_id="O1" value="3"/>
</count_list>
</analyzed>
</analyzed_list>
<class_list>
<class>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="21.7" spread="11"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
</outcome>
<outcome>
<type>Primary</type>
<title>Participant's Acceptance of VR-BA Treatment</title>
<description>This was measured using the overall Technology Acceptance Model questionnaire, which encompasses 13 questions and allows participants the option of circling Strongly Disagree (0), Disagree (1), Neutral (2), Agree (3), or Strongly Agree (4), yielding a range of 0-52 (higher scores indicate greater acceptance).</description>
<time_frame>Assessed at the end of week 3, after session 4</time_frame>
<population>This outcome measure was assessed in the Virtual Reality Behavioral Activation group only.</population>
<group_list>
<group group_id="O1">
<title>Virtual Reality Behavioral Activation</title>
<description>Participants engage in VR activities over the week for three weeks.</description>
</group>
</group_list>
<measure>
<title>Participant's Acceptance of VR-BA Treatment</title>
<description>This was measured using the overall Technology Acceptance Model questionnaire, which encompasses 13 questions and allows participants the option of circling Strongly Disagree (0), Disagree (1), Neutral (2), Agree (3), or Strongly Agree (4), yielding a range of 0-52 (higher scores indicate greater acceptance).</description>
<population>This outcome measure was assessed in the Virtual Reality Behavioral Activation group only.</population>
<units>score on a scale</units>
<param>Mean</param>
<dispersion>Standard Deviation</dispersion>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Measure</scope>
<count_list>
<count group_id="O1" value="5"/>
</count_list>
</analyzed>
</analyzed_list>
<class_list>
<class>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="42.4" spread="8.4"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
</outcome>
<outcome>
<type>Primary</type>
<title>How Well Can Participants Tolerate the VR-BA Treatment?</title>
<description>This was determined by the Simulator Sickness Questionnaire, which names 16 adverse symptoms and asks participants to circle as compared to baseline: No more than usual (0), Slightly more than usual (1), Moderately more than usual (2), or Severely more than usual (3), yielding a range of 0-48 (lower scores indicate greater tolerability).</description>
<time_frame>Assessed at the end of week 3, after session 4</time_frame>
<population>This outcome measure was assessed in the Virtual Reality Behavioral Activation group only.</population>
<group_list>
<group group_id="O1">
<title>Virtual Reality Behavioral Activation</title>
<description>Participants engage in VR activities over the week for three weeks.</description>
</group>
</group_list>
<measure>
<title>How Well Can Participants Tolerate the VR-BA Treatment?</title>
<description>This was determined by the Simulator Sickness Questionnaire, which names 16 adverse symptoms and asks participants to circle as compared to baseline: No more than usual (0), Slightly more than usual (1), Moderately more than usual (2), or Severely more than usual (3), yielding a range of 0-48 (lower scores indicate greater tolerability).</description>
<population>This outcome measure was assessed in the Virtual Reality Behavioral Activation group only.</population>
<units>score on a scale</units>
<param>Mean</param>
<dispersion>Full Range</dispersion>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Measure</scope>
<count_list>
<count group_id="O1" value="5"/>
</count_list>
</analyzed>
</analyzed_list>
<class_list>
<class>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="2.9" lower_limit="0.4" upper_limit="8.7"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
</outcome>
<outcome>
<type>Primary</type>
<title>How Present Did Individuals in the VR-BA Treatment Feel?</title>
<description>This was measured using the Presence Questionnaire, which asks three questions and asks the participants to circle either Not at all (0), Slightly (1), Moderately (2), Strongly (3), or Very Strongly (4), yielding a range of 0-12 (higher scores indicate greater presence).</description>
<time_frame>Assessed at the end of week 3, after session 4</time_frame>
<population>This outcome measure was assessed in the Virtual Reality Behavioral Activation group only.</population>
<group_list>
<group group_id="O1">
<title>Virtual Reality Behavioral Activation</title>
<description>Participants engage in VR activities over the week for three weeks.</description>
</group>
</group_list>
<measure>
<title>How Present Did Individuals in the VR-BA Treatment Feel?</title>
<description>This was measured using the Presence Questionnaire, which asks three questions and asks the participants to circle either Not at all (0), Slightly (1), Moderately (2), Strongly (3), or Very Strongly (4), yielding a range of 0-12 (higher scores indicate greater presence).</description>
<population>This outcome measure was assessed in the Virtual Reality Behavioral Activation group only.</population>
<units>score on a scale</units>
<param>Mean</param>
<dispersion>Standard Deviation</dispersion>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Measure</scope>
<count_list>
<count group_id="O1" value="5"/>
</count_list>
</analyzed>
</analyzed_list>
<class_list>
<class>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="7.1" spread="2.8"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
</outcome>
<outcome>
<type>Secondary</type>
<title>Change in Depression Scores on the PHQ-9 From Baseline to Session 4, Compared Across Three Study Arms</title>
<description>How participants' depression scores on the Patient Health Questionnaire (PHQ-9) change over time using VR-BA compared to BA in real life and a waitlist control. The PHQ-9 is a 9-question screener with a score range of 0-29, with 29 indicating the most severe depression and 0 indicating a lack of depression symptoms. The greater the change over time, the greater the symptom reduction.</description>
<time_frame>Assessed at baseline and session 4.</time_frame>
<population>Protocol Completers</population>
<group_list>
<group group_id="O1">
<title>Virtual Reality Behavioral Activation</title>
<description>Participants engage in VR activities over the week for three weeks.</description>
</group>
<group group_id="O2">
<title>Behavioral Activation in Real-life</title>
<description>Participants engage in real life pleasurable activities over the week for three weeks.</description>
</group>
<group group_id="O3">
<title>Waitlist Control</title>
<description>Participants answer the PHQ-9 weekly for four sessions.</description>
</group>
</group_list>
<measure>
<title>Change in Depression Scores on the PHQ-9 From Baseline to Session 4, Compared Across Three Study Arms</title>
<description>How participants' depression scores on the Patient Health Questionnaire (PHQ-9) change over time using VR-BA compared to BA in real life and a waitlist control. The PHQ-9 is a 9-question screener with a score range of 0-29, with 29 indicating the most severe depression and 0 indicating a lack of depression symptoms. The greater the change over time, the greater the symptom reduction.</description>
<population>Protocol Completers</population>
<units>score on a scale</units>
<param>Mean</param>
<dispersion>Full Range</dispersion>
<analyzed_list>
<analyzed>
<units>Participants</units>
<scope>Measure</scope>
<count_list>
<count group_id="O1" value="3"/>
<count group_id="O2" value="3"/>
<count group_id="O3" value="4"/>
</count_list>
</analyzed>
</analyzed_list>
<class_list>
<class>
<category_list>
<category>
<measurement_list>
<measurement group_id="O1" value="5.7" lower_limit="2" upper_limit="12"/>
<measurement group_id="O2" value="3" lower_limit="2" upper_limit="5"/>
<measurement group_id="O3" value=".25" lower_limit="-5" upper_limit="3"/>
</measurement_list>
</category>
</category_list>
</class>
</class_list>
</measure>
</outcome>
</outcome_list>
<reported_events>
<time_frame>3-weeks</time_frame>
<group_list>
<group group_id="E1">
<title>Virtual Reality Behavioral Activation</title>
<description>Participants engage in VR activities over the week for three weeks.</description>
</group>
<group group_id="E2">
<title>Behavioral Activation in Real-life</title>
<description>Participants engage in real life pleasurable activities over the week for three weeks.</description>
</group>
<group group_id="E3">
<title>Waitlist Control</title>
<description>Participants answer the PHQ-9 weekly for four sessions.</description>
</group>
</group_list>
<serious_events>
<category_list>
<category>
<title>Total</title>
<event_list>
<event>
<sub_title>Total, all-cause mortality</sub_title>
<counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
<counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
<counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
</event>
<event>
<sub_title>Total, serious adverse events</sub_title>
<counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
<counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
<counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
</event>
</event_list>
</category>
</category_list>
</serious_events>
<other_events>
<frequency_threshold>0</frequency_threshold>
<category_list>
<category>
<title>Total</title>
<event_list>
<event>
<sub_title>Total, other adverse events</sub_title>
<counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
<counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
<counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
</event>
</event_list>
</category>
</category_list>
</other_events>
</reported_events>
<certain_agreements>
<pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
<restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
</certain_agreements>
<limitations_and_caveats>This study did not enroll to its planned sample size of 30.</limitations_and_caveats>
<point_of_contact>
<name_or_title>Margot Paul</name_or_title>
<organization>Stanford University</organization>
<phone>415-625-3127</phone>
<email>mdpaul@stanford.edu</email>
</point_of_contact>
</clinical_results>
</clinical_study>
|
The primary purpose of this study is to test the safety and feasibility of virtual reality
(VR) technology in the use of behavioral activation (BA) as a treatment for major depressive
disorder (MDD). The secondary purpose of this study is to examine whether any evidence of
clinical efficacy exists for VR delivered BA.
This is a treatment development trial. Participants will be randomly assigned to BA in VR, BA
in real-life, or a waitlist control group. The former two groups will follow a BA protocol
developed for primary care settings over a four-week treatment period. This study is taking
place over Zoom, due to COVID-19.
Inclusion Criteria:
- Patient must meet DSM V criteria for MDD
- Patient must be at least 18 years of age
- Patient must be English speaking
Exclusion Criteria:
- Substance Use Disorders in past year
- Any psychosis or bipolar I disorder
- Any seizure in the last 6 months or untreated epilepsy
- Current nonsuicidal self-injury or parasuicidal behavior
- Current suicidal urges and intent
|
NCT0426xxxx/NCT04268329.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268329</url>
</required_header>
<id_info>
<org_study_id>2017-0725</org_study_id>
<nct_id>NCT04268329</nct_id>
</id_info>
<brief_title>Evaluating the Use of an Informational Head and Neck Cancer Website.</brief_title>
<official_title>Evaluating the Use of an Informational Head and Neck Cancer Website for Patient and Family Education</official_title>
<sponsors>
<lead_sponsor>
<agency>University of Illinois at Chicago</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>University of Illinois at Chicago</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
It can be difficult for head and neck cancer patients and their families to fully understand
the impact that cancer procedures and treatments can have on the cancer patients life.
Procedures used to treat head and neck cancer may result in significant changes to the
patients' physical appearance and/or functional abilities (talking, eating, and breathing).
The lack of understanding as it relates to the effects of cancer treatments can have a
significant impact on the patients post-operative success.

In an effort to help educate head and neck cancer patients and their families during this
difficult time, the UIC department of Otolaryngology-HNS has created an informational
website. The website is designed to educate cancer patients and their families regarding
various cancer treatments and therapies.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Head and neck cancer patients and their families often struggle to fully understand the
degree to which cancer procedures and treatments may have on the cancer patient's life. The
procedures involved in cancer treatment may result in significant changes to the patient's
physical appearance and/or functional abilities (talking, eating, and breathing).
Unfortunately, healthcare workers have a limited amount of time to spend educating their
patients on all of the possibilities that may result from cancer related treatments. This
lack of patient education and understanding can increase patient anxiety, compromise patient
compliance, and result in less than optimum long-term outcomes.

Many patients are using the internet to educate themselves and to help them make their health
care related decisions. However, for head and neck cancer patients, the information available
on head and neck cancer websites is somewhat limited. In many cases, the information fails to
provide adequate details as to the life changing, and at times disfiguring, results that head
and neck cancer related treatments can have.

In an effort to help educate head and neck cancer patients and their families during this
difficult time, the UIC department of Otolaryngology-HNS has created an informational
website. The website includes information and educational videos about what to expect during
the cancer treatment process. Specifically, the website is designed to educate cancer
patients and their families on 1) the procedures that may be used to treat their specific
cancer, 2) the side effects and post-operative hospital care of various treatments, 3) the
physical changes that are possible as a result of their treatment, 4) functional changes that
may occur as a result of their surgery/treatment, and 5) potential therapies that can be used
to help improve their long-term outcome. The purpose of the website is to provide an
educational and informative format, centered on head and neck cancer patients, that will help
improve patient knowledge, understanding, and expectations during the course of cancer
treatment and recovery.

Currently there are no studies that evaluate and or measure a change in patient/family member
knowledge about head and neck cancer surgeries based on internet based information. However,
there has been significant research related to the increased use of the internet for health
care related decisions. These studies show that patients and families are more frequently
turning to the internet and other forms of social media to learn about their diagnosis in
order to make informed decisions about their medical care. Studies have also shown that
websites are often written at a level well above the recommended reading level thereby
inhibiting patient education.

3.0 Objectives/Aims

The objectives of this research are to evaluate 1) the change in subject knowledge before and
after using the study head and neck cancer website, and 2) to determine whether a head and
neck website is beneficial to study subjects in providing information that will result in
improved compliance and ultimately long-term outcomes. Specifically, the PI's will be
evaluating how the website educates cancer patients and their families on 1) the procedures
that may be used to treat their specific cancer, 2) the side effects and post-operative care
of various treatments, 3) the physical changes that are possible as a result of their
treatment, 4) functional changes that may occur as a result of their surgery/treatment, and
5) potential therapies that can be used to minimize the physical and functional changes that
may result from their cancer care.
</textblock>
</detailed_description>
<overall_status>Terminated</overall_status>
<why_stopped>
The study was not providing useful information.
</why_stopped>
<start_date type="Actual">August 16, 2016</start_date>
<completion_date type="Actual">June 18, 2020</completion_date>
<primary_completion_date type="Actual">June 18, 2020</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Non-Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>Patient's with head and neck cancer and 1 of their family members will be asked to visit an instructional head and neck cancer website to learn about what they might expect during the process of head and neck cancer treatment.</intervention_model_description>
<primary_purpose>Supportive Care</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Evaluating the change in knowledge of head and neck cancer procedures before and after participants use of the study head and neck cancer website.</measure>
<time_frame>4 weeks</time_frame>
<description>Participants will be asked to complete an 8 item questionnaire measurement tool (Website Study Questionnaire) about head and neck cancer procedures during their initial study visit. The questionnaire will be used to measure the participant's understanding of head and neck procedures before and after the use of an educational website. The participants will be provided a link to an educational website about head and neck cancer and they will be asked to view the website on several occasions in order to learn more about head and neck cancer procedures and what they or their family member might experience during and after their treatments. One to 4 weeks after the initial visit the participant will be asked to once again complete the same 8 item questionnaire. An increase in knowledge will be measured by counting the number of correct answers on the questionnaires before and after use of the website.</description>
</primary_outcome>
<secondary_outcome>
<measure>The correlation between the use of an instructional head and neck cancer website and knowledge about head and neck cancer as measured by a study questionnaire.</measure>
<time_frame>4 weeks</time_frame>
<description>Participants will be asked to record the time and date they visit the website onto a provided study log sheet. The number of correct answers recorded by participants during the completion of the second visit questionnaire will be correlated to the amount of time the participant spent using the educational website. It is expected that participants that visit and spend the greatest amount of time reviewing the website will have a greater understanding (a better questionnaire score) than participants that fail to use the website or who use of the website minimally.
Participants will also complete an Otolaryngology/Head and Neck Surgery Website Study Survey that will be used to qualitatively measure if the participant found the educational website to be useful in their understanding of head and neck cancer.</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">14</enrollment>
<condition>Head and Neck Cancer</condition>
<arm_group>
<arm_group_label>Educational website: Patient</arm_group_label>
<arm_group_type>Other</arm_group_type>
<description>Patients with a head and neck cancer will be asked to complete an 8 item questionnaire during their clinic visit. Patients will be shown the head and neck website (available in both English and Spanish) by a member of the study investigation team on a computer and also given the URL address to the study website. Patients will be asked to review the material on the website between their initial visit and there second follow-up visit. The time between visits will be between 1 and 4 weeks. Patients will be asked to record the number of times they visit the website and the time spent during each visit. Patients will be given a log sheet to document their use/time on the website. During the 2nd clinic visit patients will be asked to complete the same questionnaire that they completed during their initial study visit along with an additional 7 item survey. Following completion of the 2 documents, the patient's participation in the study will be completed.</description>
</arm_group>
<arm_group>
<arm_group_label>Educational website: Family member</arm_group_label>
<arm_group_type>Other</arm_group_type>
<description>A family member of a patient with a head and neck cancer will be asked to complete an 8 item questionnaire during their clinic visit. They will be shown the head and neck website (available in both English and Spanish) by a member of the study investigation team on a computer and also given the URL address to the study website. They will be asked to review the material on the website between their relatives initial visit and there second follow-up visit. The time between visits will be between 1 and 4 weeks. The family member will be asked to record the number of times they visit the website and the time spent during each visit. They will be given a log sheet to document their use/time on the website. During the 2nd clinic visit the family member will be asked to complete the same questionnaire that they completed during their initial study visit along with an additional 7 item survey. Following completion of the 2 documents, their participation in the study will be completed.</description>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Educational website</intervention_name>
<description>A website is used to educate patients and family members about head and neck cancer.</description>
<arm_group_label>Educational website: Family member</arm_group_label>
<arm_group_label>Educational website: Patient</arm_group_label>
<other_name>Educational Website: Patient</other_name>
<other_name>Educational Website: Family Member</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Male and female subjects greater than 18 years of age.

2. Subjects that present to the UIC dept. of Otolaryngology-HNS with a head and neck
cancer requiring surgery of the tongue, mandibulectomy, neck dissection, laryngectomy,
or tracheostomy surgery and that have not previously had head and neck cancer
resection surgery. (The surgeries listed are currently available on the website.)

3. One (1) family member of the cancer subject who will be treated at UIC for a head and
neck cancer as noted in item 2 above, and who have not had a head and neck cancer
surgery resection themselves. Patients undergoing treatment will remain eligible to
participate independent of whether or not their family member takes part in the study.

4. Subjects that have access to the internet to view the study website either by using a
desktop or laptop computer, a tablet or a smartphone.

5. Subjects who are willing to document their time on the website for study purposes.

6. Both English and Spanish speaking subjects who are literate and are able to read from
a computer screen.

7. Subjects that understand the purpose and procedures of the study, who wish to
participate, and who sign the study consent.

Exclusion Criteria:

1. Subjects under 18 years of age.

2. Subjects who do not have a head and neck cancer, or a family member with recently
diagnosed head and neck cancer, or who have already had a head and neck cancer
resection surgery.

3. Subjects that do not have access to the internet.

4. Subjects that do not understand or are not willing to follow the procedures as
outlined in the study consent.

5. Subjects and/or their family member who cannot read or are legally blind.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Virginie Achim, MD</last_name>
<role>Principal Investigator</role>
<affiliation>University of Illinois at Chicago</affiliation>
</overall_official>
<location>
<facility>
<name>University of Illinois at Chicago</name>
<address>
<city>Chicago</city>
<state>Illinois</state>
<zip>60612</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<reference>
<citation>Kasabwala K, Agarwal N, Hansberry DR, Baredes S, Eloy JA. Readability assessment of patient education materials from the American Academy of Otolaryngology--Head and Neck Surgery Foundation. Otolaryngol Head Neck Surg. 2012 Sep;147(3):466-71. doi: 10.1177/0194599812442783. Epub 2012 Apr 3.</citation>
<PMID>22473833</PMID>
</reference>
<reference>
<citation>Lopez-Jornet P, Camacho-Alonso F. The quality of internet sites providing information relating to oral cancer. Oral Oncol. 2009 Sep;45(9):e95-8. doi: 10.1016/j.oraloncology.2009.03.017. Epub 2009 May 19.</citation>
<PMID>19457707</PMID>
</reference>
<reference>
<citation>Rice RE. Influences, usage, and outcomes of Internet health information searching: multivariate results from the Pew surveys. Int J Med Inform. 2006 Jan;75(1):8-28. doi: 10.1016/j.ijmedinf.2005.07.032. Epub 2005 Aug 24.</citation>
<PMID>16125453</PMID>
</reference>
<verification_date>April 2021</verification_date>
<study_first_submitted>January 30, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>April 6, 2021</last_update_submitted>
<last_update_submitted_qc>April 6, 2021</last_update_submitted_qc>
<last_update_posted type="Actual">April 9, 2021</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>University of Illinois at Chicago</investigator_affiliation>
<investigator_full_name>Virginie Achim</investigator_full_name>
<investigator_title>Assitant Professor</investigator_title>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Head and Neck Neoplasms</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
<ipd_description>Case Report Forms (CRF), questionnaires, and surveys will be assigned a code number that corresponds to the participant. A copy of the master list with subject name, MRN, and code number will be maintained by the study investigator in a separate file on a secured, password protected, encrypted UI Health System server. The coded data, without PHI, will be maintained on study personnel laptop computers. A hard copy of each subject's consent will be kept by the PI in a locked office in the EEI clinic Rm 3.87.
Study data will be gathered from the cancer subjects medical record, directly from study subjects, and from completed surveys and questionnaires. Data with the linking code for each subject will be kept in an excel file database on an encrypted password protected laptop computer. Only approved study personnel will have access to the study data and the Master List.</ipd_description>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
It can be difficult for head and neck cancer patients and their families to fully understand
the impact that cancer procedures and treatments can have on the cancer patients life.
Procedures used to treat head and neck cancer may result in significant changes to the
patients' physical appearance and/or functional abilities (talking, eating, and breathing).
The lack of understanding as it relates to the effects of cancer treatments can have a
significant impact on the patients post-operative success.
In an effort to help educate head and neck cancer patients and their families during this
difficult time, the UIC department of Otolaryngology-HNS has created an informational
website. The website is designed to educate cancer patients and their families regarding
various cancer treatments and therapies.
Head and neck cancer patients and their families often struggle to fully understand the
degree to which cancer procedures and treatments may have on the cancer patient's life. The
procedures involved in cancer treatment may result in significant changes to the patient's
physical appearance and/or functional abilities (talking, eating, and breathing).
Unfortunately, healthcare workers have a limited amount of time to spend educating their
patients on all of the possibilities that may result from cancer related treatments. This
lack of patient education and understanding can increase patient anxiety, compromise patient
compliance, and result in less than optimum long-term outcomes.
Many patients are using the internet to educate themselves and to help them make their health
care related decisions. However, for head and neck cancer patients, the information available
on head and neck cancer websites is somewhat limited. In many cases, the information fails to
provide adequate details as to the life changing, and at times disfiguring, results that head
and neck cancer related treatments can have.
In an effort to help educate head and neck cancer patients and their families during this
difficult time, the UIC department of Otolaryngology-HNS has created an informational
website. The website includes information and educational videos about what to expect during
the cancer treatment process. Specifically, the website is designed to educate cancer
patients and their families on 1) the procedures that may be used to treat their specific
cancer, 2) the side effects and post-operative hospital care of various treatments, 3) the
physical changes that are possible as a result of their treatment, 4) functional changes that
may occur as a result of their surgery/treatment, and 5) potential therapies that can be used
to help improve their long-term outcome. The purpose of the website is to provide an
educational and informative format, centered on head and neck cancer patients, that will help
improve patient knowledge, understanding, and expectations during the course of cancer
treatment and recovery.
Currently there are no studies that evaluate and or measure a change in patient/family member
knowledge about head and neck cancer surgeries based on internet based information. However,
there has been significant research related to the increased use of the internet for health
care related decisions. These studies show that patients and families are more frequently
turning to the internet and other forms of social media to learn about their diagnosis in
order to make informed decisions about their medical care. Studies have also shown that
websites are often written at a level well above the recommended reading level thereby
inhibiting patient education.
3.0 Objectives/Aims
The objectives of this research are to evaluate 1) the change in subject knowledge before and
after using the study head and neck cancer website, and 2) to determine whether a head and
neck website is beneficial to study subjects in providing information that will result in
improved compliance and ultimately long-term outcomes. Specifically, the PI's will be
evaluating how the website educates cancer patients and their families on 1) the procedures
that may be used to treat their specific cancer, 2) the side effects and post-operative care
of various treatments, 3) the physical changes that are possible as a result of their
treatment, 4) functional changes that may occur as a result of their surgery/treatment, and
5) potential therapies that can be used to minimize the physical and functional changes that
may result from their cancer care.
Inclusion Criteria:
1. Male and female subjects greater than 18 years of age.
2. Subjects that present to the UIC dept. of Otolaryngology-HNS with a head and neck
cancer requiring surgery of the tongue, mandibulectomy, neck dissection, laryngectomy,
or tracheostomy surgery and that have not previously had head and neck cancer
resection surgery. (The surgeries listed are currently available on the website.)
3. One (1) family member of the cancer subject who will be treated at UIC for a head and
neck cancer as noted in item 2 above, and who have not had a head and neck cancer
surgery resection themselves. Patients undergoing treatment will remain eligible to
participate independent of whether or not their family member takes part in the study.
4. Subjects that have access to the internet to view the study website either by using a
desktop or laptop computer, a tablet or a smartphone.
5. Subjects who are willing to document their time on the website for study purposes.
6. Both English and Spanish speaking subjects who are literate and are able to read from
a computer screen.
7. Subjects that understand the purpose and procedures of the study, who wish to
participate, and who sign the study consent.
Exclusion Criteria:
1. Subjects under 18 years of age.
2. Subjects who do not have a head and neck cancer, or a family member with recently
diagnosed head and neck cancer, or who have already had a head and neck cancer
resection surgery.
3. Subjects that do not have access to the internet.
4. Subjects that do not understand or are not willing to follow the procedures as
outlined in the study consent.
5. Subjects and/or their family member who cannot read or are legally blind.
|
NCT0426xxxx/NCT04268342.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268342</url>
</required_header>
<id_info>
<org_study_id>17/180</org_study_id>
<nct_id>NCT04268342</nct_id>
</id_info>
<brief_title>Gonorrhoea Resistance Assessment by Nucleic Acid Detection (GRANDII)</brief_title>
<acronym>GRANDII</acronym>
<official_title>Gonorrhoea Resistance Assessment by Nucleic Acid Detection: A Program Evaluation</official_title>
<sponsors>
<lead_sponsor>
<agency>The University of Queensland</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Kirby Institute</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>Monash University</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>South Australian Health and Medical Research Institute</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>University of Melbourne</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>University of California, Los Angeles</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>Griffith University</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>Queensland Health</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>St Vincent's Hospital, Sydney</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>SpeeDx Pty. Ltd.</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>NSW Health Pathology</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>University of Sydney</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>The University of Queensland</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Three sexual health clinical services across Australia and their associated pathology testing
laboratories are implementing a new management program for gonorrhoea infection. The services
are implementing the use of gonorrhoea drug resistance testing as part of routine clinical
and laboratory practice, where drug resistance test results are provided to clinicians
quickly to guide choice of antibiotic therapy. Clinicians will identify gonorrhoea infection
that is ciprofloxacin susceptible so that it can be treated with ciprofloxacin therapy,
rather than ceftriaxone.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
This study aims to demonstrate the feasibility of a new approach to antibiotic stewardship
based on individually tailored antibiotic prescribing. Three sexual health clinical services
in New South Wales Australia with high caseloads of gay and bisexual men will adopt a new
management practice for gonorrhoea infection involving provision of tailored antibiotic
therapy by clinicians at the time of gonorrhoea diagnosis and treatment, guided by the
results of resistance testing. The services are implementing the use of gonorrhoea drug
resistance testing as part of routine clinical and laboratory practice, where drug resistance
test results are provided to clinicians quickly to guide choice of antibiotic therapy. This
differs from existing practice where the prolonged turn-around times for drug resistance
testing results mean clinicians must prescribe drug therapy without knowing these results.
This can lead to increasing levels of drug resistance to ceftriaxone.

The drug resistance test used in the new program detects genetic material (nucleic acids). It
was developed and validated in Australia and is as accurate as existing culture-based drug
resistance testing but provides quicker results. Patients treated presumptively at their
first clinic visit will be treated with standard of care ceftriaxone. However, for cases
treated at the return visit, clinicians will identify gonorrhoea infection that is
ciprofloxacin susceptible so that it can be treated with ciprofloxacin therapy, rather than
ceftriaxone. This will preserve ceftriaxone for situations where it must be used as the only
effective drug available. Established patient follow-up procedures at clinical services will
confirm that treatment has been successful.

Quantitative data from the clinical and laboratory services in the study will be used to
assess the proportion of all cases treated with ceftriaxone. The cure rate in gonorrhoea
cases within the new management program versus standard care will also be assessed which will
help illustrate the impact of the new management program.
</textblock>
</detailed_description>
<overall_status>Active, not recruiting</overall_status>
<start_date type="Actual">April 26, 2022</start_date>
<completion_date type="Anticipated">July 30, 2024</completion_date>
<primary_completion_date type="Anticipated">July 30, 2023</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Non-Randomized</allocation>
<intervention_model>Sequential Assignment</intervention_model>
<intervention_model_description>A before-after study design will be used to evaluate the proportion of all cases treated with ceftriaxone at return visit within standard care and the new management program respectively. Cure rates within the standard care and the new management program will also be assessed which will help illustrate the impact of the new management program.</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Change in ceftriaxone use</measure>
<time_frame>12 months after implementation commences</time_frame>
<description>The proportion of gonorrhoea cases treated at the return visit with ceftriaxone</description>
</primary_outcome>
<secondary_outcome>
<measure>Cure rate</measure>
<time_frame>At 12 months after implementation commences</time_frame>
<description>The proportion of gonorrhoea cases treated at the return visit with a negative test of cure within 2-4 weeks within the new management program versus standard care</description>
</secondary_outcome>
<secondary_outcome>
<measure>Acceptability</measure>
<time_frame>1-12 months after implementation commences</time_frame>
<description>The acceptability of the new management program to clinic and laboratory staff and stakeholders will be assessed through a qualitative research study design. Service staff and external stakeholders will be selected purposively to take part in semi-structured in-depth interviews at different stages of the study. Sampling will be informed by data saturation. All interviews will be audio-recorded and transcribed verbatim. Qualitative data will be analysed using a system of thematic 'open' and 'axial' coding. Findings will be descriptive.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Cost effectiveness</measure>
<time_frame>12 months after implementation commences</time_frame>
<description>The cost effectiveness of the new management program compared to standard care from the health service perspective</description>
</secondary_outcome>
<secondary_outcome>
<measure>Process evaluation</measure>
<time_frame>12 months after implementation commences</time_frame>
<description>To document the processes involved in the implementation of the new management program</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">1626</enrollment>
<condition>Drug Resistance, Microbial</condition>
<condition>Antimicrobial Stewardship</condition>
<condition>Gonorrhea</condition>
<arm_group>
<arm_group_label>Standard care</arm_group_label>
<arm_group_type>No Intervention</arm_group_type>
<description>When clinical services are in the standard case phase of the study, all cases of gonorrhoea infection diagnosed at those services will be managed according to current standard of care management guidelines i.e. all cases of gonorrhoea infection will be treated with ceftriaxone by injection plus oral azithromycin tablets as first line therapy, regardless of whether the treatment is given at the initial clinic or the return clinic visit.</description>
</arm_group>
<arm_group>
<arm_group_label>Implementation</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>When clinical services are assigned to the implementation phase, first line treatment for gonorrhoea infection for patients treated at their first clinic visit will remain the same as it is currently: ceftriaxone by injection plus oral azithromycin tablets. However, patients who are not treated presumptively will be treated at their return visit on the basis of the drug resistance test results. Patients with gonorrhoea infection that is shown to be susceptible to ciprofloxacin will be treated with oral ciprofloxacin therapy when they return for review at clinical services in the implementation phase. Patients with gonorrhoea infection that is not susceptible to ciprofloxacin or with an indeterminate ciprofloxacin result will be treated with ceftriaxone by injection.</description>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Resistance guided treatment for gonorrhoea infection</intervention_name>
<description>For cases of gonorrhoea infection treated at the return visit, a nucleic acid assay will be used to determine individual eligibility for ciprofloxacin treatment</description>
<arm_group_label>Implementation</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Patients diagnosed with gonorrhoea infection at the return visit

Exclusion Criteria:

- Patients for whom ciprofloxacin is contraindicated
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>N/A</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>David Whiley, PhD</last_name>
<role>Principal Investigator</role>
<affiliation>The University of Queensland</affiliation>
</overall_official>
<location>
<facility>
<name>University of Queensland</name>
<address>
<city>Brisbane</city>
<state>Queensland</state>
<zip>0733651111</zip>
<country>Australia</country>
</address>
</facility>
</location>
<location_countries>
<country>Australia</country>
</location_countries>
<verification_date>October 2022</verification_date>
<study_first_submitted>February 6, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>November 21, 2022</last_update_submitted>
<last_update_submitted_qc>November 21, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">November 28, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Gonorrhea</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
<ipd_description>There is not a plan to make individual participant data available at this stage.</ipd_description>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Three sexual health clinical services across Australia and their associated pathology testing
laboratories are implementing a new management program for gonorrhoea infection. The services
are implementing the use of gonorrhoea drug resistance testing as part of routine clinical
and laboratory practice, where drug resistance test results are provided to clinicians
quickly to guide choice of antibiotic therapy. Clinicians will identify gonorrhoea infection
that is ciprofloxacin susceptible so that it can be treated with ciprofloxacin therapy,
rather than ceftriaxone.
This study aims to demonstrate the feasibility of a new approach to antibiotic stewardship
based on individually tailored antibiotic prescribing. Three sexual health clinical services
in New South Wales Australia with high caseloads of gay and bisexual men will adopt a new
management practice for gonorrhoea infection involving provision of tailored antibiotic
therapy by clinicians at the time of gonorrhoea diagnosis and treatment, guided by the
results of resistance testing. The services are implementing the use of gonorrhoea drug
resistance testing as part of routine clinical and laboratory practice, where drug resistance
test results are provided to clinicians quickly to guide choice of antibiotic therapy. This
differs from existing practice where the prolonged turn-around times for drug resistance
testing results mean clinicians must prescribe drug therapy without knowing these results.
This can lead to increasing levels of drug resistance to ceftriaxone.
The drug resistance test used in the new program detects genetic material (nucleic acids). It
was developed and validated in Australia and is as accurate as existing culture-based drug
resistance testing but provides quicker results. Patients treated presumptively at their
first clinic visit will be treated with standard of care ceftriaxone. However, for cases
treated at the return visit, clinicians will identify gonorrhoea infection that is
ciprofloxacin susceptible so that it can be treated with ciprofloxacin therapy, rather than
ceftriaxone. This will preserve ceftriaxone for situations where it must be used as the only
effective drug available. Established patient follow-up procedures at clinical services will
confirm that treatment has been successful.
Quantitative data from the clinical and laboratory services in the study will be used to
assess the proportion of all cases treated with ceftriaxone. The cure rate in gonorrhoea
cases within the new management program versus standard care will also be assessed which will
help illustrate the impact of the new management program.
Inclusion Criteria:
- Patients diagnosed with gonorrhoea infection at the return visit
Exclusion Criteria:
- Patients for whom ciprofloxacin is contraindicated
|
NCT0426xxxx/NCT04268355.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268355</url>
</required_header>
<id_info>
<org_study_id>CambridgeHA</org_study_id>
<secondary_id>UH3AT009145</secondary_id>
<nct_id>NCT04268355</nct_id>
</id_info>
<brief_title>MINDFUL-PC for Portuguese Speakers Pilot Study 2020</brief_title>
<official_title>MINDFUL-PC for Portuguese Speakers Pilot #2 Study 2020 (Integrating Mindfulness Into the Patient-Centered Medical Home)</official_title>
<sponsors>
<lead_sponsor>
<agency>Cambridge Health Alliance</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>National Center for Complementary and Integrative Health (NCCIH)</agency>
<agency_class>NIH</agency_class>
</collaborator>
</sponsors>
<source>Cambridge Health Alliance</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
<is_us_export>No</is_us_export>
</oversight_info>
<brief_summary>
<textblock>
The study evaluates the effects of the Mindfulness Training for Primary Care (MTPC)
Portuguese-adapted version on heart rate variability during a demanding cognitive task. The
study also evaluates the effects on mental health, quality of life, self-regulation and
behavior outcomes. The study will also complete the MTPC cultural adaptation process for
Brazilian culture.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
This single-arm, pre-post, non-randomized, unblinded, pilot trial evaluates the effects of
Mindfulness Training for Primary Care (MTPC) Portuguese-adapted version on heart rate
variability during a demanding cognitive task, i.e., Sustained Attention to Response Task
(SART). Secondary aims are the following: 1) to measure pre/post outcomes for a) mental
health (anxiety, depression, stress); b) quality of life; c) self-regulation
(self-compassion, mindfulness, interoceptive awareness, difficulties in emotion regulation);
and to determine the rate of d) chronic disease self-management action plan initiation; and
2) to complete the MTPC cultural adaptation for Brazilian culture through a) Satisfaction and
Suggestions Survey; and b) Interviews of MTPC Group Leaders about their experience teaching
the program Portuguese-adapted version.
</textblock>
</detailed_description>
<overall_status>Terminated</overall_status>
<why_stopped>
In order to ensure patients and research staff safety due to COVID-19 pandemic
</why_stopped>
<start_date type="Actual">January 21, 2020</start_date>
<completion_date type="Actual">April 10, 2020</completion_date>
<primary_completion_date type="Actual">April 10, 2020</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<intervention_model_description>Single-arm, pre-post, non-randomized, unblinded pilot trial including up to 36 participants over 2 MTPC group cohorts</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>High-Frequency power (HF) - Heart Rate Variability (HRV) during Sustained Attention to Response Task (SART) last 5 minutes</measure>
<time_frame>Week 9</time_frame>
<description>High-Frequency power (HF) - Heart Rate Variability (HRV) during Sustained Attention to Response Task (SART) last 5 minutes will be measured using Biostamp nPoint® medical device. During SART participants complete a computerized test measuring sustained attention and response inhibition. They are asked to press a key in response to rapidly displayed integers (1-9) and withhold a response to a designated "no-go" integer.</description>
</primary_outcome>
<secondary_outcome>
<measure>Root Mean Square of the Successive Differences (RMSSD) - Heart Rate Variability (HRV) during Sustained Attention to Response Task (SART) last 5 minutes</measure>
<time_frame>Week 9</time_frame>
<description>Root Mean Square of the Successive Differences (RMSSD) - Heart Rate Variability (HRV) during Sustained Attention to Response Task (SART) last 5 minutes will be measured using Biostamp nPoint® medical device. During SART participants complete a computerized test measuring sustained attention and response inhibition. They are asked to press a key in response to rapidly displayed integers (1-9) and withhold a response to a designated "no-go" integer.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Perceived Stress Scale (PSS-14)</measure>
<time_frame>Week 8</time_frame>
<description>The Perceived Stress Scale (PSS-14) (14 items) measures the degree to which situations in life are stressful. Items are designed to evaluate how overloaded, unpredictable, and uncontrollable one finds one's life. Each item is scored on a 5 point Likert scale from 0 (Never) to 4 (Very often).</description>
</secondary_outcome>
<secondary_outcome>
<measure>Patient Reported Outcomes Measurement Information System - Anxiety Short Form (PROMIS-ASF)</measure>
<time_frame>Week 8</time_frame>
<description>The Patient Reported Outcomes Measurement Information System - Anxiety Short Form 8a (PROMIS-ASF) is an 8-item scale used to assess patient-reported health status for anxiety. PROMIS instruments are funded by the National Institutes of Health (NIH) and used to reliably and validly measure patient-reported outcomes for clinical research and practice. Participants are asked to rate their experience of the item in the past seven days on a 5-point scale from 1 (Never) to 5 (Always).</description>
</secondary_outcome>
<secondary_outcome>
<measure>Patient Reported Outcomes Measurement Information System - Depression Short Form (PROMIS-DSF)</measure>
<time_frame>Week 8</time_frame>
<description>The Patient Reported Outcomes Measurement Information System - Depression Short Form 8a (PROMIS-DSF) is an 8-item scale used to assess patient-reported health status for depression. PROMIS instruments are funded by the National Institutes of Health (NIH) and used to reliably and validly measure patient-reported outcomes for clinical research and practice. Participants are asked to rate their experience of the item in the past seven days on a 5-point scale from 1 (Never) to 5 (Always).</description>
</secondary_outcome>
<other_outcome>
<measure>High-Frequency power (HF) - Heart Rate Variability (HRV) during four 5-minute Sustained Attention to Response Task (SART) time blocks</measure>
<time_frame>Week 9</time_frame>
<description>High-Frequency power (HF) - Heart Rate Variability (HRV) during four 5-minute Sustained Attention to Response Task (SART) time blocks will be measured using Biostamp nPoint® medical device. During SART participants complete a computerized test measuring sustained attention and response inhibition. They are asked to press a key in response to rapidly displayed integers (1-9) and withhold a response to a designated "no-go" integer. Relationship between HF-HRV and SART performance will be evaluated and the effect of over time during the demanding SART task will also be evaluated.</description>
</other_outcome>
<other_outcome>
<measure>Root Mean Square of the Successive Differences (RMSSD) - Heart Rate Variability (HRV) during four 5-minute Sustained Attention to Response Task (SART) time blocks</measure>
<time_frame>Week 9</time_frame>
<description>Root Mean Square of the Successive Differences (RMSSD) - Heart Rate Variability (HRV) during four 5-minute Sustained Attention to Response Task (SART) time blocks will be measured using Biostamp nPoint® medical device. During SART participants complete a computerized test measuring sustained attention and response inhibition. They are asked to press a key in response to rapidly displayed integers (1-9) and withhold a response to a designated "no-go" integer. Relationship between RMSSD and SART performance will be evaluated and the effect of over time during the demanding SART task will also be evaluated.</description>
</other_outcome>
<other_outcome>
<measure>Action Plan Initiation Survey (APIS-5)</measure>
<time_frame>Week 9</time_frame>
<description>Patient self-reported Action Plan Initiation is based on two-item in the APIS-5 self-report survey in which patients are asked to list their action plan SMART goal, if they met the goal and how much control they had over meeting the goal. The main outcome is a single-item response determining whether they met or did not meet the goal using a 7-point Likert scale (ranging from 1-7) with scores >=5 representing self-reported initiation of the goal.</description>
</other_outcome>
<other_outcome>
<measure>World Health Organization Quality of Life- BREF (WHOQOL-BREF)</measure>
<time_frame>Week 8</time_frame>
<description>The World Health Organization has developed a quality of life instrument, the WHOQOL, which captures many subjective aspects of quality of life. The WHOQOL-BREF is a WHOQOL shorter version, comprises 26 items that produces scores for four domains related to quality of life: physical health, psychological, social relationships and environment. It also includes one facet on overall quality of life and general health.</description>
</other_outcome>
<other_outcome>
<measure>Multidimensional Assessment of Interoceptive Awareness (MAIA)</measure>
<time_frame>Week 8</time_frame>
<description>The Multidimensional Assessment of Interoceptive Awareness (MAIA) is a 32-item self-report scale designed to assess multiple aspects of interoception and interoceptive awareness. The 6 point Likert scale (ranging from 0-6) assesses 8 aspects of interoceptive awareness: noticing, not-distracting, not-worrying, attention regulation, emotional awareness, self-regulation, body listening, and trusting. Subscales are averaged, and a higher total score represents a better outcome.</description>
</other_outcome>
<other_outcome>
<measure>Difficulty in Emotion Regulation Scale (DERS)</measure>
<time_frame>Week 8</time_frame>
<description>The Difficulties in Emotion Regulation (DERS) Scale is a 36-item self-report scale designed to assess emotional dysregulation using a 5 point Likert scale. The scale assesses 6 aspects of emotional dysregulation: non-acceptance of emotional responses, difficulties engaging in goal directed behavior, impulse control difficulties, lack of emotional awareness, limited access to emotion regulation strategies, and lack of emotional clarity. Subscales are summed and a lower total score represents a better outcome.</description>
</other_outcome>
<other_outcome>
<measure>Five Facet Mindfulness Questionnaire (FFMQ)</measure>
<time_frame>Week 8</time_frame>
<description>The Five Facet Mindfulness Questionnaire (FFMQ) is a 39-item scale that examines five factors that represent aspects of the current empirical conception of mindfulness. These five facets include: "observing, describing, acting with awareness, non-judging of inner experience, and non-reactivity to inner experience." Participants rate their degree of agreement with each of the items on a Likert-type scale ranging from 1 (Never or very rarely true) to 5 (Very often or always true), with higher scores indicating higher experience of mindfulness.</description>
</other_outcome>
<other_outcome>
<measure>Self-Compassion Scale (SCS)</measure>
<time_frame>Week 8</time_frame>
<description>The Self-Compassion Scale is composed by 26 items measuring six components of self-compassion: self-kindness, self-judgment, common humanity, isolation, mindfulness and over-identification.The items are rated on a five-point response scale ranging from 1 (almost never) to 5 (almost always).</description>
</other_outcome>
<other_outcome>
<measure>Satisfaction Survey</measure>
<time_frame>Week 8</time_frame>
<description>Satisfaction Survey is an 18-item survey contains two parts. First is a series of 12 questions scored on a 5-point Likert scale from 1 (Strongly Disagree/Poor) to 5 (Strongly Agree/Excellent), with statements such as "I found this program helpful." Next is a series of six open-ended questions in which patients enter a written response to statements including "The most important thing I learned during this program."</description>
</other_outcome>
<other_outcome>
<measure>Suggestions Survey</measure>
<time_frame>Week 8</time_frame>
<description>The Suggestions Survey consist of 4 questions focusing on the intervention cultural aspects.</description>
</other_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Actual">15</enrollment>
<condition>Depression</condition>
<condition>Anxiety Disorders</condition>
<condition>Stress Related Disorder</condition>
<condition>Adjustment Disorders</condition>
<condition>Chronic Illness</condition>
<arm_group>
<arm_group_label>Mindfulness Training for Primary Care</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Mindfulness Training for Primary Care (MTPC) is a primary care adaptation that includes core common Mindfulness-Based Intervention (MBI) elements integrated with novel mindfulness-oriented behavior change elements into a format that is adaptable to delivery in primary care health centers</description>
</arm_group>
<intervention>
<intervention_type>Behavioral</intervention_type>
<intervention_name>Mindfulness Training for Primary Care</intervention_name>
<description>MTPC is a referral-based, insurance-reimbursable 8-week program delivered as group psychotherapy by Patient-Centered Medical Home-integrated behavioral clinicians or as an 8-week primary care group visit delivered by a primary care provider. MTPC groups are 2 hours for 8 weeks with a 7-hour weekend day of silent practice. MTPC emphasizes mindfulness-oriented skills for self-regulation, self-management of chronic illness, and health behavior change. All participants complete an action plan during Week 7. Participants are called every two weeks for the first eight weeks for 5-10 minute engagement calls which focus helping participants cultivate a relationship with study staff, giving participants a place to ask questions, and supporting participants in completing study visits.</description>
<arm_group_label>Mindfulness Training for Primary Care</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Current CHA patient with an enrolled CHA primary care doctor.

- CHA patients 18 years of age and older.

- Able to tolerate and participate in interviews and engage in all procedures.

- Diagnosis eligible to be covered by insurance for group visits (e.g., anxiety
disorder, depression, stress disorders including adjustment disorder related to
chronic illness, pain, insomnia, etc.).

- Must be able to fill out the study questionnaires on a computer or compatible mobile
device.

- Must be willing to attend the two computer task sessions.

- Able to give written consent in Portuguese

Exclusion Criteria:

- Any cognitive impairment that precludes informed consent.

- Patients who, in the opinion of the Principal Investigator, pose an imminent risk of
suicide or danger to self or others.

- Likelihood of potential incarceration such as a conviction or pending charges that may
potentially result in imprisonment.

- Behaviors that may cause disruption to a mindfulness group.

- Patients with symptoms of psychosis, thought disorder, and/or severe mental illness,
including schizophrenia, schizoaffective, bipolar disorder, or a current severe
episode of major depressive disorder.

- Refusal of insurance to cover group psychotherapy treatment may lead to exclusion from
participation in groups.

- Patients in their third trimester of pregnancy who foresee conflicts that preclude
their commitment to completing all activities.

- Patients with highly unstable medical problems that put them at a high risk of
hospitalization.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>70 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Zev Schuman-Olivier, MD</last_name>
<role>Principal Investigator</role>
<affiliation>Cambridge Health Alliance</affiliation>
</overall_official>
<location>
<facility>
<name>Cambridge Health Alliance</name>
<address>
<city>Somerville</city>
<state>Massachusetts</state>
<zip>02143</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<reference>
<citation>Gawande R, To MN, Pine E, Griswold T, Creedon TB, Brunel A, Lozada A, Loucks EB, Schuman-Olivier Z. Mindfulness Training Enhances Self-Regulation and Facilitates Health Behavior Change for Primary Care Patients: a Randomized Controlled Trial. J Gen Intern Med. 2019 Feb;34(2):293-302. doi: 10.1007/s11606-018-4739-5. Epub 2018 Dec 3.</citation>
<PMID>30511291</PMID>
</reference>
<reference>
<citation>Gawande R, Pine E, Griswold T, Creedon T, Vallejo Z, Rosenbaum E, Lozada A, Schuman-Olivier Z. Insurance-Reimbursable Mindfulness for Safety-Net Primary Care Patients: A Pilot Randomized Controlled Trial. Mindfulness (N Y). 2019 Sep;10(9):1744-1759. doi: 10.1007/s12671-019-01116-8. Epub 2019 Mar 18.</citation>
<PMID>32042349</PMID>
</reference>
<verification_date>February 2021</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 9, 2021</last_update_submitted>
<last_update_submitted_qc>February 9, 2021</last_update_submitted_qc>
<last_update_posted type="Actual">February 11, 2021</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Chronic Disease</mesh_term>
<mesh_term>Anxiety Disorders</mesh_term>
<mesh_term>Adjustment Disorders</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The study evaluates the effects of the Mindfulness Training for Primary Care (MTPC)
Portuguese-adapted version on heart rate variability during a demanding cognitive task. The
study also evaluates the effects on mental health, quality of life, self-regulation and
behavior outcomes. The study will also complete the MTPC cultural adaptation process for
Brazilian culture.
This single-arm, pre-post, non-randomized, unblinded, pilot trial evaluates the effects of
Mindfulness Training for Primary Care (MTPC) Portuguese-adapted version on heart rate
variability during a demanding cognitive task, i.e., Sustained Attention to Response Task
(SART). Secondary aims are the following: 1) to measure pre/post outcomes for a) mental
health (anxiety, depression, stress); b) quality of life; c) self-regulation
(self-compassion, mindfulness, interoceptive awareness, difficulties in emotion regulation);
and to determine the rate of d) chronic disease self-management action plan initiation; and
2) to complete the MTPC cultural adaptation for Brazilian culture through a) Satisfaction and
Suggestions Survey; and b) Interviews of MTPC Group Leaders about their experience teaching
the program Portuguese-adapted version.
Inclusion Criteria:
- Current CHA patient with an enrolled CHA primary care doctor.
- CHA patients 18 years of age and older.
- Able to tolerate and participate in interviews and engage in all procedures.
- Diagnosis eligible to be covered by insurance for group visits (e.g., anxiety
disorder, depression, stress disorders including adjustment disorder related to
chronic illness, pain, insomnia, etc.).
- Must be able to fill out the study questionnaires on a computer or compatible mobile
device.
- Must be willing to attend the two computer task sessions.
- Able to give written consent in Portuguese
Exclusion Criteria:
- Any cognitive impairment that precludes informed consent.
- Patients who, in the opinion of the Principal Investigator, pose an imminent risk of
suicide or danger to self or others.
- Likelihood of potential incarceration such as a conviction or pending charges that may
potentially result in imprisonment.
- Behaviors that may cause disruption to a mindfulness group.
- Patients with symptoms of psychosis, thought disorder, and/or severe mental illness,
including schizophrenia, schizoaffective, bipolar disorder, or a current severe
episode of major depressive disorder.
- Refusal of insurance to cover group psychotherapy treatment may lead to exclusion from
participation in groups.
- Patients in their third trimester of pregnancy who foresee conflicts that preclude
their commitment to completing all activities.
- Patients with highly unstable medical problems that put them at a high risk of
hospitalization.
|
NCT0426xxxx/NCT04268368.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268368</url>
</required_header>
<id_info>
<org_study_id>ICI-DISCOVER</org_study_id>
<nct_id>NCT04268368</nct_id>
</id_info>
<brief_title>Immune Related-adverse Events in Patients Receiving Immune Checkpoint Inhibitors</brief_title>
<acronym>ICI-DISCOVER</acronym>
<official_title>Incidence, Clinical Management and Molecular Factors Associated With the Development of Immune-related Adverse Events in Cancer Patients Receiving PD-1 and PD-L1 Inhibitors: a Prospective Observational Study</official_title>
<sponsors>
<lead_sponsor>
<agency>Università Politecnica delle Marche</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Università Politecnica delle Marche</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The recent introduction of anti-PD-1 (nivolumab and pembrolizumab) and anti- PD-L1
(atezolizumab, durvalumab, avelumab) immune checkpoint inhibitors revolutionized oncological
guidelines. Durable responses and prolongation of survival with these agents come at the
price of the development of immune related adverse events (irAEs). Innovative tools are
required in order to manage irAEs and to prevent their potential relapse, with the goal to
improve the outcome of patients. In this regard, the Investigators aim to develop a
multidisciplinary clinical pathway for cancer patients that are treated with immune
checkpoint inhibitors.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Recent evidences in immuno-oncology showed an important role of the immune system in tumor
control. In fact, immune response, both innate and adaptive one, is the first defensive
mechanism against cancer. However, several tumors, during their progression, develop an
immune-tolerance characterized by the activation of immune inhibitory pathways including PD-1
and PD-L1.

The recent introduction of anti-PD-1 (nivolumab and pembrolizumab) and anti-PD-L1
(atezolizumab, durvalumab, avelumab) immune checkpoint inhibitors revolutionized oncological
guidelines.

Currently, the aforementioned agents are approved for the treatment of advanced malignant
melanoma; non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) and the number of
treatment indications for immune checkpoint inhibitors is expanding. Durable responses and
prolongation of survival with these agents come at the price of the development of
immune-related adverse events (irAEs).

Immune-related adverse events are due to the loss of immune-tolerance towards structures of
the self, with the induction of chronic inflammation with an autoimmune mechanism that can
involve numerous organs and systems. The most frequent irAEs reported in clinical trials are
represented by skin toxicity, gastrointestinal toxicity, endocrine toxicity, pulmonary
toxicity, and others such as polymyalgia rheumatica, polyarthritis, myositis, nephritis,
polyradiculoneuritis, encephalitis and myocarditis.

The irAEs reported in clinical trials with nivolumab amount to a maximum of 85% considering
all grade of toxicities, while approximately 75% of patients treated with pembrolizumab
presented irAEs. Grade 3/4 irAEs were reported in 10% of patients treated with anti-PD-1.
With atezolizumab fewer patients had treatment-related grade 3 or 4 adverse events (15%).

In most cases, irAEs occur within some weeks after starting of immunotherapy; however these
toxicities have been reported later and also years after treatment discontinuation. The
development of irAEs is associated with significant morbidity and mortality in cancer
patients treated with immune checkpoint inhibitors, and therefore they may significantly
affect the quality of life, even in patients achieve the control of neoplastic disease.

The overseeing, early diagnosis and clinical management of immune checkpoint inhibitors'
toxicities in the clinical setting are, currently, not standardized.

Innovative tools are required in order to manage irAEs and to prevent their potential
relapse, with the goal to improve the outcome and quality of life of these patients.

In this regard, the Investigators also aim to evaluate a model of multidisciplinary clinical
pathway for cancer patients that are treated with immune checkpoint inhibitors in order to
improve their management and also ameliorate the quality of life of patients that develop
irAEs.
</textblock>
</detailed_description>
<overall_status>Unknown status</overall_status>
<last_known_status>Recruiting</last_known_status>
<start_date type="Actual">January 1, 2019</start_date>
<completion_date type="Anticipated">January 1, 2022</completion_date>
<primary_completion_date type="Anticipated">January 1, 2021</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Incidence of irAEs</measure>
<time_frame>24 months</time_frame>
<description>To determine the incidence and the characteristics of irAEs in a real-world setting</description>
</primary_outcome>
<primary_outcome>
<measure>Risk factors for irAEs</measure>
<time_frame>24 months</time_frame>
<description>To determine the risk factors for the development of irAEs</description>
</primary_outcome>
<primary_outcome>
<measure>Impact of irAEs</measure>
<time_frame>24 months</time_frame>
<description>To determine the impact of irAEs on patients' prognosis</description>
</primary_outcome>
<primary_outcome>
<measure>Therapies of irAEs</measure>
<time_frame>24 months</time_frame>
<description>To determine the effect of immunosuppressive therapies on tumor progression and patient's prognosis</description>
</primary_outcome>
<secondary_outcome>
<measure>Clinical care pathway</measure>
<time_frame>24 months</time_frame>
<description>To set up an integrated clinical care pathway for cancer patients that developed an irAE following immune checkpoint inhibitor administration</description>
</secondary_outcome>
<secondary_outcome>
<measure>Quality of life</measure>
<time_frame>24 months</time_frame>
<description>The quality of life will be measured by means of the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30). It is composed by five functional scales, three symptom scales, a global health status / QoL scale, and six single items. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Biomarkers</measure>
<time_frame>24 months</time_frame>
<description>To evaluate potential biomarkers that may predict the development of irAEs and/or the response to treatment in biological samples from cancer patients treated with immune checkpoint inhibitors</description>
</secondary_outcome>
<secondary_outcome>
<measure>Exploratory analyses</measure>
<time_frame>24 months</time_frame>
<description>To get better insights on the biological basis of irAEs the response to treatment in biological samples from cancer patients treated with immune checkpoint inhibitors</description>
</secondary_outcome>
<enrollment type="Anticipated">200</enrollment>
<condition>Cancer</condition>
<condition>Lung Cancer</condition>
<condition>Renal Cell Carcinoma</condition>
<condition>Melanoma</condition>
<biospec_retention>Samples With DNA</biospec_retention>
<biospec_descr>
<textblock>
Whole blood samples will be collected for the preparation of serum and plasma at the baseline
visit and at follow-up visits for all patients.
</textblock>
</biospec_descr>
<eligibility>
<study_pop>
<textblock>
Patients referring to the Oncology and Hematology Clinics of the Azienda Ospedaliero-
Universitaria Ospedali Riuniti di Ancona (Italy) may be enrolled.
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

1. Adult patients above 18 years of age;

2. Cyto-histological diagnosis of one of the following cancers:

1. advanced melanoma;

2. metastatic or locally advanced non-small cell lung cancer;

3. advanced renal cell carcinoma;

4. metastatic or locally advanced urotelial carcinoma;

5. squamous cell carcinoma of the head and neck;

6. Hodgkin lymphoma;

7. Merkel-cell carcinoma;

3. New prescription of one of the following PD-1/PD-L1 inhibitors:

1. nivolumab

2. pembrolizumab

3. atezolizumab

4. avelumab

5. durvalumab alone or in combination therapy, following the indications of the
Italian regulatory agency (AIFA).

Exclusion Criteria:

1. Patients that refuse and/or are not able to sign the Informed Consent;

2. Parents/guardians or subjects who, in the opinion of the Investigator, may be
noncompliant with study schedules or procedures;

3. No contraindications to the treatment with PD-1/PD-L1 antibodies, following the
indications of the Italian regulatory agency (AIFA).

Subjects that do not meet all of the enrollment criteria may not be enrolled.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_contact>
<last_name>Armando Gabrielli, M.D.</last_name>
<phone>+390712206104</phone>
<email>a.gabrielli@staff.univpm.it</email>
</overall_contact>
<location>
<facility>
<name>Università Politecnica delle Marche</name>
<address>
<city>Ancona</city>
<state>AN</state>
<zip>60020</zip>
<country>Italy</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Armando Gabrielli, MD, professor</last_name>
<phone>0712206104</phone>
<phone_ext>0039</phone_ext>
<email>a.gabrielli@staff.univpm.it</email>
</contact>
<contact_backup>
<last_name>Giovanni Pomponio, MD</last_name>
<phone>0715964205</phone>
<phone_ext>0039</phone_ext>
<email>pomponio@univpm.it</email>
</contact_backup>
</location>
<location_countries>
<country>Italy</country>
</location_countries>
<reference>
<citation>Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA; National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 Jun 10;36(17):1714-1768. doi: 10.1200/JCO.2017.77.6385. Epub 2018 Feb 14.</citation>
<PMID>29442540</PMID>
</reference>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 10, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 13, 2020</last_update_submitted>
<last_update_submitted_qc>February 13, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 17, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Università Politecnica delle Marche</investigator_affiliation>
<investigator_full_name>Armando Gabrielli</investigator_full_name>
<investigator_title>Full Professor</investigator_title>
</responsible_party>
<keyword>cancer</keyword>
<keyword>immune checkpoint inhibitors</keyword>
<keyword>immune related adverse events</keyword>
<keyword>nivolumab</keyword>
<keyword>pembrolizumab</keyword>
<keyword>avelumab</keyword>
<keyword>durvalumab</keyword>
<keyword>atezolizumab</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Carcinoma, Renal Cell</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>Undecided</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The recent introduction of anti-PD-1 (nivolumab and pembrolizumab) and anti- PD-L1
(atezolizumab, durvalumab, avelumab) immune checkpoint inhibitors revolutionized oncological
guidelines. Durable responses and prolongation of survival with these agents come at the
price of the development of immune related adverse events (irAEs). Innovative tools are
required in order to manage irAEs and to prevent their potential relapse, with the goal to
improve the outcome of patients. In this regard, the Investigators aim to develop a
multidisciplinary clinical pathway for cancer patients that are treated with immune
checkpoint inhibitors.
Recent evidences in immuno-oncology showed an important role of the immune system in tumor
control. In fact, immune response, both innate and adaptive one, is the first defensive
mechanism against cancer. However, several tumors, during their progression, develop an
immune-tolerance characterized by the activation of immune inhibitory pathways including PD-1
and PD-L1.
The recent introduction of anti-PD-1 (nivolumab and pembrolizumab) and anti-PD-L1
(atezolizumab, durvalumab, avelumab) immune checkpoint inhibitors revolutionized oncological
guidelines.
Currently, the aforementioned agents are approved for the treatment of advanced malignant
melanoma; non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) and the number of
treatment indications for immune checkpoint inhibitors is expanding. Durable responses and
prolongation of survival with these agents come at the price of the development of
immune-related adverse events (irAEs).
Immune-related adverse events are due to the loss of immune-tolerance towards structures of
the self, with the induction of chronic inflammation with an autoimmune mechanism that can
involve numerous organs and systems. The most frequent irAEs reported in clinical trials are
represented by skin toxicity, gastrointestinal toxicity, endocrine toxicity, pulmonary
toxicity, and others such as polymyalgia rheumatica, polyarthritis, myositis, nephritis,
polyradiculoneuritis, encephalitis and myocarditis.
The irAEs reported in clinical trials with nivolumab amount to a maximum of 85% considering
all grade of toxicities, while approximately 75% of patients treated with pembrolizumab
presented irAEs. Grade 3/4 irAEs were reported in 10% of patients treated with anti-PD-1.
With atezolizumab fewer patients had treatment-related grade 3 or 4 adverse events (15%).
In most cases, irAEs occur within some weeks after starting of immunotherapy; however these
toxicities have been reported later and also years after treatment discontinuation. The
development of irAEs is associated with significant morbidity and mortality in cancer
patients treated with immune checkpoint inhibitors, and therefore they may significantly
affect the quality of life, even in patients achieve the control of neoplastic disease.
The overseeing, early diagnosis and clinical management of immune checkpoint inhibitors'
toxicities in the clinical setting are, currently, not standardized.
Innovative tools are required in order to manage irAEs and to prevent their potential
relapse, with the goal to improve the outcome and quality of life of these patients.
In this regard, the Investigators also aim to evaluate a model of multidisciplinary clinical
pathway for cancer patients that are treated with immune checkpoint inhibitors in order to
improve their management and also ameliorate the quality of life of patients that develop
irAEs.
Whole blood samples will be collected for the preparation of serum and plasma at the baseline
visit and at follow-up visits for all patients.
Patients referring to the Oncology and Hematology Clinics of the Azienda Ospedaliero-
Universitaria Ospedali Riuniti di Ancona (Italy) may be enrolled.
Inclusion Criteria:
1. Adult patients above 18 years of age;
2. Cyto-histological diagnosis of one of the following cancers:
1. advanced melanoma;
2. metastatic or locally advanced non-small cell lung cancer;
3. advanced renal cell carcinoma;
4. metastatic or locally advanced urotelial carcinoma;
5. squamous cell carcinoma of the head and neck;
6. Hodgkin lymphoma;
7. Merkel-cell carcinoma;
3. New prescription of one of the following PD-1/PD-L1 inhibitors:
1. nivolumab
2. pembrolizumab
3. atezolizumab
4. avelumab
5. durvalumab alone or in combination therapy, following the indications of the
Italian regulatory agency (AIFA).
Exclusion Criteria:
1. Patients that refuse and/or are not able to sign the Informed Consent;
2. Parents/guardians or subjects who, in the opinion of the Investigator, may be
noncompliant with study schedules or procedures;
3. No contraindications to the treatment with PD-1/PD-L1 antibodies, following the
indications of the Italian regulatory agency (AIFA).
Subjects that do not meet all of the enrollment criteria may not be enrolled.
|
NCT0426xxxx/NCT04268381.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268381</url>
</required_header>
<id_info>
<org_study_id>20-2T/39</org_study_id>
<nct_id>NCT04268381</nct_id>
</id_info>
<brief_title>Oral and Systemic aMMP-8 in Periodontal Disease</brief_title>
<official_title>Local And Systemic Levels of aMMP-8 in Gingivitis and Stage 3 Periodontitis</official_title>
<sponsors>
<lead_sponsor>
<agency>Aydin Adnan Menderes University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Giresun University</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>Aydin Adnan Menderes University</source>
<oversight_info>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Periodontal disease is an inflammatory process that can result in tooth loss and also is
considered a modifying factor for systemic health. Matrix metalloproteinase (MMP)-8 is the
major collagenase of periodontal tissue breakdown. The aim of the present study is to analyze
active (aMMP-8) levels in gingival crevicular fluid (GCF), saliva and serum in the context of
new criteria of gingivitis and stage 3 grade C periodontitis.
</textblock>
</brief_summary>
<overall_status>Completed</overall_status>
<start_date type="Actual">January 20, 2020</start_date>
<completion_date type="Actual">March 20, 2020</completion_date>
<primary_completion_date type="Actual">March 20, 2020</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Case-Only</observational_model>
<time_perspective>Cross-Sectional</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Oral (GCF and saliva) and serum levels of aMMP-8 in periodontitis and gingivitis</measure>
<time_frame>through study completion, an average of 4 months</time_frame>
<description>aMMP-8 levels</description>
</primary_outcome>
<number_of_groups>3</number_of_groups>
<enrollment type="Actual">83</enrollment>
<condition>Periodontal Diseases</condition>
<condition>Periodontal Inflammation</condition>
<arm_group>
<arm_group_label>Healthy (n=23)</arm_group_label>
</arm_group>
<arm_group>
<arm_group_label>Gingivitis (n=20)</arm_group_label>
</arm_group>
<arm_group>
<arm_group_label>Periodontitis (n=40)</arm_group_label>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Biochemical analysis</intervention_name>
<description>aMMP-8 is measured by immunofluorometric assay (IFMA).</description>
<arm_group_label>Gingivitis (n=20)</arm_group_label>
<arm_group_label>Healthy (n=23)</arm_group_label>
<arm_group_label>Periodontitis (n=40)</arm_group_label>
</intervention>
<eligibility>
<study_pop>
<textblock>
Healthy controls (n=23) includes volunteers with clinically healthy periodontium who had
BOP < 10% and PD ≤ 3 mm, no sites with > 1 mm attachment loss, no radiographic sign of
alveolar bone destruction and no history of periodontitis. Gingivitis patients (n=20) shows
PD ≤ 3 mm with BOP > 50% in the entire mouth as well as no clinical attachment loss or
alveolar bone loss. Periodontitis patients (Generalized Stage 3) have interdental CAL ≥ 5
mm at least 2 non-adjacent teeth, PD ≥ 6 mm and radiographic bone loss affecting 30% of the
teeth or more.They show also no more than 4 teeth loss due to periodontitis.
</textblock>
</study_pop>
<sampling_method>Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- systemically healthy and non-smoker individuals aged 25 to 50 years

- having ≥20 teeth present (except third molars)

- individuals with periodontally healthy, gingivitis and stage 3 periodontitis diagnoses

Exclusion Criteria:

- having any systemic disease

- smoking

- pregnancy or lactation

- using antibiotic or any anti-inflammatory drug or any periodontal treatment within the
past 6 months.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>25 Years</minimum_age>
<maximum_age>50 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Zeynep Pinar Keles Yucel</last_name>
<role>Principal Investigator</role>
<affiliation>Department of Periodontology, School of Dentistry, Giresun University</affiliation>
</overall_official>
<location>
<facility>
<name>Aydin Adnan Menderes University</name>
<address>
<city>Aydın</city>
<country>Turkey</country>
</address>
</facility>
</location>
<location_countries>
<country>Turkey</country>
</location_countries>
<verification_date>July 2020</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>July 10, 2020</last_update_submitted>
<last_update_submitted_qc>July 10, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">July 14, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Giresun University</investigator_affiliation>
<investigator_full_name>Zeynep Pinar KELES YUCEL</investigator_full_name>
<investigator_title>Assistant Prof.</investigator_title>
</responsible_party>
<keyword>periodontitis</keyword>
<keyword>gingivitis</keyword>
<keyword>matrix metalloproteinases</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Periodontal Diseases</mesh_term>
<mesh_term>Inflammation</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Periodontal disease is an inflammatory process that can result in tooth loss and also is
considered a modifying factor for systemic health. Matrix metalloproteinase (MMP)-8 is the
major collagenase of periodontal tissue breakdown. The aim of the present study is to analyze
active (aMMP-8) levels in gingival crevicular fluid (GCF), saliva and serum in the context of
new criteria of gingivitis and stage 3 grade C periodontitis.
Healthy controls (n=23) includes volunteers with clinically healthy periodontium who had
BOP < 10% and PD ≤ 3 mm, no sites with > 1 mm attachment loss, no radiographic sign of
alveolar bone destruction and no history of periodontitis. Gingivitis patients (n=20) shows
PD ≤ 3 mm with BOP > 50% in the entire mouth as well as no clinical attachment loss or
alveolar bone loss. Periodontitis patients (Generalized Stage 3) have interdental CAL ≥ 5
mm at least 2 non-adjacent teeth, PD ≥ 6 mm and radiographic bone loss affecting 30% of the
teeth or more.They show also no more than 4 teeth loss due to periodontitis.
Inclusion Criteria:
- systemically healthy and non-smoker individuals aged 25 to 50 years
- having ≥20 teeth present (except third molars)
- individuals with periodontally healthy, gingivitis and stage 3 periodontitis diagnoses
Exclusion Criteria:
- having any systemic disease
- smoking
- pregnancy or lactation
- using antibiotic or any anti-inflammatory drug or any periodontal treatment within the
past 6 months.
|
NCT0426xxxx/NCT04268394.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268394</url>
</required_header>
<id_info>
<org_study_id>CC-99677-CP-002</org_study_id>
<secondary_id>U1111-1247-0554</secondary_id>
<secondary_id>2019-003523-38</secondary_id>
<nct_id>NCT04268394</nct_id>
</id_info>
<brief_title>A Study to Evaluate Potential Cytochrome P450 and Transporter Protein Interactions With CC-99677</brief_title>
<official_title>A Phase 1, Open-label Study in Healthy Adult Subjects to Evaluate Effects of Cytochrome P450 Inhibition and Induction on the Pharmacokinetics of CC-99677 and the Effects of CC-99677 on the Pharmacokinetics of Digoxin, Metformin, Methotrexate, Midazolam, Rosuvastatin, and Sulfasalazine</official_title>
<sponsors>
<lead_sponsor>
<agency>Celgene</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
</sponsors>
<source>Celgene</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
It is a phase 1, open-label, single-center, three-part study to assess the safety,
tolerability, and pharmacokinetics of multiple doses of CC-99677 administered alone or in
combination with either methotrexate and sulfasalazine; itraconazole, rifampin, midazolam, or
a cocktail of digoxin, metformin, and rosuvastatin in healthy subjects
</textblock>
</brief_summary>
<detailed_description>
<textblock>
This study will allow investigation of potential drug-drug interaction mediated through
cytochrome P450 enzymes and drug transporter proteins. During each part, blood samples will
be collected at prespecified times for pharmacokinetic assessments. Subject safety will be
monitored throughout the study. There will be approximately 16 subjects enrolled into each
part.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">March 13, 2020</start_date>
<completion_date type="Actual">June 2, 2021</completion_date>
<primary_completion_date type="Actual">June 2, 2021</primary_completion_date>
<phase>Phase 1</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Pharmacokinetics-Cmax</measure>
<time_frame>Up to approximately 72 hours</time_frame>
<description>Maximum observed plasma concentration</description>
</primary_outcome>
<primary_outcome>
<measure>Pharmacokinetics-AUC0-t</measure>
<time_frame>Up to approximately 72 hours</time_frame>
<description>Area under the plasma concentration-time curve from time zero extrapolated to the last quantifiable concentration</description>
</primary_outcome>
<secondary_outcome>
<measure>Adverse Events (AEs)</measure>
<time_frame>From enrollment until at least 28 days after completion of treatment</time_frame>
<description>Number of subjects with adverse events</description>
</secondary_outcome>
<secondary_outcome>
<measure>Pharmacokinetics-Cmax</measure>
<time_frame>Up to approximately 72 hours</time_frame>
<description>Maximum observed plasma concentrations of metabolites</description>
</secondary_outcome>
<secondary_outcome>
<measure>Pharmacokinetics-AUC0-t</measure>
<time_frame>Up to approximately 72 hours</time_frame>
<description>Ratio of area under the plasma concentration-time curve from time zero extrapolated to the last quantifiable concentration of parent and metabolite</description>
</secondary_outcome>
<number_of_arms>3</number_of_arms>
<enrollment type="Actual">48</enrollment>
<condition>Healthy Volunteer</condition>
<arm_group>
<arm_group_label>Part 1: CC-99677 with Methotrexate and Sulfasalazine</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Fixed-sequence involving CC-99677 + Methotrexate 7.5 mg and sulfasalazine 1000 mg</description>
</arm_group>
<arm_group>
<arm_group_label>Part 2: CC-99677 with Itraconazole and Rifampin</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Fixed-sequence involving CC-99677 + Rifampin 600 mg and Itraconazole 200 mg</description>
</arm_group>
<arm_group>
<arm_group_label>Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Fixed-sequence involving CC-99677 + Midazolam 2 mg, Digoxin 0.25 mg, Metformin 500 mg, and Rosuvastatin 10 mg.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>CC-99677</intervention_name>
<description>CC-99677</description>
<arm_group_label>Part 1: CC-99677 with Methotrexate and Sulfasalazine</arm_group_label>
<arm_group_label>Part 2: CC-99677 with Itraconazole and Rifampin</arm_group_label>
<arm_group_label>Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Methotrexate</intervention_name>
<description>Methotrexate</description>
<arm_group_label>Part 1: CC-99677 with Methotrexate and Sulfasalazine</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Sulfasalazine</intervention_name>
<description>Sulfasalazine</description>
<arm_group_label>Part 1: CC-99677 with Methotrexate and Sulfasalazine</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Itraconazole</intervention_name>
<description>Itraconazole</description>
<arm_group_label>Part 2: CC-99677 with Itraconazole and Rifampin</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Rifampin</intervention_name>
<description>Rifampin</description>
<arm_group_label>Part 2: CC-99677 with Itraconazole and Rifampin</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Midazolam</intervention_name>
<description>Midazolam</description>
<arm_group_label>Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Digoxin</intervention_name>
<description>Digoxin</description>
<arm_group_label>Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Metformin</intervention_name>
<description>Metformin</description>
<arm_group_label>Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Rosuvastatin</intervention_name>
<description>Rosuvastatin</description>
<arm_group_label>Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

Subjects must satisfy all of the following criteria to be enrolled in the study:

1. Subject is ≥ 18 and ≤ 64 years of age at the time of signing the informed consent form
(ICF).

1. Part 1 is open to male subjects ONLY

2. Both male and female subjects may participate in Parts 2-3.

2. Subject must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted.

3. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements.

4. Subject is in good health, as determined by the Investigator based on a physical
examination at screening.

5. Female subjects of childbearing potential (FCBP) are not permitted in Part 1, but are
permitted in Parts 2 and 3, and must:

1. Have two (2) negative pregnancy tests as verified by the Investigator prior to
the first dose of IP. She must agree to ongoing pregnancy testing during the
course of the study, and prior to discharge from the study site. This applies
even if the subject practices true abstinence2 from heterosexual contact.

2. Agree to use, and be able to comply with, one highly effective3 non-hormonal
method of contraception without interruption, during the study (including any
dose interruptions), and for at least 28 days after discontinuation of IP. The
female subject's chosen form of highly effective contraception must be effective
by the time the female subject is enrolled into the study (eg, contraception
should be initiated at least 28 days prior to enrollment) and at least 28 days
after discontinuation of IP.

6. Female subjects NOT of childbearing potential are permitted in all Parts except Part
1, and must:

a. Have been surgically sterilized (hysterectomy or bilateral oophorectomy; proper
documentation is required) at least 6 months before screening, or be postmenopausal
(defined as 24 consecutive months without menses before screening, with a follicle
stimulating hormone [FSH] level of > 40 IU/L at screening).

7. Male subjects must:

1. For Part 1: Agree to use a latex or other synthetic condom during sexual contact
with a pregnant female or a FCBP while participating in the study, during any
dose interruptions, and for at least -6 months after discontinuation of
methotrexate (Methotrexate Summary of Product Characteristics [SmPC]; CTFG,
2014). In addition, any non-pregnant FCBP partner of a male subject must use a
reliable contraception method, without interruption, during the study (including
any dose interruptions) and for at least 6 months after discontinuation of
methotrexate (Methotrexate SmPC). It is recommended that non-pregnant FCBP
partners of male subjects in Part 1 use approved highly effective contraception
as a reliable method. Examples of approved methods of highly effective
contraception include combined hormonal contraception; progestogen only oral
hormonal contraception; intrauterine device; intrauterine hormone-releasing
system; bilateral tubal occlusion; vasectomized male partner (CTFG, 2014).

2. For Parts 2 and 3: Agree to use a latex or other synthetic condom during sexual
contact with a pregnant female or a FCBP while participating in the study, during
any dose interruptions, and for at least 28 days after discontinuation of IP,
even if he has undergone a successful vasectomy. In addition, any non-pregnant
FCBP partner of a male subject must use an approved method of effective
contraception, without interruption, during the study (including any dose
interruptions) and for at least 28 days after discontinuation of IP (CTFG, 2014).
Examples of approved methods of effective contraception for non-pregnant FCBP
partners include progestogen only oral hormonal contraception; male or female
condom with or without spermicide; or cap, diaphragm, or sponge with spermicide.

8. Subject has a body mass index (BMI) ≥ 18 and ≤ 30 kg/m2 at screening.

9. Subject has clinical laboratory safety test results that are within normal limits or
considered not clinically significant by the Investigator. In addition, ALT, AST, and
total bilirubin must be ≤ the upper limit of normal at screening and on Day -1.
Platelet count, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC)
must be ≥ the lower limit of normal at screening and on Day -1.

10. Subject is afebrile, with supine systolic blood pressure (BP) ≥ 90 and ≤ 140 mmHg,
supine diastolic BP ≥ 50 and ≤ 90 mmHg, and pulse rate ≥ 40 and ≤ 110 bpm at
screening.

11. Subject has normal or clinically acceptable 12 lead ECG. In addition:

1. If female, subject has a QTcF value ≤ 450 msec at screening.

2. If male, subject has a QTcF value ≤ 430 msec at screening.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Subject has any significant medical condition (including but not limited to
neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological,
pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or
other major disorders), laboratory abnormality, or psychiatric illness that would
prevent the subject from participating in the study.

2. Subject has any condition including the presence of laboratory abnormalities, which
places the subject at unacceptable risk if he/she were to participate in the study.

3. Subject has any condition that confounds the ability to interpret data from the study.

4. Female subjects are prohibited from participating in Part 1. Female subjects may
participate in Parts 2-3.

5. Subject is pregnant or breastfeeding.

6. Subject was exposed to an investigational drug (new chemical entity) within 30 days
preceding the first dose administration, or 5 half-lives of that investigational drug,
if known (whichever is longer).

7. Subject has used any prescribed systemic or topical medication (including but not
limited to analgesics, anesthetics, etc) within 30 days prior to the first dose
administration, or 5 half-lives of that investigational drug, if known (whichever is
longer). Exceptions may apply on a case-by-case basis if considered not to interfere
with the study objectives as agreed to by the Investigator and Sponsor's Medical
Monitor.

8. Subject has used any non-prescribed systemic or topical medication (including
vitamin/mineral supplements, and herbal medicines) within 14 days prior to the first
dose administration. Exceptions may apply on a case-by-case basis if considered not to
interfere with the study objectives as agreed to by the Investigator and Sponsor's
Medical Monitor.

9. Subject has used Cytochrome P450 (CYP) 3A inducers and/or inhibitors (including St.
John's Wort) within 30 days preceding the first dose administration. The Indiana
University (2016) "Cytochrome P450 Drug Interaction Table" should be utilized to
determine inducers and/or inhibitors of CYP3A
(http://medicine.iupui.edu/clinpharm/ddis/table.aspx). The Sponsor's Medical Monitor
or designee should be queried in case of uncertainty.

10. Subject has any surgical or medical conditions possibly affecting drug absorption,
distribution, metabolism, or excretion, eg, bariatric procedure. Appendectomy and
cholecystectomy are acceptable. Other previous surgeries may be acceptable with
concurrence of the Sponsor's Medical Monitor.

11. Subject donated blood or serum within 8 weeks before the first dose administration to
a blood bank or blood donation center.

12. Subject has a history of drug abuse (as defined by the current version of the
International Classification of Diseases (ICD V11.0)) within 2 years before the first
dose administration, or positive drug screening test reflecting consumption of illicit
drugs.

13. Subject has a history of alcohol abuse (as defined by the NHS alcohol tracker
https://www.nhs.uk/live-well/alcohol-support/calculating-alcohol-units/) within 2
years before the first dose administration, or positive alcohol screen.

14. Subject is known to have a history of hepatitis B and/or hepatitis C, or have a
positive result to the test for human immunodeficiency virus (HIV) antibodies at
screening.

a. Note: Subjects who received hepatitis B vaccination and who test positive for
hepatitis B surface antibody and negative for both hepatitis B surface antigen and
hepatitis B core antibody remain eligible for study participation.

15. Subject smokes > 10 cigarettes per day, or the equivalent in other tobacco products
(self-reported).

16. Subject has received immunization with a live or live attenuated vaccine within 2
months prior to the first dose administration or is planning to receive immunization
with a live or live attenuated vaccine for 2 months following the last dose
administration.

17. Subject has a history of Gilbert's syndrome or has laboratory findings at screening
that, in the opinion of the Investigator, are indicative of Gilbert's syndrome.

18. Subject has a history of incompletely treated Mycobacterium tuberculosis (TB)
infection, as indicated by:

1. Subject's medical records documenting incomplete treatment for Mycobacterium TB.

2. Subject's self-reported history of incomplete treatment for Mycobacterium TB.

3. Note: Subjects with a history of TB who have undergone treatment accepted by the
local health authorities (documented) may be eligible for study entry.

19. Subject is part of the study site staff personnel or a family member of the study site
staff.

20. Subject has previously been exposed to CC-99677 (eg in a prior clinical trial).

21. Subject has a history of photosensitivity to medications.

22. Subject has a documented allergy or history of adverse reaction to required
medications in the Part for which he/she is seeking to be enrolled, specifically:

1. Methotrexate and/or sulfasalazine (or its analogues) for Part 1

2. Itraconazole and/or rifampin (or its analogues) for Part 2

3. Midazolam and/or digoxin and/or metformin and/or rosuvastatin (or other HMG-CoA
reductases i.e. "statins") for Part 3
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>64 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Kofi Mensah, MD, PhD</last_name>
<role>Study Director</role>
<affiliation>Celgene</affiliation>
</overall_official>
<location>
<facility>
<name>Richmond Pharmacology Limited</name>
<address>
<city>London</city>
<zip>SW17 ORE</zip>
<country>United Kingdom</country>
</address>
</facility>
</location>
<location_countries>
<country>United Kingdom</country>
</location_countries>
<verification_date>August 2021</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>August 17, 2021</last_update_submitted>
<last_update_submitted_qc>August 17, 2021</last_update_submitted_qc>
<last_update_posted type="Actual">August 18, 2021</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Healthy Volunteer</keyword>
<keyword>Pharmacokinetics</keyword>
<keyword>Safety Tolerability</keyword>
<keyword>CC-99677</keyword>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Metformin</mesh_term>
<mesh_term>Itraconazole</mesh_term>
<mesh_term>Rifampin</mesh_term>
<mesh_term>Sulfasalazine</mesh_term>
<mesh_term>Methotrexate</mesh_term>
<mesh_term>Digoxin</mesh_term>
<mesh_term>Midazolam</mesh_term>
<mesh_term>Rosuvastatin Calcium</mesh_term>
</intervention_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
It is a phase 1, open-label, single-center, three-part study to assess the safety,
tolerability, and pharmacokinetics of multiple doses of CC-99677 administered alone or in
combination with either methotrexate and sulfasalazine; itraconazole, rifampin, midazolam, or
a cocktail of digoxin, metformin, and rosuvastatin in healthy subjects
This study will allow investigation of potential drug-drug interaction mediated through
cytochrome P450 enzymes and drug transporter proteins. During each part, blood samples will
be collected at prespecified times for pharmacokinetic assessments. Subject safety will be
monitored throughout the study. There will be approximately 16 subjects enrolled into each
part.
Inclusion Criteria:
Subjects must satisfy all of the following criteria to be enrolled in the study:
1. Subject is ≥ 18 and ≤ 64 years of age at the time of signing the informed consent form
(ICF).
1. Part 1 is open to male subjects ONLY
2. Both male and female subjects may participate in Parts 2-3.
2. Subject must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements.
4. Subject is in good health, as determined by the Investigator based on a physical
examination at screening.
5. Female subjects of childbearing potential (FCBP) are not permitted in Part 1, but are
permitted in Parts 2 and 3, and must:
1. Have two (2) negative pregnancy tests as verified by the Investigator prior to
the first dose of IP. She must agree to ongoing pregnancy testing during the
course of the study, and prior to discharge from the study site. This applies
even if the subject practices true abstinence2 from heterosexual contact.
2. Agree to use, and be able to comply with, one highly effective3 non-hormonal
method of contraception without interruption, during the study (including any
dose interruptions), and for at least 28 days after discontinuation of IP. The
female subject's chosen form of highly effective contraception must be effective
by the time the female subject is enrolled into the study (eg, contraception
should be initiated at least 28 days prior to enrollment) and at least 28 days
after discontinuation of IP.
6. Female subjects NOT of childbearing potential are permitted in all Parts except Part
1, and must:
a. Have been surgically sterilized (hysterectomy or bilateral oophorectomy; proper
documentation is required) at least 6 months before screening, or be postmenopausal
(defined as 24 consecutive months without menses before screening, with a follicle
stimulating hormone [FSH] level of > 40 IU/L at screening).
7. Male subjects must:
1. For Part 1: Agree to use a latex or other synthetic condom during sexual contact
with a pregnant female or a FCBP while participating in the study, during any
dose interruptions, and for at least -6 months after discontinuation of
methotrexate (Methotrexate Summary of Product Characteristics [SmPC]; CTFG,
2014). In addition, any non-pregnant FCBP partner of a male subject must use a
reliable contraception method, without interruption, during the study (including
any dose interruptions) and for at least 6 months after discontinuation of
methotrexate (Methotrexate SmPC). It is recommended that non-pregnant FCBP
partners of male subjects in Part 1 use approved highly effective contraception
as a reliable method. Examples of approved methods of highly effective
contraception include combined hormonal contraception; progestogen only oral
hormonal contraception; intrauterine device; intrauterine hormone-releasing
system; bilateral tubal occlusion; vasectomized male partner (CTFG, 2014).
2. For Parts 2 and 3: Agree to use a latex or other synthetic condom during sexual
contact with a pregnant female or a FCBP while participating in the study, during
any dose interruptions, and for at least 28 days after discontinuation of IP,
even if he has undergone a successful vasectomy. In addition, any non-pregnant
FCBP partner of a male subject must use an approved method of effective
contraception, without interruption, during the study (including any dose
interruptions) and for at least 28 days after discontinuation of IP (CTFG, 2014).
Examples of approved methods of effective contraception for non-pregnant FCBP
partners include progestogen only oral hormonal contraception; male or female
condom with or without spermicide; or cap, diaphragm, or sponge with spermicide.
8. Subject has a body mass index (BMI) ≥ 18 and ≤ 30 kg/m2 at screening.
9. Subject has clinical laboratory safety test results that are within normal limits or
considered not clinically significant by the Investigator. In addition, ALT, AST, and
total bilirubin must be ≤ the upper limit of normal at screening and on Day -1.
Platelet count, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC)
must be ≥ the lower limit of normal at screening and on Day -1.
10. Subject is afebrile, with supine systolic blood pressure (BP) ≥ 90 and ≤ 140 mmHg,
supine diastolic BP ≥ 50 and ≤ 90 mmHg, and pulse rate ≥ 40 and ≤ 110 bpm at
screening.
11. Subject has normal or clinically acceptable 12 lead ECG. In addition:
1. If female, subject has a QTcF value ≤ 450 msec at screening.
2. If male, subject has a QTcF value ≤ 430 msec at screening.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
1. Subject has any significant medical condition (including but not limited to
neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological,
pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or
other major disorders), laboratory abnormality, or psychiatric illness that would
prevent the subject from participating in the study.
2. Subject has any condition including the presence of laboratory abnormalities, which
places the subject at unacceptable risk if he/she were to participate in the study.
3. Subject has any condition that confounds the ability to interpret data from the study.
4. Female subjects are prohibited from participating in Part 1. Female subjects may
participate in Parts 2-3.
5. Subject is pregnant or breastfeeding.
6. Subject was exposed to an investigational drug (new chemical entity) within 30 days
preceding the first dose administration, or 5 half-lives of that investigational drug,
if known (whichever is longer).
7. Subject has used any prescribed systemic or topical medication (including but not
limited to analgesics, anesthetics, etc) within 30 days prior to the first dose
administration, or 5 half-lives of that investigational drug, if known (whichever is
longer). Exceptions may apply on a case-by-case basis if considered not to interfere
with the study objectives as agreed to by the Investigator and Sponsor's Medical
Monitor.
8. Subject has used any non-prescribed systemic or topical medication (including
vitamin/mineral supplements, and herbal medicines) within 14 days prior to the first
dose administration. Exceptions may apply on a case-by-case basis if considered not to
interfere with the study objectives as agreed to by the Investigator and Sponsor's
Medical Monitor.
9. Subject has used Cytochrome P450 (CYP) 3A inducers and/or inhibitors (including St.
John's Wort) within 30 days preceding the first dose administration. The Indiana
University (2016) "Cytochrome P450 Drug Interaction Table" should be utilized to
determine inducers and/or inhibitors of CYP3A
(http://medicine.iupui.edu/clinpharm/ddis/table.aspx). The Sponsor's Medical Monitor
or designee should be queried in case of uncertainty.
10. Subject has any surgical or medical conditions possibly affecting drug absorption,
distribution, metabolism, or excretion, eg, bariatric procedure. Appendectomy and
cholecystectomy are acceptable. Other previous surgeries may be acceptable with
concurrence of the Sponsor's Medical Monitor.
11. Subject donated blood or serum within 8 weeks before the first dose administration to
a blood bank or blood donation center.
12. Subject has a history of drug abuse (as defined by the current version of the
International Classification of Diseases (ICD V11.0)) within 2 years before the first
dose administration, or positive drug screening test reflecting consumption of illicit
drugs.
13. Subject has a history of alcohol abuse (as defined by the NHS alcohol tracker
https://www.nhs.uk/live-well/alcohol-support/calculating-alcohol-units/) within 2
years before the first dose administration, or positive alcohol screen.
14. Subject is known to have a history of hepatitis B and/or hepatitis C, or have a
positive result to the test for human immunodeficiency virus (HIV) antibodies at
screening.
a. Note: Subjects who received hepatitis B vaccination and who test positive for
hepatitis B surface antibody and negative for both hepatitis B surface antigen and
hepatitis B core antibody remain eligible for study participation.
15. Subject smokes > 10 cigarettes per day, or the equivalent in other tobacco products
(self-reported).
16. Subject has received immunization with a live or live attenuated vaccine within 2
months prior to the first dose administration or is planning to receive immunization
with a live or live attenuated vaccine for 2 months following the last dose
administration.
17. Subject has a history of Gilbert's syndrome or has laboratory findings at screening
that, in the opinion of the Investigator, are indicative of Gilbert's syndrome.
18. Subject has a history of incompletely treated Mycobacterium tuberculosis (TB)
infection, as indicated by:
1. Subject's medical records documenting incomplete treatment for Mycobacterium TB.
2. Subject's self-reported history of incomplete treatment for Mycobacterium TB.
3. Note: Subjects with a history of TB who have undergone treatment accepted by the
local health authorities (documented) may be eligible for study entry.
19. Subject is part of the study site staff personnel or a family member of the study site
staff.
20. Subject has previously been exposed to CC-99677 (eg in a prior clinical trial).
21. Subject has a history of photosensitivity to medications.
22. Subject has a documented allergy or history of adverse reaction to required
medications in the Part for which he/she is seeking to be enrolled, specifically:
1. Methotrexate and/or sulfasalazine (or its analogues) for Part 1
2. Itraconazole and/or rifampin (or its analogues) for Part 2
3. Midazolam and/or digoxin and/or metformin and/or rosuvastatin (or other HMG-CoA
reductases i.e. "statins") for Part 3
|
NCT0426xxxx/NCT04268407.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268407</url>
</required_header>
<id_info>
<org_study_id>201902024A3</org_study_id>
<nct_id>NCT04268407</nct_id>
</id_info>
<brief_title>2-day Prophylactic Antibiotic is Effective in Transoral Endoscopic Thyroidectomy</brief_title>
<official_title>2-day Prophylactic Antibiotic is Effective in Transoral Endoscopic Thyroidectomy</official_title>
<sponsors>
<lead_sponsor>
<agency>Chang Gung Memorial Hospital</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Chang Gung Memorial Hospital</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
In transoral thyroidectomy via vestibular approach (TOETVA), prophylactic antibiotic for 5~7
days is recommended for the clean-contaminated wound. In this study, the investigators design
a 2-day versus 7-day antibiotic prophylaxis to compare the surgical result and infection
rate.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Remote-access thyroid surgery has gained popularity and has advanced significantly over the
past two decades, given the patient desire to avoid cosmetically displeasing scarring. The
mostly recently introduced remote thyroid surgery is the transoral endoscopic thyroid surgery
via vestibular approach (TOETVA). Because of the several advantages comparing with other
removeaccess thyroid surgery, making it nowadays growing in popularity since 2016. However,
TOETVA carry some inherent risks, including mental nerve injury, tumor seeding and local
recurrence, fibrosis-induced long-lasting pulling sensation below the lower jaws, and
surgical site infection coming from the clean-contaminated environment of oral incision.

Comparing with clean wound via the traditional open surgery, TOETVA carry the potential risk
of infection. Based on the author's recommendation, prophylactic antibiotic (augmentin) will
be administered 30 minutes before incision at operative room, followed by 2-day course of
intravenous antibiotic, then shift to 5-day course of oral antibiotic finally. Up to date,
only few case complicating postoperative infection were reported with extremely low infection
rate (<1%). Therefore, the investigators want to study the short-course (2 days) of
antibiotic coverage is also effective to prevent surgical site infection. It was proved in
the preliminary study, comprising 5 patients in each group (2-day course in the study group
and 7-day course in the control group). Later, the investigators will recruit more patients
(n=100) to confirm this study.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">February 26, 2020</start_date>
<completion_date type="Actual">December 31, 2021</completion_date>
<primary_completion_date type="Actual">December 31, 2021</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>thyroid nodules, plan for transoral thyroidectomy</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>post-operative infection</measure>
<time_frame>within one month after operation</time_frame>
<description>incidence of post-operative infection</description>
</primary_outcome>
<secondary_outcome>
<measure>post-op complication</measure>
<time_frame>within one month after operation</time_frame>
<description>intensity of pain, measured by VAS(visual analogue score)</description>
</secondary_outcome>
<other_outcome>
<measure>post-op complication</measure>
<time_frame>within one month after operation</time_frame>
<description>mental nerve injury, measured by patient description of chin numbness</description>
</other_outcome>
<other_outcome>
<measure>post-op complication</measure>
<time_frame>within one month after operation</time_frame>
<description>skin thermal or penetrated injury, noted during operation</description>
</other_outcome>
<other_outcome>
<measure>post-op complication</measure>
<time_frame>within one month after operation</time_frame>
<description>post-operative hypoparathyroidism, measured by post-operative serum intact PTH level</description>
</other_outcome>
<other_outcome>
<measure>post-op complication</measure>
<time_frame>within one month after operation</time_frame>
<description>recurrent laryngeal nerve injury, measured by clinical symptom and proved by laryngoscope</description>
</other_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">60</enrollment>
<condition>Thyroid Nodule</condition>
<arm_group>
<arm_group_label>2-day prophylactic antibiotics</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>use prophylactic antibiotic for 2 days after transoral thyroidectomy</description>
</arm_group>
<arm_group>
<arm_group_label>7-day prophylactic antibiotic</arm_group_label>
<arm_group_type>Other</arm_group_type>
<description>use prophylactic antibiotic for 7 days after transoral thyroidectomy</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Amoxicillin Clavulanate</intervention_name>
<description>compare the duration of antbiotic use: 2 day versus 7 day</description>
<arm_group_label>2-day prophylactic antibiotics</arm_group_label>
<arm_group_label>7-day prophylactic antibiotic</arm_group_label>
<other_name>Augmentin</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Suspicious or proved thyroid cancer with size smaller than 4cm

2. Symptomatic benign thyroid nodules less than 6cm in size

3. Thyroid cyst

4. Follicular neoplasm

5. Graves' disease

Exclusion Criteria:

1. Previous thyroid or parathyroid surgery

2. History of radiation at neck

3. Could not tolerate the general anesthesia.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>20 Years</minimum_age>
<maximum_age>80 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Yichia Chan, doctor</last_name>
<role>Principal Investigator</role>
<affiliation>Kaohsing Chang Gung memorial hospital</affiliation>
</overall_official>
<location>
<facility>
<name>Yi-Chia Chan</name>
<address>
<city>Kaohsiung</city>
<state>鳥松區</state>
<zip>833</zip>
<country>Taiwan</country>
</address>
</facility>
</location>
<location_countries>
<country>Taiwan</country>
</location_countries>
<reference>
<citation>Anuwong A, Ketwong K, Jitpratoom P, Sasanakietkul T, Duh QY. Safety and Outcomes of the Transoral Endoscopic Thyroidectomy Vestibular Approach. JAMA Surg. 2018 Jan 1;153(1):21-27. doi: 10.1001/jamasurg.2017.3366.</citation>
<PMID>28877292</PMID>
</reference>
<reference>
<citation>Fernandez-Ranvier G, Meknat A, Guevara DE, Inabnet WB 3rd. Transoral Endoscopic Thyroidectomy Vestibular Approach. JSLS. 2019 Oct-Dec;23(4):e2019.00036. doi: 10.4293/JSLS.2019.00036.</citation>
<PMID>31719772</PMID>
</reference>
<reference>
<citation>Wang C, Zhai H, Liu W, Li J, Yang J, Hu Y, Huang J, Yang W, Pan Y, Ding H. Thyroidectomy: a novel endoscopic oral vestibular approach. Surgery. 2014 Jan;155(1):33-8. doi: 10.1016/j.surg.2013.06.010. Epub 2013 Jul 24.</citation>
<PMID>23890962</PMID>
</reference>
<verification_date>July 2022</verification_date>
<study_first_submitted>February 7, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>July 28, 2022</last_update_submitted>
<last_update_submitted_qc>July 28, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">August 1, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Chang Gung Memorial Hospital</investigator_affiliation>
<investigator_full_name>Yichia Chan</investigator_full_name>
<investigator_title>principal investigator</investigator_title>
</responsible_party>
<keyword>transoral surgery</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Thyroid Nodule</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Amoxicillin</mesh_term>
<mesh_term>Clavulanic Acid</mesh_term>
<mesh_term>Clavulanic Acids</mesh_term>
<mesh_term>Amoxicillin-Potassium Clavulanate Combination</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
<ipd_description>only for request</ipd_description>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
In transoral thyroidectomy via vestibular approach (TOETVA), prophylactic antibiotic for 5~7
days is recommended for the clean-contaminated wound. In this study, the investigators design
a 2-day versus 7-day antibiotic prophylaxis to compare the surgical result and infection
rate.
Remote-access thyroid surgery has gained popularity and has advanced significantly over the
past two decades, given the patient desire to avoid cosmetically displeasing scarring. The
mostly recently introduced remote thyroid surgery is the transoral endoscopic thyroid surgery
via vestibular approach (TOETVA). Because of the several advantages comparing with other
removeaccess thyroid surgery, making it nowadays growing in popularity since 2016. However,
TOETVA carry some inherent risks, including mental nerve injury, tumor seeding and local
recurrence, fibrosis-induced long-lasting pulling sensation below the lower jaws, and
surgical site infection coming from the clean-contaminated environment of oral incision.
Comparing with clean wound via the traditional open surgery, TOETVA carry the potential risk
of infection. Based on the author's recommendation, prophylactic antibiotic (augmentin) will
be administered 30 minutes before incision at operative room, followed by 2-day course of
intravenous antibiotic, then shift to 5-day course of oral antibiotic finally. Up to date,
only few case complicating postoperative infection were reported with extremely low infection
rate (<1%). Therefore, the investigators want to study the short-course (2 days) of
antibiotic coverage is also effective to prevent surgical site infection. It was proved in
the preliminary study, comprising 5 patients in each group (2-day course in the study group
and 7-day course in the control group). Later, the investigators will recruit more patients
(n=100) to confirm this study.
Inclusion Criteria:
1. Suspicious or proved thyroid cancer with size smaller than 4cm
2. Symptomatic benign thyroid nodules less than 6cm in size
3. Thyroid cyst
4. Follicular neoplasm
5. Graves' disease
Exclusion Criteria:
1. Previous thyroid or parathyroid surgery
2. History of radiation at neck
3. Could not tolerate the general anesthesia.
|
NCT0426xxxx/NCT04268420.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268420</url>
</required_header>
<id_info>
<org_study_id>S-19-04</org_study_id>
<nct_id>NCT04268420</nct_id>
</id_info>
<brief_title>A Trial For The Study of Falciparum Malaria Protein 013 Administered Via Intramuscular Injection in Healthy Adults</brief_title>
<official_title>Phase 1 Clinical Trial With Controlled Human Malaria Infection (CHMI) for Safety, Protective Efficacy, and Immunogenicity of Plasmodium Falciparum Malaria Protein (FMP013) Administered Intramuscularly With ALFQ Healthy Malaria-Naïve Adults</official_title>
<sponsors>
<lead_sponsor>
<agency>U.S. Army Medical Research and Development Command</agency>
<agency_class>U.S. Fed</agency_class>
</lead_sponsor>
<collaborator>
<agency>Walter Reed Army Institute of Research (WRAIR)</agency>
<agency_class>U.S. Fed</agency_class>
</collaborator>
</sponsors>
<source>U.S. Army Medical Research and Development Command</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
A Phase 1, open label clinical study to evaluate the safety, immunogenicity, tolerability and
efficacy of Plasmodium falciparum Malaria Protein 013 (FMP013) combined with (ALF with
QS-21), saponin molecule derived from the bark of Quillaja species (ALFQ)) in healthy adult
volunteers at different doses and dosing schedules.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
This is an open-label immunization with Controlled Human Malaria Infection (CHMI) study.
Healthy, malaria-naïve adults, aged 18-55 years old will be recruited into one of 5
experimental cohorts in 2 parts.

In Part A, 2 experimental cohorts of 5 subjects each will receive a series of 3 vaccinations
at 0, 1, and 2 months at 2 doses (the "low dose" arm and the "high dose" arm).

In Part B, 3 experimental cohorts of 10 subjects will receive a series of 3 vaccinations at
0, 1, 6 months (called the "delayed dose" arm), the "delayed fractional dose" arm is
vaccinated at 0, 1, and 6 months with the 6 month dose being 1/5 the other doses, and the
"standard" arm" at the 4th, 5th, and 6th month (after the first 2 vaccinations of the other 2
arms in Part B).
</textblock>
</detailed_description>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">March 20, 2020</start_date>
<completion_date type="Anticipated">December 2023</completion_date>
<primary_completion_date type="Anticipated">July 2023</primary_completion_date>
<phase>Phase 1</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Non-Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Prevention</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Safety Dosage of Candidate Malaria Vaccine FMP013/ALFQ</measure>
<time_frame>393 Days (+/-14)</time_frame>
<description>To assess the safety of candidate malaria vaccine FMP013/ALFQ. Safety dosage as indicated by incidence of solicited adverse events and serious adverse events through the end of the study.</description>
</primary_outcome>
<primary_outcome>
<measure>Assess Reactogenicity of Candidate Malaria Vaccine FMP013/ALFQ</measure>
<time_frame>393 Days (+/-14)</time_frame>
<description>To assess reactogenicity of candidate malaria vaccine. Occurrence of solicited local and systemic reactogenicity to FMP013/ALFQ</description>
</primary_outcome>
<secondary_outcome>
<measure>Determine the Protective Efficacy of FMP013/ALFQ against a Plasmodium falciparum controlled human malaria infection.</measure>
<time_frame>505 Days (+/-14)</time_frame>
<description>Proportion of vaccinated subjects without P.falciparum parasitemia (defined as one positive qRT-PCR test. Time to onset of P. falciparum parasitemia (defined as one positive qRT-PCR test) following CHMI.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Measure Immune Responses to CSP, induced by FMP013/ALFQ using various immunoassays.</measure>
<time_frame>505 Days (+/-14)</time_frame>
<description>The Quantitative Anti-CSP IgG antibody titers, isotypes, and avidity measured by ELISA, ELISpot, and multiplex-based detection systems. Assess cellular immune responses to CSP by multicolor flow cytometry, ELISpot, and stimulation assays.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Measure Immune Responses to CSP, induced by FMP013/ALFQ using various immunoassays.</measure>
<time_frame>505 Days (+/-14)</time_frame>
<description>The Qualitative Anti-CSP IgG antibody titers, isotypes, and avidity measured by ELISA, ELISpot, and multiplex-based detection systems. Assess cellular immune responses to CSP by multicolor flow cytometry, ELISpot, and stimulation assays.</description>
</secondary_outcome>
<other_outcome>
<measure>Compare the efficacy of standard, delayed dosing, and delayed fractional dosing</measure>
<time_frame>505 Days (+/-14)</time_frame>
<description>Proportion of vaccinated subjects without P. falciparum parasitemia (defined as one positive qRT-PCR test and/or one positive TBS, whichever is first) following CHMI. Comparisons will be made across treatment groups.</description>
</other_outcome>
<number_of_arms>6</number_of_arms>
<enrollment type="Anticipated">46</enrollment>
<condition>Vaccine Reaction</condition>
<arm_group>
<arm_group_label>Part A - "Low" Dose</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Part A vaccinees in the "low dose" arm will receive the lower dosing (20 μg FMP013 per 0.5 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 0,1,2 month.</description>
</arm_group>
<arm_group>
<arm_group_label>Part A - "High" Dose</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Part A vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP013 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination.
Vaccination to be delivered on 0,1,2 month.</description>
</arm_group>
<arm_group>
<arm_group_label>Part B - "Standard" Dose</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Part B vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP013 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination.
Vaccination to be delivered on 4,5,6 month.</description>
</arm_group>
<arm_group>
<arm_group_label>Part B - "Delayed" Dose</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Part B vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP013 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination.
Vaccination to be delivered on 0,1,6 month.</description>
</arm_group>
<arm_group>
<arm_group_label>Part B - "Delayed Fractional" Dose</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Part B vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP013 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination.
Vaccination to be delivered on 0,1,6 month.</description>
</arm_group>
<arm_group>
<arm_group_label>Control</arm_group_label>
<arm_group_type>No Intervention</arm_group_type>
<description>Up to 6 subjects will be enrolled (defined as receiving malaria challenge) later in the trial to serve as challenge controls. Additional subjects may be recruited as alternates to ensure that 6 control subjects undergo the challenge. Any alternates not challenged will be released from the study at day of challenge.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>FMP013</intervention_name>
<description>Falciparum Malaria Protein-13</description>
<arm_group_label>Part A - "High" Dose</arm_group_label>
<arm_group_label>Part A - "Low" Dose</arm_group_label>
<arm_group_label>Part B - "Delayed Fractional" Dose</arm_group_label>
<arm_group_label>Part B - "Delayed" Dose</arm_group_label>
<arm_group_label>Part B - "Standard" Dose</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>ALFQ</intervention_name>
<description>ALF with QS-21, saponin molecule derived from the tree bark of Quillaja species</description>
<arm_group_label>Part A - "High" Dose</arm_group_label>
<arm_group_label>Part A - "Low" Dose</arm_group_label>
<arm_group_label>Part B - "Delayed Fractional" Dose</arm_group_label>
<arm_group_label>Part B - "Delayed" Dose</arm_group_label>
<arm_group_label>Part B - "Standard" Dose</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Healthy adults between the ages 18-55 (inclusive);

2. Able and willing to provide written, informed consent;

3. Able and willing to comply with all research requirements, in the opinion of the
Investigator;

4. Agreement to refrain from blood donation during the course of the study. Volunteers
who have undergone CHMI can donate to other research once the study is complete but
cannot donate to the American Red Cross for at least 3 years after the CHMI event;

5. Laboratory Criteria within 90 days before enrollment:

- Hemoglobin ≥ 11.7 g/dL for women; ≥ 12.0 g/dL for men;

- White Blood Cell count = 3,800-10,800 cells/mm3;

- Platelets = 140,000-400,000/mm3;

- Alanine aminotransferase (ALT; SGPT) 9-46 U/L male and 6-29 U/L female;

- Serum creatinine ≤ 1.5 mg/dL;

- Negative HIV testing (HIV Ab / antigen 4th generation screen with reflex
confirmatory RNA testing);

- Negative hepatitis B surface antigen (HBsAg) and hepatitis C antibody testing;
Note: As above, Grade 1 lab abnormalities detected on screening may be repeated
at PI discretion. Persistent Grade 1 abnormalities that are felt to represent the
non-pathologic baseline for the subject will be discussed with the research
monitor and documented before a subject is enrolled in the trial, and are
allowable per discretion and agreement of the PI and Research Monitor

6. Birth control requirements:

Female subjects must meet one of the following 2 criteria:

- No reproductive potential due to post-menopausal status (12 months of natural
[spontaneous] amenorrhea) or hysterectomy, bilateral oophorectomy or tubal
ligation;

- Women of childbearing potential should agree to practice highly effective
contraception at least 30 days before enrollment and through 3 months post-CHMI
or post-last vaccination (whichever is latest), using one of the following
methods: condoms (male or female) with spermicide; diaphragm, or cervical cap
with spermicide; intrauterine device; contraceptive pills, patch, injection,
intravaginal ring or other FDA-approved contraceptive method; male partner has
previously undergone a vasectomy; abstinence.

Male subjects are encouraged but not required to practice highly effective
contraception to avoid pregnancy in their partner from 30 days prior to enrollment
through 60 days post-CHMI. This is due to the potential impact of malaria and
antimalarial medications on spermatogenesis.

7. For all female subjects except those with a history of hysterectomy or bilateral
oophorectomy, a negative β-HCG pregnancy test (urine) on day of enrollment, each day
of vaccination, and the day of CHMI (tubal ligations have a not insignificant failure
rate, 12 months of spontaneous amenorrhea does not completely preclude pregnancy and
can be a result of polycystic ovarian syndrome);

8. Reachable (24/7) by mobile phone or other method of communication (email, landline,
etc) during the period between CHMI and 28 days post-CHMI, per volunteer report;

9. No plans to travel outside the Washington DC metro area (DC, Maryland, and Virginia)
between the day of challenge and 28 days post-challenge; For Travel outside the US
occurring 28 days post-challenge to a malaria endemic area inclusion will be at the
discretion of the PI.

10. If a subject is active duty military, he or she must obtain approval from his or her
supervisor per WRAIR Policy 11-45;

11. Must have low (< 10%) cardiac risk factors according to clinical Gaziano (NHANES I)
criteria assessed at screening, and a normal or normal variant ECG;

12. Completion of Study Comprehension Quiz (minimum passing score of 80% with 2 attempts
permitted).

13. Subject must be willing to take anti-malarial treatment after CHMI;

14. Subject must provide 2 emergency contacts who will be made aware of the subject's
participation in this trial and the vital importance of being reached during the
challenge phase of the study. Both contacts must be verified by pone prior to subject
enrollment.

Verification will be define as either speaking to the emergency contact over the phone,
hearing their name included in the voicemail response, or confirming the emergency contact
uses the number if a third party answers the phone.

Exclusion Criteria:

1. History of malaria infection (any species) or residence in a malaria-endemic area for
more than 5 years (includes previous participation in CHMI studies).

2. Previous travel to malaria endemic regions within the past 6 months before study
enrollment defined as first vaccination or day of challenge (for infectivity controls)
or planned travel to malaria endemic regions during the vaccination, CHMI and 28-day
CHMI follow-up period; For Travel outside the US occurring 28 days post-challenge to a
malaria endemic area exclusion will be at the discretion of the PI.

3. Any history of receiving a malaria vaccine.

4. Received an investigational product in the 30 days before enrollment, or planned to
receive during the study period.

5. Concurrent participation in another clinical research study.

6. Any use of medications that prevent or treat malaria during the 1 month prior to
challenge or planned use during the study (outside of the drugs provided by the study
team).

7. Any serious medical illness or condition involving the heart, liver, lungs, or
kidneys.

8. Any significant risk for developing heart disease in the next 5 years, assessed
according to clinical Gaziano (NHANES I) criteria assessed at screening, and an ECG.

9. Receipt of immunoglobulins or blood products within 3 months before enrollment.

10. Any history of anaphylaxis.

11. History of sickle cell trait or disease, or any condition that could affect
susceptibility to malaria infection, per subject verbal report.

12. Pregnancy, lactation, or intention to become pregnant during the study, and 3 months
after malaria challenge, if applicable.

13. Contraindications or allergies to the use of all 3 proposed anti-malarial medications;
Malarone (atovaquone/proguanil), Coartem (artemether/lumefantrine) and chloroquine;
contraindication to 1 or 2 is not exclusionary.

14. History of active/recent cancer still within treatment or active surveillance
follow-up (except basal cell carcinoma of the skin and cervical carcinoma in situ).
Treated/resolved cancers with no likelihood of recurrence may be deemed acceptable at
Principal investigator discretion

15. History of autoimmune disease.

16. Significant (eg systemic anaphylaxis) hypersensitivity reactions to mosquito bites
(local reactions at the site of mosquito bites are not an exclusion criterion)
requiring hospitalization.

17. Suspected or known current alcohol or drug abuse as defined by an alcohol intake of
greater than 3 drinks a day on average for a man, and greater than 2 drinks a day on
average for a woman.

18. Any other significant disease, disorder or finding which may significantly increase
the risk to the volunteer because of participation in the study, affect the ability of
the volunteer to give informed consent, participate in the study, or impair
interpretation of the study data, in the opinion of the Investigator.

19. Current anti-tuberculosis prophylaxis or treatment.

20. History of splenectomy.

21. History of confirmed or suspected immunodeficiency.

22. History of Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms
of angioedema.

23. History of Asthma that is unstable or required emergent care, urgent care,
hospitalization or intubation during the past 2 years.

24. History of Diabetes mellitus (type I or II), with the exception of gestational
diabetes.

25. History of Thyroid disease (except for well controlled hypothyroidism).

26. History of Idiopathic urticaria within the past year.

27. History of hypertension that is not well controlled by medication or that is
persistently greater than 150/95 at screening...

28. History of bleeding disorder diagnosed by a doctor (eg, factor deficiency,
coagulopathy, or platelet disorder requiring special precautions) or significant
bruising or bleeding difficulties with IM injections or blood draws.

29. History of chronic or active neurologic disease to include seizure disorder and
chronic migraine headaches. Exceptions are: i) childhood febrile seizures, or ii)
seizures secondary to alcohol withdrawal more than 3 years ago.

30. Subjects receiving any of the following substances:

- Systemic immunosuppressive medications or cytotoxic medications within 12 weeks
before enrollment [with the exception of a short course of corticosteroids (≤ 14
days duration or a single injection) for a self-limited condition at least 2
weeks before enrollment; inhaled, intranasal or topical steroids are not
considered exclusionary]

- Treatment with known immunomodulators (other than nonsteroidal anti-inflammatory
drugs [NSAIDs]) for any reason.

- History of receipt of medication that prevent or treat malaria within 1 month of
CHMI

- Live attenuated vaccines within 30 days before initial study vaccine
administration

- Medically indicated subunit or killed vaccines, eg, influenza, pneumococcal, or
allergy treatment with antigen injections, planned for administration 14 days
before or after study vaccine administration

31. History of arthritis diagnosis other than osteoarthritis.

32. History of other diagnosed rheumatoid disorders.

33. Any history of psoriasis (itchy skin rash) or porphyria (rare disturbance of
metabolism), since these conditions could get worse after treatment with chloroquine
(a medication for treating malaria).

34. Subject must not have a fever in order to receive the study vaccine or participate in
the malaria challenge.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>55 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_contact>
<last_name>Jack N Hutter MD, MPH&TM, MAJ,MC,USA</last_name>
<phone>301-319-3095</phone>
<email>jack.n.hutter.mil@mail.mil</email>
</overall_contact>
<location>
<facility>
<name>WRAIR, Clinical Trials Center</name>
<address>
<city>Silver Spring</city>
<state>Maryland</state>
<zip>20910-7500</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Jack N Hutter, MD, MPH&TM, MAJ, MC, USA</last_name>
<phone>301-319-3095</phone>
<email>jack.n.hutter.mil@mail.mil</email>
</contact>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>January 2023</verification_date>
<study_first_submitted>February 4, 2020</study_first_submitted>
<study_first_submitted_qc>February 10, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>January 6, 2023</last_update_submitted>
<last_update_submitted_qc>January 6, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">January 10, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Plasmodium falciparum</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Malaria</mesh_term>
<mesh_term>Malaria, Falciparum</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<provided_document_section>
<provided_document>
<document_type>Informed Consent Form: Informed Consent Form Part B: C-D and C-F</document_type>
<document_has_protocol>No</document_has_protocol>
<document_has_icf>Yes</document_has_icf>
<document_has_sap>No</document_has_sap>
<document_date>April 14, 2021</document_date>
<document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT04268420/ICF_000.pdf</document_url>
</provided_document>
<provided_document>
<document_type>Informed Consent Form: Informed Consent Form Part B: Controls</document_type>
<document_has_protocol>No</document_has_protocol>
<document_has_icf>Yes</document_has_icf>
<document_has_sap>No</document_has_sap>
<document_date>April 14, 2021</document_date>
<document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT04268420/ICF_001.pdf</document_url>
</provided_document>
<provided_document>
<document_type>Informed Consent Form: Informed Consent Form Part B: C-S</document_type>
<document_has_protocol>No</document_has_protocol>
<document_has_icf>Yes</document_has_icf>
<document_has_sap>No</document_has_sap>
<document_date>April 14, 2021</document_date>
<document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT04268420/ICF_002.pdf</document_url>
</provided_document>
</provided_document_section>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
A Phase 1, open label clinical study to evaluate the safety, immunogenicity, tolerability and
efficacy of Plasmodium falciparum Malaria Protein 013 (FMP013) combined with (ALF with
QS-21), saponin molecule derived from the bark of Quillaja species (ALFQ)) in healthy adult
volunteers at different doses and dosing schedules.
This is an open-label immunization with Controlled Human Malaria Infection (CHMI) study.
Healthy, malaria-naïve adults, aged 18-55 years old will be recruited into one of 5
experimental cohorts in 2 parts.
In Part A, 2 experimental cohorts of 5 subjects each will receive a series of 3 vaccinations
at 0, 1, and 2 months at 2 doses (the "low dose" arm and the "high dose" arm).
In Part B, 3 experimental cohorts of 10 subjects will receive a series of 3 vaccinations at
0, 1, 6 months (called the "delayed dose" arm), the "delayed fractional dose" arm is
vaccinated at 0, 1, and 6 months with the 6 month dose being 1/5 the other doses, and the
"standard" arm" at the 4th, 5th, and 6th month (after the first 2 vaccinations of the other 2
arms in Part B).
Inclusion Criteria:
1. Healthy adults between the ages 18-55 (inclusive);
2. Able and willing to provide written, informed consent;
3. Able and willing to comply with all research requirements, in the opinion of the
Investigator;
4. Agreement to refrain from blood donation during the course of the study. Volunteers
who have undergone CHMI can donate to other research once the study is complete but
cannot donate to the American Red Cross for at least 3 years after the CHMI event;
5. Laboratory Criteria within 90 days before enrollment:
- Hemoglobin ≥ 11.7 g/dL for women; ≥ 12.0 g/dL for men;
- White Blood Cell count = 3,800-10,800 cells/mm3;
- Platelets = 140,000-400,000/mm3;
- Alanine aminotransferase (ALT; SGPT) 9-46 U/L male and 6-29 U/L female;
- Serum creatinine ≤ 1.5 mg/dL;
- Negative HIV testing (HIV Ab / antigen 4th generation screen with reflex
confirmatory RNA testing);
- Negative hepatitis B surface antigen (HBsAg) and hepatitis C antibody testing;
Note: As above, Grade 1 lab abnormalities detected on screening may be repeated
at PI discretion. Persistent Grade 1 abnormalities that are felt to represent the
non-pathologic baseline for the subject will be discussed with the research
monitor and documented before a subject is enrolled in the trial, and are
allowable per discretion and agreement of the PI and Research Monitor
6. Birth control requirements:
Female subjects must meet one of the following 2 criteria:
- No reproductive potential due to post-menopausal status (12 months of natural
[spontaneous] amenorrhea) or hysterectomy, bilateral oophorectomy or tubal
ligation;
- Women of childbearing potential should agree to practice highly effective
contraception at least 30 days before enrollment and through 3 months post-CHMI
or post-last vaccination (whichever is latest), using one of the following
methods: condoms (male or female) with spermicide; diaphragm, or cervical cap
with spermicide; intrauterine device; contraceptive pills, patch, injection,
intravaginal ring or other FDA-approved contraceptive method; male partner has
previously undergone a vasectomy; abstinence.
Male subjects are encouraged but not required to practice highly effective
contraception to avoid pregnancy in their partner from 30 days prior to enrollment
through 60 days post-CHMI. This is due to the potential impact of malaria and
antimalarial medications on spermatogenesis.
7. For all female subjects except those with a history of hysterectomy or bilateral
oophorectomy, a negative β-HCG pregnancy test (urine) on day of enrollment, each day
of vaccination, and the day of CHMI (tubal ligations have a not insignificant failure
rate, 12 months of spontaneous amenorrhea does not completely preclude pregnancy and
can be a result of polycystic ovarian syndrome);
8. Reachable (24/7) by mobile phone or other method of communication (email, landline,
etc) during the period between CHMI and 28 days post-CHMI, per volunteer report;
9. No plans to travel outside the Washington DC metro area (DC, Maryland, and Virginia)
between the day of challenge and 28 days post-challenge; For Travel outside the US
occurring 28 days post-challenge to a malaria endemic area inclusion will be at the
discretion of the PI.
10. If a subject is active duty military, he or she must obtain approval from his or her
supervisor per WRAIR Policy 11-45;
11. Must have low (< 10%) cardiac risk factors according to clinical Gaziano (NHANES I)
criteria assessed at screening, and a normal or normal variant ECG;
12. Completion of Study Comprehension Quiz (minimum passing score of 80% with 2 attempts
permitted).
13. Subject must be willing to take anti-malarial treatment after CHMI;
14. Subject must provide 2 emergency contacts who will be made aware of the subject's
participation in this trial and the vital importance of being reached during the
challenge phase of the study. Both contacts must be verified by pone prior to subject
enrollment.
Verification will be define as either speaking to the emergency contact over the phone,
hearing their name included in the voicemail response, or confirming the emergency contact
uses the number if a third party answers the phone.
Exclusion Criteria:
1. History of malaria infection (any species) or residence in a malaria-endemic area for
more than 5 years (includes previous participation in CHMI studies).
2. Previous travel to malaria endemic regions within the past 6 months before study
enrollment defined as first vaccination or day of challenge (for infectivity controls)
or planned travel to malaria endemic regions during the vaccination, CHMI and 28-day
CHMI follow-up period; For Travel outside the US occurring 28 days post-challenge to a
malaria endemic area exclusion will be at the discretion of the PI.
3. Any history of receiving a malaria vaccine.
4. Received an investigational product in the 30 days before enrollment, or planned to
receive during the study period.
5. Concurrent participation in another clinical research study.
6. Any use of medications that prevent or treat malaria during the 1 month prior to
challenge or planned use during the study (outside of the drugs provided by the study
team).
7. Any serious medical illness or condition involving the heart, liver, lungs, or
kidneys.
8. Any significant risk for developing heart disease in the next 5 years, assessed
according to clinical Gaziano (NHANES I) criteria assessed at screening, and an ECG.
9. Receipt of immunoglobulins or blood products within 3 months before enrollment.
10. Any history of anaphylaxis.
11. History of sickle cell trait or disease, or any condition that could affect
susceptibility to malaria infection, per subject verbal report.
12. Pregnancy, lactation, or intention to become pregnant during the study, and 3 months
after malaria challenge, if applicable.
13. Contraindications or allergies to the use of all 3 proposed anti-malarial medications;
Malarone (atovaquone/proguanil), Coartem (artemether/lumefantrine) and chloroquine;
contraindication to 1 or 2 is not exclusionary.
14. History of active/recent cancer still within treatment or active surveillance
follow-up (except basal cell carcinoma of the skin and cervical carcinoma in situ).
Treated/resolved cancers with no likelihood of recurrence may be deemed acceptable at
Principal investigator discretion
15. History of autoimmune disease.
16. Significant (eg systemic anaphylaxis) hypersensitivity reactions to mosquito bites
(local reactions at the site of mosquito bites are not an exclusion criterion)
requiring hospitalization.
17. Suspected or known current alcohol or drug abuse as defined by an alcohol intake of
greater than 3 drinks a day on average for a man, and greater than 2 drinks a day on
average for a woman.
18. Any other significant disease, disorder or finding which may significantly increase
the risk to the volunteer because of participation in the study, affect the ability of
the volunteer to give informed consent, participate in the study, or impair
interpretation of the study data, in the opinion of the Investigator.
19. Current anti-tuberculosis prophylaxis or treatment.
20. History of splenectomy.
21. History of confirmed or suspected immunodeficiency.
22. History of Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms
of angioedema.
23. History of Asthma that is unstable or required emergent care, urgent care,
hospitalization or intubation during the past 2 years.
24. History of Diabetes mellitus (type I or II), with the exception of gestational
diabetes.
25. History of Thyroid disease (except for well controlled hypothyroidism).
26. History of Idiopathic urticaria within the past year.
27. History of hypertension that is not well controlled by medication or that is
persistently greater than 150/95 at screening...
28. History of bleeding disorder diagnosed by a doctor (eg, factor deficiency,
coagulopathy, or platelet disorder requiring special precautions) or significant
bruising or bleeding difficulties with IM injections or blood draws.
29. History of chronic or active neurologic disease to include seizure disorder and
chronic migraine headaches. Exceptions are: i) childhood febrile seizures, or ii)
seizures secondary to alcohol withdrawal more than 3 years ago.
30. Subjects receiving any of the following substances:
- Systemic immunosuppressive medications or cytotoxic medications within 12 weeks
before enrollment [with the exception of a short course of corticosteroids (≤ 14
days duration or a single injection) for a self-limited condition at least 2
weeks before enrollment; inhaled, intranasal or topical steroids are not
considered exclusionary]
- Treatment with known immunomodulators (other than nonsteroidal anti-inflammatory
drugs [NSAIDs]) for any reason.
- History of receipt of medication that prevent or treat malaria within 1 month of
CHMI
- Live attenuated vaccines within 30 days before initial study vaccine
administration
- Medically indicated subunit or killed vaccines, eg, influenza, pneumococcal, or
allergy treatment with antigen injections, planned for administration 14 days
before or after study vaccine administration
31. History of arthritis diagnosis other than osteoarthritis.
32. History of other diagnosed rheumatoid disorders.
33. Any history of psoriasis (itchy skin rash) or porphyria (rare disturbance of
metabolism), since these conditions could get worse after treatment with chloroquine
(a medication for treating malaria).
34. Subject must not have a fever in order to receive the study vaccine or participate in
the malaria challenge.
|
NCT0426xxxx/NCT04268433.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268433</url>
</required_header>
<id_info>
<org_study_id>C&W18/005</org_study_id>
<secondary_id>242951</secondary_id>
<nct_id>NCT04268433</nct_id>
</id_info>
<brief_title>The MUSIC-HR Study</brief_title>
<official_title>Musical Heart Rhythm Regulation: The MUSIC-HR Study</official_title>
<sponsors>
<lead_sponsor>
<agency>Chelsea and Westminster NHS Foundation Trust</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>CW Plus Charity</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>Chelsea and Westminster NHS Foundation Trust</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The idea that music has an effect on heart rate and blood pressure has existed for some time.
In 1918, Hyde and Scalapino [1] reported that minor tones increased pulse rate and lowered
blood pressure, whereas "stirring" music increased both blood pressure and heart rate. In the
management of many cardiovascular disorders heart rate control is paramount. Furthermore,
many cardiovascular investigations (e.g. Cardiac CT) require adequate heart rate control in
order to achieve diagnostic images and therefore results. Whilst pharmacologic therapy is
available and remains the main strategy for heart rate control, this is not always without
consequences. Side effect profiles, patient intolerance and also variable efficacy are
limiting factors for pharmacological therapy. Alternative strategies to achieve adequate
heart rate control are therefore needed.

The aim of this study is to explore the potential use of music to control heart rates and
other physiological parameters such as respiratory rate and blood pressure. The central study
team hypothesize that by changing the tempo of the music they will be able to influence the
natural variations in heart rate.

1. Hyde IM, Scalapino W. The influence of music upon electrocardiograms and blood pressure.
Am J Physiol.1918;46:35-38.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
This is a single-arm non-randomized pilot study. Staff at Chelsea and Westminster NHS
Foundation Trust will be recruited via the placement of posters in staff only areas such as
staff rooms and via the daily communications that the Trust use. Those who meet all of the
inclusion criteria and none of the exclusion criteria will be approached for participation in
the study. The participants will be asked to listen to a series of musical genres, selected
in random order, whilst lying on a standard hospital bed for comfort. This will take place in
a private clinical room to minimise disturbance and any variation in heart rate caused by
external stressors. The participants will have an ECG recording performed by attachment of
adhesive surface lead electrodes to the chest and arms. This will be continuous throughout
the protocol. They will also have a continuous non-invasive blood pressure recording using
equipment that is in routine clinical practice (Finapress BP) and respiration monitored via a
respiration belt. They will also be asked to wear a small lightweight sensor that gives
readings of heart rate and blood pressure at 2 minute intervals.

After a period of approximately 10 minutes of ECG recording without music (control period), a
series of pieces of music will be played whilst the ECG recordings continue. Each piece of
music will last for no more than 5 minutes, 3 will be selected by the investigators and one
will be pre-chosen by the participant prior to their attendance. The order in which these
pieces will be played will be chosen at random. There will be a 3 minute recovery time in
between each piece of music. The same pieces of music will then be played back to the
participant but this time the music will subtly change tempo in reaction to the patient's
heart rate. This is achieved by the ECG feeding data into the computer playing the music,
whereupon the data is processed by Max MSP software and used to control the playback speed in
Ableton Live. The algorithm for change is a linear one: the higher a patient's heart rate is
in relation to a desired bpm target, the more the music will slow down. (There will be a
limit to the extent of the tempo adjustment, in order to prevent any noticeable distortion to
the music.)

The tempo of the music is controlled by computer. The ECG recording will feed into the
computer where the software alters the tempo of the music based on the real-time heart rate
feedback. The hypothesis is that by altering the tempo of the music the investigators will
see changes in the heart rate of the participant. These changes will then feedback to the
software which will continue to alter the tempo accordingly with the aim to achieve a degree
of heart rate control and see less heart rate variation and less high heart rates. It should
take around one hour to complete all the study procedures.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">April 26, 2018</start_date>
<completion_date type="Actual">September 30, 2019</completion_date>
<primary_completion_date type="Actual">July 12, 2019</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Cross-Sectional</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Assessment of the effect of music and music tempo on heart rate control</measure>
<time_frame>Participants will be involved in the study for a total of 1 day. No follow-up is required so data will be ready for analysis after participants have completed the music exercise.</time_frame>
<description>After a period of approximately 10 minutes of ECG recording without music (control period), a series of pieces of music will be played whilst the ECG recordings continue. Each piece of music will last for no more than 5 minutes, 3 will be selected by the investigators and one will be pre-chosen by the participant prior to their attendance. The order in which these pieces will be played will be chosen at random. There will be a 3 minute recovery time in between each piece of music. The same pieces of music will then be played back to the participant but this time the music will subtly change tempo in reaction to the patient's heart rate. This is achieved by the ECG feeding data into the computer playing the music, whereupon the data is processed by Max MSP software and used to control the playback speed in Ableton Live. The algorithm for change is a linear one: the higher a patient's heart rate is in relation to a desired bpm target, the more the music will slow down.</description>
</primary_outcome>
<secondary_outcome>
<measure>Assessment of the effect of music and music tempo on blood pressure and variability</measure>
<time_frame>Participants will be involved in the study for a total of 1 day. No follow-up is required so data will be ready for analysis after participants have completed the music exercise.</time_frame>
<description>As well as having an ECG recording performed, participants will also have a continuous non-invasive blood pressure recording using equipment that is in routine clinical practice (Finapress BP) and respiration monitored via a respiration belt. They will also be asked to wear a small lightweight sensor that gives readings of heart rate and blood pressure at 2 minute intervals.
The data obtained from all of the physiological recordings with be analysed for associations.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Assessment of the effect of music on heart rate variability</measure>
<time_frame>Participants will be involved in the study for a total of 1 day. No follow-up is required so data will be ready for analysis after participants have completed the music exercise.</time_frame>
<description>As well as having an ECG recording performed, participants will also have a continuous non-invasive blood pressure recording using equipment that is in routine clinical practice (Finapress BP) and respiration monitored via a respiration belt. They will also be asked to wear a small lightweight sensor that gives readings of heart rate and blood pressure at 2 minute intervals.
The data obtained from all of the physiological recordings with be analysed for associations.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Assessment of the effect of music on markers of repolarization instability</measure>
<time_frame>Participants will be involved in the study for a total of 1 day. No follow-up is required so data will be ready for analysis after participants have completed the music exercise.</time_frame>
<description>Effect of music on markers of repolarization instability (QT interval and T wave vector assessment).</description>
</secondary_outcome>
<secondary_outcome>
<measure>Effect of music on cardiac autonomics</measure>
<time_frame>Participants will be involved in the study for a total of 1 day. No follow-up is required so data will be ready for analysis after participants have completed the music exercise.</time_frame>
<description>This is assessed by frequency analysis of ECG.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Assessment of the effect of music and music tempo on respiratory rate and variability</measure>
<time_frame>Participants will be involved in the study for a total of 1 day. No follow-up is required so data will be ready for analysis after participants have completed the music exercise.</time_frame>
<description>Respiration of participants will be monitored via a respiration belt whilst they are listening to music.</description>
</secondary_outcome>
<enrollment type="Actual">19</enrollment>
<condition>Musical Heart Rhythm Regulation</condition>
<condition>Cardiovascular Diseases</condition>
<condition>Heart Rate Control</condition>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>N/A - Non-interventional study</intervention_name>
<description>Stages:
Patient information and written informed consent (3 Copies. To be carried out >24 hours after receiving the patient information sheet)
Physiological recording set up (ECG, BP, sensor and respiratory band)
Control period - no music played
Series of pieces of music without tempo control
Repeat series of pieces of music with tempo control
Participant leaves the study</description>
</intervention>
<eligibility>
<study_pop>
<textblock>
As above.
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- Employed by Chelsea and Westminster NHS Foundation Trust with any contract type
(substantive, fixed term, honorary or bank)

- Age 18 or above

- Capable of giving informed consent

- Normal 12 lead ECG and blood pressure recording

Exclusion Criteria:

- Under 18 years of age

- Incapable of giving informed consent

- Regular use of any medications that interact with physiological control of the
parameters being measured

- Hearing impairment

- Skin sensitivity to ECG electrodes
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>N/A</minimum_age>
<maximum_age>N/A</maximum_age>
</eligibility>
<overall_official>
<last_name>Sadia Khan</last_name>
<role>Principal Investigator</role>
<affiliation>Chelsea and Westminster NHS Foundation Trust</affiliation>
</overall_official>
<location>
<facility>
<name>Chelsea and Westminster Hospital</name>
<address>
<city>London</city>
<state>Greater London</state>
<zip>SW10 9NH</zip>
<country>United Kingdom</country>
</address>
</facility>
</location>
<location_countries>
<country>United Kingdom</country>
</location_countries>
<reference>
<citation>Hyde IM, Scalapino W. The influence of music upon electrocardiograms and blood pressure. Am J Physiol. 1918;46:35-38.</citation>
</reference>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 11, 2020</last_update_submitted>
<last_update_submitted_qc>February 11, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Cardiovascular Diseases</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The idea that music has an effect on heart rate and blood pressure has existed for some time.
In 1918, Hyde and Scalapino [1] reported that minor tones increased pulse rate and lowered
blood pressure, whereas "stirring" music increased both blood pressure and heart rate. In the
management of many cardiovascular disorders heart rate control is paramount. Furthermore,
many cardiovascular investigations (e.g. Cardiac CT) require adequate heart rate control in
order to achieve diagnostic images and therefore results. Whilst pharmacologic therapy is
available and remains the main strategy for heart rate control, this is not always without
consequences. Side effect profiles, patient intolerance and also variable efficacy are
limiting factors for pharmacological therapy. Alternative strategies to achieve adequate
heart rate control are therefore needed.
The aim of this study is to explore the potential use of music to control heart rates and
other physiological parameters such as respiratory rate and blood pressure. The central study
team hypothesize that by changing the tempo of the music they will be able to influence the
natural variations in heart rate.
1. Hyde IM, Scalapino W. The influence of music upon electrocardiograms and blood pressure.
Am J Physiol.1918;46:35-38.
This is a single-arm non-randomized pilot study. Staff at Chelsea and Westminster NHS
Foundation Trust will be recruited via the placement of posters in staff only areas such as
staff rooms and via the daily communications that the Trust use. Those who meet all of the
inclusion criteria and none of the exclusion criteria will be approached for participation in
the study. The participants will be asked to listen to a series of musical genres, selected
in random order, whilst lying on a standard hospital bed for comfort. This will take place in
a private clinical room to minimise disturbance and any variation in heart rate caused by
external stressors. The participants will have an ECG recording performed by attachment of
adhesive surface lead electrodes to the chest and arms. This will be continuous throughout
the protocol. They will also have a continuous non-invasive blood pressure recording using
equipment that is in routine clinical practice (Finapress BP) and respiration monitored via a
respiration belt. They will also be asked to wear a small lightweight sensor that gives
readings of heart rate and blood pressure at 2 minute intervals.
After a period of approximately 10 minutes of ECG recording without music (control period), a
series of pieces of music will be played whilst the ECG recordings continue. Each piece of
music will last for no more than 5 minutes, 3 will be selected by the investigators and one
will be pre-chosen by the participant prior to their attendance. The order in which these
pieces will be played will be chosen at random. There will be a 3 minute recovery time in
between each piece of music. The same pieces of music will then be played back to the
participant but this time the music will subtly change tempo in reaction to the patient's
heart rate. This is achieved by the ECG feeding data into the computer playing the music,
whereupon the data is processed by Max MSP software and used to control the playback speed in
Ableton Live. The algorithm for change is a linear one: the higher a patient's heart rate is
in relation to a desired bpm target, the more the music will slow down. (There will be a
limit to the extent of the tempo adjustment, in order to prevent any noticeable distortion to
the music.)
The tempo of the music is controlled by computer. The ECG recording will feed into the
computer where the software alters the tempo of the music based on the real-time heart rate
feedback. The hypothesis is that by altering the tempo of the music the investigators will
see changes in the heart rate of the participant. These changes will then feedback to the
software which will continue to alter the tempo accordingly with the aim to achieve a degree
of heart rate control and see less heart rate variation and less high heart rates. It should
take around one hour to complete all the study procedures.
As above.
Inclusion Criteria:
- Employed by Chelsea and Westminster NHS Foundation Trust with any contract type
(substantive, fixed term, honorary or bank)
- Age 18 or above
- Capable of giving informed consent
- Normal 12 lead ECG and blood pressure recording
Exclusion Criteria:
- Under 18 years of age
- Incapable of giving informed consent
- Regular use of any medications that interact with physiological control of the
parameters being measured
- Hearing impairment
- Skin sensitivity to ECG electrodes
|
NCT0426xxxx/NCT04268446.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268446</url>
</required_header>
<id_info>
<org_study_id>turkishbriefBESTest</org_study_id>
<nct_id>NCT04268446</nct_id>
</id_info>
<brief_title>Turkish Version of the Brief-BESTest Scale</brief_title>
<official_title>Investigation of the Turkish Version, Validity and Reliability of Brief-BESTest Scale in Stroke Patients</official_title>
<sponsors>
<lead_sponsor>
<agency>Kırıkkale University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Kırıkkale University</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The aim of this study is to investigate the validity and reliability of the Turkish version
of the brief-BESTest (short BESTest) scale in stroke patients.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Brief Balance Evaluation Systems Test (Brief-BESTest) is a short version of the Balance
evaluation systems test (BESTest). Balance assessment systems test (BESTest) The balance
assessment systems test developed by Horak consists of 6 sub-sections that evaluate the
systems related to balance; 1) biomechanical limitations, 2) stability limit, 3) postural
responses, 4) intuitive postural adjustments, 5) sensory orientation and 6) walking. It
consists of 36 tests in total. Each question is rated between 0-3. The highest score that can
be obtained is 108. Low test scores show that the balance is disturbed. BESTest has been
found to be reliable among raters evaluating a cohort of individuals with and without various
neurological diagnoses. In studies conducted, it was stated that BESTest is reliable when
compared to other scales evaluating balance.

The necessary permissions have been obtained from the authors for Short BESTest, whose
validity and reliability features will be tested, and the translation process to Turkish has
been completed and the survey has been finalized. The basis for the use of special tools such
as the scale is to prove the usability of the tool in the sample group to which it will be
applied. The first step for this is the translation stage from the original language to the
other language.

At the stage of translation into Turkish, two experts who knew a good level of English
translated the questionnaire from English into Turkish. These translations have been
translated back into Turkish by two native speakers of English and distant medical subjects.
In addition, these translations were re-examined by the researchers and turned into a single
form. This form was sent to five specialists in the field, checking the content and
compliance with Turkish was evaluated. With the opinion of experts, the scale was finalized.

The study will include individuals over 40 years of age who have been diagnosed with an
ischemic or hemorhagic stroke, who applied to the Kırıkkale University Faculty of Medicine
Physical Therapy and Rehabilitation Hospital.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">March 29, 2019</start_date>
<completion_date type="Actual">June 30, 2020</completion_date>
<primary_completion_date type="Actual">May 30, 2020</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Other</observational_model>
<time_perspective>Cross-Sectional</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Berg Balance Test</measure>
<time_frame>15 minutes</time_frame>
<description>It is a 14-item scale that evaluates the tasks used in daily life activities.Standing up without support, standing without support, sitting without support, standing up, transfers, standing with feet, standing with legs while standing, reaching out while standing, picking up from the ground, looking back, 360 degree rotation, firm side standing on the stool, one foot standstill and standstill functions are evaluated.Each item is planned between 0-4; 0 is unable to fulfill the task, 4 is to fulfill the task successfully. The total score of the test is between 0-56.0-20 points: wheelchair dependent, 21-40: assisted walking, 41-56: means independent ambulation.</description>
</primary_outcome>
<primary_outcome>
<measure>Functional Reach Test</measure>
<time_frame>5 minutes</time_frame>
<description>Subjects will asked to stand comfortably, to make a fist, and to raise their arm until it was parallel to the yardstick (position 1). The placement of the end of the third metacarpal along the yardstick will recorded. Subjects will then asked to reach as far forward as they could without losing their balance (position 2), and the position of the end of the third metacarpal along the yardstick will again recorded. No attempt will make to control the subject's method of reach, but if he will touch the wall or took a step during the maneuver, that trial will consider invalid and repeated.</description>
</primary_outcome>
<primary_outcome>
<measure>Time Up and Go Test</measure>
<time_frame>5 minutes</time_frame>
<description>This test is applied to assess the risk of falling and mobility.This test starts with the individual leaving the chair without receiving arm support by giving the go command while sitting in a chair.The distance of 3 meters is asked to return and sit again in the chair.The elapsed time is recorded in seconds.</description>
</primary_outcome>
<primary_outcome>
<measure>10 Meter Walk Tests</measure>
<time_frame>3 minutes</time_frame>
<description>Walking speed are measure by timing subjects over 10 meters with a stopwatch. To avoid the effects of acceleration and deceleration, measurements take over the middle 10 meters of a 14-meter walkway. It is repeated 2 times.</description>
</primary_outcome>
<primary_outcome>
<measure>Falls Efficacy Scale</measure>
<time_frame>5 minutes</time_frame>
<description>FES is a 10-item scale and these items are; To enter and get out of bed, to sit and stand on the chair, to take a bath or shower, to dress and undress, to lie on the shelves, to walk in the house, to answer the door or phone, to prepare food without lifting heavy objects and to do simple shopping. Individuals score between 0 (not safe) and 10 (very safe) for each question, and when all scores are summed, a total score between 0 and 100 is obtained.</description>
</primary_outcome>
<enrollment type="Actual">40</enrollment>
<condition>Stroke Patients</condition>
<eligibility>
<study_pop>
<textblock>
Patients who are able to walk 10 m independently with or without a device over 40 years old
with a diagnosis of stroke.
</textblock>
</study_pop>
<sampling_method>Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- Being 40 years old or older,

- Diagnosis of stroke,

- No cooperation and communication problems

- To be able to walk 10 m independently with or without an auxiliary device

Exclusion Criteria:

- Another neurological or orthopedic problem other than stroke that will affect
functionality and balance

- Individuals with advanced contraindications for cardiovascular disease and
mobilization will not be included in the study.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>40 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Saniye Aydoğan Arslan</last_name>
<role>Study Director</role>
<affiliation>Kırıkkale University</affiliation>
</overall_official>
<overall_official>
<last_name>Kübra Uğurlu</last_name>
<role>Principal Investigator</role>
<affiliation>Kırıkkale University</affiliation>
</overall_official>
<overall_official>
<last_name>Cevher Demirci</last_name>
<role>Principal Investigator</role>
<affiliation>Balikesir University</affiliation>
</overall_official>
<overall_official>
<last_name>Zekiye İpek Katırcı Kırmacı</last_name>
<role>Principal Investigator</role>
<affiliation>Sanko University</affiliation>
</overall_official>
<location>
<facility>
<name>Kırıkkale University</name>
<address>
<city>Kırıkkale</city>
<zip>71000</zip>
<country>Turkey</country>
</address>
</facility>
</location>
<location_countries>
<country>Turkey</country>
</location_countries>
<reference>
<citation>Padgett PK, Jacobs JV, Kasser SL. Is the BESTest at its best? A suggested brief version based on interrater reliability, validity, internal consistency, and theoretical construct. Phys Ther. 2012 Sep;92(9):1197-207. doi: 10.2522/ptj.20120056. Epub 2012 Jun 7.</citation>
<PMID>22677295</PMID>
</reference>
<reference>
<citation>Smith PS, Hembree JA, Thompson ME. Berg Balance Scale and Functional Reach: determining the best clinical tool for individuals post acute stroke. Clin Rehabil. 2004 Nov;18(7):811-8. doi: 10.1191/0269215504cr817oa.</citation>
<PMID>15573838</PMID>
</reference>
<reference>
<citation>Schmidt S, Bullinger M. Current issues in cross-cultural quality of life instrument development. Arch Phys Med Rehabil. 2003 Apr;84(4 Suppl 2):S29-34. doi: 10.1053/apmr.2003.50244.</citation>
<PMID>12692769</PMID>
</reference>
<reference>
<citation>Chinsongkram B, Chaikeeree N, Saengsirisuwan V, Viriyatharakij N, Horak FB, Boonsinsukh R. Reliability and validity of the Balance Evaluation Systems Test (BESTest) in people with subacute stroke. Phys Ther. 2014 Nov;94(11):1632-43. doi: 10.2522/ptj.20130558. Epub 2014 Jun 12.</citation>
<PMID>24925073</PMID>
</reference>
<reference>
<citation>Bergstrom M, Lenholm E, Franzen E. Translation and validation of the Swedish version of the mini-BESTest in subjects with Parkinson's disease or stroke: a pilot study. Physiother Theory Pract. 2012 Oct;28(7):509-14. doi: 10.3109/09593985.2011.653707. Epub 2012 Jan 30.</citation>
<PMID>22288658</PMID>
</reference>
<reference>
<citation>O'Hoski S, Sibley KM, Brooks D, Beauchamp MK. Construct validity of the BESTest, mini-BESTest and briefBESTest in adults aged 50 years and older. Gait Posture. 2015 Sep;42(3):301-5. doi: 10.1016/j.gaitpost.2015.06.006. Epub 2015 Jun 25.</citation>
<PMID>26183191</PMID>
</reference>
<reference>
<citation>Franchignoni F, Horak F, Godi M, Nardone A, Giordano A. Using psychometric techniques to improve the Balance Evaluation Systems Test: the mini-BESTest. J Rehabil Med. 2010 Apr;42(4):323-31. doi: 10.2340/16501977-0537.</citation>
<PMID>20461334</PMID>
</reference>
<reference>
<citation>Horak FB, Wrisley DM, Frank J. The Balance Evaluation Systems Test (BESTest) to differentiate balance deficits. Phys Ther. 2009 May;89(5):484-98. doi: 10.2522/ptj.20080071. Epub 2009 Mar 27.</citation>
<PMID>19329772</PMID>
</reference>
<verification_date>November 2020</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>November 5, 2020</last_update_submitted>
<last_update_submitted_qc>November 5, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">November 6, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Kırıkkale University</investigator_affiliation>
<investigator_full_name>Kübra Uğurlu</investigator_full_name>
<investigator_title>Research Assistant</investigator_title>
</responsible_party>
<keyword>brief BESTest</keyword>
<keyword>stroke patients</keyword>
<keyword>Turkish version</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Stroke</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The aim of this study is to investigate the validity and reliability of the Turkish version
of the brief-BESTest (short BESTest) scale in stroke patients.
Brief Balance Evaluation Systems Test (Brief-BESTest) is a short version of the Balance
evaluation systems test (BESTest). Balance assessment systems test (BESTest) The balance
assessment systems test developed by Horak consists of 6 sub-sections that evaluate the
systems related to balance; 1) biomechanical limitations, 2) stability limit, 3) postural
responses, 4) intuitive postural adjustments, 5) sensory orientation and 6) walking. It
consists of 36 tests in total. Each question is rated between 0-3. The highest score that can
be obtained is 108. Low test scores show that the balance is disturbed. BESTest has been
found to be reliable among raters evaluating a cohort of individuals with and without various
neurological diagnoses. In studies conducted, it was stated that BESTest is reliable when
compared to other scales evaluating balance.
The necessary permissions have been obtained from the authors for Short BESTest, whose
validity and reliability features will be tested, and the translation process to Turkish has
been completed and the survey has been finalized. The basis for the use of special tools such
as the scale is to prove the usability of the tool in the sample group to which it will be
applied. The first step for this is the translation stage from the original language to the
other language.
At the stage of translation into Turkish, two experts who knew a good level of English
translated the questionnaire from English into Turkish. These translations have been
translated back into Turkish by two native speakers of English and distant medical subjects.
In addition, these translations were re-examined by the researchers and turned into a single
form. This form was sent to five specialists in the field, checking the content and
compliance with Turkish was evaluated. With the opinion of experts, the scale was finalized.
The study will include individuals over 40 years of age who have been diagnosed with an
ischemic or hemorhagic stroke, who applied to the Kırıkkale University Faculty of Medicine
Physical Therapy and Rehabilitation Hospital.
Patients who are able to walk 10 m independently with or without a device over 40 years old
with a diagnosis of stroke.
Inclusion Criteria:
- Being 40 years old or older,
- Diagnosis of stroke,
- No cooperation and communication problems
- To be able to walk 10 m independently with or without an auxiliary device
Exclusion Criteria:
- Another neurological or orthopedic problem other than stroke that will affect
functionality and balance
- Individuals with advanced contraindications for cardiovascular disease and
mobilization will not be included in the study.
|
NCT0426xxxx/NCT04268459.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268459</url>
</required_header>
<id_info>
<org_study_id>1WF_CT_1_2020</org_study_id>
<nct_id>NCT04268459</nct_id>
</id_info>
<brief_title>Estimation of Benefit From Regular Versus Leakage-related Exchange of Voice Prosthesis in Patients Post Laryngectomy.</brief_title>
<acronym>RvLPE</acronym>
<official_title>Estimation of Benefit From Regular Versus Leakage-related Exchange of Voice Prosthesis in Patients Post Laryngectomy Considering Complications Rate, Fistula Colonization by Candida Species and Patients Satisfaction Feedback.</official_title>
<sponsors>
<lead_sponsor>
<agency>Medical University of Warsaw</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Medical University of Warsaw</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
<is_us_export>No</is_us_export>
</oversight_info>
<brief_summary>
<textblock>
The tracheoesophageal voice with voice prosthesis is currently the mainstay of voice
rehabilitation post laryngectomy. The primary surgical technique of tracheoesophageal fistula
formation with insertion of prosthesis and quick and easy process of voice rehabilitation are
main encouraging factors. However, the usage of the prosthesis relates to a significant
number of complications rated from 10 to 60%. The most common reported complication is
transprosthetic leakage that determines the need of device exchange. However in some patients
occur more serious complications eg. periprosthetic leakage, granulation or atrophy of mucosa
around the fistula, dislocation of prosthesis, that may require anti-inflammatory treatment,
temporary nasogastric tube feeding or surgical procedure. The standard protocol is voice
prosthesis exchange due to transprosthetic leakage. Optionally the device could be replaced
regularly to prevent both transprosthetic leakage and other complication occurrence.

In the study we plan to compare the benefits from regular (each three month) versus
leakage-related exchange of voice prosthesis post laryngectomy including the rate of
complications, fistula colonization by Candida species and patients feedback.
</textblock>
</brief_summary>
<overall_status>Unknown status</overall_status>
<last_known_status>Not yet recruiting</last_known_status>
<start_date type="Anticipated">March 10, 2020</start_date>
<completion_date type="Anticipated">March 31, 2022</completion_date>
<primary_completion_date type="Anticipated">March 10, 2021</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>randomized controlled trial</intervention_model_description>
<primary_purpose>Prevention</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Comparison of complications rate.</measure>
<time_frame>Control will be continued for 12 months post laryngectomy.</time_frame>
<description>In both arms of the study we will compare the incidence of following complications: periprosthetic leakage, granulation or atrophy of mucosa around the fistula, dislocation of prosthesis</description>
</primary_outcome>
<secondary_outcome>
<measure>Fistula colonization with Candida species.</measure>
<time_frame>Control will be continued for 12 months post laryngectomy.</time_frame>
<description>We will compare microbiological results on subsequent prosthesis exchanges in both arms.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Prosthesis replacement scheme and patient satisfaction.</measure>
<time_frame>Control will be continued for 12 months post laryngectomy.</time_frame>
<description>On each voice prosthesis exchange patients will be asked three questions, assessed with Visual Analog Scale, on their feedback on voice prosthesis use, procedure of prosthesis replacement and voice quality.</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">70</enrollment>
<condition>Laryngectomy</condition>
<condition>Voice</condition>
<condition>Prosthesis Failure</condition>
<arm_group>
<arm_group_label>Regular exchange</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Patients will be appointed each 3 months for regular exchange of voice prosthesis.</description>
</arm_group>
<arm_group>
<arm_group_label>Leakage exchange</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Patients will have voice prosthesis exchange when leakage occurs.</description>
</arm_group>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>Provox prosthesis exchange</intervention_name>
<description>Each patient post laryngectomy will be randomly assigned to one arm of intervention. The voice prosthesis exchange in all patients will be performed in local anaesthesia. The microbiological samples with cotton swabs will be collected from tracheoesophageal fistula on prosthesis exchange. The clinical evaluation and patients satisfaction from prosthesis usage will be performed on each exchange.</description>
<arm_group_label>Leakage exchange</arm_group_label>
<arm_group_label>Regular exchange</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- patients post laryngectomy with primary insertion of voice prosthesis

Exclusion Criteria:

- patients post laryngopharyngectomy with digestive tract reconstruction with jejunum of
free flap
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Anna Rzepakowska, PhD</last_name>
<role>Study Chair</role>
<affiliation>Medical University of Warsaw</affiliation>
</overall_official>
<overall_contact>
<last_name>Anna Rzepakowska, PhD</last_name>
<phone>+48225992521</phone>
<email>arzepakowska@wum.edu.pl</email>
</overall_contact>
<overall_contact_backup>
<last_name>Daniel Majszyk, PhD</last_name>
<phone>+48225992521</phone>
<email>daniel.majszyk@wum.edu.pl</email>
</overall_contact_backup>
<location>
<facility>
<name>Department of Otorhinolaryngology, Head andNeck Surgery of Medical University of Warsaw</name>
<address>
<city>Warsaw</city>
<zip>02-097</zip>
<country>Poland</country>
</address>
</facility>
<contact>
<last_name>Anna Rzepakowska, PhD</last_name>
<phone>+48225992521</phone>
<email>arzepakowska@wum.edu.pl</email>
</contact>
<contact_backup>
<last_name>Ewa Osuch-Wójcikiewicz, Professor</last_name>
<phone>+48225992521</phone>
<email>eosuch@wum.edu.pl</email>
</contact_backup>
</location>
<location_countries>
<country>Poland</country>
</location_countries>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 10, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 10, 2020</last_update_submitted>
<last_update_submitted_qc>February 10, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Medical University of Warsaw</investigator_affiliation>
<investigator_full_name>Anna Rzepakowska</investigator_full_name>
<investigator_title>MD, PhD</investigator_title>
</responsible_party>
<keyword>voice prosthesis, laryngectomy, complications</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Prosthesis Failure</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>Yes</sharing_ipd>
<ipd_info_type>Study Protocol</ipd_info_type>
<ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
<ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
<ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
<ipd_time_frame>Date will become available from April 2022 until April 2023.</ipd_time_frame>
<ipd_access_criteria>on request</ipd_access_criteria>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The tracheoesophageal voice with voice prosthesis is currently the mainstay of voice
rehabilitation post laryngectomy. The primary surgical technique of tracheoesophageal fistula
formation with insertion of prosthesis and quick and easy process of voice rehabilitation are
main encouraging factors. However, the usage of the prosthesis relates to a significant
number of complications rated from 10 to 60%. The most common reported complication is
transprosthetic leakage that determines the need of device exchange. However in some patients
occur more serious complications eg. periprosthetic leakage, granulation or atrophy of mucosa
around the fistula, dislocation of prosthesis, that may require anti-inflammatory treatment,
temporary nasogastric tube feeding or surgical procedure. The standard protocol is voice
prosthesis exchange due to transprosthetic leakage. Optionally the device could be replaced
regularly to prevent both transprosthetic leakage and other complication occurrence.
In the study we plan to compare the benefits from regular (each three month) versus
leakage-related exchange of voice prosthesis post laryngectomy including the rate of
complications, fistula colonization by Candida species and patients feedback.
Inclusion Criteria:
- patients post laryngectomy with primary insertion of voice prosthesis
Exclusion Criteria:
- patients post laryngopharyngectomy with digestive tract reconstruction with jejunum of
free flap
|
NCT0426xxxx/NCT04268472.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268472</url>
</required_header>
<id_info>
<org_study_id>GP30101-P4-11</org_study_id>
<nct_id>NCT04268472</nct_id>
</id_info>
<brief_title>Bioequivalence Study of GP30101 800 mg (GEROPHARM) Versus PREZISTA® 800 mg ("Jonson&Jonson", Russia)</brief_title>
<official_title>Crossover, Open-label, Randomized, Single-dose, Bioequivalence Study of GP30101 Film-coated Tablets (LLC "GEROPHARM", Russia) 800 mg Versus Prezista® (Jonson&Jonson, Russia) Film-coated Tablets 800 mg in Healthy Volunteers Under Fed Conditions</official_title>
<sponsors>
<lead_sponsor>
<agency>Geropharm</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
</sponsors>
<source>Geropharm</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Bioequivalence Study of GP30101 800 mg (GEROPHARM) Versus PREZISTA® 800 mg ("Jonson&Jonson",
Russia)
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Study to evaluate the pharmacokinetic parameters, relative bioavailability and bioequivalence
of drugs containing darunavir - GP30101 and Prezista® in healthy volunteers after single
orally administered dose, under fed conditions A comparative analysis of adverse events
aditionally conducted in this study.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">June 6, 2019</start_date>
<completion_date type="Actual">September 6, 2019</completion_date>
<primary_completion_date type="Actual">September 6, 2019</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Crossover Assignment</intervention_model>
<intervention_model_description>Crossover Assignment two-way crossover</intervention_model_description>
<primary_purpose>Basic Science</primary_purpose>
<masking>None (Open Label)</masking>
<masking_description>Open Label</masking_description>
</study_design_info>
<primary_outcome>
<measure>C(max)</measure>
<time_frame>-35 min prior dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72 hour post-dose</time_frame>
<description>Pharmacokinetics by Assessment of Observed Maximum Plasma Concentration (Cmax)</description>
</primary_outcome>
<primary_outcome>
<measure>AUC(0-t)</measure>
<time_frame>-35 min prior dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72 hour post-dose</time_frame>
<description>Pharmacokinetics by Assessment of Area Under the Curve From Time Zero Extrapolated to "t" (AUC(0-t)</description>
</primary_outcome>
<secondary_outcome>
<measure>T(max)</measure>
<time_frame>-35 min prior dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72 hour post-dose</time_frame>
<description>Pharmacokinetics by Assessment of Time of Maximum concentration observed (T(max)</description>
</secondary_outcome>
<secondary_outcome>
<measure>T(1/2)</measure>
<time_frame>-35 min prior dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72 hour post-dose</time_frame>
<description>Pharmacokinetics by Assessment of elimination half-life T(1/2)</description>
</secondary_outcome>
<secondary_outcome>
<measure>K(e)</measure>
<time_frame>-35 min prior dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72 hour post-dose</time_frame>
<description>Pharmacokinetics by Assessment of elimination rate constant</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">44</enrollment>
<condition>Bioequivalence</condition>
<arm_group>
<arm_group_label>TR Sequence</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>In first Intervention period subjects was administered test medecine (GP30101) and in seconde Intervention period subjects was administered reference medecine (Prezista)</description>
</arm_group>
<arm_group>
<arm_group_label>RT Sequence</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>In first Intervention period subjects was administered reference medecine (Prezista) and in seconde Intervention period subjects was administered test medecine (GP30101)</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>GP30101</intervention_name>
<description>Single oral dose 800 mg, administered in a fed condition, co-administered with low dose ritonavir as a pharmacokinetic enhancer</description>
<arm_group_label>TR Sequence</arm_group_label>
<other_name>First aIntervention Period</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Prezista®</intervention_name>
<description>Single oral dose 800 mg, administered in a fed condition, co-administered with low dose ritonavir as a pharmacokinetic enhancer</description>
<arm_group_label>RT Sequence</arm_group_label>
<other_name>First aIntervention Period</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>GP30101</intervention_name>
<description>Single oral dose 800 mg, administered in a fed condition, co-administered with low dose ritonavir as a pharmacokinetic enhancer</description>
<arm_group_label>RT Sequence</arm_group_label>
<other_name>Second Intervention Period</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Prezista®</intervention_name>
<description>Single oral dose 800 mg, administered in a fed condition, co-administered with low dose ritonavir as a pharmacokinetic enhancer</description>
<arm_group_label>TR Sequence</arm_group_label>
<other_name>Second Intervention Period</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Signed informed consent form.

- Male aged 18 to 45 years.

- Verified diagnosis is "healthy" according to data Standard clinical, laboratory and
Instrumental methods of examination.

- Body mass index between 18,5 and 30 kg/m2, with body weight 60-100 kg

- Consent to comply with an adequate method of effective contraception throughout the
study.

- The consent of volunteers to all restrictions imposed during the study.

- Russian Federation Citizens

Exclusion Criteria:

- History of allergic problems/events.

- Hypersensitivity to heparin, darunavir or any of the excipients of the drugs studied.

- Any acute and chronic diseases, including but not limited to cardiovascular system
diseases, bronchopulmonary diseases, neuroendocrine systems diseases, as well as
diseases of the gastrointestinal tract, liver, kidneys, blood.

- Positive testing for hepatitis C (antibodies) or hepatitis B (surface antigen), HIV
(antibodies to HIV-1/2), syphilis (antibodies to Treponema pallidum).

- The WHO norms deviations of the heart rate (60-89), Sistolic BP (100-130 mm Hg),
Diatolic BP (60-89 mm Hg), respiratory rate (12-20), body temperature (35.7 - 37.6
°C).

- Abnormal ECG during screening.

- Inaccessible veins of the upper extremities, vein thrombosis, thrombophlebitis in the
anamnesis or in the family history of the next of kin, "compromised" veins due to
frequent previous venipuncture.

- Psychiatric disorders, history of epilepsy and seizures.

- Surgical interventions on the gastrointestinal tract (except appendectomy).

- Acute infectious diseases in less than 4 weeks before the start of the study.

- Regular medication use (intake) less than 2 weeks before the start of the study.

- Significant loss of blood within 3 months prior to screening, including but not
limited to blood donation or extended surgery or trauma resulting in the blood loss.

- History of alcohol or drugs abuse or any indication of the regular use of more than 10
units of alcohol per week (1 Unit = 200 mL of wine or 500 mL of beer or 50 mL of
alcohol 40%).

- Positive test results for alcohol or drug use.

- Nicotine addiction, regular use of tobacco, including all types of electronic
cigarettes, less than 6 months prior to screening.

- Participation in a clinical trial of any drugs (including experimental) or
experimental medical devices for 3 months or 5 half-lives, whichever is longer, before
the study.

- Dehydration due to diarrhea, vomiting, or other causes within the last 24 hours before
the start of the study.

- Any diet (for example, vegetarian, fasting, etc.) or lifestyle (including night work
and extreme physical activity) that may interfere with the study.

- Taking medications that have a pronounced effect on hemodynamics, liver function, etc.
(barbiturates, omeprazole, cimetidine, etc.) less than 30 days before the start of the
study.

- Volunteers who are obvious or likely, according to the investigator, are unable to
understand and evaluate the information on this study as part of the process of
signing informed consent, in particular regarding the expected risks and possible
discomfort.
</textblock>
</criteria>
<gender>Male</gender>
<gender_based>Yes</gender_based>
<minimum_age>18 Years</minimum_age>
<maximum_age>45 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<location>
<facility>
<name>Yarosslavl Clinical Hospital #3</name>
<address>
<city>Yaroslavl</city>
<country>Russian Federation</country>
</address>
</facility>
</location>
<location_countries>
<country>Russian Federation</country>
</location_countries>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 12, 2020</last_update_submitted>
<last_update_submitted_qc>February 12, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Darunavir</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Bioequivalence Study of GP30101 800 mg (GEROPHARM) Versus PREZISTA® 800 mg ("Jonson&Jonson",
Russia)
Study to evaluate the pharmacokinetic parameters, relative bioavailability and bioequivalence
of drugs containing darunavir - GP30101 and Prezista® in healthy volunteers after single
orally administered dose, under fed conditions A comparative analysis of adverse events
aditionally conducted in this study.
Inclusion Criteria:
- Signed informed consent form.
- Male aged 18 to 45 years.
- Verified diagnosis is "healthy" according to data Standard clinical, laboratory and
Instrumental methods of examination.
- Body mass index between 18,5 and 30 kg/m2, with body weight 60-100 kg
- Consent to comply with an adequate method of effective contraception throughout the
study.
- The consent of volunteers to all restrictions imposed during the study.
- Russian Federation Citizens
Exclusion Criteria:
- History of allergic problems/events.
- Hypersensitivity to heparin, darunavir or any of the excipients of the drugs studied.
- Any acute and chronic diseases, including but not limited to cardiovascular system
diseases, bronchopulmonary diseases, neuroendocrine systems diseases, as well as
diseases of the gastrointestinal tract, liver, kidneys, blood.
- Positive testing for hepatitis C (antibodies) or hepatitis B (surface antigen), HIV
(antibodies to HIV-1/2), syphilis (antibodies to Treponema pallidum).
- The WHO norms deviations of the heart rate (60-89), Sistolic BP (100-130 mm Hg),
Diatolic BP (60-89 mm Hg), respiratory rate (12-20), body temperature (35.7 - 37.6
°C).
- Abnormal ECG during screening.
- Inaccessible veins of the upper extremities, vein thrombosis, thrombophlebitis in the
anamnesis or in the family history of the next of kin, "compromised" veins due to
frequent previous venipuncture.
- Psychiatric disorders, history of epilepsy and seizures.
- Surgical interventions on the gastrointestinal tract (except appendectomy).
- Acute infectious diseases in less than 4 weeks before the start of the study.
- Regular medication use (intake) less than 2 weeks before the start of the study.
- Significant loss of blood within 3 months prior to screening, including but not
limited to blood donation or extended surgery or trauma resulting in the blood loss.
- History of alcohol or drugs abuse or any indication of the regular use of more than 10
units of alcohol per week (1 Unit = 200 mL of wine or 500 mL of beer or 50 mL of
alcohol 40%).
- Positive test results for alcohol or drug use.
- Nicotine addiction, regular use of tobacco, including all types of electronic
cigarettes, less than 6 months prior to screening.
- Participation in a clinical trial of any drugs (including experimental) or
experimental medical devices for 3 months or 5 half-lives, whichever is longer, before
the study.
- Dehydration due to diarrhea, vomiting, or other causes within the last 24 hours before
the start of the study.
- Any diet (for example, vegetarian, fasting, etc.) or lifestyle (including night work
and extreme physical activity) that may interfere with the study.
- Taking medications that have a pronounced effect on hemodynamics, liver function, etc.
(barbiturates, omeprazole, cimetidine, etc.) less than 30 days before the start of the
study.
- Volunteers who are obvious or likely, according to the investigator, are unable to
understand and evaluate the information on this study as part of the process of
signing informed consent, in particular regarding the expected risks and possible
discomfort.
|
NCT0426xxxx/NCT04268485.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268485</url>
</required_header>
<id_info>
<org_study_id>ManchesterUNHS</org_study_id>
<nct_id>NCT04268485</nct_id>
</id_info>
<brief_title>Longitudinal Changes in Serum KL-6 in IPF</brief_title>
<acronym>LOCK-IPF</acronym>
<official_title>Longitudinal Changes in Serum KL-6 Levels in Idiopathic Pulmonary Fibrosis (LOCK-IPF)</official_title>
<sponsors>
<lead_sponsor>
<agency>Manchester University NHS Foundation Trust</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Manchester University NHS Foundation Trust</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with a poor prognosis. More
accurate tests to predict disease progression and response to treatment are required.

Krebs von den Lungen-6 (KL-6) is a blood marker associated with IPF. Results from previous
studies have shown that levels of KL-6 are higher in patients with IPF compared to people
without the disease. In addition, it is not clear what impact treatment has on KL-6 levels,
and whether this could help us to monitor how effective treatment for IPF is.

The investigators plan to perform a study in which KL-6 levels in the blood of patients with
a new diagnosis of IPF are measured at baseline, 3, 6 and 12 months to look for and changes
in the levels of KL-6 in the blood.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with a poor prognosis.
Effective treatment which slows the progression of IPF has recently become available however,
it is costly and at present is limited to patients who meet specific criteria based on their
breathing tests. The breathing tests currently available to monitor progression of the
disease are not always reliable and do not predict which patients will respond to treatment.
More accurate tests to predict disease progression and response to treatment are required.

Krebs von den Lungen-6 (KL-6) is a blood marker associated with IPF. Results from previous
studies have shown that levels of KL-6 are higher in patients with IPF compared to people
without the disease. The majority of studies using KL-6 in IPF have taken place in Japan and
there is limited evidence of how useful it is in a European population. In addition, it is
not clear what impact treatment has on KL-6 levels, and whether this could help us to monitor
how effective treatment for IPF is.

The investigators plan to perform a study in which KL-6 levels in the blood of patients with
a new diagnosis of IPF are measured at baseline, 3, 6 and 12 months to look for and changes
in the levels of KL-6 in the blood

The objective of this study is to assess changes in serum KL-6 levels in patients with IPF
over a 12-month period and assess if this correlates with changes in lung function and if
KL-6 levels change in response to treatment with antifibrotic therapy.
</textblock>
</detailed_description>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">February 1, 2021</start_date>
<completion_date type="Anticipated">December 30, 2024</completion_date>
<primary_completion_date type="Anticipated">December 30, 2024</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Serum KL-6 level</measure>
<time_frame>12 months</time_frame>
<description>Change in serum KL-6 level between baseline and 12 months</description>
</primary_outcome>
<secondary_outcome>
<measure>Serum KL-6 level at 3, 6 months</measure>
<time_frame>3 and 6 months</time_frame>
<description>Change in serum KL-6 at 3 and 6 months compared to baseline</description>
</secondary_outcome>
<secondary_outcome>
<measure>KL-6 forced vital capacity (FVC) correlation</measure>
<time_frame>3, 6 and12 months</time_frame>
<description>Correlation of KL-6 and FVC change at 3, 6 and 12 months</description>
</secondary_outcome>
<secondary_outcome>
<measure>KL-6 diffusion capacity (DLCO)</measure>
<time_frame>3, 6 and12 months</time_frame>
<description>Correlation of KL-6 and DLCO change at 3, 6 and 12 months</description>
</secondary_outcome>
<secondary_outcome>
<measure>KL-6 symptoms</measure>
<time_frame>3, 6 and12 months</time_frame>
<description>Correlation of KL-6 and symptom scores at 3, 6 and 12 months</description>
</secondary_outcome>
<secondary_outcome>
<measure>KL-6 antifibrotics</measure>
<time_frame>12 months</time_frame>
<description>Change in KL-6 levels in response to antifibrotic therapy</description>
</secondary_outcome>
<secondary_outcome>
<measure>KL-6 Gender Age and Physiology (GAP) stage</measure>
<time_frame>At baseline</time_frame>
<description>Differences in KL-6 levels between Gender Age Physiology (GAP) stage at baseline</description>
</secondary_outcome>
<secondary_outcome>
<measure>KL-6 CPI</measure>
<time_frame>At baseline</time_frame>
<description>Correlation between KL-6 levels and Composite Physiology Index (CPI)</description>
</secondary_outcome>
<secondary_outcome>
<measure>KL-6 CT pattern</measure>
<time_frame>At baseline</time_frame>
<description>Difference in KL-6 levels between patients with indeterminate, probable and definite usual interstitial pneumonia pattern (UIP) on HRCT</description>
</secondary_outcome>
<number_of_groups>1</number_of_groups>
<enrollment type="Anticipated">60</enrollment>
<condition>Idiopathic Pulmonary Fibrosis</condition>
<arm_group>
<arm_group_label>IPF patients</arm_group_label>
<description>Patients with an MDT diagnosis of idiopathic pulmonary fibrosis. Patients will be observed over a 12 month period and have serial serum samples taken for KL-6 level.</description>
</arm_group>
<intervention>
<intervention_type>Diagnostic Test</intervention_type>
<intervention_name>Serum KL-6 level</intervention_name>
<description>Serum blood biomarker which has been shown to be of interest in idiopathic pulmonary fibrosis</description>
<arm_group_label>IPF patients</arm_group_label>
</intervention>
<biospec_retention>Samples Without DNA</biospec_retention>
<biospec_descr>
<textblock>
Serum samples taken on four separate visits over 12 months. Samples tested for KL-6 level
onyl
</textblock>
</biospec_descr>
<eligibility>
<study_pop>
<textblock>
Patients with an MDT diagnosis of idiopathic pulmonary fibrosis attending routine follow-up
care
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- Age 18 or older

- Multi-disciplinary team (MDT) diagnosis of idiopathic pulmonary fibrosis as per
international consensus guidelines

Exclusion criteria

- Significant respiratory co-morbidity (i.e. where the major respiratory diagnosis is
not IPF)

- FEV1/FVC ratio < 70% on full lung function testing

- Current smoker (within 4 week of enrollment)

- Received treatment for acute lower respiratory tract infection with last 4 weeks

- Use of long-term (greater than 4 weeks) oral corticosteroids or immunosuppression
within 4 weeks of enrolment

- Current participation in a double-blind placebo-controlled pharmaceutical trial
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Conal Hayton</last_name>
<role>Principal Investigator</role>
<affiliation>Manchester University NHS Foundation Trust</affiliation>
</overall_official>
<overall_contact>
<last_name>Conal Hayton, MBChB</last_name>
<phone>+441612915388</phone>
<email>conalhayton@doctors.org.uk</email>
</overall_contact>
<overall_contact_backup>
<last_name>Nazia Chaudhuri</last_name>
<phone>+441612915054</phone>
<email>nazia.chaudhuri@mft.nhs.uk</email>
</overall_contact_backup>
<location>
<facility>
<name>Manchester University hospitals NHS Foundation Trust</name>
<address>
<city>Manchester</city>
<country>United Kingdom</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Conal Hayton</last_name>
<email>conal.hayton@mft.nhs.uk</email>
</contact>
</location>
<location_countries>
<country>United Kingdom</country>
</location_countries>
<verification_date>June 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>June 2, 2023</last_update_submitted>
<last_update_submitted_qc>June 2, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">June 5, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>KL-6</keyword>
<keyword>Krebs von den Lungen-6</keyword>
<keyword>Biomarker</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Pulmonary Fibrosis</mesh_term>
<mesh_term>Idiopathic Pulmonary Fibrosis</mesh_term>
<mesh_term>Fibrosis</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with a poor prognosis. More
accurate tests to predict disease progression and response to treatment are required.
Krebs von den Lungen-6 (KL-6) is a blood marker associated with IPF. Results from previous
studies have shown that levels of KL-6 are higher in patients with IPF compared to people
without the disease. In addition, it is not clear what impact treatment has on KL-6 levels,
and whether this could help us to monitor how effective treatment for IPF is.
The investigators plan to perform a study in which KL-6 levels in the blood of patients with
a new diagnosis of IPF are measured at baseline, 3, 6 and 12 months to look for and changes
in the levels of KL-6 in the blood.
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with a poor prognosis.
Effective treatment which slows the progression of IPF has recently become available however,
it is costly and at present is limited to patients who meet specific criteria based on their
breathing tests. The breathing tests currently available to monitor progression of the
disease are not always reliable and do not predict which patients will respond to treatment.
More accurate tests to predict disease progression and response to treatment are required.
Krebs von den Lungen-6 (KL-6) is a blood marker associated with IPF. Results from previous
studies have shown that levels of KL-6 are higher in patients with IPF compared to people
without the disease. The majority of studies using KL-6 in IPF have taken place in Japan and
there is limited evidence of how useful it is in a European population. In addition, it is
not clear what impact treatment has on KL-6 levels, and whether this could help us to monitor
how effective treatment for IPF is.
The investigators plan to perform a study in which KL-6 levels in the blood of patients with
a new diagnosis of IPF are measured at baseline, 3, 6 and 12 months to look for and changes
in the levels of KL-6 in the blood
The objective of this study is to assess changes in serum KL-6 levels in patients with IPF
over a 12-month period and assess if this correlates with changes in lung function and if
KL-6 levels change in response to treatment with antifibrotic therapy.
Serum samples taken on four separate visits over 12 months. Samples tested for KL-6 level
onyl
Patients with an MDT diagnosis of idiopathic pulmonary fibrosis attending routine follow-up
care
Inclusion Criteria:
- Age 18 or older
- Multi-disciplinary team (MDT) diagnosis of idiopathic pulmonary fibrosis as per
international consensus guidelines
Exclusion criteria
- Significant respiratory co-morbidity (i.e. where the major respiratory diagnosis is
not IPF)
- FEV1/FVC ratio < 70% on full lung function testing
- Current smoker (within 4 week of enrollment)
- Received treatment for acute lower respiratory tract infection with last 4 weeks
- Use of long-term (greater than 4 weeks) oral corticosteroids or immunosuppression
within 4 weeks of enrolment
- Current participation in a double-blind placebo-controlled pharmaceutical trial
|
NCT0426xxxx/NCT04268498.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268498</url>
</required_header>
<id_info>
<org_study_id>20201316</org_study_id>
<secondary_id>2019-001645-41</secondary_id>
<secondary_id>19-339</secondary_id>
<nct_id>NCT04268498</nct_id>
</id_info>
<brief_title>A Study of Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly-Diagnosed Multiple Myeloma</brief_title>
<acronym>ADVANCE</acronym>
<official_title>Phase 2, Open-Label Randomized Study of Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone vs Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma</official_title>
<sponsors>
<lead_sponsor>
<agency>University of Miami</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Amgen</agency>
<agency_class>Industry</agency_class>
</collaborator>
<collaborator>
<agency>Janssen Pharmaceuticals</agency>
<agency_class>Industry</agency_class>
</collaborator>
</sponsors>
<source>University of Miami</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This study is being done to find out whether carfilzomib, lenalidomide, and dexamethasone
(KRD) or KRD and Daratumumab (KRD+DARA) might be safer and more effective ways of controlling
multiple myeloma than the stand or care treatment, which is lenalidomide, bortezomib, and
dexamethasone (VRD).
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Per protocol amendment version 4.0 (May 23, 2022), Arm A will be closed and no additional
participants will be enrolled in this arm.
</textblock>
</detailed_description>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">February 11, 2020</start_date>
<completion_date type="Anticipated">February 1, 2027</completion_date>
<primary_completion_date type="Anticipated">February 1, 2027</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Rate of Minimal Residual Disease (MRD) Negativity</measure>
<time_frame>Up to 32 weeks</time_frame>
<description>MRD will be assessed by the MRD scale ranging from 10 (increased disease detection) to -5 (less to no disease detection) after 8 cycles of therapy.</description>
</primary_outcome>
<secondary_outcome>
<measure>Overall Survival</measure>
<time_frame>Up to 16 weeks</time_frame>
<description>Overall survival is defined as the time from date of randomization to death from any cause</description>
</secondary_outcome>
<secondary_outcome>
<measure>Progression Free Survival (PFS)</measure>
<time_frame>Up to 16 weeks</time_frame>
<description>PFS is defined as time from date of randomization to time of progression or death, whichever occurs first.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Event Free Survival (EFS)</measure>
<time_frame>Up to 16 weeks</time_frame>
<description>EFS is defined as time from date of randomization to the time of 1) achieving a PR or less with the first four cycles of therapy, 2) transplant, 3) progression, or 4) death, whichever occurs first.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Rate of Response</measure>
<time_frame>Up to 3 years</time_frame>
<description>Rate of Response will be reported as the percentage of participants achieving a response of: a) Partial Response (PR) or better, b) Very Good Partial Response (VGPR) or better and c) Complete Response (CR) and Stringent Complete Response (sCR). Responses will be evaluated from participant serum, urine and bone marrow samples.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Rate of MRD Negativity as best response</measure>
<time_frame>Up to 3 years</time_frame>
<description>MRD will be evaluated from bone marrow samples.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Incidence of treatment related toxicity</measure>
<time_frame>Up to 9 months</time_frame>
<description>Toxicity will be evaluated by treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Minimal Residual Disease (MRD) Negativity</measure>
<time_frame>Up to 3 years</time_frame>
<description>MRD Negativity using bone marrow and blood samples</description>
</secondary_outcome>
<number_of_arms>3</number_of_arms>
<enrollment type="Anticipated">306</enrollment>
<condition>Multiple Myeloma</condition>
<arm_group>
<arm_group_label>Arm A - Bortezomib, Lenalidomide and Dexamethasone (VRD)</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Participants in this group will receive Bortezomib, Lenalidomide and Dexamethasone on a 21 day treatment cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.</description>
</arm_group>
<arm_group>
<arm_group_label>Arm B - Carfilzomib, Lenalidomide and Dexamethasone (KRD)</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Participants in this group will receive Carfilzomib, Lenalidomide and Dexamethasone on a 28 day cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.</description>
</arm_group>
<arm_group>
<arm_group_label>Arm C- Carfilzomib, Lenalidomide and Dexamethasone with Daratumumab (DKrd)</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Participants in this group will receive Carfilzomib, Lenalidomide, Dexamethasone with Daratumumab, Acetaminophen, Diphenhydramine and Montelukast on a 28 day cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Bortezomib</intervention_name>
<description>1.3 mg/m2 administered Subcutaneous (SC) or intravenous (IV) on days 1, 4, 8 and 11 of a 21 day treatment cycle for participants randomized to Arm A.</description>
<arm_group_label>Arm A - Bortezomib, Lenalidomide and Dexamethasone (VRD)</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Dexamethasone</intervention_name>
<description>20 mg or 40 mg per dose administered by mouth (PO) or IV.
Participants randomized in Arm A:
20 mg/dose on days 1, 4, 8 and 11 on a 21 day treatment cycle;
Participants randomized in Arm B:
Cycles 1 through 8 - 40mg/dose on days 1, 8 and 15 on a 28-day cycle
Participants randomized in Arm C:
Cycle 1-2 - 40 mg/dose on days 1, 8, 15 and 22 on a 28-day cycle; Cycles 3-8 - 40mg/dose on Days 1, 8, 15 on a 28-day cycle;</description>
<arm_group_label>Arm A - Bortezomib, Lenalidomide and Dexamethasone (VRD)</arm_group_label>
<arm_group_label>Arm B - Carfilzomib, Lenalidomide and Dexamethasone (KRD)</arm_group_label>
<arm_group_label>Arm C- Carfilzomib, Lenalidomide and Dexamethasone with Daratumumab (DKrd)</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Lenalidomide</intervention_name>
<description>10 or 25 mg/day capsules administered PO.
Participants randomized in Arm A:
25 mg/day capsules on Days 1 through 14 of a 21 day cycle.;
Participants randomized in Arm B:
Cycles 1 through 8 - 25 mg/day capsules on Days 1 through 21 of a 28 day cycle;
Participants randomized in Arm C:
Cycles 1 - 25 mg/day capsules on Days 2 through 21 of a 28 day cycle; Cycles 2 through 8 - 25 mg/day capsules on Days 1 through 21 of a 28 day cycle;
Maintenance Therapy:
10 mg capsules on Days 1 through 21 on a 28 days cycle.</description>
<arm_group_label>Arm A - Bortezomib, Lenalidomide and Dexamethasone (VRD)</arm_group_label>
<arm_group_label>Arm B - Carfilzomib, Lenalidomide and Dexamethasone (KRD)</arm_group_label>
<arm_group_label>Arm C- Carfilzomib, Lenalidomide and Dexamethasone with Daratumumab (DKrd)</arm_group_label>
<other_name>Revlimid</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Acetaminophen</intervention_name>
<description>650 mg administered PO.
Participants randomized to Arm C:
Cycles 1 through 8 - 650 mg administered on Days 1, 8 and 15.</description>
<arm_group_label>Arm C- Carfilzomib, Lenalidomide and Dexamethasone with Daratumumab (DKrd)</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Diphenhydramine</intervention_name>
<description>25 mg administered via IV
Participants randomized to Arm C:
Cycles 1 through 8 - 25 mg administered on Days 1, 8 and 15.</description>
<arm_group_label>Arm C- Carfilzomib, Lenalidomide and Dexamethasone with Daratumumab (DKrd)</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Montelukast</intervention_name>
<description>10 mg administered PO to participants randomized to Arm C prior to the first 4 doses of Daratumumab.</description>
<arm_group_label>Arm C- Carfilzomib, Lenalidomide and Dexamethasone with Daratumumab (DKrd)</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Carfilzomib</intervention_name>
<description>20 mg or 56 mg/m2 per dose administered via IV.
Participants randomized to Arm B:
Cycle 1 - 20 mg/m2 per dose on Day 1 and 56 mg/m2 per dose on days 8 and 15 of a 28 day cycle; Cycles 2 through 8 - 56 mg/m2 per dose on days 1, 8 and 15 of a 28 day cycle;
Participants randomized to Arm C:
Cycle 1 - 20 mg/m2 per dose on Day 2 and 56 mg/m2 per dose on days 8 and 15 of a 28 day cycle; Cycles 2 through 8 - 56 mg/m2 per dose on days 1, 8 and 15 of a 28 day cycle</description>
<arm_group_label>Arm B - Carfilzomib, Lenalidomide and Dexamethasone (KRD)</arm_group_label>
<arm_group_label>Arm C- Carfilzomib, Lenalidomide and Dexamethasone with Daratumumab (DKrd)</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Daratumumab</intervention_name>
<description>16 mg/kg administered via IV or 1800 mg SC, per treating physician discretion.
Participants randomized to Arm C:
Cycles 1 though 2 - 16 mg/kg IV or 1800 mg SC on days 1, 8, 15, and 22 of a 28 day cycle; Cycles 3 through 6- 16 mg/kg IV or 1800 mg SC on days 1 and 15 of a 28 day cycle; Cycles 7 through 8 - 16 mg/kg IV or 1800 mg SC on day 1 of a 28 day cycle</description>
<arm_group_label>Arm C- Carfilzomib, Lenalidomide and Dexamethasone with Daratumumab (DKrd)</arm_group_label>
</intervention>
<intervention>
<intervention_type>Biological</intervention_type>
<intervention_name>Autologous Stem Cell Transplant (ASCT)</intervention_name>
<description>Participants who are MRD positive at the conclusion of 8 cycles of study treatment, and were able to have their stem cells that were extracted, will receive ASCT from participants' bone marrow samples.</description>
<arm_group_label>Arm A - Bortezomib, Lenalidomide and Dexamethasone (VRD)</arm_group_label>
<arm_group_label>Arm B - Carfilzomib, Lenalidomide and Dexamethasone (KRD)</arm_group_label>
<arm_group_label>Arm C- Carfilzomib, Lenalidomide and Dexamethasone with Daratumumab (DKrd)</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Newly diagnosed patients with histologically confirmed Multiple Myeloma (MM) based on
the IMWG diagnostic criteria and measurable disease within the past 4 weeks (or past 8
weeks if patient received pre-study MM therapy) based on one of the following:

- Serum monoclonal protein ≥ 1.0 g/dL

- Urine monoclonal protein ≥ 200 mg/24 hour

- Involved serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal
kappa/lambda ratio.

2. Evidence of underlying end organ damage and/or myeloma defining event attributed to
underlying plasma cell proliferative disorder meeting at least one of the following
(Note: Myeloma defining event does not need to be based on repeat testing done at
screening, if previous pathology, radiology, etc., confirm diagnosis of myeloma per
IMWG)

- Hypercalcemia: serum calcium >0.25 mmol/L (> 1 mg/dL) above upper limit of normal
or ≥ 2.75 mmol/L (11 mg/dL)

- Anemia: hemoglobin value <10 g/dL or > 2 g/dL below lower limit of normal

- Bone disease: ≥ 1 lytic lesions on skeletal X-ray, CT, or Positron Emission
Tomography (PET)-C. For patients with 1 lytic lesion, bone marrow should
demonstrate ≥10% clonal plasma cells

- Clonal bone marrow plasma cell percentage ≥60%

- Involved/un-involved serum free light chain ratio ≥100 and involved free light
chain

≥100 mg/L.

- > 1 focal lesion on magnetic resonance imaging study (lesion must be >5 mm) in
size

- For patients with 1 lytic lesion, bone marrow should demonstrate ≥10% clonal
plasma cells

3. Creatinine Clearance (CrCl) ≥ 60 ml/min. CrCl can be measured or estimated using
Cockcroft-Gault method, Modification of Diet in Renal Disease (MDRD), or Chronic
Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae

4. Age ≥ 18 years at the time of signing the informed consent documentation. Age limit of
≤ 75 years.

5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

6. Absolute neutrophil count (ANC) ≥ 1.0 K/microliter (uL), hemoglobin ≥ 8 g/dL, and
platelet count ≥ 75 K/uL, unless if cytopenias are deemed to be due disease at
discretion of clinical investigator. Transfusions and growth factors are permissible.

7. Adequate hepatic function, with bilirubin < 1.5 x the pper Limit of Normal (ULN), and
Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 3.0 x ULN.

8. All study participants must be able to tolerate one of the following
thromboprophylactic strategies: aspirin, oral facto Xa inhibitors, low molecular
weight heparin, warfarin (coumadin), or alternative anti-coagulant.

9. All study participants must be registered into the mandatory electronic REMS (eREMS)
program and be willing and able to comply with the requirements of Risk Evaluation
Management and Safety (REMS).

10. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide
for Cycle 1 (prescriptions must be filled within 7 days) and must either commit to
continued abstinence from heterosexual intercourse or begin two acceptable methods of
birth control, one highly effective method and one additional effective method at the
same time, at least 28 days before she starts taking lenalidomide. FCBP must also
agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual
contact with a FCBP even if they have had a successful vasectomy.

A female of childbearing potential is a sexually mature female who: 1) has not undergone a
hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at
least 24 consecutive months (i.e., has had menses at any time in the preceding 24
consecutive months).

Exclusion Criteria:

1. Patients receiving >1 cycle of prior treatment or concurrent systemic treatment for
multiple myeloma:

- Treatment of hypercalcemia or spinal cord compression or aggressively progressing
myeloma with current or prior corticosteroids is permitted

- Bone targeting agents are permitted

- Concurrent or prior treatment with corticosteroids for indications other than
multiple myeloma is permitted

- Prior treatment with radiotherapy is permitted

- Prior MM treatments, such as Immunomodulating Drugs (IMIDs) or non-MM drugs in
clinical trials for smoldering myeloma is permitted with a washout period of 2
weeks from last dose. Smoldering patients previously treated with carfilzomib are
excluded.

- Patients with measurable disease who received up to one cycle of any therapy
within 60 days with a washout period of 2 weeks from last dose (on a trial or
outside a trial) are eligible (Note: Measurable disease is defined as one or more
of the following: Serum monoclonal protein ≥ 1.0 g/dL, Urine monoclonal protein ≥
200 mg/24 hour and/ or Involved serum immunoglobulin free light chain ≥ 10 mg/dL
AND abnormal kappa/lambda ratio)

2. Prior or current exposure to any of the following:

- To daratumumab or other anti- Cluster of Differentiation (CD) -38 therapies
(unless a re-treatment study)

- Exposure to an investigational drug (including investigational vaccine) or
invasive investigational medical device for any indication within 4 weeks or 5
pharmacokinetic half-lives, whichever is longer.

- Focal radiation therapy within 14 days prior to randomization with the exception
of palliative radiotherapy for symptomatic management but not on measurable
extramedullary plasmacytoma.

3. Patients with plasma cell leukemia

4. Patients with Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin
changes syndrome (POEMS syndrome)

5. Patients with amyloidosis

6. Patients with known Chronic Obstructive Pulmonary Disorder (COPD) with a forced
expiratory volume in 1 second (FEV1) < 50% of predicted normal. Note that FEV1 testing
is required for subjects suspected of having COPD, and subjects must be excluded if
FEV1 <50% of predicted normal.

7. Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma
of any classification. Note that participants who currently have controlled
intermittent asthma or controlled mild persistent asthma are allowed to participate in
the study.

8. Pregnant or lactating females. Because there is a potential risk for AEs in nursing
infants secondary to treatment of the mother with carfilzomib in combination with
lenalidomide, pregnant or lactating females are excluded from study participation.
These potential risks may also apply to other agents used in this study.

9. Uncontrolled hypertension (i.e., systolic blood pressure (BP) >160 mmHg, diastolic BP
> 100 mmHg)

10. Uncontrolled diabetes (i.e., two independent glucose readings >200 mg/dL)

11. Active hepatitis B or C infection

12. Subject is:

- Seropositive for human immunodeficiency virus (HIV)

- Seropositive for hepatitis B (defined by a positive test for hepatitis B surface
antigen [HBsAg]). Subjects with resolved infection (i.e., subjects who are HBsAg
negative but positive for antibodies to hepatitis B core (HBc) antigen [anti-HBc]
and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened
using real-time polymerase chain reaction (RT-PCR) measurement of hepatitis B
virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION:
Subjects with serologic findings suggestive of HBV vaccination (anti-HBs
positivity as the only serologic marker) AND a known history of prior HBV
vaccination do not need to be tested for HBV DNA by PCR.

- Seropositive for hepatitis C (except in the setting of a sustained virologic
response (SVR), defined as aviremia at least 12 weeks after completion of
antiviral therapy).

- Patients with active Coronavirus Disease of 2019 (COVID-19) infection are not to
be enrolled until 10 days have passed from the initial positive test, and the
patient is symptom-free. COVID-19 vaccinations following national guidelines
(i.e., CDC) are encouraged; however, the series should be completed prior to the
first day of study treatment. If this is not possible, every effort should be
made to administer vaccines at a time when patient is not scheduled to receive
study treatment (e.g., "off-weeks").

13. Clinically significant cardiac disease, including:

- Myocardial infarction within 6 months before randomization, or unstable or
uncontrolled disease/condition related to or affection cardiac function (e.g.,
unstable angina, congestive heart failure, New York Heart Association (NYHA)
Class III-IV) or a left ventricular ejection fraction of <40%.

- Uncontrolled cardiac arrhythmia

- Intolerance to hydration due to pre-existing pulmonary or cardiac impairment.

14. Pulmonary hypertension

15. Has refractory gastrointestinal (GI) disease with refractory nausea/vomiting,
inflammatory bowel disease, or bowel resection that would prevent absorption of oral
agents

16. Uncontrolled intercurrent illness including but not limited to active infection or
psychiatric illness/social situations that would compromise compliance with study
requirements

17. Significant neuropathy ≥ Grade 3 or Grade 2 neuropathy with pain at baseline

18. Contraindication to any concomitant medication, including antivirals or
anticoagulation

19. Major surgery within 3 weeks prior to first dose
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>75 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Carl Landgren, MD</last_name>
<role>Principal Investigator</role>
<affiliation>University of Miami</affiliation>
</overall_official>
<overall_contact>
<last_name>Philip Arlen</last_name>
<phone>305-243-5247</phone>
<email>paa107@miami.edu</email>
</overall_contact>
<location>
<facility>
<name>University of Miami</name>
<address>
<city>Miami</city>
<state>Florida</state>
<zip>33136</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Philip Arlen, MD</last_name>
<phone>305-243-5247</phone>
<email>paa107@miami.edu</email>
</contact>
<investigator>
<last_name>Carl Landgren, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Moffitt Cancer Center</name>
<address>
<city>Tampa</city>
<state>Florida</state>
<zip>33612-9497</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Ken Shain, MD</last_name>
<phone>888-663-3488</phone>
<email>Ken.Shain@moffitt.org</email>
</contact>
<investigator>
<last_name>Ken Shain, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Rush University Medical Center</name>
<address>
<city>Chicago</city>
<state>Illinois</state>
<zip>606012</zip>
<country>United States</country>
</address>
</facility>
<status>Withdrawn</status>
</location>
<location>
<facility>
<name>Roswell Park Comprehensive Cancer Center</name>
<address>
<city>Buffalo</city>
<state>New York</state>
<zip>14203</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Ariffa Kariapper</last_name>
<phone>716-845-3838</phone>
<email>Ariffa.Kariapper@RoswellPark.org</email>
</contact>
<investigator>
<last_name>Jens Hillengass, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Memorial Sloan Kettering Cancer Center</name>
<address>
<city>New York</city>
<state>New York</state>
<zip>10065</zip>
<country>United States</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Stony Brook University</name>
<address>
<city>Stony Brook</city>
<state>New York</state>
<zip>11794</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Aisha Hashmi</last_name>
<phone>631-638-0836</phone>
<email>Aisha.Hashmi@stonybrookmedicine.edu</email>
</contact>
<investigator>
<last_name>Thomas Jandl, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>MD Anderson Cancer Center</name>
<address>
<city>Houston</city>
<state>Texas</state>
<zip>77030</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Elisabet Manasanch, MD</last_name>
<phone>713-745-8092</phone>
<email>EEManasanch@mdanderson.org</email>
</contact>
<investigator>
<last_name>Elisabet Manasanch, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Huntsman Cancer Institue</name>
<address>
<city>Salt Lake City</city>
<state>Utah</state>
<zip>84113</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Douglas Sborov, MD</last_name>
<phone>801-585-2626</phone>
<email>Douglas.Sborov@hsc.utah.edu</email>
</contact>
<investigator>
<last_name>Douglas Sborov, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Skåne University Hospital</name>
<address>
<city>Malmö</city>
<zip>9, 214</zip>
<country>Sweden</country>
</address>
</facility>
<status>Withdrawn</status>
</location>
<location_countries>
<country>Sweden</country>
<country>United States</country>
</location_countries>
<verification_date>July 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>July 6, 2023</last_update_submitted>
<last_update_submitted_qc>July 6, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">July 10, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Daratumumab</keyword>
<keyword>Carfilzomib</keyword>
<keyword>Lenalidomide</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Multiple Myeloma</mesh_term>
<mesh_term>Neoplasms, Plasma Cell</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Acetaminophen</mesh_term>
<mesh_term>Diphenhydramine</mesh_term>
<mesh_term>Promethazine</mesh_term>
<mesh_term>Dexamethasone</mesh_term>
<mesh_term>Lenalidomide</mesh_term>
<mesh_term>Bortezomib</mesh_term>
<mesh_term>Daratumumab</mesh_term>
<mesh_term>Montelukast</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This study is being done to find out whether carfilzomib, lenalidomide, and dexamethasone
(KRD) or KRD and Daratumumab (KRD+DARA) might be safer and more effective ways of controlling
multiple myeloma than the stand or care treatment, which is lenalidomide, bortezomib, and
dexamethasone (VRD).
Per protocol amendment version 4.0 (May 23, 2022), Arm A will be closed and no additional
participants will be enrolled in this arm.
Inclusion Criteria:
1. Newly diagnosed patients with histologically confirmed Multiple Myeloma (MM) based on
the IMWG diagnostic criteria and measurable disease within the past 4 weeks (or past 8
weeks if patient received pre-study MM therapy) based on one of the following:
- Serum monoclonal protein ≥ 1.0 g/dL
- Urine monoclonal protein ≥ 200 mg/24 hour
- Involved serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal
kappa/lambda ratio.
2. Evidence of underlying end organ damage and/or myeloma defining event attributed to
underlying plasma cell proliferative disorder meeting at least one of the following
(Note: Myeloma defining event does not need to be based on repeat testing done at
screening, if previous pathology, radiology, etc., confirm diagnosis of myeloma per
IMWG)
- Hypercalcemia: serum calcium >0.25 mmol/L (> 1 mg/dL) above upper limit of normal
or ≥ 2.75 mmol/L (11 mg/dL)
- Anemia: hemoglobin value <10 g/dL or > 2 g/dL below lower limit of normal
- Bone disease: ≥ 1 lytic lesions on skeletal X-ray, CT, or Positron Emission
Tomography (PET)-C. For patients with 1 lytic lesion, bone marrow should
demonstrate ≥10% clonal plasma cells
- Clonal bone marrow plasma cell percentage ≥60%
- Involved/un-involved serum free light chain ratio ≥100 and involved free light
chain
≥100 mg/L.
- > 1 focal lesion on magnetic resonance imaging study (lesion must be >5 mm) in
size
- For patients with 1 lytic lesion, bone marrow should demonstrate ≥10% clonal
plasma cells
3. Creatinine Clearance (CrCl) ≥ 60 ml/min. CrCl can be measured or estimated using
Cockcroft-Gault method, Modification of Diet in Renal Disease (MDRD), or Chronic
Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae
4. Age ≥ 18 years at the time of signing the informed consent documentation. Age limit of
≤ 75 years.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
6. Absolute neutrophil count (ANC) ≥ 1.0 K/microliter (uL), hemoglobin ≥ 8 g/dL, and
platelet count ≥ 75 K/uL, unless if cytopenias are deemed to be due disease at
discretion of clinical investigator. Transfusions and growth factors are permissible.
7. Adequate hepatic function, with bilirubin < 1.5 x the pper Limit of Normal (ULN), and
Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 3.0 x ULN.
8. All study participants must be able to tolerate one of the following
thromboprophylactic strategies: aspirin, oral facto Xa inhibitors, low molecular
weight heparin, warfarin (coumadin), or alternative anti-coagulant.
9. All study participants must be registered into the mandatory electronic REMS (eREMS)
program and be willing and able to comply with the requirements of Risk Evaluation
Management and Safety (REMS).
10. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide
for Cycle 1 (prescriptions must be filled within 7 days) and must either commit to
continued abstinence from heterosexual intercourse or begin two acceptable methods of
birth control, one highly effective method and one additional effective method at the
same time, at least 28 days before she starts taking lenalidomide. FCBP must also
agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual
contact with a FCBP even if they have had a successful vasectomy.
A female of childbearing potential is a sexually mature female who: 1) has not undergone a
hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at
least 24 consecutive months (i.e., has had menses at any time in the preceding 24
consecutive months).
Exclusion Criteria:
1. Patients receiving >1 cycle of prior treatment or concurrent systemic treatment for
multiple myeloma:
- Treatment of hypercalcemia or spinal cord compression or aggressively progressing
myeloma with current or prior corticosteroids is permitted
- Bone targeting agents are permitted
- Concurrent or prior treatment with corticosteroids for indications other than
multiple myeloma is permitted
- Prior treatment with radiotherapy is permitted
- Prior MM treatments, such as Immunomodulating Drugs (IMIDs) or non-MM drugs in
clinical trials for smoldering myeloma is permitted with a washout period of 2
weeks from last dose. Smoldering patients previously treated with carfilzomib are
excluded.
- Patients with measurable disease who received up to one cycle of any therapy
within 60 days with a washout period of 2 weeks from last dose (on a trial or
outside a trial) are eligible (Note: Measurable disease is defined as one or more
of the following: Serum monoclonal protein ≥ 1.0 g/dL, Urine monoclonal protein ≥
200 mg/24 hour and/ or Involved serum immunoglobulin free light chain ≥ 10 mg/dL
AND abnormal kappa/lambda ratio)
2. Prior or current exposure to any of the following:
- To daratumumab or other anti- Cluster of Differentiation (CD) -38 therapies
(unless a re-treatment study)
- Exposure to an investigational drug (including investigational vaccine) or
invasive investigational medical device for any indication within 4 weeks or 5
pharmacokinetic half-lives, whichever is longer.
- Focal radiation therapy within 14 days prior to randomization with the exception
of palliative radiotherapy for symptomatic management but not on measurable
extramedullary plasmacytoma.
3. Patients with plasma cell leukemia
4. Patients with Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin
changes syndrome (POEMS syndrome)
5. Patients with amyloidosis
6. Patients with known Chronic Obstructive Pulmonary Disorder (COPD) with a forced
expiratory volume in 1 second (FEV1) < 50% of predicted normal. Note that FEV1 testing
is required for subjects suspected of having COPD, and subjects must be excluded if
FEV1 <50% of predicted normal.
7. Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma
of any classification. Note that participants who currently have controlled
intermittent asthma or controlled mild persistent asthma are allowed to participate in
the study.
8. Pregnant or lactating females. Because there is a potential risk for AEs in nursing
infants secondary to treatment of the mother with carfilzomib in combination with
lenalidomide, pregnant or lactating females are excluded from study participation.
These potential risks may also apply to other agents used in this study.
9. Uncontrolled hypertension (i.e., systolic blood pressure (BP) >160 mmHg, diastolic BP
> 100 mmHg)
10. Uncontrolled diabetes (i.e., two independent glucose readings >200 mg/dL)
11. Active hepatitis B or C infection
12. Subject is:
- Seropositive for human immunodeficiency virus (HIV)
- Seropositive for hepatitis B (defined by a positive test for hepatitis B surface
antigen [HBsAg]). Subjects with resolved infection (i.e., subjects who are HBsAg
negative but positive for antibodies to hepatitis B core (HBc) antigen [anti-HBc]
and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened
using real-time polymerase chain reaction (RT-PCR) measurement of hepatitis B
virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION:
Subjects with serologic findings suggestive of HBV vaccination (anti-HBs
positivity as the only serologic marker) AND a known history of prior HBV
vaccination do not need to be tested for HBV DNA by PCR.
- Seropositive for hepatitis C (except in the setting of a sustained virologic
response (SVR), defined as aviremia at least 12 weeks after completion of
antiviral therapy).
- Patients with active Coronavirus Disease of 2019 (COVID-19) infection are not to
be enrolled until 10 days have passed from the initial positive test, and the
patient is symptom-free. COVID-19 vaccinations following national guidelines
(i.e., CDC) are encouraged; however, the series should be completed prior to the
first day of study treatment. If this is not possible, every effort should be
made to administer vaccines at a time when patient is not scheduled to receive
study treatment (e.g., "off-weeks").
13. Clinically significant cardiac disease, including:
- Myocardial infarction within 6 months before randomization, or unstable or
uncontrolled disease/condition related to or affection cardiac function (e.g.,
unstable angina, congestive heart failure, New York Heart Association (NYHA)
Class III-IV) or a left ventricular ejection fraction of <40%.
- Uncontrolled cardiac arrhythmia
- Intolerance to hydration due to pre-existing pulmonary or cardiac impairment.
14. Pulmonary hypertension
15. Has refractory gastrointestinal (GI) disease with refractory nausea/vomiting,
inflammatory bowel disease, or bowel resection that would prevent absorption of oral
agents
16. Uncontrolled intercurrent illness including but not limited to active infection or
psychiatric illness/social situations that would compromise compliance with study
requirements
17. Significant neuropathy ≥ Grade 3 or Grade 2 neuropathy with pain at baseline
18. Contraindication to any concomitant medication, including antivirals or
anticoagulation
19. Major surgery within 3 weeks prior to first dose
|
NCT0426xxxx/NCT04268511.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268511</url>
</required_header>
<id_info>
<org_study_id>1374</org_study_id>
<nct_id>NCT04268511</nct_id>
</id_info>
<brief_title>Caudal Epidural Block Versus Ultrasound-Guided Pudendal Nerve Block for Pediatric Circumcision</brief_title>
<official_title>Ultrasound-Guided Low-dose Caudal Epidural Block Versus Ultrasound-Guided Pudendal Nerve Block for Pediatric Circumcision: A Prospective Observational Study</official_title>
<sponsors>
<lead_sponsor>
<agency>Prof. Dr. Cemil Tascıoglu Education and Research Hospital Organization</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Prof. Dr. Cemil Tascıoglu Education and Research Hospital Organization</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The regional anesthesia methods of caudal epidural block (CEB) and dorsal penile nerve block
(DPNB) play an important role in providing postoperative pain control in pediatric
circumcision surgery. However, the short-term postoperative analgesic effect and the risk of
block failure limit the use of DPNB, a peripheral nerve block.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
CEB is a neuraxial block and commonly used to control moderate and severe postoperative pain
following surgery related to the lumbosacral and midthoracic dermatomes. CEB can have serious
undesirable complications such as intravascular and subarachnoid injection, urinary retention
and motor block. Pudendal nerve block can be used as an alternative to both DPNB and CEB for
penile surgery such as circumcision. The pudendal nerve is a peripheral nerve combining the
anterior rami of the sacral plexus nerves (S2-S4) and provides motor and sensory innervation
to the perineal region.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">August 1, 2019</start_date>
<completion_date type="Actual">December 20, 2019</completion_date>
<primary_completion_date type="Actual">October 1, 2019</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Other</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Time of Postoperative analgesic requirement</measure>
<time_frame>Up to 12 hours</time_frame>
<description>It was assessed five times after the operation with Children's Hospital Eastern Ontario Pain Scale. The lowest scale score is 4 points and the highest 13 points. Significant pain behavior for Children's Hospital Eastern Ontario Pain Scale has been identified as 7 points or more. Following transfer from the recovery unit to the ward, the 30 minutes, 1st, 2nd, 6th, and 12th hour pain levels were evaluated by the ward nurse.</description>
</primary_outcome>
<primary_outcome>
<measure>Level of Postoperative pain</measure>
<time_frame>Up to 12 hours</time_frame>
<description>It was assessed five times after the operation with Children's Hospital Eastern Ontario Pain Scale. The lowest scale score is 4 points and the highest 13 points. Significant pain behavior for Children's Hospital Eastern Ontario Pain Scale has been identified as 7 points or more. Following transfer from the recovery unit to the ward, the 30 minutes, 1st, 2nd, 6th, and 12th hour pain levels were evaluated by the ward nurse.</description>
</primary_outcome>
<primary_outcome>
<measure>Level of Postoperative pain</measure>
<time_frame>At the 24th hour</time_frame>
<description>It was assessed one time for 24th hour by parents with Faces Pain Scale-Revised. The scale is scored in even numbers from 0 to 10, which themselves indicate no pain and significant pain, respectively. The parents were also informed that a scale score of 4 or more</description>
</primary_outcome>
<secondary_outcome>
<measure>Rate of Postoperative complications</measure>
<time_frame>Up to 12 hours</time_frame>
<description>Urinary retention, nausea, vomiting, lower extremity numbness, motor block were postoperative complications. They were assessed by ward nurse.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Level of Parent satisfaction</measure>
<time_frame>Up to 24 hours</time_frame>
<description>The parents were asked about their satisfaction with the child's comfort and activity level [1, unsatisfied; 2, satisfied (good); 3, absolutely satisfied (excellent)] at the 24-hour follow-up</description>
</secondary_outcome>
<number_of_groups>2</number_of_groups>
<enrollment type="Actual">100</enrollment>
<condition>Circumcision</condition>
<arm_group>
<arm_group_label>Caudal epidural block group</arm_group_label>
<description>Linear ultrasound probe and the sacral hiatus at the sacral cornu level was visualized using an out-of-plane transverse view at 5-10 megahertz . The linear probe was then rotated 90 degrees and placed longitudinally in the midline to evaluate the sacral cornus, sacrococcygeal ligament and sacral bone.</description>
</arm_group>
<arm_group>
<arm_group_label>Pudendal nerve block group</arm_group_label>
<description>The long axis of the ultrasound probe was positioned on a horizontal line connecting the ischial tuberosity that had been previously located by palpation to the anus. The ischial tuberosity could be easily identified as a hypoechoic area that is bounded superiorly by a hyperechoic line. The probe was then moved medially on the same axis until the rectum appeared as another hypoechoic area.</description>
</arm_group>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>Caudal epidural block group</intervention_name>
<description>The linear probe of ultrasound was then rotated 90 degrees and placed longitudinally in the midline to evaluate the sacral cornus, sacrococcygeal ligament and sacral bone. A 22 Gauge 50 mm echogenic block needle was advanced</description>
<arm_group_label>Caudal epidural block group</arm_group_label>
</intervention>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>Pudendal nerve block group</intervention_name>
<description>A 22 Gauge 50 mm insulated needle was then introduced in the anterior-posterior direction at the middle of the ultrasound probe's superior edge with an out-of-plane approach and using an inclination of 15° in the sagittal plane. The needle tip's position was identified by direct visualization using the movement of adjacent anatomical structures.</description>
<arm_group_label>Pudendal nerve block group</arm_group_label>
</intervention>
<eligibility>
<study_pop>
<textblock>
Male patients aged between 4-12 years in the ASA (American Society of Anesthesiologists)
I-II group and scheduled for circumcision
</textblock>
</study_pop>
<sampling_method>Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- Male patients aged between 4-12 years

- ASA (American Society of Anesthesiologists) I-II group

- Scheduled for circumcision

- Able to communicate in Turkish

- Willing to participate to the study (parents and children)

Exclusion Criteria:

- Patients aged less than 4 or more than 12 years

- Neurological deficit

- Bleeding diathesis

- History of local anesthetic allergy

- Current infection or redness in the region to be injected

- Congenital lower back anomaly

- Liver disease

- Psychiatric disorder

- Mental retardation

- Communication problem

- Refusal to participate in the study.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>4 Years</minimum_age>
<maximum_age>12 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Volkan Ozen, MD</last_name>
<role>Principal Investigator</role>
<affiliation>Prof. Dr. Cemil Tascıoglu Education and Research Hospital Organization</affiliation>
</overall_official>
<location>
<facility>
<name>Okmeydani Training and Research Hospital</name>
<address>
<city>Istanbul</city>
<state>Şişli</state>
<zip>34384</zip>
<country>Turkey</country>
</address>
</facility>
</location>
<location_countries>
<country>Turkey</country>
</location_countries>
<reference>
<citation>Tutuncu AC, Kendigelen P, Ashyyeralyeva G, Altintas F, Emre S, Ozcan R, Kaya G. Pudendal Nerve Block Versus Penile Nerve Block in Children Undergoing Circumcision. Urol J. 2018 May 3;15(3):109-115. doi: 10.22037/uj.v0i0.4292.</citation>
<PMID>29299888</PMID>
</reference>
<reference>
<citation>Gaudet-Ferrand I, De La Arena P, Bringuier S, Raux O, Hertz L, Kalfa N, Sola C, Dadure C. Ultrasound-guided pudendal nerve block in children: A new technique of ultrasound-guided transperineal approach. Paediatr Anaesth. 2018 Jan;28(1):53-58. doi: 10.1111/pan.13286. Epub 2017 Dec 5.</citation>
<PMID>29205687</PMID>
</reference>
<reference>
<citation>Kendigelen P, Tutuncu AC, Emre S, Altindas F, Kaya G. Pudendal Versus Caudal Block in Children Undergoing Hypospadias Surgery: A Randomized Controlled Trial. Reg Anesth Pain Med. 2016 Sep-Oct;41(5):610-5. doi: 10.1097/AAP.0000000000000447.</citation>
<PMID>27501015</PMID>
</reference>
<verification_date>August 2020</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>August 10, 2020</last_update_submitted>
<last_update_submitted_qc>August 10, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">August 11, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Prof. Dr. Cemil Tascıoglu Education and Research Hospital Organization</investigator_affiliation>
<investigator_full_name>Volkan Ozen</investigator_full_name>
<investigator_title>MD</investigator_title>
</responsible_party>
<keyword>Ultrasound</keyword>
<keyword>Pudendal nerve block</keyword>
<keyword>Caudal epidural block</keyword>
<keyword>Pain</keyword>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The regional anesthesia methods of caudal epidural block (CEB) and dorsal penile nerve block
(DPNB) play an important role in providing postoperative pain control in pediatric
circumcision surgery. However, the short-term postoperative analgesic effect and the risk of
block failure limit the use of DPNB, a peripheral nerve block.
CEB is a neuraxial block and commonly used to control moderate and severe postoperative pain
following surgery related to the lumbosacral and midthoracic dermatomes. CEB can have serious
undesirable complications such as intravascular and subarachnoid injection, urinary retention
and motor block. Pudendal nerve block can be used as an alternative to both DPNB and CEB for
penile surgery such as circumcision. The pudendal nerve is a peripheral nerve combining the
anterior rami of the sacral plexus nerves (S2-S4) and provides motor and sensory innervation
to the perineal region.
Male patients aged between 4-12 years in the ASA (American Society of Anesthesiologists)
I-II group and scheduled for circumcision
Inclusion Criteria:
- Male patients aged between 4-12 years
- ASA (American Society of Anesthesiologists) I-II group
- Scheduled for circumcision
- Able to communicate in Turkish
- Willing to participate to the study (parents and children)
Exclusion Criteria:
- Patients aged less than 4 or more than 12 years
- Neurological deficit
- Bleeding diathesis
- History of local anesthetic allergy
- Current infection or redness in the region to be injected
- Congenital lower back anomaly
- Liver disease
- Psychiatric disorder
- Mental retardation
- Communication problem
- Refusal to participate in the study.
|
NCT0426xxxx/NCT04268524.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268524</url>
</required_header>
<id_info>
<org_study_id>CL_RCT_MF_vs_TT_2020</org_study_id>
<nct_id>NCT04268524</nct_id>
</id_info>
<brief_title>Randomised Clinical Trial for New Treatment Modalities for Cutaneous Leishmaniasis Caused by Leishmania Tropica, in Pakistan</brief_title>
<official_title>Randomised, Open Label, Multicentre, Non-inferiority Clinical Trial for New Treatment Modalities for Cutaneous Leishmaniasis Caused by Leishmania Tropica, in Pakistan</official_title>
<sponsors>
<lead_sponsor>
<agency>Medecins Sans Frontieres, Netherlands</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Medecins Sans Frontieres, Netherlands</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
randomised control clinical trial to evaluate miltefosine, thermotherapy and the combination
miltefosine-thermotherapy are effective, safe and tolerable alternative treatment options to
treat cutaneous leishmaniasis caused by L. tropica, in Pakistan compared to the standard of
care.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Until now, there is no well-established evidence based option to treat CL caused by the
Leishmania tropica, besides antimonial injections. Alternative treatment options are not
available in Pakistan, or there is limited evidence of the effectivity.

Effectiveness of thermotherapy in L. tropica is studied in only three studies in OWCL with a
variable cure rate (54.1% - 98%). But it could be an attractive option, because only one
treatment session is required and studies report less scarring tissue. Another promising
treatment option is oral miltefosine. There is considerable evidence in the literature of the
efficacy of miltefosine in treatment of CL caused by L. major, however no studies have been
conducted to evaluate the efficacy in CL caused by L. tropica species. This oral treatment
could have major benefits for CL patients as it can be provided in peripheral health
facilities and to patients who have contraindications to antimony treatment (elderly, and
patients with cardiac or renal disease, or diabetes). A combination of thermotherapy and
miltefosine, the advantages offered by this combination are that a) the use of a topical plus
a systemic treatment would hypothetically have an additive effect of two treatments with
different modes of action. For the reason that systemic treatment could eliminate those
circulating or remaining parasites located in the periphery of the lesion that topical
treatment fails to remove, which might be the cause of a relapse, b) it may reduce the
necessary length of treatment with miltefosine. For these above reasons, in a prospective
trial we aim to evaluate the effectiveness and safety of thermotherapy, miltefosine and the
combination of thermotherapy and miltefosine in CL caused by L. tropica, with the objective
to find a treatment with an efficacy which is non-inferior to the standard of care with
antimony injections.
</textblock>
</detailed_description>
<overall_status>Unknown status</overall_status>
<last_known_status>Not yet recruiting</last_known_status>
<start_date type="Anticipated">February 1, 2021</start_date>
<completion_date type="Anticipated">December 30, 2022</completion_date>
<primary_completion_date type="Anticipated">July 31, 2022</primary_completion_date>
<phase>Phase 3</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>randomised control trial</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>The initial clinical cure rate in each study arm</measure>
<time_frame>by Day 91.</time_frame>
<description>Initial Cure: Ulcerated lesions: 100% re-epithelialization of the lesion(s) Non-Ulcerated lesions: flattening and/or no signs of induration of the lesion(s) by Day 91.</description>
</primary_outcome>
<primary_outcome>
<measure>Adverse events</measure>
<time_frame>by Day 91.</time_frame>
<description>Frequency, severity and seriousness of AEs by treatment group</description>
</primary_outcome>
<secondary_outcome>
<measure>initial cure and no relapse</measure>
<time_frame>initial cure at D91 and have no relapse by D120.</time_frame>
<description>The proportion of patients in each study arm who have fulfilled the criteria of initial cure and have no relapse</description>
</secondary_outcome>
<secondary_outcome>
<measure>100% re-epithelialized/ flattened</measure>
<time_frame>at visit until D120</time_frame>
<description>The number of patients with lesions 100% re-epithelialized/ flattened at each measurement time point.</description>
</secondary_outcome>
<number_of_arms>4</number_of_arms>
<enrollment type="Anticipated">832</enrollment>
<condition>Old World Cutaneous Leishmaniasis</condition>
<arm_group>
<arm_group_label>monotherapy miltefosine</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Miltefosine capsules (Impavido®) 2.5 mg/kg daily PO for 28 days <30 kg BW allometric miltefosine dose based on fat-free mass. (approx. 2.5 mg/kg); >30 - ≤44kg BW: 100 mg/day BID; ≥45kg BW 150mg TDS</description>
</arm_group>
<arm_group>
<arm_group_label>Thermotherapy</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Thermotherapy (ThermoMed 1.8 ®) 50°C for 30 seconds, 1 session</description>
</arm_group>
<arm_group>
<arm_group_label>Combination miltefosine and thermotherapy</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Miltefosine capsules 2.5 mg/kg daily PO for 21days, and thermotherapy 50°C for 30 seconds, one session on day 1 of the miltefosine.</description>
</arm_group>
<arm_group>
<arm_group_label>° Meglumine antimoniate (Glucantime®) intralesional</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Meglumine antimoniate (Glucantime®) intralesional injections 0.5-3ml, 8 sessions, bi-weekly</description>
</arm_group>
<intervention>
<intervention_type>Combination Product</intervention_type>
<intervention_name>drug: miltefosine with thermotherapy</intervention_name>
<description>see previous</description>
<arm_group_label>Combination miltefosine and thermotherapy</arm_group_label>
<arm_group_label>Thermotherapy</arm_group_label>
<arm_group_label>monotherapy miltefosine</arm_group_label>
<arm_group_label>° Meglumine antimoniate (Glucantime®) intralesional</arm_group_label>
<other_name>device ThermoMed 1.8</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Male and female patients with clinical and laboratory confirmed CL, and who can be
treated with localised intralesional antimonial injections and/or thermotherapy:

- lesion size ≥0.5 cm and ≤4 cm

- not located on the ear, nose, near to the eye or mucosal membranes, on joints, or on a
location that in the opinion of the principle investigator (PI) is difficult to apply
thermotherapy (TT) or intralesional (IL) injections

- patient with ≤4 lesions

- duration of lesions less than five months by patient history

- Patients who have signed the informed consent form.

Exclusion Criteria:

- Pregnant women and breast feeding women

- Non-pregnant women in reproductive age refusing effective (injectable) contraception
for a period of five months

- Patients <10years old

- Patients who cannot be treated with localised IL antimonial injections or TT (patients
with more than 4 lesions, lesions >4cm in diameter, or located on joints, lips, nose,
ears or near eyes)

- History of clinically significant medical problems or treatment that might interact
with the study treatment and interact with wound healing, such as diabetes, vascular
diseases and any immunocompromising condition

- Within eight weeks of trial D1 received treatment for leishmaniasis with any
medication

- History of known or suspected hypersensitivity of idiosyncratic reactions to trial
medication or excipients

- Has laboratory values at screening: serum creatinine above normal level; ALT 3 times
above normal range

- Patient who is not willing to attend the trial visits, or is not able to comply with
follow-up visits up to three months.

- Known history of drug addiction and/or alcohol abuse
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>10 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Koert Ritmeijer</last_name>
<role>Study Director</role>
<affiliation>Medecins Sans Frontieres, Netherlands</affiliation>
</overall_official>
<overall_contact>
<last_name>Suzette Kämink</last_name>
<phone>+31687680573</phone>
<email>s.s.kamink@gmail.com</email>
</overall_contact>
<overall_contact_backup>
<last_name>Koert Ritmeijer</last_name>
<phone>+31205208767</phone>
<email>koert.ritmeijer@oca.msf.org</email>
</overall_contact_backup>
<verification_date>June 2020</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>June 17, 2020</last_update_submitted>
<last_update_submitted_qc>June 17, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">June 18, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>miltefosine</keyword>
<keyword>Thermotherapy</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Leishmaniasis</mesh_term>
<mesh_term>Leishmaniasis, Cutaneous</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Miltefosine</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>Undecided</sharing_ipd>
<ipd_description>Plan need to be made what wilkl be shared with whom (such as study protocol, SAP, ICF etc)</ipd_description>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
randomised control clinical trial to evaluate miltefosine, thermotherapy and the combination
miltefosine-thermotherapy are effective, safe and tolerable alternative treatment options to
treat cutaneous leishmaniasis caused by L. tropica, in Pakistan compared to the standard of
care.
Until now, there is no well-established evidence based option to treat CL caused by the
Leishmania tropica, besides antimonial injections. Alternative treatment options are not
available in Pakistan, or there is limited evidence of the effectivity.
Effectiveness of thermotherapy in L. tropica is studied in only three studies in OWCL with a
variable cure rate (54.1% - 98%). But it could be an attractive option, because only one
treatment session is required and studies report less scarring tissue. Another promising
treatment option is oral miltefosine. There is considerable evidence in the literature of the
efficacy of miltefosine in treatment of CL caused by L. major, however no studies have been
conducted to evaluate the efficacy in CL caused by L. tropica species. This oral treatment
could have major benefits for CL patients as it can be provided in peripheral health
facilities and to patients who have contraindications to antimony treatment (elderly, and
patients with cardiac or renal disease, or diabetes). A combination of thermotherapy and
miltefosine, the advantages offered by this combination are that a) the use of a topical plus
a systemic treatment would hypothetically have an additive effect of two treatments with
different modes of action. For the reason that systemic treatment could eliminate those
circulating or remaining parasites located in the periphery of the lesion that topical
treatment fails to remove, which might be the cause of a relapse, b) it may reduce the
necessary length of treatment with miltefosine. For these above reasons, in a prospective
trial we aim to evaluate the effectiveness and safety of thermotherapy, miltefosine and the
combination of thermotherapy and miltefosine in CL caused by L. tropica, with the objective
to find a treatment with an efficacy which is non-inferior to the standard of care with
antimony injections.
Inclusion Criteria:
- Male and female patients with clinical and laboratory confirmed CL, and who can be
treated with localised intralesional antimonial injections and/or thermotherapy:
- lesion size ≥0.5 cm and ≤4 cm
- not located on the ear, nose, near to the eye or mucosal membranes, on joints, or on a
location that in the opinion of the principle investigator (PI) is difficult to apply
thermotherapy (TT) or intralesional (IL) injections
- patient with ≤4 lesions
- duration of lesions less than five months by patient history
- Patients who have signed the informed consent form.
Exclusion Criteria:
- Pregnant women and breast feeding women
- Non-pregnant women in reproductive age refusing effective (injectable) contraception
for a period of five months
- Patients <10years old
- Patients who cannot be treated with localised IL antimonial injections or TT (patients
with more than 4 lesions, lesions >4cm in diameter, or located on joints, lips, nose,
ears or near eyes)
- History of clinically significant medical problems or treatment that might interact
with the study treatment and interact with wound healing, such as diabetes, vascular
diseases and any immunocompromising condition
- Within eight weeks of trial D1 received treatment for leishmaniasis with any
medication
- History of known or suspected hypersensitivity of idiosyncratic reactions to trial
medication or excipients
- Has laboratory values at screening: serum creatinine above normal level; ALT 3 times
above normal range
- Patient who is not willing to attend the trial visits, or is not able to comply with
follow-up visits up to three months.
- Known history of drug addiction and/or alcohol abuse
|
NCT0426xxxx/NCT04268537.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268537</url>
</required_header>
<id_info>
<org_study_id>2020YFC0841300-03</org_study_id>
<nct_id>NCT04268537</nct_id>
</id_info>
<brief_title>Immunoregulatory Therapy for 2019-nCoV</brief_title>
<official_title>Immunoregulatory Therapy for 2019-nCoV-induced Severe Pneumonia Patients</official_title>
<sponsors>
<lead_sponsor>
<agency>Southeast University, China</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Southeast University, China</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Sepsis, including viral infections, are major causes of death worldwide. Studies show that in
2017, the number of sepsis patients worldwide reached as high as 48.9 million, of which 11
million patients died. Studies in China also showed that more than 1 million patients died of
sepsis in 2015. Previous studies have suggested that sepsis are often secondary to excessive
inflammatory response syndrome. However, treatment measures targeting excessive inflammatory
response failed to effectively improve the prognosis of patients. PD-1 and PD-L1 are key
mediators in T cell depletion in sepsis patients. Therefore, the investigators try to
performe a clinical research to investigate the efficacy of PD-1 and thymosin in patients
with severe pneumonia associated with lymphocytopenia in 2019 novel coronavirus infection.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Sepsis, including viral infections, are major causes of death worldwide. Studies show that in
2017, the number of sepsis patients worldwide reached as high as 48.9 million, of which
eleven million patients died. Studies in China also showed that more than one million
patients died of sepsis in 2015. Therefore, how to effectively reduce the mortality of
patients with sepsis has become a focus of clinical and basic research.

Previous studies have suggested that sepsis are often secondary to excessive inflammatory
response syndrome. However, treatment measures targeting excessive inflammatory response
failed to effectively improve the prognosis of patients. The reason is that sepsis-related
immune dysfunction can increase the risk of secondary infection and even affect the fatality
rate.

The immune checkpoint pathway is the endogenous component of the immune system, which is
responsible for checking the immune response and keeping it in a normal physiological state.
Tumor cells can evade host recognition through this pathway. One of these immunocheckpoint
pathways is the PD-1 and PD-L1 pathways. PD-1 is a receptor expressed on the surface of T
cells and ACTS as a negative regulator of T cell function. Monoclonal antibody blocking the
activity of PD-1 can successfully reduce tumor load and has been widely used in the clinical
treatment of various tumors.

The immune imbalance in patients with sepsis has many similarities tumors. PD-1 and PD-L1 are
key mediators in T cell depletion in sepsis patients. Animal models have shown that blocking
PD-1 or PD-L1 can prevent T cell death, regulate cytokine production, reduce organ
dysfunction and reduce death in sepsis. Previous study showed the clinical safety of
anti-PD-1 antibody in sepsis patients through randomized, placebo-controlled trials.

Thymosin has also been proved to regulate cellular immunity in sepsis patients. Some studies
have shown that thymosin can significantly reduce the mortality of sepsis patients. At
present, phase III clinical research is in progress to further clarify the role of thymosin
in patients with sepsis. The purpose of this study was to investigate the efficacy of PD-1
and thymosin in patients with severe pneumonia associated with lymphocytopenia in 2019 novel
coronavirus infection.
</textblock>
</detailed_description>
<overall_status>Unknown status</overall_status>
<last_known_status>Not yet recruiting</last_known_status>
<start_date type="Anticipated">February 10, 2020</start_date>
<completion_date type="Anticipated">October 31, 2020</completion_date>
<primary_completion_date type="Anticipated">April 30, 2020</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>Single (Participant)</masking>
</study_design_info>
<primary_outcome>
<measure>lung injury score</measure>
<time_frame>7 days</time_frame>
<description>proportion of lung injury score decreased 1 or more points</description>
</primary_outcome>
<secondary_outcome>
<measure>absolute lymphocyte counts</measure>
<time_frame>7, 14 and 28 days</time_frame>
<description>lymphocyte counts at day 7, 14 and 28 after randimization</description>
</secondary_outcome>
<secondary_outcome>
<measure>serum level of CRP, PCT and IL-6</measure>
<time_frame>3, 7 and 14 days</time_frame>
<description>serum level of CRP, PCT and IL-6 at day 3,7 and 14 after randimization</description>
</secondary_outcome>
<secondary_outcome>
<measure>SOFA score</measure>
<time_frame>7 days</time_frame>
<description>SOFA score at Day 7, with scores range from 0 to 24 and higher score means worse outcome</description>
</secondary_outcome>
<secondary_outcome>
<measure>all cause mortality rate</measure>
<time_frame>28 days</time_frame>
<description>died at day 28</description>
</secondary_outcome>
<secondary_outcome>
<measure>ventilation free days</measure>
<time_frame>28 days</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>ICU free days</measure>
<time_frame>up to 28 days</time_frame>
</secondary_outcome>
<number_of_arms>3</number_of_arms>
<enrollment type="Anticipated">120</enrollment>
<condition>2019 nCoV, PD-1</condition>
<arm_group>
<arm_group_label>PD-1 group</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Anti-PD-1 antibody, 200mg, IV, one time</description>
</arm_group>
<arm_group>
<arm_group_label>thymosin group</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Thymosin, 1.6 mg sc qd, last for 5 days</description>
</arm_group>
<arm_group>
<arm_group_label>control group</arm_group_label>
<arm_group_type>Placebo Comparator</arm_group_type>
<description>stand treatment</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>PD-1 blocking antibody+standard treatment</intervention_name>
<description>After randomization, PD-1 blocking antibody 200mg iv, one time. Standard treatment is according to the protocol of treatment of 2019-nCoV infection</description>
<arm_group_label>PD-1 group</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Thymosin+standard treatment</intervention_name>
<description>Thymosin 1.6 mg sc qd, last for 5 days. Standard treatment is according to the protocol of treatment of 2019-nCoV infection</description>
<arm_group_label>thymosin group</arm_group_label>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>standard treatment</intervention_name>
<description>Standard treatment is according to the protocol of treatment of 2019-nCoV infection</description>
<arm_group_label>control group</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Adult SARI patients with 2019-ncov infection confirmed by PCR;

2. Absolute value of lymphocytes < 0. 6x 109/L;

3. Severe respiratory failure within 48 hours and requires admission to ICU. (severe
respiratory failure was defined as PaO2/FiO2 < 200 mmHg and was supported by positive
pressure mechanical ventilation (including non-invasive and invasive mechanical
ventilation, PEEP>=5cmH2O))

Exclusion Criteria:

1. Age < 18

2. Pregnant

3. Allergic to experimental drugs

4. The underlying disease is very serious and the expected survival time is less than 6
months (such as advanced malignant tumor);

5. COPD or end-stage lung disease requires home oxygen therapy

6. Expected survival time not exceeding 48 hours

7. Participated in other clinical intervention trials within the last 3 months

8. Autoimmune diseases

9. A history of organ, bone marrow or hematopoietic stem cell transplantation 10.
Received radiotherapy and chemotherapy for malignant tumor within 6 months

11.HIV infected patients or diagnosed with acquired immunodeficiency within the past year
(CD4 T cells <=200/mm3) 12. Patients receiving anti-hcv treatment 13.90 days of retinal
detachment or eye surgery 14. Permanent blindness in one eye 15. History of iritis,
endophthalmitis, scleral inflammation or retinitis 16. The competent physician considered
it inappropriate to participate in the study
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 8, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 12, 2020</last_update_submitted>
<last_update_submitted_qc>February 12, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Southeast University, China</investigator_affiliation>
<investigator_full_name>Jianfeng Xie</investigator_full_name>
<investigator_title>Director Assistant of ICU</investigator_title>
</responsible_party>
<keyword>2019-ncov</keyword>
<keyword>immunotherapy</keyword>
<keyword>PD-1</keyword>
<keyword>respiratory failure</keyword>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Antibodies</mesh_term>
<mesh_term>Antibodies, Blocking</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>Undecided</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Sepsis, including viral infections, are major causes of death worldwide. Studies show that in
2017, the number of sepsis patients worldwide reached as high as 48.9 million, of which 11
million patients died. Studies in China also showed that more than 1 million patients died of
sepsis in 2015. Previous studies have suggested that sepsis are often secondary to excessive
inflammatory response syndrome. However, treatment measures targeting excessive inflammatory
response failed to effectively improve the prognosis of patients. PD-1 and PD-L1 are key
mediators in T cell depletion in sepsis patients. Therefore, the investigators try to
performe a clinical research to investigate the efficacy of PD-1 and thymosin in patients
with severe pneumonia associated with lymphocytopenia in 2019 novel coronavirus infection.
Sepsis, including viral infections, are major causes of death worldwide. Studies show that in
2017, the number of sepsis patients worldwide reached as high as 48.9 million, of which
eleven million patients died. Studies in China also showed that more than one million
patients died of sepsis in 2015. Therefore, how to effectively reduce the mortality of
patients with sepsis has become a focus of clinical and basic research.
Previous studies have suggested that sepsis are often secondary to excessive inflammatory
response syndrome. However, treatment measures targeting excessive inflammatory response
failed to effectively improve the prognosis of patients. The reason is that sepsis-related
immune dysfunction can increase the risk of secondary infection and even affect the fatality
rate.
The immune checkpoint pathway is the endogenous component of the immune system, which is
responsible for checking the immune response and keeping it in a normal physiological state.
Tumor cells can evade host recognition through this pathway. One of these immunocheckpoint
pathways is the PD-1 and PD-L1 pathways. PD-1 is a receptor expressed on the surface of T
cells and ACTS as a negative regulator of T cell function. Monoclonal antibody blocking the
activity of PD-1 can successfully reduce tumor load and has been widely used in the clinical
treatment of various tumors.
The immune imbalance in patients with sepsis has many similarities tumors. PD-1 and PD-L1 are
key mediators in T cell depletion in sepsis patients. Animal models have shown that blocking
PD-1 or PD-L1 can prevent T cell death, regulate cytokine production, reduce organ
dysfunction and reduce death in sepsis. Previous study showed the clinical safety of
anti-PD-1 antibody in sepsis patients through randomized, placebo-controlled trials.
Thymosin has also been proved to regulate cellular immunity in sepsis patients. Some studies
have shown that thymosin can significantly reduce the mortality of sepsis patients. At
present, phase III clinical research is in progress to further clarify the role of thymosin
in patients with sepsis. The purpose of this study was to investigate the efficacy of PD-1
and thymosin in patients with severe pneumonia associated with lymphocytopenia in 2019 novel
coronavirus infection.
Inclusion Criteria:
1. Adult SARI patients with 2019-ncov infection confirmed by PCR;
2. Absolute value of lymphocytes < 0. 6x 109/L;
3. Severe respiratory failure within 48 hours and requires admission to ICU. (severe
respiratory failure was defined as PaO2/FiO2 < 200 mmHg and was supported by positive
pressure mechanical ventilation (including non-invasive and invasive mechanical
ventilation, PEEP>=5cmH2O))
Exclusion Criteria:
1. Age < 18
2. Pregnant
3. Allergic to experimental drugs
4. The underlying disease is very serious and the expected survival time is less than 6
months (such as advanced malignant tumor);
5. COPD or end-stage lung disease requires home oxygen therapy
6. Expected survival time not exceeding 48 hours
7. Participated in other clinical intervention trials within the last 3 months
8. Autoimmune diseases
9. A history of organ, bone marrow or hematopoietic stem cell transplantation 10.
Received radiotherapy and chemotherapy for malignant tumor within 6 months
11.HIV infected patients or diagnosed with acquired immunodeficiency within the past year
(CD4 T cells <=200/mm3) 12. Patients receiving anti-hcv treatment 13.90 days of retinal
detachment or eye surgery 14. Permanent blindness in one eye 15. History of iritis,
endophthalmitis, scleral inflammation or retinitis 16. The competent physician considered
it inappropriate to participate in the study
|
NCT0426xxxx/NCT04268550.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268550</url>
</required_header>
<id_info>
<org_study_id>S1900B</org_study_id>
<secondary_id>NCI-2019-08097</secondary_id>
<secondary_id>S1900B</secondary_id>
<secondary_id>S1900B</secondary_id>
<secondary_id>U10CA180888</secondary_id>
<nct_id>NCT04268550</nct_id>
</id_info>
<brief_title>Targeted Treatment for RET Fusion-Positive Advanced Non-Small Cell Lung Cancer (A LUNG-MAP Treatment Trial)</brief_title>
<official_title>A Phase II Study of LOXO-292 in Patients With RET Fusion-Positive Stage IV or Recurrent Non-Small Cell Lung Cancer (LUNG-MAP Sub-Study)</official_title>
<sponsors>
<lead_sponsor>
<agency>SWOG Cancer Research Network</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>National Cancer Institute (NCI)</agency>
<agency_class>NIH</agency_class>
</collaborator>
</sponsors>
<source>SWOG Cancer Research Network</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This phase II LUNG-MAP treatment trial studies how well selpercatinib works in treating
patients with RET fusion-positive non-small cell lung cancer that is stage IV or has come
back (recurrent). Selpercatinib may stop the growth of tumor cells by blocking some of the
enzymes needed for cell growth.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
PRIMARY OBJECTIVE:

I. To evaluate the objective response rate (ORR) (confirmed complete or partial response) by
blinded independent centralized review (BICR) associated with selpercatinib (LOXO-292) in
patients with previously-treated stage IV or recurrent RET fusion-positive non-small cell
lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To evaluate the duration of BICR-assessed response among BICR responders. II. To evaluate
the frequency and severity of toxicities. III. To evaluate the investigator-assessed
objective response rate (confirmed complete or partial response).

IV. To evaluate duration of investigator-assessed response among patients with a response as
determined by the local investigator.

V. To evaluate investigator-assessed progression-free survival (IA-PFS). VI. To evaluate
BICR-assessed PFS. VII. To evaluate overall survival (OS).

VIII. Among patients with brain metastases at baseline:

VIIIa. To evaluate the central nervous system (CNS) response rate (confirmed complete
response [CR]).

VIIIb. To evaluate the duration of intracranial response among patients with a CNS response.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To collect, process, and bank cell-free deoxyribonucleic acid (cfDNA) at baseline,
progression, and end of treatment for future development of a proposal to evaluate
comprehensive next-generation sequencing of circulating tumor deoxyribonucleic acid (ctDNA).

II. To establish a tissue/blood repository from patients with refractory non-small cell lung
cancer (NSCLC).

OUTLINE:

Patients receive selpercatinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat
every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years and
then at the end of 3 years from date of sub-study registration.
</textblock>
</detailed_description>
<overall_status>Active, not recruiting</overall_status>
<start_date type="Actual">April 8, 2020</start_date>
<completion_date type="Anticipated">April 1, 2024</completion_date>
<primary_completion_date type="Anticipated">April 1, 2024</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Response rate by blinded independent centralized review (BICR)</measure>
<time_frame>Up to 3 years from date of sub-study registration</time_frame>
<description>A response will be confirmed by a complete response (CR) or partial response (PR). Proportions and associated confidence intervals will be calculated.</description>
</primary_outcome>
<secondary_outcome>
<measure>Incidence of adverse events</measure>
<time_frame>Up to 3 years from date of sub-study registration</time_frame>
<description>Will be assessed using Common Terminology Criteria for Adverse Event version 5.0.</description>
</secondary_outcome>
<secondary_outcome>
<measure>BICR-progression-free survival (PFS)</measure>
<time_frame>From date of sub-study registration to date of first documentation of progression assessed by BICR or symptomatic deterioration, or death due to any cause, assessed up to 3 years from date of sub-study registration</time_frame>
<description>Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to estimate confidence intervals for the median using Greenwood's formula and based on a log-log transformation applied on the survival function for landmark times</description>
</secondary_outcome>
<secondary_outcome>
<measure>Investigator-assessed (IA) PFS</measure>
<time_frame>From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 3 years from date of sub-study registration</time_frame>
<description>Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to estimate confidence intervals for the median using Greenwood's formula and based on a log-log transformation applied on the survival function for landmark times</description>
</secondary_outcome>
<secondary_outcome>
<measure>Overall survival</measure>
<time_frame>Up to 3 years from date of sub-study registration</time_frame>
<description>Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to estimate confidence intervals for the median using Greenwood's formula and based on a log-log transformation applied on the survival function for landmark times</description>
</secondary_outcome>
<secondary_outcome>
<measure>BICR-duration of response (DOR)</measure>
<time_frame>From date of first documentation of confirmed response (CR or PR) to date of first documentation of progression assessed by BICR or symptomatic deterioration, or death due to any cause among patients who achieve, assessed at 6 and 12 months</time_frame>
<description>Will be evaluated among patients who achieve a confirmed response. Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to estimate confidence intervals for the median using Greenwood's formula and based on a log-log transformation applied on the survival function for landmark times. The median DOR and percentage with DOR at landmark times at 6 and 12 months after documentation of confirmed response will be estimated.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Central nervous system (CNS) response rate</measure>
<time_frame>Baseline</time_frame>
<description>Will be assessed among patients with brain metastases. Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to estimate confidence intervals for the median using Greenwood's formula and based on a log-log transformation applied on the survival function for landmark times</description>
</secondary_outcome>
<secondary_outcome>
<measure>Duration of intracranial response among patients with a CNS response</measure>
<time_frame>Baseline</time_frame>
<description>Will be assessed among patients with brain metastases. Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to estimate confidence intervals for the median using Greenwood's formula and based on a log-log transformation applied on the survival function for landmark times</description>
</secondary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Anticipated">124</enrollment>
<condition>Recurrent Lung Non-Small Cell Carcinoma</condition>
<condition>Stage IV Lung Cancer AJCC v8</condition>
<condition>Stage IVA Lung Cancer AJCC v8</condition>
<condition>Stage IVB Lung Cancer AJCC v8</condition>
<arm_group>
<arm_group_label>Treatment (selpercatinib)</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Patients receive selpercatinib orally PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Selpercatinib</intervention_name>
<description>Given PO</description>
<arm_group_label>Treatment (selpercatinib)</arm_group_label>
<other_name>LOXO-292</other_name>
<other_name>RET Kinase Inhibitor LOXO-292</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Patients must have been assigned to S1900B based on biomarker analysis of tissue
and/or blood and determined to have RET fusion-positive NSCLC as defined here:

- Patients must have RET fusion-positive NSCLC as determined by the Foundation
Medicine (FMI) tissue-assay, other tumor-based assays such as next-generation
sequencing (NGS), polymerase chain reaction (PCR), or follicular in situ
hybridization (FISH), or by cfDNA blood assay. Patients with RET fusions detected
by immunohistochemistry (IHC) alone are not eligible. The testing must be done
within a laboratory with Clinical Laboratory Improvement Act (CLIA),
International Organization for Standardization (ISO/International
Electrotechnical Commission (IEC), College of American Pathologists (CAP), or
similar certification. Presence of RET fusions detected on tests performed
outside of LUNGMAP must have been confirmed by the study biomarker review panel

- For patients whose prior therapy was for stage IV or recurrent disease, the patient
must have received at least one line of a platinum-based chemotherapy regimen. For
patients whose prior systemic therapy was for stage I-III disease only (i.e. patient
has not received any treatment for stage IV or recurrent disease), disease progression
on platinum-based chemotherapy must have occurred within one year from the last date
that the patient received that therapy. Prior anti-PD-1/PD-L1 therapy, alone or in
combination (e.g. nivolumab, pembrolizumab, or durvalumab) is allowed

- Patients must be negative for all additional validated oncogenic drivers that could
cause resistance to LOXO-292 treatment. This includes EGFR sensitizing mutations, EGFR
T790M, ALK gene fusion, ROS1 gene fusion, KRAS activating mutation, BRAF V600E
mutation and MET exon 14 skipping mutation or high-level amplification and expression

- Note: EGFR, ALK, ROS, KRAS, and BRAF testing is performed as part of the LUNGMAP
screening/pre-screening FoundationOne test. If prior data is not available,
results from the FMI testing must be obtained prior to sub-study registration

- Patients must have measurable disease documented by computed tomography (CT) or
magnetic resonance imaging (MRI). The CT from a combined positron emission tomography
(PET)/CT may be used to document only non-measurable disease unless it is of
diagnostic quality. Measurable disease must be assessed within 28 days prior to
sub-study registration. Pleural effusions, ascites and laboratory parameters are not
acceptable as the only evidence of disease. Non-measurable disease must be assessed
within 42 days prior to sub-study registration. All disease must be assessed and
documented on the Baseline Tumor Assessment Form. Patients whose only measurable
disease is within a previous radiation therapy port must demonstrate clearly
progressive disease (in the opinion of the treating investigator) prior to
registration. CT and MRI scans must be submitted for central review via transfer of
images and data (TRIAD)

- Patients must have a CT or MRI scan of the brain to evaluate for CNS disease within 42
days prior to sub-study registration

- Patients with evidence of chronic hepatitis B virus (HBV) infection must have
undetectable HBV viral load on suppressive therapy within 28 days prior to
registration

- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. Patients with HCV infection who are currently on treatment must have an
undetectable HCV viral load within 28 days prior to registration

- Patients with known human immunodeficiency virus (HIV) infection are eligible,
provided they are on effective anti-retroviral therapy and have undetectable viral
load at their most recent viral load test and within 6 months prior to registration

- Patients must be able to swallow capsules

- Patients must have progressed (in the opinion of the treating physician) following the
most recent line of therapy

- Patients must have recovered (=< grade 1) from any side effects of prior therapy.
Patients must not have received any radiation therapy within 14 days prior to
sub-study registration

- Absolute neutrophil count (ANC) >= 1,500/mcl (obtained within 28 days prior to
sub-study registration)

- Platelet count >= 100,000 mcl (obtained within 28 days prior to sub-study
registration)

- Serum bilirubin =< institutional upper limit of normal (IULN) (within 28 days prior to
sub-study registration). For patients with liver metastases, bilirubin must be =< 5 x
IULN

- Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN
(within 28 days prior to sub-study registration) (if both ALT and AST are done, both
must be =< 2 IULN). For patients with liver metastases, bilirubin and either ALT or
AST must be =< 5 x IULN (if both ALT and AST are done, both must be =< 5 x IULN)

- Serum creatinine =< the IULN or calculated creatinine clearance >= 50 mL/min using the
following Cockcroft-Gault formula (within 28 days prior to sub-study registration)

- Patients must have Zubrod performance status 0-1 documented within 28 days prior to
sub-study registration

- Pre-study history and physical exam must be obtained within 28 days prior to sub-study
registration

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
stage I or II cancer from which the patient is currently in complete remission, or any
other cancer from which the patient has been disease free for five years

- Patients must have electrolytes and blood urea nitrogen (BUN) performed within 14 days
prior to sub-study registration

- Patients must agree to have blood specimens submitted for circulating tumor DNA
(ctDNA)

- Patients must also be offered participation in banking and in the correlative studies
for collection and future use of specimens

- Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines

- As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has been
entered in the system

- Patients with impaired decision-making capacity are eligible as long as their
neurological or psychological condition does not preclude their safe participation in
the study (e.g., tracking pill consumption and reporting adverse events to the
investigator)

Exclusion Criteria:

- Patients must not have received any prior treatment with selective anti-RET inhibitors
(anti-RET multikinase inhibitors are permitted)

- Patient must not have leptomeningeal disease, spinal cord compression or brain
metastases unless: (1) metastases have been locally treated and have remained
clinically controlled and asymptomatic for at least 14 days following treatment, and
prior to registration, AND (2) patient has no residual neurological dysfunction and
has been off corticosteroids for at least 24 hours prior to sub-study registration

- Patients must not have received any prior systemic therapy (systemic chemotherapy,
immunotherapy or investigational drug) within 14 days prior to sub-study registration

- Patients must not be planning to receive any concurrent chemotherapy, immunotherapy,
biologic or hormonal therapy for cancer treatment while receiving treatment on this
study. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for
diabetes and hormone replacement therapy) is acceptable

- Patient must not have had a major surgery within 14 days prior to sub-study
registration. Patient must have fully recovered from the effects of prior surgery in
the opinion of the treating investigator

- Patients must not have any grade III/IV cardiac disease as defined by the New York
Heart Association Criteria (i.e., patients with cardiac disease resulting in marked
limitation of physical activity or resulting in inability to carry on any physical
activity without discomfort), unstable angina pectoris, and myocardial infarction
within 6 months, or serious uncontrolled cardiac arrhythmia

- Patients must not have a QT interval by Fridericia (QTcF) > 470 msec based on the
electrocardiogram (ECG) within 28 days prior to registration. It is suggested that a
local cardiologist review the QTcF intervals

- Patients must not have any clinically significant uncontrolled systemic illness,
including but not limited to uncontrolled infection, requiring intravenous
antibiotics, unstable angina pectoris, myocardial infarction within the past 6 months,
uncontrolled cardiac arrhythmias, uncontrolled hypertension, or uncontrolled diabetes
mellitus

- Uncontrolled diabetes: Patients who have a diagnosis of diabetes must have an
hemoglobin (Hb) A1C < 7% within 28 days prior to registration. The same criterion
will be used in patients with confirmed diagnosis of diabetes mellitus who have
been on a stable dietary or therapeutic regimen for this condition in the last
three months

- Uncontrolled blood pressure and hypertension: All blood pressure measurements
within the 28 days prior to registration must be systolic blood pressure (SBP) =<
180 and diastolic blood pressure (DBP) =< 100. An exception can be made by a
healthcare provider for a patient with a single blood pressure elevation who upon
rechecking has a blood pressure within the parameters above

- Patients must not have any impairment of gastrointestinal function or gastrointestinal
disease that may significantly alter the absorption of LOXO-292 (e.g., ulcerative
disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel
resection, or active peptic ulcer disease)

- Patients must not be planning to receive any strong inhibitors or inducers of CYP3A4
at least 14 days prior to sub-study registration and throughout protocol treatment

- Patients must not be planning to use proton pump inhibitors (PPIs) at least one week
prior to sub-study registration and throughout protocol treatment

- Patients must not be pregnant or nursing. Women study patients of reproductive
potential and fertile men study patients and their partners must abstain or use
effective contraception (including barrier method) while receiving study treatment and
for at least 3 months after the last dose of LOXO-292. Male study patients must agree
not to donate sperm for 6 months after the last dose of LOXO-292. A woman is
considered to be of "reproductive potential" if she has had menses at any time in the
preceding 12 consecutive months. In addition to routine contraceptive methods,
"effective contraception" also includes heterosexual celibacy and surgery intended to
prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a
hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any
point a previously celibate patient chooses to become heterosexually active during the
time period for use of contraceptive measures outlined in the protocol, he/she is
responsible for beginning contraceptive measures
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>N/A</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Yasir Y Elamin</last_name>
<role>Principal Investigator</role>
<affiliation>SWOG Cancer Research Network</affiliation>
</overall_official>
<location>
<facility>
<name>Fairbanks Memorial Hospital</name>
<address>
<city>Fairbanks</city>
<state>Alaska</state>
<zip>99701</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Arkansas for Medical Sciences</name>
<address>
<city>Little Rock</city>
<state>Arkansas</state>
<zip>72205</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente-Anaheim</name>
<address>
<city>Anaheim</city>
<state>California</state>
<zip>92806</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Sutter Auburn Faith Hospital</name>
<address>
<city>Auburn</city>
<state>California</state>
<zip>95602</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente-Baldwin Park</name>
<address>
<city>Baldwin Park</city>
<state>California</state>
<zip>91706</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente-Bellflower</name>
<address>
<city>Bellflower</city>
<state>California</state>
<zip>90706</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Alta Bates Summit Medical Center-Herrick Campus</name>
<address>
<city>Berkeley</city>
<state>California</state>
<zip>94704</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente-Fontana</name>
<address>
<city>Fontana</city>
<state>California</state>
<zip>92335</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Palo Alto Medical Foundation-Fremont</name>
<address>
<city>Fremont</city>
<state>California</state>
<zip>94538</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente - Harbor City</name>
<address>
<city>Harbor City</city>
<state>California</state>
<zip>90710</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente-Irvine</name>
<address>
<city>Irvine</city>
<state>California</state>
<zip>92618</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Loma Linda University Medical Center</name>
<address>
<city>Loma Linda</city>
<state>California</state>
<zip>92354</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente Los Angeles Medical Center</name>
<address>
<city>Los Angeles</city>
<state>California</state>
<zip>90027</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente-Cadillac</name>
<address>
<city>Los Angeles</city>
<state>California</state>
<zip>90034</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Palo Alto Medical Foundation-Camino Division</name>
<address>
<city>Mountain View</city>
<state>California</state>
<zip>94040</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente-Ontario</name>
<address>
<city>Ontario</city>
<state>California</state>
<zip>91761</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Palo Alto Medical Foundation Health Care</name>
<address>
<city>Palo Alto</city>
<state>California</state>
<zip>94301</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Stanford Cancer Institute Palo Alto</name>
<address>
<city>Palo Alto</city>
<state>California</state>
<zip>94304</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente - Panorama City</name>
<address>
<city>Panorama City</city>
<state>California</state>
<zip>91402</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente-Riverside</name>
<address>
<city>Riverside</city>
<state>California</state>
<zip>92505</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Sutter Roseville Medical Center</name>
<address>
<city>Roseville</city>
<state>California</state>
<zip>95661</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Sutter Medical Center Sacramento</name>
<address>
<city>Sacramento</city>
<state>California</state>
<zip>95816</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of California Davis Comprehensive Cancer Center</name>
<address>
<city>Sacramento</city>
<state>California</state>
<zip>95817</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente-San Diego Zion</name>
<address>
<city>San Diego</city>
<state>California</state>
<zip>92120</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>California Pacific Medical Center-Pacific Campus</name>
<address>
<city>San Francisco</city>
<state>California</state>
<zip>94115</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente-San Marcos</name>
<address>
<city>San Marcos</city>
<state>California</state>
<zip>92078</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Palo Alto Medical Foundation-Santa Cruz</name>
<address>
<city>Santa Cruz</city>
<state>California</state>
<zip>95065</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Palo Alto Medical Foundation-Sunnyvale</name>
<address>
<city>Sunnyvale</city>
<state>California</state>
<zip>94086</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Sutter Solano Medical Center/Cancer Center</name>
<address>
<city>Vallejo</city>
<state>California</state>
<zip>94589</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Presbyterian Intercommunity Hospital</name>
<address>
<city>Whittier</city>
<state>California</state>
<zip>90602</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente-Woodland Hills</name>
<address>
<city>Woodland Hills</city>
<state>California</state>
<zip>91367</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Colorado Hospital</name>
<address>
<city>Aurora</city>
<state>Colorado</state>
<zip>80045</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers-Boulder</name>
<address>
<city>Boulder</city>
<state>Colorado</state>
<zip>80304</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UCHealth Memorial Hospital Central</name>
<address>
<city>Colorado Springs</city>
<state>Colorado</state>
<zip>80909</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Memorial Hospital North</name>
<address>
<city>Colorado Springs</city>
<state>Colorado</state>
<zip>80920</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers-Midtown</name>
<address>
<city>Denver</city>
<state>Colorado</state>
<zip>80218</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Poudre Valley Hospital</name>
<address>
<city>Fort Collins</city>
<state>Colorado</state>
<zip>80524</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Cancer Care and Hematology-Fort Collins</name>
<address>
<city>Fort Collins</city>
<state>Colorado</state>
<zip>80528</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>North Colorado Medical Center</name>
<address>
<city>Greeley</city>
<state>Colorado</state>
<zip>80631</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UCHealth Greeley Hospital</name>
<address>
<city>Greeley</city>
<state>Colorado</state>
<zip>80631</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UCHealth Highlands Ranch Hospital</name>
<address>
<city>Highlands Ranch</city>
<state>Colorado</state>
<zip>80129</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers-Littleton</name>
<address>
<city>Littleton</city>
<state>Colorado</state>
<zip>80120</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Rocky Mountain Cancer Centers-Sky Ridge</name>
<address>
<city>Lone Tree</city>
<state>Colorado</state>
<zip>80124</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UCHealth Lone Tree Health Center</name>
<address>
<city>Lone Tree</city>
<state>Colorado</state>
<zip>80124</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Medical Center of the Rockies</name>
<address>
<city>Loveland</city>
<state>Colorado</state>
<zip>80538</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>McKee Medical Center</name>
<address>
<city>Loveland</city>
<state>Colorado</state>
<zip>80539</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Hartford Hospital</name>
<address>
<city>Hartford</city>
<state>Connecticut</state>
<zip>06102</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Veterans Affairs Connecticut Healthcare System-West Haven Campus</name>
<address>
<city>West Haven</city>
<state>Connecticut</state>
<zip>06516</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Bayhealth Hospital Kent Campus</name>
<address>
<city>Dover</city>
<state>Delaware</state>
<zip>19901</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Bayhealth Hospital Sussex Campus</name>
<address>
<city>Milford</city>
<state>Delaware</state>
<zip>19963</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Mount Sinai Comprehensive Cancer Center at Aventura</name>
<address>
<city>Aventura</city>
<state>Florida</state>
<zip>33180</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Mount Sinai Medical Center</name>
<address>
<city>Miami Beach</city>
<state>Florida</state>
<zip>33140</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Moffitt Cancer Center</name>
<address>
<city>Tampa</city>
<state>Florida</state>
<zip>33612</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Northside Hospital</name>
<address>
<city>Atlanta</city>
<state>Georgia</state>
<zip>30342</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Northeast Georgia Medical Center Braselton</name>
<address>
<city>Braselton</city>
<state>Georgia</state>
<zip>30517</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Atlanta VA Medical Center</name>
<address>
<city>Decatur</city>
<state>Georgia</state>
<zip>30033</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Northside Hospital - Duluth</name>
<address>
<city>Duluth</city>
<state>Georgia</state>
<zip>30096</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Northeast Georgia Medical Center-Gainesville</name>
<address>
<city>Gainesville</city>
<state>Georgia</state>
<zip>30501</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Northside Hospital - Gwinnett</name>
<address>
<city>Lawrenceville</city>
<state>Georgia</state>
<zip>30046</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Lewis Cancer and Research Pavilion at Saint Joseph's/Candler</name>
<address>
<city>Savannah</city>
<state>Georgia</state>
<zip>31405</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Suburban Hematology Oncology Associates - Snellville</name>
<address>
<city>Snellville</city>
<state>Georgia</state>
<zip>30078</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Hawaii Cancer Care - Savio</name>
<address>
<city>'Aiea</city>
<state>Hawaii</state>
<zip>96701</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Pali Momi Medical Center</name>
<address>
<city>'Aiea</city>
<state>Hawaii</state>
<zip>96701</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Hawaii Cancer Care Inc-POB II</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96813</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Queen's Cancer Cenrer - POB I</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96813</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Queen's Medical Center</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96813</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Straub Clinic and Hospital</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96813</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Queen's Cancer Center - Kuakini</name>
<address>
<city>Honolulu</city>
<state>Hawaii</state>
<zip>96817</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Saint Luke's Mountain States Tumor Institute</name>
<address>
<city>Boise</city>
<state>Idaho</state>
<zip>83712</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Saint Luke's Cancer Institute - Fruitland</name>
<address>
<city>Fruitland</city>
<state>Idaho</state>
<zip>83619</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Saint Luke's Cancer Institute - Meridian</name>
<address>
<city>Meridian</city>
<state>Idaho</state>
<zip>83642</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Saint Luke's Cancer Institute - Nampa</name>
<address>
<city>Nampa</city>
<state>Idaho</state>
<zip>83686</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Saint Luke's Cancer Institute - Twin Falls</name>
<address>
<city>Twin Falls</city>
<state>Idaho</state>
<zip>83301</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Illinois CancerCare-Bloomington</name>
<address>
<city>Bloomington</city>
<state>Illinois</state>
<zip>61704</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Illinois CancerCare-Canton</name>
<address>
<city>Canton</city>
<state>Illinois</state>
<zip>61520</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Illinois CancerCare-Carthage</name>
<address>
<city>Carthage</city>
<state>Illinois</state>
<zip>62321</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Northwestern University</name>
<address>
<city>Chicago</city>
<state>Illinois</state>
<zip>60611</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Cancer Care Specialists of Illinois - Decatur</name>
<address>
<city>Decatur</city>
<state>Illinois</state>
<zip>62526</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Illinois CancerCare-Dixon</name>
<address>
<city>Dixon</city>
<state>Illinois</state>
<zip>61021</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Crossroads Cancer Center</name>
<address>
<city>Effingham</city>
<state>Illinois</state>
<zip>62401</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Illinois CancerCare-Eureka</name>
<address>
<city>Eureka</city>
<state>Illinois</state>
<zip>61530</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>NorthShore University HealthSystem-Evanston Hospital</name>
<address>
<city>Evanston</city>
<state>Illinois</state>
<zip>60201</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Illinois CancerCare-Galesburg</name>
<address>
<city>Galesburg</city>
<state>Illinois</state>
<zip>61401</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>NorthShore University HealthSystem-Glenbrook Hospital</name>
<address>
<city>Glenview</city>
<state>Illinois</state>
<zip>60026</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>NorthShore University HealthSystem-Highland Park Hospital</name>
<address>
<city>Highland Park</city>
<state>Illinois</state>
<zip>60035</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Illinois CancerCare-Kewanee Clinic</name>
<address>
<city>Kewanee</city>
<state>Illinois</state>
<zip>61443</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Illinois CancerCare-Macomb</name>
<address>
<city>Macomb</city>
<state>Illinois</state>
<zip>61455</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Loyola University Medical Center</name>
<address>
<city>Maywood</city>
<state>Illinois</state>
<zip>60153</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Cancer Care Center of O'Fallon</name>
<address>
<city>O'Fallon</city>
<state>Illinois</state>
<zip>62269</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Illinois CancerCare-Ottawa Clinic</name>
<address>
<city>Ottawa</city>
<state>Illinois</state>
<zip>61350</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Illinois CancerCare-Pekin</name>
<address>
<city>Pekin</city>
<state>Illinois</state>
<zip>61554</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Illinois CancerCare-Peoria</name>
<address>
<city>Peoria</city>
<state>Illinois</state>
<zip>61615</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Illinois CancerCare-Peru</name>
<address>
<city>Peru</city>
<state>Illinois</state>
<zip>61354</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Illinois CancerCare-Princeton</name>
<address>
<city>Princeton</city>
<state>Illinois</state>
<zip>61356</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Genesis Cancer Center - Silvis</name>
<address>
<city>Silvis</city>
<state>Illinois</state>
<zip>61282</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Parkview Regional Medical Center</name>
<address>
<city>Fort Wayne</city>
<state>Indiana</state>
<zip>46845</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Goshen Center for Cancer Care</name>
<address>
<city>Goshen</city>
<state>Indiana</state>
<zip>46526</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Franciscan Health Indianapolis</name>
<address>
<city>Indianapolis</city>
<state>Indiana</state>
<zip>46237</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Franciscan Health Mooresville</name>
<address>
<city>Mooresville</city>
<state>Indiana</state>
<zip>46158</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Memorial Hospital of South Bend</name>
<address>
<city>South Bend</city>
<state>Indiana</state>
<zip>46601</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Mary Greeley Medical Center</name>
<address>
<city>Ames</city>
<state>Iowa</state>
<zip>50010</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>McFarland Clinic PC - Ames</name>
<address>
<city>Ames</city>
<state>Iowa</state>
<zip>50010</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>McFarland Clinic PC-Boone</name>
<address>
<city>Boone</city>
<state>Iowa</state>
<zip>50036</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Medical Oncology and Hematology Associates-West Des Moines</name>
<address>
<city>Clive</city>
<state>Iowa</state>
<zip>50325</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Mercy Cancer Center-West Lakes</name>
<address>
<city>Clive</city>
<state>Iowa</state>
<zip>50325</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Greater Regional Medical Center</name>
<address>
<city>Creston</city>
<state>Iowa</state>
<zip>50801</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Genesis Medical Center - East Campus</name>
<address>
<city>Davenport</city>
<state>Iowa</state>
<zip>52803</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Genesis Cancer Care Institute</name>
<address>
<city>Davenport</city>
<state>Iowa</state>
<zip>52804</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Iowa Cancer Specialists</name>
<address>
<city>Davenport</city>
<state>Iowa</state>
<zip>52807</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Medical Oncology and Hematology Associates-Laurel</name>
<address>
<city>Des Moines</city>
<state>Iowa</state>
<zip>50314</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Mercy Medical Center - Des Moines</name>
<address>
<city>Des Moines</city>
<state>Iowa</state>
<zip>50314</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>McFarland Clinic PC-Trinity Cancer Center</name>
<address>
<city>Fort Dodge</city>
<state>Iowa</state>
<zip>50501</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>McFarland Clinic PC-Jefferson</name>
<address>
<city>Jefferson</city>
<state>Iowa</state>
<zip>50129</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>McFarland Clinic PC-Marshalltown</name>
<address>
<city>Marshalltown</city>
<state>Iowa</state>
<zip>50158</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Mercy Medical Center-West Lakes</name>
<address>
<city>West Des Moines</city>
<state>Iowa</state>
<zip>50266</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>HaysMed University of Kansas Health System</name>
<address>
<city>Hays</city>
<state>Kansas</state>
<zip>67601</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Kansas Cancer Center</name>
<address>
<city>Kansas City</city>
<state>Kansas</state>
<zip>66160</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Olathe Health Cancer Center</name>
<address>
<city>Olathe</city>
<state>Kansas</state>
<zip>66061</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Kansas Cancer Center-Overland Park</name>
<address>
<city>Overland Park</city>
<state>Kansas</state>
<zip>66210</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Salina Regional Health Center</name>
<address>
<city>Salina</city>
<state>Kansas</state>
<zip>67401</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Kansas Health System Saint Francis Campus</name>
<address>
<city>Topeka</city>
<state>Kansas</state>
<zip>66606</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Kansas Hospital-Westwood Cancer Center</name>
<address>
<city>Westwood</city>
<state>Kansas</state>
<zip>66205</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Kentucky/Markey Cancer Center</name>
<address>
<city>Lexington</city>
<state>Kentucky</state>
<zip>40536</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Medical Center of Baton Rouge</name>
<address>
<city>Baton Rouge</city>
<state>Louisiana</state>
<zip>70816</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Ochsner High Grove</name>
<address>
<city>Baton Rouge</city>
<state>Louisiana</state>
<zip>70836</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Ochsner Medical Center Kenner</name>
<address>
<city>Kenner</city>
<state>Louisiana</state>
<zip>70065</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Ochsner Medical Center Jefferson</name>
<address>
<city>New Orleans</city>
<state>Louisiana</state>
<zip>70121</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Harold Alfond Center for Cancer Care</name>
<address>
<city>Augusta</city>
<state>Maine</state>
<zip>04330</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Waldo County General Hospital</name>
<address>
<city>Belfast</city>
<state>Maine</state>
<zip>04915</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford</name>
<address>
<city>Biddeford</city>
<state>Maine</state>
<zip>04005</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Penobscot Bay Medical Center</name>
<address>
<city>Rockport</city>
<state>Maine</state>
<zip>04856</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford</name>
<address>
<city>Sanford</city>
<state>Maine</state>
<zip>04073</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Maine Medical Partners - South Portland</name>
<address>
<city>South Portland</city>
<state>Maine</state>
<zip>04106</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Western Maryland Regional Medical Center</name>
<address>
<city>Cumberland</city>
<state>Maryland</state>
<zip>21502</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UMass Memorial Medical Center - University Campus</name>
<address>
<city>Worcester</city>
<state>Massachusetts</state>
<zip>01655</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Saint Joseph Mercy Hospital</name>
<address>
<city>Ann Arbor</city>
<state>Michigan</state>
<zip>48106</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Bronson Battle Creek</name>
<address>
<city>Battle Creek</city>
<state>Michigan</state>
<zip>49017</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>IHA Hematology Oncology Consultants-Brighton</name>
<address>
<city>Brighton</city>
<state>Michigan</state>
<zip>48114</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Saint Joseph Mercy Brighton</name>
<address>
<city>Brighton</city>
<state>Michigan</state>
<zip>48114</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>IHA Hematology Oncology Consultants-Canton</name>
<address>
<city>Canton</city>
<state>Michigan</state>
<zip>48188</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Saint Joseph Mercy Canton</name>
<address>
<city>Canton</city>
<state>Michigan</state>
<zip>48188</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>IHA Hematology Oncology Consultants-Chelsea</name>
<address>
<city>Chelsea</city>
<state>Michigan</state>
<zip>48118</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Saint Joseph Mercy Chelsea</name>
<address>
<city>Chelsea</city>
<state>Michigan</state>
<zip>48118</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Henry Ford Macomb Hospital-Clinton Township</name>
<address>
<city>Clinton Township</city>
<state>Michigan</state>
<zip>48038</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Henry Ford Hospital</name>
<address>
<city>Detroit</city>
<state>Michigan</state>
<zip>48202</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Genesee Cancer and Blood Disease Treatment Center</name>
<address>
<city>Flint</city>
<state>Michigan</state>
<zip>48503</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Genesee Hematology Oncology PC</name>
<address>
<city>Flint</city>
<state>Michigan</state>
<zip>48503</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Genesys Hurley Cancer Institute</name>
<address>
<city>Flint</city>
<state>Michigan</state>
<zip>48503</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Spectrum Health at Butterworth Campus</name>
<address>
<city>Grand Rapids</city>
<state>Michigan</state>
<zip>49503</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Allegiance Health</name>
<address>
<city>Jackson</city>
<state>Michigan</state>
<zip>49201</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>West Michigan Cancer Center</name>
<address>
<city>Kalamazoo</city>
<state>Michigan</state>
<zip>49007</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Sparrow Hospital</name>
<address>
<city>Lansing</city>
<state>Michigan</state>
<zip>48912</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Hope Cancer Clinic</name>
<address>
<city>Livonia</city>
<state>Michigan</state>
<zip>48154</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Saint Mary Mercy Hospital</name>
<address>
<city>Livonia</city>
<state>Michigan</state>
<zip>48154</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Spectrum Health Reed City Hospital</name>
<address>
<city>Reed City</city>
<state>Michigan</state>
<zip>49677</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Ascension Saint Mary's Hospital</name>
<address>
<city>Saginaw</city>
<state>Michigan</state>
<zip>48601</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Oncology Hematology Associates of Saginaw Valley PC</name>
<address>
<city>Saginaw</city>
<state>Michigan</state>
<zip>48604</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Marie Yeager Cancer Center</name>
<address>
<city>Saint Joseph</city>
<state>Michigan</state>
<zip>49085</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Ascension Saint Joseph Hospital</name>
<address>
<city>Tawas City</city>
<state>Michigan</state>
<zip>48764</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Munson Medical Center</name>
<address>
<city>Traverse City</city>
<state>Michigan</state>
<zip>49684</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Metro Health Hospital</name>
<address>
<city>Wyoming</city>
<state>Michigan</state>
<zip>49519</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>IHA Hematology Oncology Consultants-Ann Arbor</name>
<address>
<city>Ypsilanti</city>
<state>Michigan</state>
<zip>48197</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Sanford Joe Lueken Cancer Center</name>
<address>
<city>Bemidji</city>
<state>Minnesota</state>
<zip>56601</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Essentia Health - Deer River Clinic</name>
<address>
<city>Deer River</city>
<state>Minnesota</state>
<zip>56636</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Essentia Health Cancer Center</name>
<address>
<city>Duluth</city>
<state>Minnesota</state>
<zip>55805</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Essentia Health Hibbing Clinic</name>
<address>
<city>Hibbing</city>
<state>Minnesota</state>
<zip>55746</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Minneapolis VA Medical Center</name>
<address>
<city>Minneapolis</city>
<state>Minnesota</state>
<zip>55417</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>United Hospital</name>
<address>
<city>Saint Paul</city>
<state>Minnesota</state>
<zip>55102</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Essentia Health Sandstone</name>
<address>
<city>Sandstone</city>
<state>Minnesota</state>
<zip>55072</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Essentia Health Virginia Clinic</name>
<address>
<city>Virginia</city>
<state>Minnesota</state>
<zip>55792</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Mississippi Medical Center</name>
<address>
<city>Jackson</city>
<state>Mississippi</state>
<zip>39216</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Saint Francis Medical Center</name>
<address>
<city>Cape Girardeau</city>
<state>Missouri</state>
<zip>63703</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Siteman Cancer Center at West County Hospital</name>
<address>
<city>Creve Coeur</city>
<state>Missouri</state>
<zip>63141</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Parkland Health Center - Farmington</name>
<address>
<city>Farmington</city>
<state>Missouri</state>
<zip>63640</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Truman Medical Centers</name>
<address>
<city>Kansas City</city>
<state>Missouri</state>
<zip>64108</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Kansas Cancer Center - North</name>
<address>
<city>Kansas City</city>
<state>Missouri</state>
<zip>64154</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Kansas Cancer Center - Lee's Summit</name>
<address>
<city>Lee's Summit</city>
<state>Missouri</state>
<zip>64064</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Kansas Cancer Center at North Kansas City Hospital</name>
<address>
<city>North Kansas City</city>
<state>Missouri</state>
<zip>64116</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Washington University School of Medicine</name>
<address>
<city>Saint Louis</city>
<state>Missouri</state>
<zip>63110</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Mercy Hospital South</name>
<address>
<city>Saint Louis</city>
<state>Missouri</state>
<zip>63128</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Siteman Cancer Center-South County</name>
<address>
<city>Saint Louis</city>
<state>Missouri</state>
<zip>63129</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Missouri Baptist Medical Center</name>
<address>
<city>Saint Louis</city>
<state>Missouri</state>
<zip>63131</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Mercy Hospital Saint Louis</name>
<address>
<city>Saint Louis</city>
<state>Missouri</state>
<zip>63141</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Siteman Cancer Center at Saint Peters Hospital</name>
<address>
<city>Saint Peters</city>
<state>Missouri</state>
<zip>63376</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Sainte Genevieve County Memorial Hospital</name>
<address>
<city>Sainte Genevieve</city>
<state>Missouri</state>
<zip>63670</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Mercy Hospital Springfield</name>
<address>
<city>Springfield</city>
<state>Missouri</state>
<zip>65804</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Missouri Baptist Sullivan Hospital</name>
<address>
<city>Sullivan</city>
<state>Missouri</state>
<zip>63080</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Missouri Baptist Outpatient Center-Sunset Hills</name>
<address>
<city>Sunset Hills</city>
<state>Missouri</state>
<zip>63127</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Community Hospital of Anaconda</name>
<address>
<city>Anaconda</city>
<state>Montana</state>
<zip>59711</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Bozeman Deaconess Hospital</name>
<address>
<city>Bozeman</city>
<state>Montana</state>
<zip>59715</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Benefis Healthcare- Sletten Cancer Institute</name>
<address>
<city>Great Falls</city>
<state>Montana</state>
<zip>59405</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>OptumCare Cancer Care at Oakey</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89102</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>OptumCare Cancer Care at Fort Apache</name>
<address>
<city>Las Vegas</city>
<state>Nevada</state>
<zip>89148</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Renown Regional Medical Center</name>
<address>
<city>Reno</city>
<state>Nevada</state>
<zip>89502</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>New Hampshire Oncology Hematology PA-Concord</name>
<address>
<city>Concord</city>
<state>New Hampshire</state>
<zip>03301</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Solinsky Center for Cancer Care</name>
<address>
<city>Manchester</city>
<state>New Hampshire</state>
<zip>03103</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Virtua Samson Cancer Center</name>
<address>
<city>Moorestown</city>
<state>New Jersey</state>
<zip>08057</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Virtua Voorhees</name>
<address>
<city>Voorhees</city>
<state>New Jersey</state>
<zip>08043</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of New Mexico Cancer Center</name>
<address>
<city>Albuquerque</city>
<state>New Mexico</state>
<zip>87102</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>New Mexico Oncology Hematology Consultants</name>
<address>
<city>Albuquerque</city>
<state>New Mexico</state>
<zip>87109</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Presbyterian Kaseman Hospital</name>
<address>
<city>Albuquerque</city>
<state>New Mexico</state>
<zip>87110</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Presbyterian Rust Medical Center/Jorgensen Cancer Center</name>
<address>
<city>Rio Rancho</city>
<state>New Mexico</state>
<zip>87124</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>James J Peters VA Medical Center</name>
<address>
<city>Bronx</city>
<state>New York</state>
<zip>10468</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Mary Imogene Bassett Hospital</name>
<address>
<city>Cooperstown</city>
<state>New York</state>
<zip>13326</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Arnot Ogden Medical Center/Falck Cancer Center</name>
<address>
<city>Elmira</city>
<state>New York</state>
<zip>14905</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Rochester</name>
<address>
<city>Rochester</city>
<state>New York</state>
<zip>14642</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Randolph Hospital</name>
<address>
<city>Asheboro</city>
<state>North Carolina</state>
<zip>27203</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Cone Health Cancer Center at Alamance Regional</name>
<address>
<city>Burlington</city>
<state>North Carolina</state>
<zip>27215</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Rex Hematology Oncology Associates-Cary</name>
<address>
<city>Cary</city>
<state>North Carolina</state>
<zip>27518</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Durham VA Medical Center</name>
<address>
<city>Durham</city>
<state>North Carolina</state>
<zip>27705</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Rex Hematology Oncology Associates-Garner</name>
<address>
<city>Garner</city>
<state>North Carolina</state>
<zip>27529</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Cone Health Cancer Center</name>
<address>
<city>Greensboro</city>
<state>North Carolina</state>
<zip>27403</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Margaret R Pardee Memorial Hospital</name>
<address>
<city>Hendersonville</city>
<state>North Carolina</state>
<zip>28791</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Rex Cancer Center</name>
<address>
<city>Raleigh</city>
<state>North Carolina</state>
<zip>27607</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Rex Hematology Oncology Associates-Blue Ridge</name>
<address>
<city>Raleigh</city>
<state>North Carolina</state>
<zip>27607</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Rex Cancer Center of Wakefield</name>
<address>
<city>Raleigh</city>
<state>North Carolina</state>
<zip>27614</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Sanford Bismarck Medical Center</name>
<address>
<city>Bismarck</city>
<state>North Dakota</state>
<zip>58501</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Sanford Broadway Medical Center</name>
<address>
<city>Fargo</city>
<state>North Dakota</state>
<zip>58122</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Sanford Roger Maris Cancer Center</name>
<address>
<city>Fargo</city>
<state>North Dakota</state>
<zip>58122</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UHHS-Chagrin Highlands Medical Center</name>
<address>
<city>Beachwood</city>
<state>Ohio</state>
<zip>44122</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Strecker Cancer Center-Belpre</name>
<address>
<city>Belpre</city>
<state>Ohio</state>
<zip>45714</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Geauga Hospital</name>
<address>
<city>Chardon</city>
<state>Ohio</state>
<zip>44024</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Adena Regional Medical Center</name>
<address>
<city>Chillicothe</city>
<state>Ohio</state>
<zip>45601</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Case Western Reserve University</name>
<address>
<city>Cleveland</city>
<state>Ohio</state>
<zip>44106</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Columbus Oncology and Hematology Associates Inc</name>
<address>
<city>Columbus</city>
<state>Ohio</state>
<zip>43214</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Grant Medical Center</name>
<address>
<city>Columbus</city>
<state>Ohio</state>
<zip>43215</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>The Mark H Zangmeister Center</name>
<address>
<city>Columbus</city>
<state>Ohio</state>
<zip>43219</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Doctors Hospital</name>
<address>
<city>Columbus</city>
<state>Ohio</state>
<zip>43228</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Delaware Health Center-Grady Cancer Center</name>
<address>
<city>Delaware</city>
<state>Ohio</state>
<zip>43015</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Marietta Memorial Hospital</name>
<address>
<city>Marietta</city>
<state>Ohio</state>
<zip>45750</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>OhioHealth Marion General Hospital</name>
<address>
<city>Marion</city>
<state>Ohio</state>
<zip>43302</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UH Seidman Cancer Center at Landerbrook Health Center</name>
<address>
<city>Mayfield Heights</city>
<state>Ohio</state>
<zip>44124</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UH Seidman Cancer Center at Lake Health Mentor Campus</name>
<address>
<city>Mentor</city>
<state>Ohio</state>
<zip>44060</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UH Seidman Cancer Center at Southwest General Hospital</name>
<address>
<city>Middleburg Heights</city>
<state>Ohio</state>
<zip>44130</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Licking Memorial Hospital</name>
<address>
<city>Newark</city>
<state>Ohio</state>
<zip>43055</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University Hospitals Parma Medical Center</name>
<address>
<city>Parma</city>
<state>Ohio</state>
<zip>44129</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Southern Ohio Medical Center</name>
<address>
<city>Portsmouth</city>
<state>Ohio</state>
<zip>45662</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University Hospitals Portage Medical Center</name>
<address>
<city>Ravenna</city>
<state>Ohio</state>
<zip>44266</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UH Seidman Cancer Center at Firelands Regional Medical Center</name>
<address>
<city>Sandusky</city>
<state>Ohio</state>
<zip>44870</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>ProMedica Flower Hospital</name>
<address>
<city>Sylvania</city>
<state>Ohio</state>
<zip>43560</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University Hospitals Sharon Health Center</name>
<address>
<city>Wadsworth</city>
<state>Ohio</state>
<zip>44281</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UH Seidman Cancer Center at Saint John Medical Center</name>
<address>
<city>Westlake</city>
<state>Ohio</state>
<zip>44145</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UHHS-Westlake Medical Center</name>
<address>
<city>Westlake</city>
<state>Ohio</state>
<zip>44145</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Genesis Healthcare System Cancer Care Center</name>
<address>
<city>Zanesville</city>
<state>Ohio</state>
<zip>43701</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Oklahoma Health Sciences Center</name>
<address>
<city>Oklahoma City</city>
<state>Oklahoma</state>
<zip>73104</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Mercy Hospital Oklahoma City</name>
<address>
<city>Oklahoma City</city>
<state>Oklahoma</state>
<zip>73120</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Kaiser Permanente Northwest</name>
<address>
<city>Portland</city>
<state>Oregon</state>
<zip>97227</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Oregon Health and Science University</name>
<address>
<city>Portland</city>
<state>Oregon</state>
<zip>97239</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Salem Hospital</name>
<address>
<city>Salem</city>
<state>Oregon</state>
<zip>97301</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Fox Chase Cancer Center - East Norriton Hospital Outpatient Center</name>
<address>
<city>East Norriton</city>
<state>Pennsylvania</state>
<zip>19401</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Ephrata Cancer Center</name>
<address>
<city>Ephrata</city>
<state>Pennsylvania</state>
<zip>17522</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Adams Cancer Center</name>
<address>
<city>Gettysburg</city>
<state>Pennsylvania</state>
<zip>17325</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Cherry Tree Cancer Center</name>
<address>
<city>Hanover</city>
<state>Pennsylvania</state>
<zip>17331</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UPMC Pinnacle Cancer Center/Community Osteopathic Campus</name>
<address>
<city>Harrisburg</city>
<state>Pennsylvania</state>
<zip>17109</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Sechler Family Cancer Center</name>
<address>
<city>Lebanon</city>
<state>Pennsylvania</state>
<zip>17042</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Thomas Jefferson University Hospital</name>
<address>
<city>Philadelphia</city>
<state>Pennsylvania</state>
<zip>19107</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Fox Chase Cancer Center</name>
<address>
<city>Philadelphia</city>
<state>Pennsylvania</state>
<zip>19111</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Temple University Hospital</name>
<address>
<city>Philadelphia</city>
<state>Pennsylvania</state>
<zip>19140</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Pittsburgh Cancer Institute (UPCI)</name>
<address>
<city>Pittsburgh</city>
<state>Pennsylvania</state>
<zip>15232</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Pottstown Hospital</name>
<address>
<city>Pottstown</city>
<state>Pennsylvania</state>
<zip>19464</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UPMC Susquehanna</name>
<address>
<city>Williamsport</city>
<state>Pennsylvania</state>
<zip>17701</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>WellSpan Health-York Cancer Center</name>
<address>
<city>York</city>
<state>Pennsylvania</state>
<zip>17403</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Medical University of South Carolina</name>
<address>
<city>Charleston</city>
<state>South Carolina</state>
<zip>29425</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Prisma Health Cancer Institute - Easley</name>
<address>
<city>Easley</city>
<state>South Carolina</state>
<zip>29640</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Prisma Health Cancer Institute - Butternut</name>
<address>
<city>Greenville</city>
<state>South Carolina</state>
<zip>29605</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Prisma Health Cancer Institute - Faris</name>
<address>
<city>Greenville</city>
<state>South Carolina</state>
<zip>29605</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Prisma Health Cancer Institute - Eastside</name>
<address>
<city>Greenville</city>
<state>South Carolina</state>
<zip>29615</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Prisma Health Cancer Institute - Greer</name>
<address>
<city>Greer</city>
<state>South Carolina</state>
<zip>29650</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Prisma Health Cancer Institute - Seneca</name>
<address>
<city>Seneca</city>
<state>South Carolina</state>
<zip>29672</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Prisma Health Cancer Institute - Spartanburg</name>
<address>
<city>Spartanburg</city>
<state>South Carolina</state>
<zip>29307</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Sanford Cancer Center Oncology Clinic</name>
<address>
<city>Sioux Falls</city>
<state>South Dakota</state>
<zip>57104</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Sanford USD Medical Center - Sioux Falls</name>
<address>
<city>Sioux Falls</city>
<state>South Dakota</state>
<zip>57117-5134</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>The Don and Sybil Harrington Cancer Center</name>
<address>
<city>Amarillo</city>
<state>Texas</state>
<zip>79106</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Parkland Memorial Hospital</name>
<address>
<city>Dallas</city>
<state>Texas</state>
<zip>75235</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>UT Southwestern/Simmons Cancer Center-Dallas</name>
<address>
<city>Dallas</city>
<state>Texas</state>
<zip>75390</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Bon Secours Memorial Regional Medical Center</name>
<address>
<city>Mechanicsville</city>
<state>Virginia</state>
<zip>23116</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Bon Secours Saint Francis Medical Center</name>
<address>
<city>Midlothian</city>
<state>Virginia</state>
<zip>23114</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Bon Secours Saint Mary's Hospital</name>
<address>
<city>Richmond</city>
<state>Virginia</state>
<zip>23226</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Jefferson Healthcare</name>
<address>
<city>Port Townsend</city>
<state>Washington</state>
<zip>98368</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Edwards Comprehensive Cancer Center</name>
<address>
<city>Huntington</city>
<state>West Virginia</state>
<zip>25701</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Langlade Hospital and Cancer Center</name>
<address>
<city>Antigo</city>
<state>Wisconsin</state>
<zip>54409</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Duluth Clinic Ashland</name>
<address>
<city>Ashland</city>
<state>Wisconsin</state>
<zip>54806</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aurora Cancer Care-Southern Lakes VLCC</name>
<address>
<city>Burlington</city>
<state>Wisconsin</state>
<zip>53105</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aurora Health Care Germantown Health Center</name>
<address>
<city>Germantown</city>
<state>Wisconsin</state>
<zip>53022</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aurora Cancer Care-Grafton</name>
<address>
<city>Grafton</city>
<state>Wisconsin</state>
<zip>53024</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aurora BayCare Medical Center</name>
<address>
<city>Green Bay</city>
<state>Wisconsin</state>
<zip>54311</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aurora Cancer Care-Kenosha South</name>
<address>
<city>Kenosha</city>
<state>Wisconsin</state>
<zip>53142</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Gundersen Lutheran Medical Center</name>
<address>
<city>La Crosse</city>
<state>Wisconsin</state>
<zip>54601</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aurora Bay Area Medical Group-Marinette</name>
<address>
<city>Marinette</city>
<state>Wisconsin</state>
<zip>54143</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aspirus Medford Hospital</name>
<address>
<city>Medford</city>
<state>Wisconsin</state>
<zip>54451</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Froedtert Menomonee Falls Hospital</name>
<address>
<city>Menomonee Falls</city>
<state>Wisconsin</state>
<zip>53051</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aurora Cancer Care-Milwaukee</name>
<address>
<city>Milwaukee</city>
<state>Wisconsin</state>
<zip>53209</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aurora Saint Luke's Medical Center</name>
<address>
<city>Milwaukee</city>
<state>Wisconsin</state>
<zip>53215</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Medical College of Wisconsin</name>
<address>
<city>Milwaukee</city>
<state>Wisconsin</state>
<zip>53226</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aurora Sinai Medical Center</name>
<address>
<city>Milwaukee</city>
<state>Wisconsin</state>
<zip>53233</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Vince Lombardi Cancer Clinic - Oshkosh</name>
<address>
<city>Oshkosh</city>
<state>Wisconsin</state>
<zip>54904</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aurora Cancer Care-Racine</name>
<address>
<city>Racine</city>
<state>Wisconsin</state>
<zip>53406</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Vince Lombardi Cancer Clinic-Sheboygan</name>
<address>
<city>Sheboygan</city>
<state>Wisconsin</state>
<zip>53081</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aurora Medical Center in Summit</name>
<address>
<city>Summit</city>
<state>Wisconsin</state>
<zip>53066</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Vince Lombardi Cancer Clinic-Two Rivers</name>
<address>
<city>Two Rivers</city>
<state>Wisconsin</state>
<zip>54241</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aspirus Regional Cancer Center</name>
<address>
<city>Wausau</city>
<state>Wisconsin</state>
<zip>54401</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aurora Cancer Care-Milwaukee West</name>
<address>
<city>Wauwatosa</city>
<state>Wisconsin</state>
<zip>53226</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aurora West Allis Medical Center</name>
<address>
<city>West Allis</city>
<state>Wisconsin</state>
<zip>53227</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Froedtert West Bend Hospital/Kraemer Cancer Center</name>
<address>
<city>West Bend</city>
<state>Wisconsin</state>
<zip>53095</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Marshfield Clinic - Weston Center</name>
<address>
<city>Weston</city>
<state>Wisconsin</state>
<zip>54476</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Aspirus UW Cancer Center</name>
<address>
<city>Wisconsin Rapids</city>
<state>Wisconsin</state>
<zip>54494</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>May 2023</verification_date>
<study_first_submitted>January 8, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>May 2, 2023</last_update_submitted>
<last_update_submitted_qc>May 2, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">May 3, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Lung Neoplasms</mesh_term>
<mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This phase II LUNG-MAP treatment trial studies how well selpercatinib works in treating
patients with RET fusion-positive non-small cell lung cancer that is stage IV or has come
back (recurrent). Selpercatinib may stop the growth of tumor cells by blocking some of the
enzymes needed for cell growth.
PRIMARY OBJECTIVE:
I. To evaluate the objective response rate (ORR) (confirmed complete or partial response) by
blinded independent centralized review (BICR) associated with selpercatinib (LOXO-292) in
patients with previously-treated stage IV or recurrent RET fusion-positive non-small cell
lung cancer (NSCLC).
SECONDARY OBJECTIVES:
I. To evaluate the duration of BICR-assessed response among BICR responders. II. To evaluate
the frequency and severity of toxicities. III. To evaluate the investigator-assessed
objective response rate (confirmed complete or partial response).
IV. To evaluate duration of investigator-assessed response among patients with a response as
determined by the local investigator.
V. To evaluate investigator-assessed progression-free survival (IA-PFS). VI. To evaluate
BICR-assessed PFS. VII. To evaluate overall survival (OS).
VIII. Among patients with brain metastases at baseline:
VIIIa. To evaluate the central nervous system (CNS) response rate (confirmed complete
response [CR]).
VIIIb. To evaluate the duration of intracranial response among patients with a CNS response.
TRANSLATIONAL MEDICINE OBJECTIVES:
I. To collect, process, and bank cell-free deoxyribonucleic acid (cfDNA) at baseline,
progression, and end of treatment for future development of a proposal to evaluate
comprehensive next-generation sequencing of circulating tumor deoxyribonucleic acid (ctDNA).
II. To establish a tissue/blood repository from patients with refractory non-small cell lung
cancer (NSCLC).
OUTLINE:
Patients receive selpercatinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat
every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 2 years and
then at the end of 3 years from date of sub-study registration.
Inclusion Criteria:
- Patients must have been assigned to S1900B based on biomarker analysis of tissue
and/or blood and determined to have RET fusion-positive NSCLC as defined here:
- Patients must have RET fusion-positive NSCLC as determined by the Foundation
Medicine (FMI) tissue-assay, other tumor-based assays such as next-generation
sequencing (NGS), polymerase chain reaction (PCR), or follicular in situ
hybridization (FISH), or by cfDNA blood assay. Patients with RET fusions detected
by immunohistochemistry (IHC) alone are not eligible. The testing must be done
within a laboratory with Clinical Laboratory Improvement Act (CLIA),
International Organization for Standardization (ISO/International
Electrotechnical Commission (IEC), College of American Pathologists (CAP), or
similar certification. Presence of RET fusions detected on tests performed
outside of LUNGMAP must have been confirmed by the study biomarker review panel
- For patients whose prior therapy was for stage IV or recurrent disease, the patient
must have received at least one line of a platinum-based chemotherapy regimen. For
patients whose prior systemic therapy was for stage I-III disease only (i.e. patient
has not received any treatment for stage IV or recurrent disease), disease progression
on platinum-based chemotherapy must have occurred within one year from the last date
that the patient received that therapy. Prior anti-PD-1/PD-L1 therapy, alone or in
combination (e.g. nivolumab, pembrolizumab, or durvalumab) is allowed
- Patients must be negative for all additional validated oncogenic drivers that could
cause resistance to LOXO-292 treatment. This includes EGFR sensitizing mutations, EGFR
T790M, ALK gene fusion, ROS1 gene fusion, KRAS activating mutation, BRAF V600E
mutation and MET exon 14 skipping mutation or high-level amplification and expression
- Note: EGFR, ALK, ROS, KRAS, and BRAF testing is performed as part of the LUNGMAP
screening/pre-screening FoundationOne test. If prior data is not available,
results from the FMI testing must be obtained prior to sub-study registration
- Patients must have measurable disease documented by computed tomography (CT) or
magnetic resonance imaging (MRI). The CT from a combined positron emission tomography
(PET)/CT may be used to document only non-measurable disease unless it is of
diagnostic quality. Measurable disease must be assessed within 28 days prior to
sub-study registration. Pleural effusions, ascites and laboratory parameters are not
acceptable as the only evidence of disease. Non-measurable disease must be assessed
within 42 days prior to sub-study registration. All disease must be assessed and
documented on the Baseline Tumor Assessment Form. Patients whose only measurable
disease is within a previous radiation therapy port must demonstrate clearly
progressive disease (in the opinion of the treating investigator) prior to
registration. CT and MRI scans must be submitted for central review via transfer of
images and data (TRIAD)
- Patients must have a CT or MRI scan of the brain to evaluate for CNS disease within 42
days prior to sub-study registration
- Patients with evidence of chronic hepatitis B virus (HBV) infection must have
undetectable HBV viral load on suppressive therapy within 28 days prior to
registration
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. Patients with HCV infection who are currently on treatment must have an
undetectable HCV viral load within 28 days prior to registration
- Patients with known human immunodeficiency virus (HIV) infection are eligible,
provided they are on effective anti-retroviral therapy and have undetectable viral
load at their most recent viral load test and within 6 months prior to registration
- Patients must be able to swallow capsules
- Patients must have progressed (in the opinion of the treating physician) following the
most recent line of therapy
- Patients must have recovered (=< grade 1) from any side effects of prior therapy.
Patients must not have received any radiation therapy within 14 days prior to
sub-study registration
- Absolute neutrophil count (ANC) >= 1,500/mcl (obtained within 28 days prior to
sub-study registration)
- Platelet count >= 100,000 mcl (obtained within 28 days prior to sub-study
registration)
- Serum bilirubin =< institutional upper limit of normal (IULN) (within 28 days prior to
sub-study registration). For patients with liver metastases, bilirubin must be =< 5 x
IULN
- Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN
(within 28 days prior to sub-study registration) (if both ALT and AST are done, both
must be =< 2 IULN). For patients with liver metastases, bilirubin and either ALT or
AST must be =< 5 x IULN (if both ALT and AST are done, both must be =< 5 x IULN)
- Serum creatinine =< the IULN or calculated creatinine clearance >= 50 mL/min using the
following Cockcroft-Gault formula (within 28 days prior to sub-study registration)
- Patients must have Zubrod performance status 0-1 documented within 28 days prior to
sub-study registration
- Pre-study history and physical exam must be obtained within 28 days prior to sub-study
registration
- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
stage I or II cancer from which the patient is currently in complete remission, or any
other cancer from which the patient has been disease free for five years
- Patients must have electrolytes and blood urea nitrogen (BUN) performed within 14 days
prior to sub-study registration
- Patients must agree to have blood specimens submitted for circulating tumor DNA
(ctDNA)
- Patients must also be offered participation in banking and in the correlative studies
for collection and future use of specimens
- Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines
- As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has been
entered in the system
- Patients with impaired decision-making capacity are eligible as long as their
neurological or psychological condition does not preclude their safe participation in
the study (e.g., tracking pill consumption and reporting adverse events to the
investigator)
Exclusion Criteria:
- Patients must not have received any prior treatment with selective anti-RET inhibitors
(anti-RET multikinase inhibitors are permitted)
- Patient must not have leptomeningeal disease, spinal cord compression or brain
metastases unless: (1) metastases have been locally treated and have remained
clinically controlled and asymptomatic for at least 14 days following treatment, and
prior to registration, AND (2) patient has no residual neurological dysfunction and
has been off corticosteroids for at least 24 hours prior to sub-study registration
- Patients must not have received any prior systemic therapy (systemic chemotherapy,
immunotherapy or investigational drug) within 14 days prior to sub-study registration
- Patients must not be planning to receive any concurrent chemotherapy, immunotherapy,
biologic or hormonal therapy for cancer treatment while receiving treatment on this
study. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for
diabetes and hormone replacement therapy) is acceptable
- Patient must not have had a major surgery within 14 days prior to sub-study
registration. Patient must have fully recovered from the effects of prior surgery in
the opinion of the treating investigator
- Patients must not have any grade III/IV cardiac disease as defined by the New York
Heart Association Criteria (i.e., patients with cardiac disease resulting in marked
limitation of physical activity or resulting in inability to carry on any physical
activity without discomfort), unstable angina pectoris, and myocardial infarction
within 6 months, or serious uncontrolled cardiac arrhythmia
- Patients must not have a QT interval by Fridericia (QTcF) > 470 msec based on the
electrocardiogram (ECG) within 28 days prior to registration. It is suggested that a
local cardiologist review the QTcF intervals
- Patients must not have any clinically significant uncontrolled systemic illness,
including but not limited to uncontrolled infection, requiring intravenous
antibiotics, unstable angina pectoris, myocardial infarction within the past 6 months,
uncontrolled cardiac arrhythmias, uncontrolled hypertension, or uncontrolled diabetes
mellitus
- Uncontrolled diabetes: Patients who have a diagnosis of diabetes must have an
hemoglobin (Hb) A1C < 7% within 28 days prior to registration. The same criterion
will be used in patients with confirmed diagnosis of diabetes mellitus who have
been on a stable dietary or therapeutic regimen for this condition in the last
three months
- Uncontrolled blood pressure and hypertension: All blood pressure measurements
within the 28 days prior to registration must be systolic blood pressure (SBP) =<
180 and diastolic blood pressure (DBP) =< 100. An exception can be made by a
healthcare provider for a patient with a single blood pressure elevation who upon
rechecking has a blood pressure within the parameters above
- Patients must not have any impairment of gastrointestinal function or gastrointestinal
disease that may significantly alter the absorption of LOXO-292 (e.g., ulcerative
disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel
resection, or active peptic ulcer disease)
- Patients must not be planning to receive any strong inhibitors or inducers of CYP3A4
at least 14 days prior to sub-study registration and throughout protocol treatment
- Patients must not be planning to use proton pump inhibitors (PPIs) at least one week
prior to sub-study registration and throughout protocol treatment
- Patients must not be pregnant or nursing. Women study patients of reproductive
potential and fertile men study patients and their partners must abstain or use
effective contraception (including barrier method) while receiving study treatment and
for at least 3 months after the last dose of LOXO-292. Male study patients must agree
not to donate sperm for 6 months after the last dose of LOXO-292. A woman is
considered to be of "reproductive potential" if she has had menses at any time in the
preceding 12 consecutive months. In addition to routine contraceptive methods,
"effective contraception" also includes heterosexual celibacy and surgery intended to
prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a
hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any
point a previously celibate patient chooses to become heterosexually active during the
time period for use of contraceptive measures outlined in the protocol, he/she is
responsible for beginning contraceptive measures
|
NCT0426xxxx/NCT04268563.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268563</url>
</required_header>
<id_info>
<org_study_id>11367</org_study_id>
<nct_id>NCT04268563</nct_id>
</id_info>
<brief_title>Comparing the Effect of Sitagliptin/Metformin and Metformin in PCOS Patients</brief_title>
<official_title>Comparing the Therapeutic Effect of Sitagliptin/Metformin and Metformin on Biochemical Factors and Expression of GDF-9 and BMP-15 Genes in Patients With Classic PCOS Undergoing Intra-cytoplasmic Sperm Injection (ICSI)</official_title>
<sponsors>
<lead_sponsor>
<agency>Shahid Beheshti University of Medical Sciences</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Shahid Beheshti University of Medical Sciences</source>
<oversight_info>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
<is_us_export>No</is_us_export>
</oversight_info>
<brief_summary>
<textblock>
Investigators will evaluate and compare the efficacy of Sitagliptin/Metformin to metformin
and sitagliptin on gdf9 and bmp15 gene expression on PCOS patients undergoing
intracytoplasmic sperm injection(ICSI).
</textblock>
</brief_summary>
<detailed_description>
<textblock>
This study was conducted in Infertility clinic of Mahdiyeh Educational Hospital, Tehran.
Patients in the four groups receive the drug 2 months before the start of the ovulation
cycle, and treatment will continue until the day of the oocyte aspiration. The drug provide
by midwife to patients and both patient and physician blind to the treatment regimen. The
participants randomly divide into four groups.The ovulation induction stimulate with GnRh
antagonist.
</textblock>
</detailed_description>
<overall_status>Unknown status</overall_status>
<last_known_status>Recruiting</last_known_status>
<start_date type="Actual">January 10, 2020</start_date>
<completion_date type="Anticipated">July 30, 2021</completion_date>
<primary_completion_date type="Anticipated">July 19, 2021</primary_completion_date>
<phase>Phase 1/Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>Double (Participant, Care Provider)</masking>
</study_design_info>
<primary_outcome>
<measure>Fasting insulin</measure>
<time_frame>24 hours after last dose</time_frame>
<description>ELIZA hormone assay</description>
</primary_outcome>
<primary_outcome>
<measure>Growth differentiation factor-9(GDF-9) expression</measure>
<time_frame>24 hours after last dose</time_frame>
<description>Realtime PCR</description>
</primary_outcome>
<primary_outcome>
<measure>Bone morphogenetic protein-15(BMP-15) expression</measure>
<time_frame>24 hours after last dose</time_frame>
<description>Realtime PCR</description>
</primary_outcome>
<primary_outcome>
<measure>Total Testosterone</measure>
<time_frame>24 hours after last dose</time_frame>
<description>ELIZA hormone assay</description>
</primary_outcome>
<primary_outcome>
<measure>Follicle-stimulating hormone(FSH)</measure>
<time_frame>24 hours after last dose</time_frame>
<description>ELIZA hormone assay</description>
</primary_outcome>
<number_of_arms>4</number_of_arms>
<enrollment type="Anticipated">80</enrollment>
<condition>Polycystic Ovary Syndrome</condition>
<condition>Infertility</condition>
<condition>ART</condition>
<arm_group>
<arm_group_label>Placebo</arm_group_label>
<arm_group_type>Placebo Comparator</arm_group_type>
<description>Control group: oral rehydration salts (ORS, Poursina, Tehran, Iran), two times daily</description>
</arm_group>
<arm_group>
<arm_group_label>Metformin</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Intervention group 1: received Metformin (Glucophage, Merck, West Drayton, UK; 500 mg ,two times daily</description>
</arm_group>
<arm_group>
<arm_group_label>Sitagliptin</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Intervention group2: received Sitagliptin (Januvia, Merck,West Drayton, UK. 50 mg, two times daily</description>
</arm_group>
<arm_group>
<arm_group_label>sitagliptin/metformin</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Intervention group3: received Sitagliptin/metformin (Janumet, Merck,West Drayton, UK. 50/500 mg), two times daily</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>placebo</intervention_name>
<description>Oral rehydration solution</description>
<arm_group_label>Placebo</arm_group_label>
<other_name>rehydration solution</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>metformin</intervention_name>
<description>metformin tablet</description>
<arm_group_label>Metformin</arm_group_label>
<other_name>Glucophage</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Sitagliptin</intervention_name>
<description>Sitagliptin tablet</description>
<arm_group_label>Sitagliptin</arm_group_label>
<other_name>JANUVIA</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Sitagliptin/metformin</intervention_name>
<description>Sitagliptin/metformin tablet</description>
<arm_group_label>sitagliptin/metformin</arm_group_label>
<other_name>JANUMET</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- subject has clinical or biochemical hyperandrogenic symptoms

- subject has oligo/amenorrhea cycles

Exclusion Criteria:

- Hypersensitivity to metformin

- Hypersensitivity to sitagliptin presence of infertility factors other than
anovulation,

- male infertility

- pelvic organic pathologies

- congenital adrenal hyperplasia

- thyroid dysfunction

- Cushing's syndrome

- hyper prolactinemia

- androgen secreting neoplasia

- diabetes mellitus

- consumption of medications affecting carbohydrate metabolism

- consumption hormonal analogues other than progesterone 2 months prior to enrolment in
the study

- severe hepatic

- pancreatitis

- kidney diseases

- gallbladder diseases
</textblock>
</criteria>
<gender>Female</gender>
<gender_based>Yes</gender_based>
<gender_description>Study is based women with polycystic ovary syndrome.</gender_description>
<minimum_age>25 Years</minimum_age>
<maximum_age>35 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Shahrzad Shahrzad Zadehmodarres, Professor</last_name>
<role>Study Director</role>
<affiliation>Shahid Beheshti University of Medical Sciences</affiliation>
</overall_official>
<overall_contact>
<last_name>Delbar Daneshjou, PHD student</last_name>
<phone>989120823342</phone>
<email>db.daneshjou@gmail.com</email>
</overall_contact>
<location>
<facility>
<name>Mahdiyeh educational hospital</name>
<address>
<city>Tehran</city>
<zip>1989930002</zip>
<country>Iran, Islamic Republic of</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Delbar Daneshjou, PHD student</last_name>
<phone>989120823342</phone>
<email>db.daneshjou@gmail.com</email>
</contact>
</location>
<location_countries>
<country>Iran, Islamic Republic of</country>
</location_countries>
<verification_date>March 2021</verification_date>
<study_first_submitted>January 28, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>March 19, 2021</last_update_submitted>
<last_update_submitted_qc>March 19, 2021</last_update_submitted_qc>
<last_update_posted type="Actual">March 22, 2021</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Shahid Beheshti University of Medical Sciences</investigator_affiliation>
<investigator_full_name>Delbar Daneshjou</investigator_full_name>
<investigator_title>Principal Investigator</investigator_title>
</responsible_party>
<keyword>metformin</keyword>
<keyword>sitagliptin</keyword>
<keyword>Polycystic Ovary Syndrome</keyword>
<keyword>Intracytoplastic sperm injection</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Polycystic Ovary Syndrome</mesh_term>
<mesh_term>Infertility</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Metformin</mesh_term>
<mesh_term>Sitagliptin Phosphate</mesh_term>
</intervention_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Investigators will evaluate and compare the efficacy of Sitagliptin/Metformin to metformin
and sitagliptin on gdf9 and bmp15 gene expression on PCOS patients undergoing
intracytoplasmic sperm injection(ICSI).
This study was conducted in Infertility clinic of Mahdiyeh Educational Hospital, Tehran.
Patients in the four groups receive the drug 2 months before the start of the ovulation
cycle, and treatment will continue until the day of the oocyte aspiration. The drug provide
by midwife to patients and both patient and physician blind to the treatment regimen. The
participants randomly divide into four groups.The ovulation induction stimulate with GnRh
antagonist.
Inclusion Criteria:
- subject has clinical or biochemical hyperandrogenic symptoms
- subject has oligo/amenorrhea cycles
Exclusion Criteria:
- Hypersensitivity to metformin
- Hypersensitivity to sitagliptin presence of infertility factors other than
anovulation,
- male infertility
- pelvic organic pathologies
- congenital adrenal hyperplasia
- thyroid dysfunction
- Cushing's syndrome
- hyper prolactinemia
- androgen secreting neoplasia
- diabetes mellitus
- consumption of medications affecting carbohydrate metabolism
- consumption hormonal analogues other than progesterone 2 months prior to enrolment in
the study
- severe hepatic
- pancreatitis
- kidney diseases
- gallbladder diseases
|
NCT0426xxxx/NCT04268576.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268576</url>
</required_header>
<id_info>
<org_study_id>2018-08-CHRMT</org_study_id>
<nct_id>NCT04268576</nct_id>
</id_info>
<brief_title>Impact of an Improved Rehabilitation Program After a Scheduled Hysterectomy.</brief_title>
<acronym>RAACHYS</acronym>
<official_title>Impact of an Improved Rehabilitation Program After a Scheduled Hysterectomy.</official_title>
<sponsors>
<lead_sponsor>
<agency>Centre Hospitalier Régional Metz-Thionville</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Centre Hospitalier Régional Metz-Thionville</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
It is an observational study, prospective in order to assess the impact of the implementation
of an early rehabilitation program on post-operative recovery. this is measured by the qOR15
questionnaire in patients operated on for a programmed hysterectomy, it takes place in the
gynecology department of the CHR Metz-Thionville hospital.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
This program implemented will comply with HAS recommendations. The only change in management
for patients participating in the study is the completion of the self-questionnaire QOR-15 on
D-1 (the day before surgery), D0 (the day of the surgery) and D1 (the day after the surgery).

It is planned to include 74 patients before the implementation of the early rehabilitation
protocol and 74 patients after the implementation of the early rehabilitation protocol. The
total duration of inclusion is established at 18 months.

The measures applied should improve the patient's well-being and accelerate his return to
normal life and therefore reduce the length of his stay.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">November 18, 2019</start_date>
<completion_date type="Actual">April 15, 2023</completion_date>
<primary_completion_date type="Actual">April 15, 2023</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Case-Control</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Evaluation of the QoR-15 score D1</measure>
<time_frame>day 1</time_frame>
<description>The QoR score 15 is a self-questionnaire of 15 items, each scored from 0 to 10. These items assess 5 dimensions of post-operative recovery: pain, physical comfort, functional autonomy, emotions and psychological support. These 15 items represent the quality of post-operative rehabilitation in its physical and mental dimensions.
A variation of 8 points is considered significant.</description>
</primary_outcome>
<secondary_outcome>
<measure>Overall duration of the hospital stay D-1</measure>
<time_frame>One day before surgery</time_frame>
<description>Overall duration of the hospital stay in days</description>
</secondary_outcome>
<secondary_outcome>
<measure>Overall duration of the hospital stay day of discharge from hospital</measure>
<time_frame>Up to 30 days</time_frame>
<description>Overall duration of the hospital stay in days</description>
</secondary_outcome>
<secondary_outcome>
<measure>Duration of fasting pre and post-operative</measure>
<time_frame>Up to 30 days</time_frame>
<description>Duration of fasting pre and post-operative in hours</description>
</secondary_outcome>
<secondary_outcome>
<measure>Post-operative nausea / vomiting Day 0</measure>
<time_frame>Day of surgery</time_frame>
<description>Occurrence of nausea / vomiting postoperative (yes / no)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Post-operative nausea / vomiting D+1</measure>
<time_frame>One day after surgery</time_frame>
<description>Occurrence of nausea / vomiting postoperative (yes / no)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Post-operative nausea / vomiting day of hospital discharge</measure>
<time_frame>Up to 30 days</time_frame>
<description>Occurrence of nausea / vomiting postoperative (yes / no)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Intraoperative maximum Visual Analog Scale (VAS) on day 0</measure>
<time_frame>day 0</time_frame>
<description>Maximum Visual Analog Scale (VAS) (from 0 to 100mm), 0 mm (minimum, none) 100 mm (maximum, worst pain possible)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Intraoperative maximum visual analog scale (VAS) on day 1</measure>
<time_frame>One day after surgery</time_frame>
<description>Maximum Visual Analog Scale (VAS) (from 0 to 100mm), 0 mm (minimum, none) 100 mm (maximum, worst pain possible)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Intraoperative maximum visual analog scale (VAS) on day of discharge from hospital</measure>
<time_frame>Up to 30 days</time_frame>
<description>Maximum Visual Analog Scale (VAS) (from 0 to 100mm), 0 mm (minimum, none) 100 mm (maximum, worst pain possible)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Time to return gastrointestinal function</measure>
<time_frame>Up to 30 days</time_frame>
<description>Transit recovery time in hours</description>
</secondary_outcome>
<secondary_outcome>
<measure>Enhancement of gastrointestinal motility on Day 0</measure>
<time_frame>day 0</time_frame>
<description>Whether or not chewing gum is taken (yes/no)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Enhancement of gastrointestinal motility on day 1</measure>
<time_frame>One day after surgery</time_frame>
<description>whether or not chewing gum is taken (yes/no)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Enhancement of gastrointestinal motility on the day of discharge from the hospital</measure>
<time_frame>Up to 30 days</time_frame>
<description>whether or not chewing gum is taken (yes/no)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Presence of a urinary catheter or drain in postoperative</measure>
<time_frame>day 0</time_frame>
<description>Presence of a urinary catheter or drain in postoperative (yes / no)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Time before first standing</measure>
<time_frame>Up to 30 days</time_frame>
<description>Time before first standing in hours</description>
</secondary_outcome>
<secondary_outcome>
<measure>occurrence of postoperative complications</measure>
<time_frame>day 30</time_frame>
<description>occurrence of postoperative complications (resumption of surgery at 30 days)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Evaluation of the QoR-15 score D0</measure>
<time_frame>Day 0</time_frame>
<description>The QoR score 15 is a self-questionnaire of 15 items, each scored from 0 to 10. These items assess 5 dimensions of post-operative recovery: pain, physical comfort, functional autonomy, emotions and psychological support. These 15 items represent the quality of post-operative rehabilitation in its physical and mental dimensions.
A variation of 8 points is considered significant.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Evaluation of the QoR-15 score D-1</measure>
<time_frame>Day -1</time_frame>
<description>The QoR score 15 is a self-questionnaire of 15 items, each scored from 0 to 10. These items assess 5 dimensions of post-operative recovery: pain, physical comfort, functional autonomy, emotions and psychological support. These 15 items represent the quality of post-operative rehabilitation in its physical and mental dimensions.
A variation of 8 points is considered significant.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Rate of laparotomy</measure>
<time_frame>day 0</time_frame>
<description>percentage</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mobility on day 0</measure>
<time_frame>day 0</time_frame>
<description>The time between the end of surgery and the first time to get up in hours,</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mobility on day 1</measure>
<time_frame>One day after surgery</time_frame>
<description>The time between the end of surgery and the first time to get up in hours</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mobility on the day of discharge from the hospital</measure>
<time_frame>Up to 30 days</time_frame>
<description>The time between the end of surgery and the first time to get up in hours</description>
</secondary_outcome>
<enrollment type="Actual">220</enrollment>
<condition>Post-Op Complication</condition>
<eligibility>
<study_pop>
<textblock>
Patients will be selected according to the inclusion and exclusion criteria when they go to
the operating room. It is planned to include 74 patients for rehabilitation before the
implementation of the protocol and 74 patients after the implementation of the protocol.
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- Indication of a scheduled hysterectomy

- Presence of a utero-ovarian affection, deemed resectable and requiring a regulated
hysterectomy (outside the context of the emergency) associated or not with pelvic or
lumbar-aortic dissection.

- classified ASA 1 to 3

- informed about the principles of improved rehabilitation by the surgeon and the
anesthesiologist + written document (accessible on the site www.grace-asso.fr).

- able to return home after discharge from the hospital, having a telephone and being
able to contact their doctor or the service if necessary or transferred to a
convalescent home at their request.

Exclusion Criteria:

- Patients included in another study

- Refusal to use data by the patient

- Inability to respond to self-questionnaires due to cognitive impairment, difficulties
in reading or understanding the French language

- Patients included in another study

- Patients with severe or unbalanced associated conditions
</textblock>
</criteria>
<gender>Female</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Antoine BECRET, MD</last_name>
<role>Principal Investigator</role>
<affiliation>CHR Metz-Thionville</affiliation>
</overall_official>
<location>
<facility>
<name>CHR Metz-Thionville</name>
<address>
<city>Metz</city>
<zip>57085</zip>
<country>France</country>
</address>
</facility>
</location>
<location_countries>
<country>France</country>
</location_countries>
<verification_date>May 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>May 4, 2023</last_update_submitted>
<last_update_submitted_qc>May 4, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">May 6, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>hysterectomy</keyword>
<keyword>post operative</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Postoperative Complications</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
It is an observational study, prospective in order to assess the impact of the implementation
of an early rehabilitation program on post-operative recovery. this is measured by the qOR15
questionnaire in patients operated on for a programmed hysterectomy, it takes place in the
gynecology department of the CHR Metz-Thionville hospital.
This program implemented will comply with HAS recommendations. The only change in management
for patients participating in the study is the completion of the self-questionnaire QOR-15 on
D-1 (the day before surgery), D0 (the day of the surgery) and D1 (the day after the surgery).
It is planned to include 74 patients before the implementation of the early rehabilitation
protocol and 74 patients after the implementation of the early rehabilitation protocol. The
total duration of inclusion is established at 18 months.
The measures applied should improve the patient's well-being and accelerate his return to
normal life and therefore reduce the length of his stay.
Patients will be selected according to the inclusion and exclusion criteria when they go to
the operating room. It is planned to include 74 patients for rehabilitation before the
implementation of the protocol and 74 patients after the implementation of the protocol.
Inclusion Criteria:
- Indication of a scheduled hysterectomy
- Presence of a utero-ovarian affection, deemed resectable and requiring a regulated
hysterectomy (outside the context of the emergency) associated or not with pelvic or
lumbar-aortic dissection.
- classified ASA 1 to 3
- informed about the principles of improved rehabilitation by the surgeon and the
anesthesiologist + written document (accessible on the site www.grace-asso.fr).
- able to return home after discharge from the hospital, having a telephone and being
able to contact their doctor or the service if necessary or transferred to a
convalescent home at their request.
Exclusion Criteria:
- Patients included in another study
- Refusal to use data by the patient
- Inability to respond to self-questionnaires due to cognitive impairment, difficulties
in reading or understanding the French language
- Patients included in another study
- Patients with severe or unbalanced associated conditions
|
NCT0426xxxx/NCT04268589.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268589</url>
</required_header>
<id_info>
<org_study_id>OGUU</org_study_id>
<nct_id>NCT04268589</nct_id>
</id_info>
<brief_title>Virtual Reality Effect in Geriatric Individuals</brief_title>
<official_title>Effect of Virtual Reality Application on Pain, Functional Independence and Depression in Geriatric Individuals</official_title>
<sponsors>
<lead_sponsor>
<agency>Selcuk University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Selcuk University</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This study aimed to determine the effect of a virtual reality experience on pain, depression
and functional adequacy in geriatric individuals living in a nursing home.

A virtual reality video with dance moves has been applied to the experimental group
participants. Each video takes 3 minutes, and the elderly person has been put into practice
at least 30 minutes after having breakfast in 3-minute periods and at least 30 minutes after
dinner. In the morning and evening, 15 minutes, 2 times a day, a total of 9 days were applied
for 3 weeks. The application lasted a total of 3 weeks. Scales were applied 1 week after the
virtual reality application was completed and 1 month after the experimental group. The
scales were filled in the control group at the same time.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
It is recommended that the future studies be conducted with larger samples on pain,
depression, life quality and functionality.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">May 1, 2019</start_date>
<completion_date type="Actual">June 30, 2019</completion_date>
<primary_completion_date type="Actual">June 30, 2019</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Non-Randomized</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<primary_purpose>Supportive Care</primary_purpose>
<masking>Single (Care Provider)</masking>
</study_design_info>
<primary_outcome>
<measure>The visual analog scale (VAS)</measure>
<time_frame>nine days</time_frame>
<description>This form includes numbers and is used in the assessment of pain severity. Patients mark their pain severity on a 10 cm ruler which is written no pain on one side and the most severe pain as possible on the other side. It has been stated that VAS is more sensitive and reliable in the measurement of pain severity than one sized scales</description>
</primary_outcome>
<primary_outcome>
<measure>Geriatric Depression Scale</measure>
<time_frame>nine days</time_frame>
<description>The scale was developed by Yesavage with the aim of assessing the depression symptoms of old persons and consists of 15 questions in total. In the assessment, 1 point is given to each "no" answer in the positive questions and to each "yes" answer in the negative questions. A score of 6 and higher in the scale is accepted as meaningful for the diagnosis of depression. Reliability and validity tests were performed in our country and Chronbach alpha internal consistency coefficient was found to be 0.92</description>
</primary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">14</enrollment>
<condition>Pain</condition>
<condition>Depression</condition>
<arm_group>
<arm_group_label>control group</arm_group_label>
<arm_group_type>No Intervention</arm_group_type>
<description>routine study</description>
</arm_group>
<arm_group>
<arm_group_label>virtual reality group</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Three days a week, 2 times a day, 15 minutes in the morning and in the evening for 9 days in total</description>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>virtual reality game</intervention_name>
<description>routine</description>
<arm_group_label>virtual reality group</arm_group_label>
<other_name>routine</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Suffering from musculoskeletal pain in the last 3 years,

- Being energetic (Being independent in the daily life activities),

- Being able to stand up without help before 30 seconds and walk at least six meters
without help,

- Individuals with blood sugar ranging between 90-200 mg/dl prior to the application,

- Individuals with blood pressure ranging between 130-70 mm/Hg prior to the application,

- Not having neurological and psychiatric diseases,

- No history of fall,

- Being literate,

- Not being visually-hearing impaired,

- Being able to communicate verbally.

Exclusion Criteria:

- Pependent patients

- Patients with psychiatric illness

- Patients with joint pain disease diagnosis
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>65 Years</minimum_age>
<maximum_age>75 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Gamze Unver</last_name>
<role>Principal Investigator</role>
<affiliation>Kutahya University of Health Sciences</affiliation>
</overall_official>
<overall_official>
<last_name>Halil Ibrahim Tuna</last_name>
<role>Principal Investigator</role>
<affiliation>Selcuk University</affiliation>
</overall_official>
<overall_official>
<last_name>Guler Balci Alparslan</last_name>
<role>Principal Investigator</role>
<affiliation>Osmangazi University</affiliation>
</overall_official>
<location>
<facility>
<name>Osmangazi University</name>
<address>
<city>Eskişehir</city>
<country>Turkey</country>
</address>
</facility>
</location>
<location_countries>
<country>Turkey</country>
</location_countries>
<verification_date>February 2020</verification_date>
<study_first_submitted>January 21, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 13, 2020</last_update_submitted>
<last_update_submitted_qc>February 13, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 17, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Selcuk University</investigator_affiliation>
<investigator_full_name>Halil İbrahim Tuna</investigator_full_name>
<investigator_title>Director</investigator_title>
</responsible_party>
<keyword>geriatric pain</keyword>
<keyword>geriatric depression</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Depression</mesh_term>
<mesh_term>Depressive Disorder</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This study aimed to determine the effect of a virtual reality experience on pain, depression
and functional adequacy in geriatric individuals living in a nursing home.
A virtual reality video with dance moves has been applied to the experimental group
participants. Each video takes 3 minutes, and the elderly person has been put into practice
at least 30 minutes after having breakfast in 3-minute periods and at least 30 minutes after
dinner. In the morning and evening, 15 minutes, 2 times a day, a total of 9 days were applied
for 3 weeks. The application lasted a total of 3 weeks. Scales were applied 1 week after the
virtual reality application was completed and 1 month after the experimental group. The
scales were filled in the control group at the same time.
It is recommended that the future studies be conducted with larger samples on pain,
depression, life quality and functionality.
Inclusion Criteria:
- Suffering from musculoskeletal pain in the last 3 years,
- Being energetic (Being independent in the daily life activities),
- Being able to stand up without help before 30 seconds and walk at least six meters
without help,
- Individuals with blood sugar ranging between 90-200 mg/dl prior to the application,
- Individuals with blood pressure ranging between 130-70 mm/Hg prior to the application,
- Not having neurological and psychiatric diseases,
- No history of fall,
- Being literate,
- Not being visually-hearing impaired,
- Being able to communicate verbally.
Exclusion Criteria:
- Pependent patients
- Patients with psychiatric illness
- Patients with joint pain disease diagnosis
|
NCT0426xxxx/NCT04268602.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268602</url>
</required_header>
<id_info>
<org_study_id>HNEAH-KAEK2019/23-757</org_study_id>
<nct_id>NCT04268602</nct_id>
</id_info>
<brief_title>The Effect of Intradermal Local Anesthetic Injection in FBSS (Failed Back Surgery Syndrome)</brief_title>
<acronym>FBSS</acronym>
<official_title>The Effect of Intradermal Local Anesthetic Injection on Pain and Functionality in Failed Back Surgery Syndrome</official_title>
<sponsors>
<lead_sponsor>
<agency>Haydarpasa Numune Training and Research Hospital</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Haydarpasa Numune Training and Research Hospital</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
<is_us_export>No</is_us_export>
</oversight_info>
<brief_summary>
<textblock>
Failed Back Surgery Syndrome is described as chronic pain in the low back and/or legs after a
spinal procedure. It is estimated that %10 - 40 of the patients who had spinal surgery will
have Failed Back Surgery Syndrome. The aim of this study is to research whether intradermal
injection of the local anesthetic on the operation scar area and the area in which pain
referred to in patients with Failed Back Surgery Syndrome has effects on pain and
functionality or not.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
The prevalence of low back pain is around 60% - 80% and its the 5th most common disease to
seek medical help. 80% of patients who have an acute onset of low back pain whether treated
or not relieved on symptoms, while unfortunately 10% of patients' low back pain will worsen
end eventually progress to chronic low back pain. With the increase on the number of
different techniques on spinal surgery, and an increase in the number of patients who had
risk factors undergone spinal surgery caused an increase in the number of patients who had
new complaints after surgery. The term Failed Back Surgery Syndrome describes new complaints
or not enough ease on the complaints of a patient who had spinal surgery. Due to the
variation of the criteria of assessment, it is noted that around 10% -40% of the patients who
had spinal surgery will have Failed Back Surgery Syndrome.

Failed Back Surgery Syndrome is commonly described as pain in low back and/or legs with
difficulty in daily activities. Pain might be radicular or localized to the low back, it
might be mechanic or neuropathic in nature.

Some of the pathologies that cause Failed Back Surgery Syndrome are loss of height on the
disc, arthrosis, spinal stenosis caused by the hypertrophy of the facet joints, recurrent
disc herniation, arachnoiditis, central stenosis, epidural fibrosis, instability,
pseudoarthrosis, and discitis.

Rehabilitation is one of the vital parts of the treatment of Failed Back Surgery Syndrome.
After a detailed patient history and a complete physical examination, clinicians should
create a rehabilitation program that aims improvements on pain, functionality, quality of
life and activities of daily living and is tailored for the patient. It is shown that
patients who undergo rehabilitation programs had improvements in physical functionality,
posture, and difficulties with walking. Other conservative treatments include cognitive
behavioral therapy and noninvasive injection techniques.

Literature shows that multifidus muscle is damaged and atrophied in the patients who had
spinal surgery. Also, there is a correlation between functional impairment and atrophy.
Usually, the muscles that control flexion and extension of the low back are weak in patients
who have low back pain. Extensor muscles, especially the erector spinae muscle group are the
posterior stabilisers of the vertebral colon. Loss of endurance and weakness of these muscles
and low back pain have a correlation and strengthening these muscles will result in an
improvement in low back pain.

Injections of local anesthetics on chronic pain syndromes are being used successfully for a
long time. There are some examples of successful interventions on pelvic pain, myofascial
pain syndrome and nonspecific chronic low back pain in the literature. While surgery is the
first line of treatment in cases where the cause is the compromise of the neural structures
or spinal instability, the pain will increase with recurrent surgery in other causes.
Ligaments of the intervertebral disc complex which are innervated by the nociceptive neurons,
facet joints, and paravertebral muscles are thought to be the reason for pain in Failed Back
Surgery Syndrome. In a systemic review that took place in 2015; the superiority of injections
done with saline, a mixture of steroids and local anesthetics and steroids alone for facet
joints and epidural injection procedure was investigated. Investigators demonstrated that
injection with local anesthetics alone was effective in treatment. Another systemic review in
2019 showed that injection of local anesthetics was effective and was superior to botulinum
toxin A in the treatment of myofascial pain.

Intradermal injection of a drug is related to longer pharmacological effects compared to
intramuscular and subcutaneous injections. Lidocaine antinociceptive, analgesic,
anti-bacterial, anti-fungal, anti-viral, wound healing, releasing of endogen opioid effects
were demonstrated. In the light of all the information above, the investigators wanted to
research whether intradermal injection of the local anesthetic in patients with Failed Back
Surgery Syndrome has effects on pain and functionality or not.
</textblock>
</detailed_description>
<overall_status>Unknown status</overall_status>
<last_known_status>Not yet recruiting</last_known_status>
<start_date type="Anticipated">September 1, 2020</start_date>
<completion_date type="Anticipated">July 1, 2021</completion_date>
<primary_completion_date type="Anticipated">March 1, 2021</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>randomized controlled study</intervention_model_description>
<primary_purpose>Other</primary_purpose>
<masking>Single (Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>Change in Visual Analog Pain Scale scores</measure>
<time_frame>baseline, immediately after the intervention, 1 month</time_frame>
<description>Visual analog scale for measurement of pain. Minimum-maximum scores are 0-10. Higher scores mean worse outcome</description>
</primary_outcome>
<primary_outcome>
<measure>Change in OSWESTRY Disability Index scores</measure>
<time_frame>baseline, immediately after the intervention, 1 month</time_frame>
<description>Low Back Pain Disability Questionnaire. Minimum-maximum scores are 0-100. Higher scores mean worse outcome</description>
</primary_outcome>
<secondary_outcome>
<measure>Change in Hospital anxiety and depression scores</measure>
<time_frame>baseline, immediately after the intervention, 1 month</time_frame>
<description>anxiety and depression evaluation. Minimum-maximum scores are 0-21. Higher scores mean worse outcome</description>
</secondary_outcome>
<secondary_outcome>
<measure>change in modified schober test measurement</measure>
<time_frame>baseline, immediately after the intervention, 1 month</time_frame>
<description>measurement to asses the mobility of lumbar vertebrae (cm)</description>
</secondary_outcome>
<secondary_outcome>
<measure>change in Lateral hand to ground test measurement</measure>
<time_frame>baseline, immediately after the intervention, 1 month</time_frame>
<description>measurement to asses the mobility of lumbar vertebrae (cm)</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">80</enrollment>
<condition>Failed Back Surgery Syndrome</condition>
<condition>Pain, Chronic</condition>
<arm_group>
<arm_group_label>Intervention Group</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>intradermal 1% lidocain injection 4 cc+ exercise and transcutaneous electrical nerve stimulation</description>
</arm_group>
<arm_group>
<arm_group_label>Control Group</arm_group_label>
<arm_group_type>No Intervention</arm_group_type>
<description>exercise and transcutaneous electrical nerve stimulation</description>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>local anesthetic injection</intervention_name>
<description>1% lidocaine</description>
<arm_group_label>Intervention Group</arm_group_label>
<other_name>exercise and transcutaneous electrical nerve stimulation</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Having been diagnosed with failed back surgery syndrome

- 18-75 years of age

- visual analogue pain score> 4 to be

Exclusion Criteria:

- Mental problems

- Having a disease affecting the central nervous system or peripheral nervous system

- Fixation operation to the lumbar region

- Physical therapy in the lumbar region within the last 3 months

- Injection from the lumbar region in the last 3 months

- Lidocaine allergy

- Needle phobia.

- Wound, infection, allergy, burn-type lesions in the area to be injected

- Malignity history
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>75 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<verification_date>July 2020</verification_date>
<study_first_submitted>January 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>July 29, 2020</last_update_submitted>
<last_update_submitted_qc>July 29, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">July 30, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Haydarpasa Numune Training and Research Hospital</investigator_affiliation>
<investigator_full_name>Duygu Geler Külcü</investigator_full_name>
<investigator_title>Clinical Professor Dr, Head of Physical Medicine and Rehabilitation Department</investigator_title>
</responsible_party>
<keyword>FBSS</keyword>
<keyword>Failed Back Surgery Syndrome</keyword>
<keyword>Chronic Pain</keyword>
<keyword>local anesthetic</keyword>
<keyword>Intradermal Injection</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Syndrome</mesh_term>
<mesh_term>Chronic Pain</mesh_term>
<mesh_term>Failed Back Surgery Syndrome</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Anesthetics</mesh_term>
<mesh_term>Anesthetics, Local</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Failed Back Surgery Syndrome is described as chronic pain in the low back and/or legs after a
spinal procedure. It is estimated that %10 - 40 of the patients who had spinal surgery will
have Failed Back Surgery Syndrome. The aim of this study is to research whether intradermal
injection of the local anesthetic on the operation scar area and the area in which pain
referred to in patients with Failed Back Surgery Syndrome has effects on pain and
functionality or not.
The prevalence of low back pain is around 60% - 80% and its the 5th most common disease to
seek medical help. 80% of patients who have an acute onset of low back pain whether treated
or not relieved on symptoms, while unfortunately 10% of patients' low back pain will worsen
end eventually progress to chronic low back pain. With the increase on the number of
different techniques on spinal surgery, and an increase in the number of patients who had
risk factors undergone spinal surgery caused an increase in the number of patients who had
new complaints after surgery. The term Failed Back Surgery Syndrome describes new complaints
or not enough ease on the complaints of a patient who had spinal surgery. Due to the
variation of the criteria of assessment, it is noted that around 10% -40% of the patients who
had spinal surgery will have Failed Back Surgery Syndrome.
Failed Back Surgery Syndrome is commonly described as pain in low back and/or legs with
difficulty in daily activities. Pain might be radicular or localized to the low back, it
might be mechanic or neuropathic in nature.
Some of the pathologies that cause Failed Back Surgery Syndrome are loss of height on the
disc, arthrosis, spinal stenosis caused by the hypertrophy of the facet joints, recurrent
disc herniation, arachnoiditis, central stenosis, epidural fibrosis, instability,
pseudoarthrosis, and discitis.
Rehabilitation is one of the vital parts of the treatment of Failed Back Surgery Syndrome.
After a detailed patient history and a complete physical examination, clinicians should
create a rehabilitation program that aims improvements on pain, functionality, quality of
life and activities of daily living and is tailored for the patient. It is shown that
patients who undergo rehabilitation programs had improvements in physical functionality,
posture, and difficulties with walking. Other conservative treatments include cognitive
behavioral therapy and noninvasive injection techniques.
Literature shows that multifidus muscle is damaged and atrophied in the patients who had
spinal surgery. Also, there is a correlation between functional impairment and atrophy.
Usually, the muscles that control flexion and extension of the low back are weak in patients
who have low back pain. Extensor muscles, especially the erector spinae muscle group are the
posterior stabilisers of the vertebral colon. Loss of endurance and weakness of these muscles
and low back pain have a correlation and strengthening these muscles will result in an
improvement in low back pain.
Injections of local anesthetics on chronic pain syndromes are being used successfully for a
long time. There are some examples of successful interventions on pelvic pain, myofascial
pain syndrome and nonspecific chronic low back pain in the literature. While surgery is the
first line of treatment in cases where the cause is the compromise of the neural structures
or spinal instability, the pain will increase with recurrent surgery in other causes.
Ligaments of the intervertebral disc complex which are innervated by the nociceptive neurons,
facet joints, and paravertebral muscles are thought to be the reason for pain in Failed Back
Surgery Syndrome. In a systemic review that took place in 2015; the superiority of injections
done with saline, a mixture of steroids and local anesthetics and steroids alone for facet
joints and epidural injection procedure was investigated. Investigators demonstrated that
injection with local anesthetics alone was effective in treatment. Another systemic review in
2019 showed that injection of local anesthetics was effective and was superior to botulinum
toxin A in the treatment of myofascial pain.
Intradermal injection of a drug is related to longer pharmacological effects compared to
intramuscular and subcutaneous injections. Lidocaine antinociceptive, analgesic,
anti-bacterial, anti-fungal, anti-viral, wound healing, releasing of endogen opioid effects
were demonstrated. In the light of all the information above, the investigators wanted to
research whether intradermal injection of the local anesthetic in patients with Failed Back
Surgery Syndrome has effects on pain and functionality or not.
Inclusion Criteria:
- Having been diagnosed with failed back surgery syndrome
- 18-75 years of age
- visual analogue pain score> 4 to be
Exclusion Criteria:
- Mental problems
- Having a disease affecting the central nervous system or peripheral nervous system
- Fixation operation to the lumbar region
- Physical therapy in the lumbar region within the last 3 months
- Injection from the lumbar region in the last 3 months
- Lidocaine allergy
- Needle phobia.
- Wound, infection, allergy, burn-type lesions in the area to be injected
- Malignity history
|
NCT0426xxxx/NCT04268615.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268615</url>
</required_header>
<id_info>
<org_study_id>69HCL19_0998</org_study_id>
<secondary_id>2020-A00184-35</secondary_id>
<nct_id>NCT04268615</nct_id>
</id_info>
<brief_title>Covert Saccade Triggers in Bilateral Vestibular Hypofunction</brief_title>
<acronym>CS-TRIGGER</acronym>
<official_title>Covert Saccade Triggers in Bilateral Vestibular Hypofunction</official_title>
<sponsors>
<lead_sponsor>
<agency>Hospices Civils de Lyon</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Hospices Civils de Lyon</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Patients with chronic bilateral vestibular hypofunction may suffer from a visual instability
during head movement called oscillopsia. Visual consequence of vestibular deficit can lead to
a severe impairment of their quality of life. However, correcting saccades during rapid head
movement, called covert-saccades, have been more recently identified. These saccades, which
occur during the head movement in patients with vestibular hypofunction, present a very short
latency. They could compensate for the lack of vestibular-ocular reflex and greatly decrease
oscillopsia and visual impairment. The triggering of these covert-saccade is still not known.
They could be of visual origin but the short latency is unusual. The objective of this study
is to evaluate the potential role of visual trigger in 12 patients with chronic bilateral
areflexia, using different visuo-vestibular conditions. The latency of simple visually guided
saccades will also be tested in the group of patients and a group of 12 healthy controls.
</textblock>
</brief_summary>
<overall_status>Completed</overall_status>
<start_date type="Actual">December 15, 2020</start_date>
<completion_date type="Actual">March 21, 2022</completion_date>
<primary_completion_date type="Actual">March 21, 2022</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Non-Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Basic Science</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Latency of covert-saccades</measure>
<time_frame>Day 1</time_frame>
<description>Latency of covert saccades correspond to the time between the beginning of head impulse and the initiation of the first covert-saccade</description>
</primary_outcome>
<secondary_outcome>
<measure>Frequency of covert-saccades</measure>
<time_frame>Day 1</time_frame>
<description>Frequency of covert saccades corresponds to the total amount of covert-saccades divided by the total amount of head impulse tests multiplied by 100.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Velocity of covert-saccades</measure>
<time_frame>day 1</time_frame>
<description>Velocity of covert saccades correspond to the maximal velocity of the first covert-saccade</description>
</secondary_outcome>
<secondary_outcome>
<measure>Amplitude of covert-saccades</measure>
<time_frame>Day 1</time_frame>
<description>Amplitude of covert saccades correspond to amplitude of the first covert-saccade</description>
</secondary_outcome>
<secondary_outcome>
<measure>Latency of visually-guided saccades</measure>
<time_frame>Day 1</time_frame>
<description>Latency of visually guided saccades correspond to the time between the appearance of target and the initiation of the first saccade</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">32</enrollment>
<condition>Reflex, Abnormal</condition>
<condition>Bilateral Vestibulopathy</condition>
<condition>Healthy Volunteers</condition>
<arm_group>
<arm_group_label>Patients</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Patients suffering from chronic bilateral vestibular hypofunction</description>
</arm_group>
<arm_group>
<arm_group_label>healthy subject group</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Covert Saccades and Virtual Reality</intervention_name>
<description>During this intervention, patients will undergo head impulse testing while wearing virtual reality Headsets. During the head impulse tests the visual information will be modified in order to create a conflict between head rotation and rotation of the visual scene. Recording of head and eye movement will be done during these head impulses in order to verify if visual information modifies compensatory eye movements during head impulses.</description>
<arm_group_label>Patients</arm_group_label>
<arm_group_label>healthy subject group</arm_group_label>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Actives versus passives Head Impulses</intervention_name>
<description>Patients will undergo classic passive head rotation as well as active head rotation in order to compare latencies of covert saccades in both conditions.</description>
<arm_group_label>Patients</arm_group_label>
<arm_group_label>healthy subject group</arm_group_label>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Visually guided saccades</intervention_name>
<description>Patients as well as healthy control subjects will undergo testing of visually guided saccades in different conditions (step, gap, overlap) in order to compare latencies of covert saccades between both groups.</description>
<arm_group_label>Patients</arm_group_label>
<arm_group_label>healthy subject group</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- For all :

- Age from 18 to 90

- Understanding of the experimental instructions

- Informed Consent

- For Patients :

Bilateral vestibular hypofunction with regards to the criteria of the of the Barany Society
A. Chronic vestibular syndrome with at least three of the following symptoms

1. Postural imbalance

2. Unsteadiness of gait

3. Movement-induced blurred vision or oscillopsia during walking or quick head/body
movements

4. Worsening of postural imbalance or unsteadiness of gait in darkness and/or on uneven
ground B. No symptoms while sitting or lying down under static conditions C.
Bilaterally reduced or absent angular VOR function documented by

- bilaterally pathological horizontal angular VOR gain < 0.6, measured by the
video-HIT5or scleral-coil technique and/or

- reduced caloric response (sum of bithermal max. peak SPV on each side <
6°/sec7)and/or

- reduced horizontal angular VOR gain < 0.1 upon sinusoidal stimulation on a
rotatorychair (0.1 Hz, Vmax = 50°/sec).

D. Not better accounted for by another disease

* For Healthy control No ENT or neurological disorders

Exclusion Criteria:

- Corrected Visual Acuity lower than 5/10

- Other conditions leading to oscillopsia or ataxia

- Oculomotor palsy, ocular instability in primary position

- Treatment that may affect ocular motility (psychotropes)

- Cervical rachis pathology with instability

- Cochlear Implants

- Non-stabilized medical disease

- Pregnant women

- Patients under tutelage

- Patient without social security
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>90 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Caroline FROMENT, MD</last_name>
<role>Principal Investigator</role>
<affiliation>Hospices Civils de Lyon</affiliation>
</overall_official>
<location>
<facility>
<name>Hospices Civils de Lyon</name>
<address>
<city>Bron</city>
<zip>69500</zip>
<country>France</country>
</address>
</facility>
</location>
<location_countries>
<country>France</country>
</location_countries>
<verification_date>July 2022</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>July 27, 2022</last_update_submitted>
<last_update_submitted_qc>July 27, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">July 28, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Saccadic Eye Movements</keyword>
<keyword>Bilateral Vestibulopathy</keyword>
<keyword>Bilateral Vestibular Hypofunction</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Bilateral Vestibulopathy</mesh_term>
<mesh_term>Reflex, Abnormal</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Patients with chronic bilateral vestibular hypofunction may suffer from a visual instability
during head movement called oscillopsia. Visual consequence of vestibular deficit can lead to
a severe impairment of their quality of life. However, correcting saccades during rapid head
movement, called covert-saccades, have been more recently identified. These saccades, which
occur during the head movement in patients with vestibular hypofunction, present a very short
latency. They could compensate for the lack of vestibular-ocular reflex and greatly decrease
oscillopsia and visual impairment. The triggering of these covert-saccade is still not known.
They could be of visual origin but the short latency is unusual. The objective of this study
is to evaluate the potential role of visual trigger in 12 patients with chronic bilateral
areflexia, using different visuo-vestibular conditions. The latency of simple visually guided
saccades will also be tested in the group of patients and a group of 12 healthy controls.
Inclusion Criteria:
- For all :
- Age from 18 to 90
- Understanding of the experimental instructions
- Informed Consent
- For Patients :
Bilateral vestibular hypofunction with regards to the criteria of the of the Barany Society
A. Chronic vestibular syndrome with at least three of the following symptoms
1. Postural imbalance
2. Unsteadiness of gait
3. Movement-induced blurred vision or oscillopsia during walking or quick head/body
movements
4. Worsening of postural imbalance or unsteadiness of gait in darkness and/or on uneven
ground B. No symptoms while sitting or lying down under static conditions C.
Bilaterally reduced or absent angular VOR function documented by
- bilaterally pathological horizontal angular VOR gain < 0.6, measured by the
video-HIT5or scleral-coil technique and/or
- reduced caloric response (sum of bithermal max. peak SPV on each side <
6°/sec7)and/or
- reduced horizontal angular VOR gain < 0.1 upon sinusoidal stimulation on a
rotatorychair (0.1 Hz, Vmax = 50°/sec).
D. Not better accounted for by another disease
* For Healthy control No ENT or neurological disorders
Exclusion Criteria:
- Corrected Visual Acuity lower than 5/10
- Other conditions leading to oscillopsia or ataxia
- Oculomotor palsy, ocular instability in primary position
- Treatment that may affect ocular motility (psychotropes)
- Cervical rachis pathology with instability
- Cochlear Implants
- Non-stabilized medical disease
- Pregnant women
- Patients under tutelage
- Patient without social security
|
NCT0426xxxx/NCT04268628.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268628</url>
</required_header>
<id_info>
<org_study_id>CR108736</org_study_id>
<secondary_id>212082PCR0026</secondary_id>
<nct_id>NCT04268628</nct_id>
</id_info>
<brief_title>A Study of Pharmacodynamic and Genetic Parameters of Abira-DES Study Participants (NCT02217566) - Participants With Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Acetate Following Unresponsive Treatment With Diethylstilbestrol</brief_title>
<acronym>EXPLORE</acronym>
<official_title>Exploratory Evaluation of Genetic Polymorphism and Pharmacodynamic Parameters in Samples of Abira-DES Study Subjects (NCT02217566) - Subjects With Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Acetate Following Unresponsive Treatment With Diethylstilbestrol.</official_title>
<sponsors>
<lead_sponsor>
<agency>Janssen-Cilag Farmaceutica Ltda.</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
</sponsors>
<source>Janssen-Cilag Farmaceutica Ltda.</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
</oversight_info>
<brief_summary>
<textblock>
The primary purpose of this study is to evaluate the influence of HSD3B1 (1245C) germline
variant and potential pharmacodynamic markers on abiraterone activity in participants with
metastatic castration-resistant prostate cancer after unresponsive use of diethylstilbestrol.
</textblock>
</brief_summary>
<overall_status>Completed</overall_status>
<start_date type="Actual">March 19, 2020</start_date>
<completion_date type="Actual">November 16, 2020</completion_date>
<primary_completion_date type="Actual">November 16, 2020</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Other</observational_model>
<time_perspective>Retrospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Percentage of Participants with and Without HSD3B1 (1245C) Germline Variant'</measure>
<time_frame>Up to 12 months</time_frame>
<description>Percentage of participants with and without HSD3B1 (1245C) germline variant will be determined to evaluate the influence of HSD3B1 (1245C) germline variant on the response to abiraterone as a predictive fact.</description>
</primary_outcome>
<secondary_outcome>
<measure>Levels of HSD3B1 (1245C) Germ Variant</measure>
<time_frame>Up to 12 months</time_frame>
<description>Levels of HSD3B1 (1245C) germline variant will be determined to evaluate the response to abiraterone acetate as a predictive factor.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Levels of Metabolite Delta-(4)-Abiraterone (D4A) During the Abiraterone Acetate During Treatment Phase</measure>
<time_frame>12 Weeks</time_frame>
<description>Levels of metabolite D4A during the abiraterone acetate during treatment phase will be evaluated.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Testosterone Levels in Participants Treated with Abiraterone Acetate</measure>
<time_frame>Up to 12 months</time_frame>
<description>Testosterone levels of participants treated with abiraterone acetate will be evaluated by the molecular analyses.</description>
</secondary_outcome>
<secondary_outcome>
<measure>SDHEA Levels in Participants Treated with Abiraterone Acetate</measure>
<time_frame>Up to 12 months</time_frame>
<description>SDHEA levels of participants treated with abiraterone acetate will be evaluated by the molecular analyses.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Correlation Between HSD3B1 (1245C) Variant and Testosterone Levels</measure>
<time_frame>Up to 12 months</time_frame>
<description>Correlation between HSD3B1 (1245C) variant and testosterone levels will be reported. The genotyping of the HSD3B1 (1245 A> C) germline variant will be performed by Sanger sequencing.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Correlation Between HSD3B1 (1245C) Variant and SDHEA Levels</measure>
<time_frame>Up to 12 months</time_frame>
<description>Correlation between HSD3B1 (1245C) variant and SDHEA levels will be reported. The genotyping of the HSD3B1 (1245 A> C) germline variant will be performed by Sanger sequencing.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Correlation Between HSD3B1 (1245C) Variant and Clinical Response</measure>
<time_frame>Up to 12 months</time_frame>
<description>Correlation between HSD3B1 (1245C) variant and clinical response will be performed by univariate and multivariate analyses.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Correlation Between D4A Levels with Testosterone Dosage</measure>
<time_frame>Up to 12 months</time_frame>
<description>Testosterone ultrasensitive dosages will be performed on participant serum samples. Testosterone dosage will be performed by liquid chromatography coupled with tandem mass spectrometry.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Correlation Between D4A Levels with SDHEA Dosage</measure>
<time_frame>Up to 12 months</time_frame>
<description>SDHEA ultrasensitive dosages will be performed on participant serum samples. Dosage will be performed by liquid chromatography coupled with tandem mass spectrometry.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Correlation Between D4A Levels with Clinical Response</measure>
<time_frame>Up to 12 months</time_frame>
<description>Correlation between D4A levels with clinical response will be performed by univariate and multivariate analyses.</description>
</secondary_outcome>
<number_of_groups>1</number_of_groups>
<enrollment type="Actual">42</enrollment>
<condition>Metastatic Castration-resistant Prostate Cancer</condition>
<arm_group>
<arm_group_label>Participants with mCRPC</arm_group_label>
<description>Participants with metastatic castration resistant prostate cancer (mCRPC) will be evaluated for genetic polymorphism and pharmacodynamic parameters from serum and plasma samples collected during the Abira-DES study (NCT02217566). Serum and plasma samples were collected after use of diethylstilbestrol (DES) and subsequent abiraterone acetate therapy. Peripheral blood samples were collected prior to initiation of abiraterone acetate therapy, after 12 weeks of therapy, and at the time of disease progression (evaluated by prostate specific antigen [PSA] response).</description>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Serum and plasma samples analysis</intervention_name>
<description>This is a non-interventional study and no drug will be given as part of this study. Serum and plasma samples will be collected from the participants with metastatic castration-resistant prostate cancer to evaluate genetic polymorphism and pharmacodynamic parameters.</description>
<arm_group_label>Participants with mCRPC</arm_group_label>
</intervention>
<eligibility>
<study_pop>
<textblock>
The population of this study comprised of participants with metastatic castration-resistant
prostate cancer with disease progression following the use of diethylstilbestrol (DES) who
participated in the Abira-DES study (NCT02217566) in which they were treated with
abiraterone acetate.
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- Must have a confirmed diagnosis of prostate adenocarcinoma without neuroendocrine or
small cell differentiation and was a participant in the Abira-DES study (NCT0221756),
which includes: diethylstilbestrol pretreatment for castration-resistant prostate
cancer with evidence of disease progression or grade 3/4 toxicity with
diethylstilbestrol; metastatic disease confirmed by bone examination or metastatic
lesions by computed tomography or magnetic resonance

- Abiraterone acetate therapy during the Abira-DES study (NCT0221756), and peripheral
blood samples have been collected from at least of the three proposed study timepoints

- Must sign, and/or his/her legally acceptable representatives, where applicable, must
sign the ICF allowing the use of clinical data and biological samples in accordance
with local requirements. For deceased participants who did not provide consent prior
to death, permission to research their information must meet local requirements

Exclusion Criteria:

- Having withdrawn the consent to use the samples collected during their participation in
the Abira-DES study (NCT02217566)
</textblock>
</criteria>
<gender>Male</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Janssen-Cilag Farmaceutica Ltda. Clinical Trial</last_name>
<role>Study Director</role>
<affiliation>Janssen-Cilag Farmaceutica Ltda.</affiliation>
</overall_official>
<location>
<facility>
<name>Sociedade Beneficiante de Senhoras - Hospital Sirio Libanes</name>
<address>
<city>São Paulo</city>
<zip>01308901</zip>
<country>Brazil</country>
</address>
</facility>
</location>
<location_countries>
<country>Brazil</country>
</location_countries>
<verification_date>December 2021</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>December 30, 2021</last_update_submitted>
<last_update_submitted_qc>December 30, 2021</last_update_submitted_qc>
<last_update_posted type="Actual">January 3, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Prostatic Neoplasms</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The primary purpose of this study is to evaluate the influence of HSD3B1 (1245C) germline
variant and potential pharmacodynamic markers on abiraterone activity in participants with
metastatic castration-resistant prostate cancer after unresponsive use of diethylstilbestrol.
The population of this study comprised of participants with metastatic castration-resistant
prostate cancer with disease progression following the use of diethylstilbestrol (DES) who
participated in the Abira-DES study (NCT02217566) in which they were treated with
abiraterone acetate.
Inclusion Criteria:
- Must have a confirmed diagnosis of prostate adenocarcinoma without neuroendocrine or
small cell differentiation and was a participant in the Abira-DES study (NCT0221756),
which includes: diethylstilbestrol pretreatment for castration-resistant prostate
cancer with evidence of disease progression or grade 3/4 toxicity with
diethylstilbestrol; metastatic disease confirmed by bone examination or metastatic
lesions by computed tomography or magnetic resonance
- Abiraterone acetate therapy during the Abira-DES study (NCT0221756), and peripheral
blood samples have been collected from at least of the three proposed study timepoints
- Must sign, and/or his/her legally acceptable representatives, where applicable, must
sign the ICF allowing the use of clinical data and biological samples in accordance
with local requirements. For deceased participants who did not provide consent prior
to death, permission to research their information must meet local requirements
Exclusion Criteria:
- Having withdrawn the consent to use the samples collected during their participation in
the Abira-DES study (NCT02217566)
|
NCT0426xxxx/NCT04268641.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268641</url>
</required_header>
<id_info>
<org_study_id>GHIV0417</org_study_id>
<nct_id>NCT04268641</nct_id>
</id_info>
<brief_title>Evaluation of Positioning Protocols on a Wheelchair in Hemiplegic Patients</brief_title>
<acronym>POSIT-HEMI</acronym>
<official_title>Evaluation of Positioning Protocols With an Adapted Equipment on a Wheelchair in Hemiplegic Patients Following a Stroke</official_title>
<sponsors>
<lead_sponsor>
<agency>Hôpital NOVO</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Hôpital NOVO</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The main purpose of this study is to assess the interest of using wheelchair positioning
equipment on the decrease of postural disorders, compared to the standard use of a wheelchair
</textblock>
</brief_summary>
<detailed_description>
<textblock>
The stroke is the main cause of hemiplegia in developed countries. Fifteen percent of people
who say they have a stroke need, at home, a wheelchair to get from one room to another. The
use of a wheelchair can cause postural disorders which can lead to pain, orthopedic deformity
and pressure ulcers.

This study aims to assess the interest of using wheelchair positioning equipment (Seat back,
Positioning cushion and Belt) on the decrease of postural disorders.

This decrease will be assessed after a standardized course, performed under three different
conditions: with the positioning equipment (Positioning cushion and Seat back), with the
positioning equipment and the belt and with the wheelchair alone.

Clinical tool used to assess the decrease is the Seated Postural Control Measure for Adults
2.0 (SPCMA 2.0).

This study, which will be the first prospective, interventional, multicenter, controlled and
randomized study, could pave the way for guidelines of good practice, for wheelchair
positioning of hemiplegic patients in France
</textblock>
</detailed_description>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">August 28, 2020</start_date>
<completion_date type="Anticipated">December 2023</completion_date>
<primary_completion_date type="Anticipated">December 2023</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Factorial Assignment</intervention_model>
<primary_purpose>Supportive Care</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Degree of pelvic posterior tilt</measure>
<time_frame>Immediately after the end of the procedure, an average of 1 day</time_frame>
<description>The Primary Outcome Measure is the variation of the Degree of pelvic posterior tilt at the end of the three standardized course. These courses were performed with Standard Wheelchair, Standard Wheelchair + Seat back + Positioning cushion + Belt or with Standard Wheelchair + Seat back + Positioning cushion.
The Degree of pelvic posterior tilt was measured using the SPCMA 2.0 score (0 = normal, 1 = mild, 2 = moderate and 3 = severe retroversion)</description>
</primary_outcome>
<secondary_outcome>
<measure>Variation of Degree of pelvic posterior tilt</measure>
<time_frame>Baseline and immediately after the end of the procedure, an average of 1 day</time_frame>
<description>The variation of the Degree of pelvic posterior tilt was measured between the beginning and the end of the three standardized course using the SPCMA 2.0 score (0 = normal, 1 = mild, 2 = moderate and 3 = severe retroversion)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Variation of degree of lateral inclination of the torso</measure>
<time_frame>Baseline and immediately after the end of the procedure, an average of 1 day</time_frame>
<description>The variation of the degree of lateral inclination of the torso was measured between the beginning and the end of the three standardized course using the SPCMA 2.0 score (0 = normal, 1 = mild, 2 = moderate and 3 = severe retroversion)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Variation of the degree of Pelvis obliquity</measure>
<time_frame>Baseline and immediately after the end of the procedure, an average of 1 day</time_frame>
<description>The variation of the degree of Pelvis obliquity was measured at the end of the three standardized course using the SPCMA 2.0 score (0 = normal, 1 = mild, 2 =moderate and 3 = severe retroversion)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Degree of lateral inclination of the torso</measure>
<time_frame>Immediately after the end of the procedure, an average of 1 day</time_frame>
<description>The degree of lateral inclination of the torso was measured at the end of the three standardized course using the SPCMA 2.0 score (0 = normal, 1 = mild, 2 = moderate and 3 = severe retroversion)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Degree of Pelvis obliquity</measure>
<time_frame>Immediately after the end of the procedure, an average of 1 day</time_frame>
<description>The degree of Pelvis obliquity was measured at the end of the three standardized course using the SPCMA 2.0 score (0 = normal, 1 = mild, 2 = moderate and 3 = severe retroversion)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Measure of patient's satisfaction</measure>
<time_frame>Immediately after the end of the procedure, an average of 1 day</time_frame>
<description>The satisfaction of patient was measured with a satisfaction questionnaire scale based on ease of movement, wheelchair comfort and pain during the course. For each item, patient ticks : Very satisfied, Satisfied, Neither satisfied or unsatisfied, Unsatisfied or Very unsatisfied</description>
</secondary_outcome>
<secondary_outcome>
<measure>Ability to achieve the whole course</measure>
<time_frame>Immediately after the end of the procedure, an average of 1 day</time_frame>
<description>Binary criteria (Yes / No)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Adverse event collect</measure>
<time_frame>Immediately after the end of the procedure, an average of 1 day</time_frame>
<description>Total number of adverse event</description>
</secondary_outcome>
<number_of_arms>6</number_of_arms>
<enrollment type="Anticipated">24</enrollment>
<condition>Hemiplegia and/or Hemiparesis Following Stroke</condition>
<arm_group>
<arm_group_label>Use of positioning equipment order 1</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>One standardized course is performed 3 times by each patient : one with a standard wheelchair and the 2 other with one or two positioning equipment (Seat back or/and positioning cushion) Each arm differs from the previous by the order of use of the equipment.</description>
</arm_group>
<arm_group>
<arm_group_label>Use of positioning equipment order 2</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>One standardized course is performed 3 times by each patient : one with a standard wheelchair and the 2 other with one or two positioning equipment (Seat back or/and positioning cushion) Each arm differs from the previous by the order of use of the equipment.</description>
</arm_group>
<arm_group>
<arm_group_label>Use of positioning equipment order 3</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>One standardized course is performed 3 times by each patient : one with a standard wheelchair and the 2 other with one or two positioning equipment (Seat back or/and positioning cushion) Each arm differs from the previous by the order of use of the equipment.</description>
</arm_group>
<arm_group>
<arm_group_label>Use of positioning equipment order 4</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>One standardized course is performed 3 times by each patient : one with a standard wheelchair and the 2 other with one or two positioning equipment (Seat back or/and positioning cushion) Each arm differs from the previous by the order of use of the equipment.</description>
</arm_group>
<arm_group>
<arm_group_label>Use of positioning equipment order 5</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>One standardized course is performed 3 times by each patient : one with a standard wheelchair and the 2 other with one or two positioning equipment (Seat back or/and positioning cushion) Each arm differs from the previous by the order of use of the equipment.</description>
</arm_group>
<arm_group>
<arm_group_label>Use of positioning equipment order 6</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>One standardized course is performed 3 times by each patient : one with a standard wheelchair and the 2 other with one or two positioning equipment (Seat back or/and positioning cushion) Each arm differs from the previous by the order of use of the equipment.</description>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Arm 1</intervention_name>
<description>Materials used for the course :
: Standard Wheelchair
: Standard Wheelchair + Seat back + Positioning cushion
: Standard Wheelchair + Seat back + Positioning cushion + Belt</description>
<arm_group_label>Use of positioning equipment order 1</arm_group_label>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Arm 2</intervention_name>
<description>Materials used for the course :
: Standard Wheelchair
: Standard Wheelchair + Seat back + Positioning cushion + Belt
: Standard Wheelchair + Seat back + Positioning cushion</description>
<arm_group_label>Use of positioning equipment order 2</arm_group_label>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Arm 3</intervention_name>
<description>Materials used for the course :
: Standard Wheelchair + Seat back + Positioning cushion
: Standard Wheelchair + Seat back + Positioning cushion + Belt
: Standard Wheelchair</description>
<arm_group_label>Use of positioning equipment order 3</arm_group_label>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Arm 4</intervention_name>
<description>Materials used for the course :
: Standard Wheelchair + Seat back + Positioning cushion
: Standard Wheelchair
: Standard Wheelchair + Seat back + Positioning cushion + Belt</description>
<arm_group_label>Use of positioning equipment order 4</arm_group_label>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Arm 5</intervention_name>
<description>Materials used for the course :
: Standard Wheelchair + Seat back + Positioning cushion + Belt
: Standard Wheelchair
: Standard Wheelchair + Seat back + Positioning cushion</description>
<arm_group_label>Use of positioning equipment order 5</arm_group_label>
</intervention>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Arm 6</intervention_name>
<description>Materials used for the course :
: Standard Wheelchair + Seat back + Positioning cushion + Belt
: Standard Wheelchair + Seat back + Positioning cushion
: Standard Wheelchair</description>
<arm_group_label>Use of positioning equipment order 6</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Hemiplegic patient following a stroke

- Hospitalized in a follow-up and rehabilitative care service, after hospital stays in a
MCO service (neurology, neurosurgery or reanimation)

- With a planned exit from hospital (homecoming, residential care facilities, nursing
home, Long Term Care Unit …)

- Patient whose wheelchair choice should be already done

- Patient who propels the wheelchair with the valid hand and/or valid foot

- Written informed consent (IC) obtained

- Patients with affiliation to the social security system

Exclusion Criteria:

- Good walk recovery (FAC scale >3)

- Wheelchair with a double hand rim

- Patient who cannot use his2 wheelchair independently

- Cognitive disorders which prevent the ability to well understanding the instructions

- Other pathology which can interfere with this protocol (Spinal disorder, morbid
overweight (BMI>40…)
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Nadine Pellegrini</last_name>
<role>Principal Investigator</role>
<affiliation>Groupement Hospitalier Intercommunal du Vexin</affiliation>
</overall_official>
<overall_contact>
<last_name>Maryline DELATTRE</last_name>
<phone>0033130754131</phone>
<email>maryline.delattre@ght-novo.fr</email>
</overall_contact>
<overall_contact_backup>
<last_name>Véronique DA COSTA</last_name>
<phone>0033130755069</phone>
<email>veronique.dacosta@ght-novo.fr</email>
</overall_contact_backup>
<location>
<facility>
<name>Groupement Hospitalier Intercommunal du Vexin</name>
<address>
<city>Aincourt</city>
<zip>95510</zip>
<country>France</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Véronique Da Costa</last_name>
<phone>+33 1 30 75 50 69</phone>
<email>veronique.dacosta@ght-novo.fr</email>
</contact>
<investigator>
<last_name>Nadine Pellegrini</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Centre Sainte Barbe</name>
<address>
<city>Fouquières-Lès-Lens</city>
<zip>62740</zip>
<country>France</country>
</address>
</facility>
<status>Withdrawn</status>
</location>
<location>
<facility>
<name>Hôpital Raymond Poincaré</name>
<address>
<city>Garche</city>
<zip>92380</zip>
<country>France</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Thibaud Lansaman</last_name>
<phone>+33 1 47 10 70 60</phone>
<email>thibaud.lansaman@aphp.fr</email>
</contact>
</location>
<location>
<facility>
<name>Institut Régional de Réadaptation</name>
<address>
<city>Lay-Saint-Christophe</city>
<zip>54690</zip>
<country>France</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Centre de l'ESPOIR</name>
<address>
<city>Lille</city>
<zip>59260</zip>
<country>France</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Alexandre Coulomb</last_name>
<phone>+33 3 20 05 85 00</phone>
<phone_ext>87 42</phone_ext>
<email>alexandre.coulomb@centre-espoir.com</email>
</contact>
<investigator>
<last_name>Alexandre Coulomb</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Centre de Rééducation L'oiseau Blanc</name>
<address>
<city>Mantes-la-Jolie</city>
<zip>78200</zip>
<country>France</country>
</address>
</facility>
<status>Active, not recruiting</status>
</location>
<location>
<facility>
<name>Centre de Rééducation et de Réadaptation Fonctionnelles</name>
<address>
<city>Menucourt</city>
<zip>95180</zip>
<country>France</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Charles Fattal</last_name>
<phone>+33 1 34 46 65 65</phone>
<email>cfattal@lachataigneraie.fr</email>
</contact>
<investigator>
<last_name>Charles Fattal</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Centre Hospitalier Universitaire de Toulouse</name>
<address>
<city>Toulouse</city>
<zip>31059</zip>
<country>France</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Caroline Terracol</last_name>
<phone>+33 5 61 32 23 75</phone>
<email>terracol.c@chu-toulouse.fr</email>
</contact>
<investigator>
<last_name>Caroline Terracol</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location_countries>
<country>France</country>
</location_countries>
<verification_date>September 2023</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>September 8, 2023</last_update_submitted>
<last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">September 11, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Hemiplegia</keyword>
<keyword>Stroke</keyword>
<keyword>Wheelchair positioning</keyword>
<keyword>Propulsion</keyword>
<keyword>Pelvic posterior tilt</keyword>
<keyword>Obliquity</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Stroke</mesh_term>
<mesh_term>Hemiplegia</mesh_term>
<mesh_term>Paresis</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The main purpose of this study is to assess the interest of using wheelchair positioning
equipment on the decrease of postural disorders, compared to the standard use of a wheelchair
The stroke is the main cause of hemiplegia in developed countries. Fifteen percent of people
who say they have a stroke need, at home, a wheelchair to get from one room to another. The
use of a wheelchair can cause postural disorders which can lead to pain, orthopedic deformity
and pressure ulcers.
This study aims to assess the interest of using wheelchair positioning equipment (Seat back,
Positioning cushion and Belt) on the decrease of postural disorders.
This decrease will be assessed after a standardized course, performed under three different
conditions: with the positioning equipment (Positioning cushion and Seat back), with the
positioning equipment and the belt and with the wheelchair alone.
Clinical tool used to assess the decrease is the Seated Postural Control Measure for Adults
2.0 (SPCMA 2.0).
This study, which will be the first prospective, interventional, multicenter, controlled and
randomized study, could pave the way for guidelines of good practice, for wheelchair
positioning of hemiplegic patients in France
Inclusion Criteria:
- Hemiplegic patient following a stroke
- Hospitalized in a follow-up and rehabilitative care service, after hospital stays in a
MCO service (neurology, neurosurgery or reanimation)
- With a planned exit from hospital (homecoming, residential care facilities, nursing
home, Long Term Care Unit …)
- Patient whose wheelchair choice should be already done
- Patient who propels the wheelchair with the valid hand and/or valid foot
- Written informed consent (IC) obtained
- Patients with affiliation to the social security system
Exclusion Criteria:
- Good walk recovery (FAC scale >3)
- Wheelchair with a double hand rim
- Patient who cannot use his2 wheelchair independently
- Cognitive disorders which prevent the ability to well understanding the instructions
- Other pathology which can interfere with this protocol (Spinal disorder, morbid
overweight (BMI>40…)
|
NCT0426xxxx/NCT04268654.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268654</url>
</required_header>
<id_info>
<org_study_id>TIGOAL</org_study_id>
<nct_id>NCT04268654</nct_id>
</id_info>
<brief_title>Ischemic Conditioning of the Gastric Conduit in Esophageal Cancer.</brief_title>
<official_title>Trial on Ischemic Conditioning of the Gastric Conduit in Esophageal Cancer. Effects on Oxygenation and Anastomotic Leakage.</official_title>
<sponsors>
<lead_sponsor>
<agency>Fundación para la Investigación del Hospital Clínico de Valencia</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Fundación para la Investigación del Hospital Clínico de Valencia</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This study is a randomized clinical trial to clarify if preoperative embolization of gastric
arteries can reduce the incidence of oesophagogastric leakage after an esophagectomy for
esophageal cancer comparing an experimental group vs control group.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
In patients with infracarinal esophageal carcinoma, the surgery is a complex procedure and
with a high morbidity. It consists of a subtotal esophagectomy with tubular gastroplasty and
cervical esophagogastric anastomosis. The most important complication is the anastomotic
leakage with a high mortality. Among the possible causes of anastomotic leakage an important
factor is the impaired microcirculation in the anastomotic region after the partial
devascularization of the stomach during the surgery. There are several experimental studies
about the different techniques to improve this vascularization and their effects on mucosal
oxygenation. There are several methods currently used for assessing tissue oxygenation. The
polarographic partial pressure of oxygen (pO2) electrode has been considered as the 'gold
standard' for measuring oxygen tension. This is the reason why tissue pressure of oxygen
(PtiO2) will be measured by Licox® (Integra Neuroscience) system in two groups. There aren't
prospective randomized controlled trials to answer these questions. For this reason the
investigators propose to perform a prospective randomized controlled trial in patients
underwent on this surgery, comparing two groups: one of them will be carried out a
preoperative arterial embolization (PAE), and the other one will be operated directly, to
demonstrate if the ischemic conditioning by PAE can reduce the incidence of anastomotic
esophagogastric leakage and improve the gastric conduit oxygenation.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">June 13, 2017</start_date>
<completion_date type="Actual">December 1, 2021</completion_date>
<primary_completion_date type="Actual">December 1, 2021</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Prevention</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Anastomotic leakage</measure>
<time_frame>90 days</time_frame>
<description>Clinic, endoscopy or computed tomography with oral contrast of dehiscence of oesophagogastric anastomosis.</description>
</primary_outcome>
<secondary_outcome>
<measure>Tissue pressure oxygen (Ptio2)</measure>
<time_frame>48 hours</time_frame>
<description>Licox oxygen monitoring system placed during the surgery in the gastric conduit. Measurements: intraoperatively and 24 hours and 48 hours after surgery.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Relation between PtiO2 and anastomotic leakage</measure>
<time_frame>90 days</time_frame>
<description>We will analyse the correlation between the measurement of tissue pressure oxygen and the prevention of anastomotic leakage.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Gastric Conduit ischemia</measure>
<time_frame>90 days</time_frame>
<description>Plasty ischemia when one or more of the following criteria is present:
Endoscopic evidence of gastric mucosa ischemia
Evidence in a thoracoabdominal CT with endovenous contrast</description>
</secondary_outcome>
<secondary_outcome>
<measure>Morbidity</measure>
<time_frame>90 days</time_frame>
<description>Investigator will analyse the morbidity between the two groups with the common postoperative complications: - Anastomotic leakage
Wound infection
Pulmonary complications
Complications related to PAE
Cardiologic complications</description>
</secondary_outcome>
<secondary_outcome>
<measure>Mortality</measure>
<time_frame>90 days</time_frame>
<description>Postoperative mortality has been defined as any death, regardless of cause, occurring within 30 days after surgery in or out of the hospital.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Hospital Stay</measure>
<time_frame>90 days</time_frame>
<description>investigators will consider since the day of the surgery until the day the patient will be discharged from the hospital</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">40</enrollment>
<condition>Esophageal Anastomotic Leak</condition>
<condition>Tissue Pressure of Oxygen</condition>
<arm_group>
<arm_group_label>Ischemic Conditioning</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Preoperative artery embolization prior to esophagectomy
Tissue pressure of oxygen measurement in both arms by Licox system. The probe is inserted directly through the skin as a cervical drainage and it is fixed by Witzel technique in the gastric conduit. It is removed after the three measurements (intraoperatively, 24h and 48h after surgery) of the PtiO2 as a normal drainage.</description>
</arm_group>
<arm_group>
<arm_group_label>Control</arm_group_label>
<arm_group_type>No Intervention</arm_group_type>
<description>Surgery without previous ischemic conditioning of the gastric conduit
Tissue pressure of oxygen measurement in both arms by Licox system. The probe is inserted directly through the skin as a cervical drainage and it is fixed by Witzel technique in the gastric conduit. It is removed after the three measurements (intraoperatively, 24h and 48h after surgery) of the PtiO2 as a normal drainage.</description>
</arm_group>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>Preoperative Arterial Embolization</intervention_name>
<description>PAE will be performed by arteriographic procedure before esophageal resection surgery minimum 14 days before surgery.
An angiogram of the celiac trunk is performed through a femoral access before and after the embolization. Embolization by coils of the left gastric artery, splenic artery and the right gastric artery is realized.</description>
<arm_group_label>Ischemic Conditioning</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- All patients requiring a esophagectomy with cervical esophagogastrostomy for
esophageal cancer

- 18 or above years old

- Karnofsky>50%

- Acceptance and signing the full informed consent

Exclusion Criteria:

- Fistula tracheobronchial

- Metastatic disease

- Anatomic vascular alteration that contraindicate the embolization (congenital celiac
trunk stenosis, presence of arcuate ligament, atherosclerotic stenosis, etc,..)

- Severe cardiorespiratory failure

- Refuse to collaborate in the study
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>80 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<location>
<facility>
<name>Hospital Clínico Universitario de Valencia</name>
<address>
<city>Valencia</city>
<state>VAL</state>
<zip>46010</zip>
<country>Spain</country>
</address>
</facility>
</location>
<location_countries>
<country>Spain</country>
</location_countries>
<verification_date>November 2021</verification_date>
<study_first_submitted>February 6, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>January 19, 2022</last_update_submitted>
<last_update_submitted_qc>January 19, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">January 21, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Esophageal Neoplasms</mesh_term>
<mesh_term>Anastomotic Leak</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This study is a randomized clinical trial to clarify if preoperative embolization of gastric
arteries can reduce the incidence of oesophagogastric leakage after an esophagectomy for
esophageal cancer comparing an experimental group vs control group.
In patients with infracarinal esophageal carcinoma, the surgery is a complex procedure and
with a high morbidity. It consists of a subtotal esophagectomy with tubular gastroplasty and
cervical esophagogastric anastomosis. The most important complication is the anastomotic
leakage with a high mortality. Among the possible causes of anastomotic leakage an important
factor is the impaired microcirculation in the anastomotic region after the partial
devascularization of the stomach during the surgery. There are several experimental studies
about the different techniques to improve this vascularization and their effects on mucosal
oxygenation. There are several methods currently used for assessing tissue oxygenation. The
polarographic partial pressure of oxygen (pO2) electrode has been considered as the 'gold
standard' for measuring oxygen tension. This is the reason why tissue pressure of oxygen
(PtiO2) will be measured by Licox® (Integra Neuroscience) system in two groups. There aren't
prospective randomized controlled trials to answer these questions. For this reason the
investigators propose to perform a prospective randomized controlled trial in patients
underwent on this surgery, comparing two groups: one of them will be carried out a
preoperative arterial embolization (PAE), and the other one will be operated directly, to
demonstrate if the ischemic conditioning by PAE can reduce the incidence of anastomotic
esophagogastric leakage and improve the gastric conduit oxygenation.
Inclusion Criteria:
- All patients requiring a esophagectomy with cervical esophagogastrostomy for
esophageal cancer
- 18 or above years old
- Karnofsky>50%
- Acceptance and signing the full informed consent
Exclusion Criteria:
- Fistula tracheobronchial
- Metastatic disease
- Anatomic vascular alteration that contraindicate the embolization (congenital celiac
trunk stenosis, presence of arcuate ligament, atherosclerotic stenosis, etc,..)
- Severe cardiorespiratory failure
- Refuse to collaborate in the study
|
NCT0426xxxx/NCT04268667.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268667</url>
</required_header>
<id_info>
<org_study_id>spinal manipulation</org_study_id>
<nct_id>NCT04268667</nct_id>
</id_info>
<brief_title>Comparison of Two Spinal Manipulation Treatments in Patients With Chronic Mechanical Neck Pain</brief_title>
<official_title>A Comparative Study Between Cervicothoracic and Upper Cervical Spine Manipulation in Patients With Chronic Mechanical Neck Pain: a Randomized Controlled Trial</official_title>
<sponsors>
<lead_sponsor>
<agency>Clínica Ciudad de Almería</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Clínica Ciudad de Almería</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
There is enough evidence to suggest that the spinal manipulation of the upper cervical spine
and cervicothoracic spine are effective in decreasing neck pain. Therefore, the purpose of
this randomized controlled trial is to compare the effects of an isolated application of
upper cervical spine thrust joint manipulation with the application of a full combination of
cervical, cervico-thoracic and thoracic spine thrust joint manipulation on neck pain,
disability and cervical range of motion in individuals with chronic mechanical neck pain.
</textblock>
</brief_summary>
<overall_status>Completed</overall_status>
<start_date type="Actual">February 17, 2020</start_date>
<completion_date type="Actual">April 1, 2020</completion_date>
<primary_completion_date type="Actual">April 1, 2020</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>Single (Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>Change in neck pain at rest: Numeric Pain Rating Scale (0-10)</measure>
<time_frame>Baseline and 15 days post-treatment</time_frame>
<description>Neck pain at rest. Measured with the Numeric Pain Rating Scale (0 = ''no pain'' and 10 = ''worst imaginable pain).</description>
</primary_outcome>
<primary_outcome>
<measure>Change in neck pain in flexion: Numeric Pain Rating Scale (0-10)</measure>
<time_frame>Baseline and 15 days post-treatment</time_frame>
<description>Pain in the cervical flexion movement. Measured with the Numeric Pain Rating Scale (0 = ''no pain'' and 10 = ''worst imaginable pain).</description>
</primary_outcome>
<primary_outcome>
<measure>Change in neck pain in extension: Numeric Pain Rating Scale (0-10)</measure>
<time_frame>Baseline and 15 days post-treatment</time_frame>
<description>Pain in the cervical extension movement. Measured with the Numeric Pain Rating Scale (0 = ''no pain'' and 10 = ''worst imaginable pain).</description>
</primary_outcome>
<primary_outcome>
<measure>Change in neck pain in right lateral flexion: Numeric Pain Rating Scale (0-10)</measure>
<time_frame>Baseline and 15 days post-treatment</time_frame>
<description>Pain in the cervical right lateral flexion movement. Measured with the Numeric Pain Rating Scale (0 = ''no pain'' and 10 = ''worst imaginable pain).</description>
</primary_outcome>
<primary_outcome>
<measure>Change in neck pain in left lateral flexion: Numeric Pain Rating Scale (0-10)</measure>
<time_frame>Baseline and 15 days post-treatment</time_frame>
<description>Pain in the cervical left lateral flexion movement. Measured with the Numeric Pain Rating Scale (0 = ''no pain'' and 10 = ''worst imaginable pain).</description>
</primary_outcome>
<primary_outcome>
<measure>Change in neck pain in right rotation: Numeric Pain Rating Scale (0-10)</measure>
<time_frame>Baseline and 15 days post-treatment</time_frame>
<description>Pain in the cervical right rotation movement. Measured with the Numeric Pain Rating Scale (0 = ''no pain'' and 10 = ''worst imaginable pain).</description>
</primary_outcome>
<primary_outcome>
<measure>Change in neck pain in left rotation: Numeric Pain Rating Scale (0-10)</measure>
<time_frame>Baseline and 15 days post-treatment</time_frame>
<description>Pain in the cervical left rotation movement. Measured with the Numeric Pain Rating Scale (0 = ''no pain'' and 10 = ''worst imaginable pain).</description>
</primary_outcome>
<primary_outcome>
<measure>Change in neck disability: Neck Disability Index (0-50)</measure>
<time_frame>Baseline and 15 days post-treatment</time_frame>
<description>Neck disability is measured with Neck Disability Index (10 items). A higher score indicates greater disability.</description>
</primary_outcome>
<primary_outcome>
<measure>Change in flexion movement: Cervical Range of Motion device</measure>
<time_frame>Baseline and 15 days post-treatment</time_frame>
<description>Range of cervical motion in flexion. Measured with a Cervical Range of Motion (CROM) device</description>
</primary_outcome>
<primary_outcome>
<measure>Change in extension movement: Cervical Range of Motion device</measure>
<time_frame>Baseline and 15 days post-treatment</time_frame>
<description>Range of cervical motion in extension. Measured with a Cervical Range of Motion (CROM) device</description>
</primary_outcome>
<primary_outcome>
<measure>Change in right lateral flexion movement: Cervical Range of Motion device</measure>
<time_frame>Baseline and 15 days post-treatment</time_frame>
<description>Range of cervical motion in right lateral flexion. Measured with a Cervical Range of Motion (CROM) device</description>
</primary_outcome>
<primary_outcome>
<measure>Change in left lateral flexion movement: Cervical Range of Motion device</measure>
<time_frame>Baseline and 15 days post-treatment</time_frame>
<description>Range of cervical motion in left lateral flexion. Measured with a Cervical Range of Motion (CROM) device</description>
</primary_outcome>
<primary_outcome>
<measure>Change in right rotation movement: Cervical Range of Motion device</measure>
<time_frame>Baseline and 15 days post-treatment</time_frame>
<description>Range of cervical motion in right rotation. Measured with a Cervical Range of Motion (CROM) device</description>
</primary_outcome>
<primary_outcome>
<measure>Change in left rotation movement: Cervical Range of Motion device</measure>
<time_frame>Baseline and 15 days post-treatment</time_frame>
<description>Range of cervical motion in left rotation. Measured with a Cervical Range of Motion (CROM) device</description>
</primary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">186</enrollment>
<condition>Neck Pain</condition>
<arm_group>
<arm_group_label>Upper cervical spine manipulation group</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Spinal thrust joint manipulation on the atlantoaxial joint</description>
</arm_group>
<arm_group>
<arm_group_label>Cervicothoracic spine manipulations group</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Different spinal thrust joint manipulations on the thoracic spine (T6), mid-cervical spine (C3-C4) and cervicothoracic junction (C7-T1).</description>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Spinal manipulation</intervention_name>
<description>Application of upper cervical spine thrust joint manipulation or application of a full combination of cervical, cervico-thoracic and thoracic spine thrust joint manipulation.</description>
<arm_group_label>Cervicothoracic spine manipulations group</arm_group_label>
<arm_group_label>Upper cervical spine manipulation group</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Symptom persistence for more than 12 weeks.

- Age from 18 to 55 years.

- Localized pain in the cervical spine.

- Symptoms are caused by cervical movement or sustained postures.

Exclusion Criteria:

- Stage acute of symptoms.

- Any contraindication to cervical spinal manipulation (fracture, osteoporosis, joint
infections or vertebrobasilar insufficiency).

- Patients with previous neck trauma or cervical spine surgery.

- Patients diagnosed with cervical radiculopathy.

- Patients diagnosed with fibromyalgia.

- Have been treated with manual therapy in the last 3 months.

- Receiving other treatment during the course of the study.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>55 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Raúl Romero del Rey, Mr</last_name>
<role>Principal Investigator</role>
<affiliation>Clinica Ciudad de Almería</affiliation>
</overall_official>
<location>
<facility>
<name>Clínica Ciudad de Almería</name>
<address>
<city>Almería</city>
<zip>04008</zip>
<country>Spain</country>
</address>
</facility>
</location>
<location_countries>
<country>Spain</country>
</location_countries>
<verification_date>June 2020</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>June 8, 2020</last_update_submitted>
<last_update_submitted_qc>June 8, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">June 11, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Clínica Ciudad de Almería</investigator_affiliation>
<investigator_full_name>Raúl Romero del Rey</investigator_full_name>
<investigator_title>Principal Investigator</investigator_title>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Neck Pain</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
There is enough evidence to suggest that the spinal manipulation of the upper cervical spine
and cervicothoracic spine are effective in decreasing neck pain. Therefore, the purpose of
this randomized controlled trial is to compare the effects of an isolated application of
upper cervical spine thrust joint manipulation with the application of a full combination of
cervical, cervico-thoracic and thoracic spine thrust joint manipulation on neck pain,
disability and cervical range of motion in individuals with chronic mechanical neck pain.
Inclusion Criteria:
- Symptom persistence for more than 12 weeks.
- Age from 18 to 55 years.
- Localized pain in the cervical spine.
- Symptoms are caused by cervical movement or sustained postures.
Exclusion Criteria:
- Stage acute of symptoms.
- Any contraindication to cervical spinal manipulation (fracture, osteoporosis, joint
infections or vertebrobasilar insufficiency).
- Patients with previous neck trauma or cervical spine surgery.
- Patients diagnosed with cervical radiculopathy.
- Patients diagnosed with fibromyalgia.
- Have been treated with manual therapy in the last 3 months.
- Receiving other treatment during the course of the study.
|
NCT0426xxxx/NCT04268680.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268680</url>
</required_header>
<id_info>
<org_study_id>OpenGO</org_study_id>
<nct_id>NCT04268680</nct_id>
</id_info>
<brief_title>Perioperative Case Series: Qualitative Evaluation of Gait Cycle and Ground in Knee Arthroplasty Patients</brief_title>
<official_title>Perioperative Case Series: Qualitative Evaluation of Gait Cycle and Ground in Knee</official_title>
<sponsors>
<lead_sponsor>
<agency>Istituto Ortopedico Galeazzi</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Istituto Ortopedico Galeazzi</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Gait analysis is a quick and powerful tool with a wide range of clinical applications in
various fields. However, due to the expensive and highly specialized equipment required, gait
studies are mostly limited to academic research centers and small sample sizes and no
large-scale, randomized controlled trials have been performed. Several authors have proposed
inexpensive accelerometer-based systems to remedy this situation. Through mathematic
transformation they adequately measure step time and length. With these systems however only
temporal spatial gait parameters can be recorded; kinetic gait parameters, such as ground
reaction force, cannot be measured. As these kinetic parameters are important for clinical
studies, especially in fracture and rehabilitation research different methods are needed. Its
availability is mainly limited to research centers, conventional gait analysis is further
hindered by its stationarity and that it only allows momentary views of the patient's gait in
a confined research environment. Even smaller, wearable systems have to be attached to an
external apparatus, or are limited by their battery capacity, data storage and other device
specific factors. Furthermore, the use of these systems is at an early clinical stage and
their full potential not yet developed. As most disease processes are continuous, tools with
long-term, continuous measuring capabilities are needed. For this reason a new
pressure-measuring insole with built in battery and data storage was developed in cooperation
with the AO Foundation(AO Foundation, Davos, Switzerland). The system offers complete
independence from any external measures for up to 4 weeks and monitors a patient step during
this time.

The purpose of this pilot study is to investigate which how TKA arthroplasty may impact gait
during early and medium term rehabilitation phase. This will be done through the use of the
OpenGo Sensor Insole (Moticon GmbH).
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Advanced degenerative arthropathies of the knee ultimately manifest as pain and a loss of
function leading to impaired gait and activity. Total knee arthroplasty (TKA) is a procedure
that aim to eliminate pain, restore the function of the joint and ultimately improve the
ability of the patient to move and live an active life. TotalKneeArthroplasty has a history
of success, but as the orthopedic and healthcare sectors evolve, a greater level of scrutiny
and expectation for success will be applied to surgeons and device makers alike. In response
to these elevated levels of scrutiny and expectation more advanced methods will likely be
required to better capture and understand how a TotalKneeArthroplasty impacts patient
function both on an individual, patient by patient, basis as well as on device design and
surgical technique basis.

The present study is aimed at performing a preliminary evaluation to provide:

More advanced insight into a patient's functional recovery and rehabilitation with the
potential for phisician's to intervene earlier and with greater specificity to any challenges
encountered by the patient Objective evidence of the quality and value of the intervention on
an individualized basis. Study objectives Any change in gait as a result of arthroplasty and
dynamics of gait recovery during acute recovery and rehabilitation timeframe. Outcome
measures will be gait cycle and ground: foot interaction dynamics which will be observed
longitudinally and compared to the healthy contralateral limb (ground: foot interaction
dynamics) as well literature data (gait cycle).

Primary objective:Evaluation of gait cycle and ground in primary TotalKneeArthroplasty
patients compared to the healthy contralateral limb.

Secondary objectives:Easy of use. Qualitative user (Phisician and patient) feedback on
experience using and wearing the insoles Study design:This is, single arm, prospective,
single center, pilot study to measure the pre-operative and post-operative gait and ground:
foot interaction dynamics of 6 subjects who are undergoing TotalKneeArthroplasty .

Data that will be collected at baseline (pre-op) besides the standard clinical data
(VisualAnalogueScale, KneeSocietyScore SatisfactionForm-12, Knee Injury and Osteoarthritis
Outcome Score(KOOS)) include: gait and ground: foot interaction dynamics during a prescribed
in clinic activity as well as during activities of daily living.

Data that will be collected about the clinical follow-up include: gait and ground: foot
interaction dynamics during a prescribed in clinic activity as well as during activities of
daily living; user feedback regarding their experience using and wearing the insoles.

Total study duration for study participants will be 6 months with follow-up visits planned
at: daily until discharge, 1 week, 2 weeks, 3 weeks, 3 months and 6 months. Full enrollement
is estimated to require 1 months, therefore the total study duration is expected to be 7
months.

Subjects will be included in 1 Italian site. Data and user feedback will be analyzed
continuously as they become available throughout the study period.

Patients selection:Once a subject has completed the informed consent procedure and signed the
Informed Consent Form, the PI or delegated study research staff can complete the screening
process with the subject. All potential subjects who undergo the screening process will be
documented on a Screening and Enrollment Log, on which reasons for exclusion from or denial
to participate should be noted.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">November 7, 2017</start_date>
<completion_date type="Actual">June 8, 2018</completion_date>
<primary_completion_date type="Actual">January 9, 2018</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Perioperative Case Series: clinical evaluation of gait cycle and ground in Knee arthroplasty patients</measure>
<time_frame>baseline to 3 month</time_frame>
<description>Evaluation of gait cycle and ground in primary TKA patients compared to the healthy contralateral limb.</description>
</primary_outcome>
<secondary_outcome>
<measure>Perioperative Case Series: qualitative evaluation of gait cycle and ground in Knee arthroplasty patients</measure>
<time_frame>baseline to 3 month</time_frame>
<description>Easy of use. Qualitative user (HCP and patient) feedback on experience using and wearing the insoles</description>
</secondary_outcome>
<enrollment type="Actual">6</enrollment>
<condition>Gait, Unsteady</condition>
<eligibility>
<study_pop>
<textblock>
Patients affected by degenerative gonarthrosis who need a TKA in one of the two Knees
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- primary TKA

- 45-75 years of age (included)

- skeletally mature

- willing and able to participate in required pre-op and follow-up visits at the
investigational site and to complete study procedures and questionnaires

- consented to participating in the study by signing the IRB/EC approved informed
consent form

- BMI <32

Exclusion Criteria:

- symptomatic/debilitating co-commitant arthropathy of non-operative joints (e.g. a TKA
patient cannot have advanced arthritis of the contralateral knee or ipsilateral
hip/ankle) that would impede or otherwise confuse the peri-operative measurement of
gait.

- Significant comorbidities that would impede the patients ability to participate in
standard recovery and rehabilitation
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>45 Years</minimum_age>
<maximum_age>75 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Michele Ulivi, Dr</last_name>
<role>Principal Investigator</role>
<affiliation>IRCCS Istituto Ortopedico GaleazziMilano</affiliation>
</overall_official>
<location>
<facility>
<name>Istituto Ortopedico Galeazzi</name>
<address>
<city>Milano</city>
<zip>20161</zip>
<country>Italy</country>
</address>
</facility>
</location>
<location_countries>
<country>Italy</country>
</location_countries>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>April 22, 2020</last_update_submitted>
<last_update_submitted_qc>April 22, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">April 24, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>gait cycle</keyword>
<keyword>knee arthroplasty</keyword>
<keyword>wearable insole</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Gait Disorders, Neurologic</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Gait analysis is a quick and powerful tool with a wide range of clinical applications in
various fields. However, due to the expensive and highly specialized equipment required, gait
studies are mostly limited to academic research centers and small sample sizes and no
large-scale, randomized controlled trials have been performed. Several authors have proposed
inexpensive accelerometer-based systems to remedy this situation. Through mathematic
transformation they adequately measure step time and length. With these systems however only
temporal spatial gait parameters can be recorded; kinetic gait parameters, such as ground
reaction force, cannot be measured. As these kinetic parameters are important for clinical
studies, especially in fracture and rehabilitation research different methods are needed. Its
availability is mainly limited to research centers, conventional gait analysis is further
hindered by its stationarity and that it only allows momentary views of the patient's gait in
a confined research environment. Even smaller, wearable systems have to be attached to an
external apparatus, or are limited by their battery capacity, data storage and other device
specific factors. Furthermore, the use of these systems is at an early clinical stage and
their full potential not yet developed. As most disease processes are continuous, tools with
long-term, continuous measuring capabilities are needed. For this reason a new
pressure-measuring insole with built in battery and data storage was developed in cooperation
with the AO Foundation(AO Foundation, Davos, Switzerland). The system offers complete
independence from any external measures for up to 4 weeks and monitors a patient step during
this time.
The purpose of this pilot study is to investigate which how TKA arthroplasty may impact gait
during early and medium term rehabilitation phase. This will be done through the use of the
OpenGo Sensor Insole (Moticon GmbH).
Advanced degenerative arthropathies of the knee ultimately manifest as pain and a loss of
function leading to impaired gait and activity. Total knee arthroplasty (TKA) is a procedure
that aim to eliminate pain, restore the function of the joint and ultimately improve the
ability of the patient to move and live an active life. TotalKneeArthroplasty has a history
of success, but as the orthopedic and healthcare sectors evolve, a greater level of scrutiny
and expectation for success will be applied to surgeons and device makers alike. In response
to these elevated levels of scrutiny and expectation more advanced methods will likely be
required to better capture and understand how a TotalKneeArthroplasty impacts patient
function both on an individual, patient by patient, basis as well as on device design and
surgical technique basis.
The present study is aimed at performing a preliminary evaluation to provide:
More advanced insight into a patient's functional recovery and rehabilitation with the
potential for phisician's to intervene earlier and with greater specificity to any challenges
encountered by the patient Objective evidence of the quality and value of the intervention on
an individualized basis. Study objectives Any change in gait as a result of arthroplasty and
dynamics of gait recovery during acute recovery and rehabilitation timeframe. Outcome
measures will be gait cycle and ground: foot interaction dynamics which will be observed
longitudinally and compared to the healthy contralateral limb (ground: foot interaction
dynamics) as well literature data (gait cycle).
Primary objective:Evaluation of gait cycle and ground in primary TotalKneeArthroplasty
patients compared to the healthy contralateral limb.
Secondary objectives:Easy of use. Qualitative user (Phisician and patient) feedback on
experience using and wearing the insoles Study design:This is, single arm, prospective,
single center, pilot study to measure the pre-operative and post-operative gait and ground:
foot interaction dynamics of 6 subjects who are undergoing TotalKneeArthroplasty .
Data that will be collected at baseline (pre-op) besides the standard clinical data
(VisualAnalogueScale, KneeSocietyScore SatisfactionForm-12, Knee Injury and Osteoarthritis
Outcome Score(KOOS)) include: gait and ground: foot interaction dynamics during a prescribed
in clinic activity as well as during activities of daily living.
Data that will be collected about the clinical follow-up include: gait and ground: foot
interaction dynamics during a prescribed in clinic activity as well as during activities of
daily living; user feedback regarding their experience using and wearing the insoles.
Total study duration for study participants will be 6 months with follow-up visits planned
at: daily until discharge, 1 week, 2 weeks, 3 weeks, 3 months and 6 months. Full enrollement
is estimated to require 1 months, therefore the total study duration is expected to be 7
months.
Subjects will be included in 1 Italian site. Data and user feedback will be analyzed
continuously as they become available throughout the study period.
Patients selection:Once a subject has completed the informed consent procedure and signed the
Informed Consent Form, the PI or delegated study research staff can complete the screening
process with the subject. All potential subjects who undergo the screening process will be
documented on a Screening and Enrollment Log, on which reasons for exclusion from or denial
to participate should be noted.
Patients affected by degenerative gonarthrosis who need a TKA in one of the two Knees
Inclusion Criteria:
- primary TKA
- 45-75 years of age (included)
- skeletally mature
- willing and able to participate in required pre-op and follow-up visits at the
investigational site and to complete study procedures and questionnaires
- consented to participating in the study by signing the IRB/EC approved informed
consent form
- BMI <32
Exclusion Criteria:
- symptomatic/debilitating co-commitant arthropathy of non-operative joints (e.g. a TKA
patient cannot have advanced arthritis of the contralateral knee or ipsilateral
hip/ankle) that would impede or otherwise confuse the peri-operative measurement of
gait.
- Significant comorbidities that would impede the patients ability to participate in
standard recovery and rehabilitation
|
NCT0426xxxx/NCT04268693.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268693</url>
</required_header>
<id_info>
<org_study_id>NCR191600</org_study_id>
<nct_id>NCT04268693</nct_id>
</id_info>
<brief_title>Bisphenol and Phthalate Exposures in Triple Negative Breast Cancer</brief_title>
<acronym>EDC-TNBC</acronym>
<official_title>Bisphenol and Phthalate Exposures in Women With Triple Negative Breast Cancer Receiving Doxorubicin Chemotherapy - a Pilot Study</official_title>
<sponsors>
<lead_sponsor>
<agency>George Washington University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>George Washington University</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
In this observational pilot study urine samples will be collected from women receiving
neoadjuvant chemotherapy with doxorubicin for triple negative breast cancer to determine
whether: 1) exposures bisphenol and phthalate levels change over the course of neoadjuvant
chemotherapy, and 2) levels differ between black women and those of other racial groups.

The hypothesis is that bisphenol and phthalate levels will be similar to those of the general
US female population at the time of diagnosis, however levels will increase during treatment
due to exposure to plastics in the medical setting. The investigators also hypothesize that
because of differences in personal care product use, black women may have higher urinary
levels of bisphenols and phthalates prior to starting chemotherapy.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that does not
express estrogen, progesterone, or the human epidermal growth factor (HER2/neu) receptors,
and has a low overall survival rate compared to other types of breast cancer.

Unlike hormone and HER2/neu positive breast cancers, targeted therapies are not available for
TNBC. Thus, the systemic chemotherapeutic agent doxorubicin is widely used for the treatment
of TNBC. However, doxorubicin resistance is common, and leads to poorer treatment outcomes.

Understanding factors that contribute to doxorubicin resistance is critical to improving
cancer treatment outcomes among women with TNBC. Pre-clinical in vitro studies indicate that
exposure to endocrine disrupting chemicals, such as bisphenols and phthalates, contribute to
doxorubicin resistance, but these findings have not been evaluated in humans.
</textblock>
</detailed_description>
<overall_status>Withdrawn</overall_status>
<why_stopped>
Study never initiated due to COVID pandemic, staffing changes
</why_stopped>
<start_date type="Anticipated">September 2022</start_date>
<completion_date type="Anticipated">August 2023</completion_date>
<primary_completion_date type="Anticipated">August 2023</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>urinary bisphenol and phthalate metabolite levels</measure>
<time_frame>baseline</time_frame>
<description>quantification of bisphenol and phthalate metabolites by liquid chromotography-tandem mass spectrometry</description>
</primary_outcome>
<primary_outcome>
<measure>urinary bisphenol and phthalate metabolite levels</measure>
<time_frame>post-neoadjuvant chemotherapy (either 16 or 20 weeks)</time_frame>
<description>quantification of bisphenol and phthalate metabolites by liquid chromotography-tandem mass spectrometry</description>
</primary_outcome>
<primary_outcome>
<measure>change from baseline urinary bisphenol and phthalate levels at end of neoadjuvant chemotherapy</measure>
<time_frame>baseline and post-neoadjuvant chemotherapy (16 or 20 weeks)</time_frame>
<description>percent of change in urinary bisphenol and phthalate levels from pre- to post-neoadjuvant chemotherapy</description>
</primary_outcome>
<number_of_groups>1</number_of_groups>
<enrollment type="Actual">0</enrollment>
<condition>Triple Negative Breast Cancer</condition>
<arm_group>
<arm_group_label>Study cohort</arm_group_label>
<description>urinary bisphenol and phthalate levels</description>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>urine collection</intervention_name>
<description>Collect three urine samples either in the clinic or at home. This will occur prior to starting neoadjuvant chemotherapy, and again at the end of the scheduled course of neoadjuvant chemotherapy.</description>
<arm_group_label>Study cohort</arm_group_label>
</intervention>
<biospec_retention>Samples Without DNA</biospec_retention>
<biospec_descr>
<textblock>
urine samples
</textblock>
</biospec_descr>
<eligibility>
<study_pop>
<textblock>
Women being treated at the George Washington University for stage I - III triple negative
breast cancer who are scheduled to receive a neoadjuvant chemotherapy regimen containing
doxorubicin.
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- diagnosis of stage I - III triple negative breast cancer

- scheduled to receive a neoadjuvant chemotherapy regimen including doxorubicin

- receiving treatment at the George Washington University Cancer Center

Exclusion Criteria:

- diagnosis of other types of breast cancer

- not scheduled to receive doxorubicin as part of the neoadjuvant chemotherapy regimen

- not planning to receive neoadjuvant chemotherapy at the George Washington University
Cancer Center
</textblock>
</criteria>
<gender>Female</gender>
<minimum_age>21 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Kim Robien, PhD, RD</last_name>
<role>Principal Investigator</role>
<affiliation>Milken Institute School of Public Health, George Washington University</affiliation>
</overall_official>
<location>
<facility>
<name>Milken Institute School of Public Health, George Washington University</name>
<address>
<city>Washington</city>
<state>District of Columbia</state>
<zip>20052</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>November 2022</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>November 14, 2022</last_update_submitted>
<last_update_submitted_qc>November 14, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">November 17, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>George Washington University</investigator_affiliation>
<investigator_full_name>Kimberly Robien</investigator_full_name>
<investigator_title>Associate Professor</investigator_title>
</responsible_party>
<keyword>bisphenol</keyword>
<keyword>phthalate</keyword>
<keyword>doxorubicin</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Breast Neoplasms</mesh_term>
<mesh_term>Triple Negative Breast Neoplasms</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
<ipd_description>Will not share data until study is complete and all data deidentified</ipd_description>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
In this observational pilot study urine samples will be collected from women receiving
neoadjuvant chemotherapy with doxorubicin for triple negative breast cancer to determine
whether: 1) exposures bisphenol and phthalate levels change over the course of neoadjuvant
chemotherapy, and 2) levels differ between black women and those of other racial groups.
The hypothesis is that bisphenol and phthalate levels will be similar to those of the general
US female population at the time of diagnosis, however levels will increase during treatment
due to exposure to plastics in the medical setting. The investigators also hypothesize that
because of differences in personal care product use, black women may have higher urinary
levels of bisphenols and phthalates prior to starting chemotherapy.
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that does not
express estrogen, progesterone, or the human epidermal growth factor (HER2/neu) receptors,
and has a low overall survival rate compared to other types of breast cancer.
Unlike hormone and HER2/neu positive breast cancers, targeted therapies are not available for
TNBC. Thus, the systemic chemotherapeutic agent doxorubicin is widely used for the treatment
of TNBC. However, doxorubicin resistance is common, and leads to poorer treatment outcomes.
Understanding factors that contribute to doxorubicin resistance is critical to improving
cancer treatment outcomes among women with TNBC. Pre-clinical in vitro studies indicate that
exposure to endocrine disrupting chemicals, such as bisphenols and phthalates, contribute to
doxorubicin resistance, but these findings have not been evaluated in humans.
urine samples
Women being treated at the George Washington University for stage I - III triple negative
breast cancer who are scheduled to receive a neoadjuvant chemotherapy regimen containing
doxorubicin.
Inclusion Criteria:
- diagnosis of stage I - III triple negative breast cancer
- scheduled to receive a neoadjuvant chemotherapy regimen including doxorubicin
- receiving treatment at the George Washington University Cancer Center
Exclusion Criteria:
- diagnosis of other types of breast cancer
- not scheduled to receive doxorubicin as part of the neoadjuvant chemotherapy regimen
- not planning to receive neoadjuvant chemotherapy at the George Washington University
Cancer Center
|
NCT0426xxxx/NCT04268706.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268706</url>
</required_header>
<id_info>
<org_study_id>TESSCAR001</org_study_id>
<nct_id>NCT04268706</nct_id>
</id_info>
<brief_title>Phase 2 Study Evaluating Autologous CD30.CAR-T Cells in Patients With Relapsed/Refractory Hodgkin Lymphoma (CHARIOT)</brief_title>
<official_title>A Phase 2 Multi-Center Study Evaluating the Safety and Efficacy of CD30-Directed Genetically Modified Autologous T Cells (CD30.CAR-T) in Adult and Pediatric Patients With Relapsed or Refractory Classical Hodgkin Lymphoma</official_title>
<sponsors>
<lead_sponsor>
<agency>Tessa Therapeutics</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
</sponsors>
<source>Tessa Therapeutics</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This is a two-part, Phase 2, multicenter, open-label, single arm study to evaluate the safety
and efficacy of autologous CD30.CAR-T in adult and pediatric subjects with relapsed or
refractory CD30+ classical Hodgkin Lymphoma.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
The Pilot part of the study will evaluate the safety, tolerability, and preliminary antitumor
efficacy of CD30.CAR-T. The Pivotal part of the study will evaluate antitumor efficacy and
further evaluate safety and tolerability. All study eligibility requirements, assessments,
procedures, and follow-up are the same for patients in both Pilot and Pivotal parts of the
study.

Subjects who meet eligibility criteria will have their blood drawn by leukapheresis for
manufacture the CD30.CAR-T cells. Subjects are allowed bridging chemotherapy, as per
Investigator choice, while waiting for production of CD30.CAR-T. Lymphodepletion (LD) with
fludarabine and bendamustine will be administered for 3 consecutive days starting on Day -5
to Day -3, prior to CD30.CAR-T infusion, which will be administered on Day 0 as a single IV
infusion. Depending on disease status, eligible subjects may receive up to a total of two
CD30.CAR-T infusions at the same dose, each with preceding LD chemotherapy.

Subjects will be closely monitored for safety and efficacy throughout the Treatment Period
until the end of study (EOS) visit at Month 24. Subjects will be followed for survival,
withdrawal of consent or study closure, whichever occurs first. Health Related Quality of
Life assessments will also be collected throughout the study. After the EOS visit, subjects
will enter the long-term follow-up phase (LTFU) which will include survival follow-up,
additional safety, efficacy and biomarker assessments, as clinically indicated.
</textblock>
</detailed_description>
<overall_status>Active, not recruiting</overall_status>
<start_date type="Actual">February 1, 2021</start_date>
<completion_date type="Anticipated">March 2037</completion_date>
<primary_completion_date type="Anticipated">May 2025</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Pilot: Safety of autologous CD30.CAR-T</measure>
<time_frame>Minimum 24 months post-CD30.CAR-T infusion</time_frame>
<description>Adverse events</description>
</primary_outcome>
<primary_outcome>
<measure>Pivotal: Anti-tumor effect of autologous CD30.CAR-T using objective response rate (ORR) as assessed by an Independent Radiology Review Committee (IRRC) per the Revised Criteria for Response Assessment: The Lugano Classification (Cheson, 2014)</measure>
<time_frame>As early as 6 weeks after CD30.CAR-T treatment</time_frame>
<description>ORR</description>
</primary_outcome>
<secondary_outcome>
<measure>Pilot: Antitumor efficacy of autologous CD30.CAR-T using objective response rate (ORR) as assessed by an Independent Radiology Review Committee (IRRC) per the Revised Criteria for Response Assessment: The Lugano Classification (Cheson et al., 2014)</measure>
<time_frame>As early as 6 weeks after CD30.CAR-T treatment</time_frame>
<description>ORR</description>
</secondary_outcome>
<secondary_outcome>
<measure>Pilot: Duration of Response</measure>
<time_frame>Minimum 24 months post-CD30.CAR-T infusion</time_frame>
<description>DOR</description>
</secondary_outcome>
<secondary_outcome>
<measure>Pilot: Progression Free Survival</measure>
<time_frame>Minimum 24 months post-CD30.CAR-T infusion</time_frame>
<description>PFS</description>
</secondary_outcome>
<secondary_outcome>
<measure>Pilot: Overall Survival</measure>
<time_frame>Minimum 24 months post-CD30.CAR-T infusion</time_frame>
<description>OS</description>
</secondary_outcome>
<secondary_outcome>
<measure>Pilot: Health Related quality of life (HRQoL) questionnaire</measure>
<time_frame>Minimum 24 months post-CD30.CAR-T infusion</time_frame>
<description>QoL</description>
</secondary_outcome>
<secondary_outcome>
<measure>Pivotal: Number of patients with adverse events as a measure of safety and tolerability of CD30.CART cells</measure>
<time_frame>As early as 6 weeks after CD30.CAR-T treatment</time_frame>
<description>Adverse events</description>
</secondary_outcome>
<secondary_outcome>
<measure>Pivotal: Objective response rate (ORR as assessed by IRRC) per the Revised Criteria for Response Assessment: The Lugano Classification (Cheson, 2014)</measure>
<time_frame>Minimum 24 months post-CD30.CAR-T infusion</time_frame>
<description>ORR</description>
</secondary_outcome>
<secondary_outcome>
<measure>Pivotal: Progression Free Survival (PFS)</measure>
<time_frame>Minimum 24 months post-CD30.CAR-T infusion</time_frame>
<description>PFS</description>
</secondary_outcome>
<secondary_outcome>
<measure>Pivotal: Duration of Response (DOR)</measure>
<time_frame>Minimum 24 months post-CD30.CAR-T infusion</time_frame>
<description>DOR</description>
</secondary_outcome>
<secondary_outcome>
<measure>Pivotal: Overall Survival</measure>
<time_frame>Minimum 24 months post-CD30.CAR-T infusion</time_frame>
<description>OS</description>
</secondary_outcome>
<secondary_outcome>
<measure>Pivotal: Health Related quality of life (HRQoL) questionnaire</measure>
<time_frame>Minimum 24 months post-CD30.CAR-T infusion</time_frame>
<description>HRQoL</description>
</secondary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Anticipated">97</enrollment>
<condition>Hodgkin Lymphoma, Adult</condition>
<condition>Hodgkin Disease Recurrent</condition>
<condition>Hodgkin Disease Refractory</condition>
<condition>Hodgkin Disease, Pediatric</condition>
<arm_group>
<arm_group_label>CD30 positive r/r classical Hodgkin Lymphoma</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Patients with relapsed or refractory classical Hodgkin Lymphoma who have failed 3 prior lines of treatment, which may include a prior autologous and/or allogeneic stem cell transplant.
Patients will be treated with autologous CD30.CAR-T cells.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>CD30.CAR-T</intervention_name>
<description>Autologous CD30.CAR-T cells infused on Day 0 after the completion of lymphodepleting chemotherapy.</description>
<arm_group_label>CD30 positive r/r classical Hodgkin Lymphoma</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Fludarabine</intervention_name>
<description>Lymphodepletion chemotherapy (30 mg/m2/day) for 3 consecutive days</description>
<arm_group_label>CD30 positive r/r classical Hodgkin Lymphoma</arm_group_label>
<other_name>Fludara</other_name>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Bendamustine</intervention_name>
<description>Lymphodepletion chemotherapy (70 mg/m2/day) for 3 consecutive days</description>
<arm_group_label>CD30 positive r/r classical Hodgkin Lymphoma</arm_group_label>
<other_name>Bendeka</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

Eligibility is determined prior to blood collection . Patients must satisfy the following
criteria to be enrolled in the study:

1. Signed Informed Consent Form

2. Male or female patients who are 12 - 75 years of age

3. Histologically confirmed classical Hodgkin Lymphoma

4. Relapsed or refractory cHL that has failed at least 3 prior lines of therapy,
including:

- chemotherapy

- BV and/or

- PD-1 inhibitor Patients may have previously received an autologous and/or
allogeneic stem cell transplant

5. CD30-positive tumor

6. At least 1 measurable lesion according to The Lugano Classification

7. Laboratory parameters: Hematological, renal and hepatic functions, and coagulation
parameters

- Hgb ≥ 8.0 g/dL

- Total bilirubin ≤ 1.5 × ULN

- AST and ALT ≤ 5 × the ULN

- CrCl > 45 mL/min

- ANC >1,000/µL

- Platelets >75,000/µL

- PT or INR ≤ 1.5 × ULN; PTT or aPTT ≤ 1.5 × ULN

8. ECOG PS of 0 to 1 or equivalent [either Karnofsky PS (for patients ≥ 16 year of age)
or Lansky PS (for patients < 16 years of age)]

9. Anticipated life expectancy > 12 weeks

Exclusion Criteria:

1. Evidence of lymphomatous involvement of central nervous system (CNS)

2. Presence of clinically relevant or active seizure disorder, stroke, cerebrovascular
ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with
central nervous system (CNS) involvement

3. Active uncontrolled bleeding or a known bleeding diathesis

4. Inadequate pulmonary function defined as pulse oximetry < 90% on room air

5. ECHO or MUGA with LVEF < 45%

6. On-going treatment with immunosuppressive drugs or chronic systemic corticosteroids

7. Having received:

- Anti-CD30 antibody-based therapy within 4 weeks prior to CD30.CAR-T infusion

- Prior investigational CD30.CAR-T

- CD30 bispecific agent within 8 weeks prior to CD30.CAR-T infusion

- Autologous HSCT within 90 days or allogeneic HSCT within 180 days prior to
CD30.CAR-T infusion

8. Currently receiving any investigational agents within 4 weeks prior to study
enrollment; or received any tumor vaccines within 6 weeks prior to CD30.CAR-T infusion

9. Active acute or chronic graft versus host disease (GVHD) requiring immune suppression
regardless of grade

10. Evidence of human immunodeficiency virus (HIV) infection

11. Seropositive for and with evidence of active viral infection with hepatitis B virus
(HBV) or hepatitis C virus (HCV)

12. Unresolved > Grade 1 non-hematologic toxicity associated with any prior treatments

13. History of hypersensitivity reactions to murine protein-containing products or other
product excipients

14. Symptomatic cardiovascular disease: Class III or IV according to the New York Heart
Association (NYHA) Functional Classification

15. Active second malignancy or history of another malignancy within the last 3 years

16. Women who are pregnant or intending to become pregnant; women who are breastfeeding;
persons with procreative potential not using and not willing to use 2 highly effective
methods of contraception

17. Any other serious, life-threatening, or unstable preexisting medical conditions
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>12 Years</minimum_age>
<maximum_age>75 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Helen Heslop, MD</last_name>
<role>Principal Investigator</role>
<affiliation>Baylor College of Medicine</affiliation>
</overall_official>
<location>
<facility>
<name>City of Hope Comprehensive Cancer Center</name>
<address>
<city>Duarte</city>
<state>California</state>
<zip>91010</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Chicago Medical Center</name>
<address>
<city>Chicago</city>
<state>Illinois</state>
<zip>60637</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Children's Hospital of Philadelphia</name>
<address>
<city>Philadelphia</city>
<state>Pennsylvania</state>
<zip>19104</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Sarah Cannon Research Institute</name>
<address>
<city>Nashville</city>
<state>Tennessee</state>
<zip>37203</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>MD Anderson Cancer Center</name>
<address>
<city>Houston</city>
<state>Texas</state>
<zip>77030</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>April 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>April 4, 2023</last_update_submitted>
<last_update_submitted_qc>April 4, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">April 5, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>r/r Hodgkin Lymphoma, CD30, adult, pediatrics</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Lymphoma</mesh_term>
<mesh_term>Hodgkin Disease</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Fludarabine</mesh_term>
<mesh_term>Bendamustine Hydrochloride</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This is a two-part, Phase 2, multicenter, open-label, single arm study to evaluate the safety
and efficacy of autologous CD30.CAR-T in adult and pediatric subjects with relapsed or
refractory CD30+ classical Hodgkin Lymphoma.
The Pilot part of the study will evaluate the safety, tolerability, and preliminary antitumor
efficacy of CD30.CAR-T. The Pivotal part of the study will evaluate antitumor efficacy and
further evaluate safety and tolerability. All study eligibility requirements, assessments,
procedures, and follow-up are the same for patients in both Pilot and Pivotal parts of the
study.
Subjects who meet eligibility criteria will have their blood drawn by leukapheresis for
manufacture the CD30.CAR-T cells. Subjects are allowed bridging chemotherapy, as per
Investigator choice, while waiting for production of CD30.CAR-T. Lymphodepletion (LD) with
fludarabine and bendamustine will be administered for 3 consecutive days starting on Day -5
to Day -3, prior to CD30.CAR-T infusion, which will be administered on Day 0 as a single IV
infusion. Depending on disease status, eligible subjects may receive up to a total of two
CD30.CAR-T infusions at the same dose, each with preceding LD chemotherapy.
Subjects will be closely monitored for safety and efficacy throughout the Treatment Period
until the end of study (EOS) visit at Month 24. Subjects will be followed for survival,
withdrawal of consent or study closure, whichever occurs first. Health Related Quality of
Life assessments will also be collected throughout the study. After the EOS visit, subjects
will enter the long-term follow-up phase (LTFU) which will include survival follow-up,
additional safety, efficacy and biomarker assessments, as clinically indicated.
Inclusion Criteria:
Eligibility is determined prior to blood collection . Patients must satisfy the following
criteria to be enrolled in the study:
1. Signed Informed Consent Form
2. Male or female patients who are 12 - 75 years of age
3. Histologically confirmed classical Hodgkin Lymphoma
4. Relapsed or refractory cHL that has failed at least 3 prior lines of therapy,
including:
- chemotherapy
- BV and/or
- PD-1 inhibitor Patients may have previously received an autologous and/or
allogeneic stem cell transplant
5. CD30-positive tumor
6. At least 1 measurable lesion according to The Lugano Classification
7. Laboratory parameters: Hematological, renal and hepatic functions, and coagulation
parameters
- Hgb ≥ 8.0 g/dL
- Total bilirubin ≤ 1.5 × ULN
- AST and ALT ≤ 5 × the ULN
- CrCl > 45 mL/min
- ANC >1,000/µL
- Platelets >75,000/µL
- PT or INR ≤ 1.5 × ULN; PTT or aPTT ≤ 1.5 × ULN
8. ECOG PS of 0 to 1 or equivalent [either Karnofsky PS (for patients ≥ 16 year of age)
or Lansky PS (for patients < 16 years of age)]
9. Anticipated life expectancy > 12 weeks
Exclusion Criteria:
1. Evidence of lymphomatous involvement of central nervous system (CNS)
2. Presence of clinically relevant or active seizure disorder, stroke, cerebrovascular
ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with
central nervous system (CNS) involvement
3. Active uncontrolled bleeding or a known bleeding diathesis
4. Inadequate pulmonary function defined as pulse oximetry < 90% on room air
5. ECHO or MUGA with LVEF < 45%
6. On-going treatment with immunosuppressive drugs or chronic systemic corticosteroids
7. Having received:
- Anti-CD30 antibody-based therapy within 4 weeks prior to CD30.CAR-T infusion
- Prior investigational CD30.CAR-T
- CD30 bispecific agent within 8 weeks prior to CD30.CAR-T infusion
- Autologous HSCT within 90 days or allogeneic HSCT within 180 days prior to
CD30.CAR-T infusion
8. Currently receiving any investigational agents within 4 weeks prior to study
enrollment; or received any tumor vaccines within 6 weeks prior to CD30.CAR-T infusion
9. Active acute or chronic graft versus host disease (GVHD) requiring immune suppression
regardless of grade
10. Evidence of human immunodeficiency virus (HIV) infection
11. Seropositive for and with evidence of active viral infection with hepatitis B virus
(HBV) or hepatitis C virus (HCV)
12. Unresolved > Grade 1 non-hematologic toxicity associated with any prior treatments
13. History of hypersensitivity reactions to murine protein-containing products or other
product excipients
14. Symptomatic cardiovascular disease: Class III or IV according to the New York Heart
Association (NYHA) Functional Classification
15. Active second malignancy or history of another malignancy within the last 3 years
16. Women who are pregnant or intending to become pregnant; women who are breastfeeding;
persons with procreative potential not using and not willing to use 2 highly effective
methods of contraception
17. Any other serious, life-threatening, or unstable preexisting medical conditions
|
NCT0426xxxx/NCT04268719.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268719</url>
</required_header>
<id_info>
<org_study_id>227223</org_study_id>
<nct_id>NCT04268719</nct_id>
</id_info>
<brief_title>Near Focus NBI-Driven Artificial Intelligence for the Diagnosis of Gastro-Oesophageal Reflux Disease</brief_title>
<official_title>Near Focus NBI-Driven Artificial Intelligence for the Diagnosis of Gastro-Oesophageal Reflux Disease</official_title>
<sponsors>
<lead_sponsor>
<agency>King's College Hospital NHS Trust</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>King's College Hospital NHS Trust</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Gastro-oesophageal reflux disease (GORD) is a chronic condition with symptoms arising
secondary to the reflux of stomach contents (Vakil et al., 2006). It is divided into four
phenotypes: Erosive Oesophagitis (EO), Non-Erosive Reflux Disease (NERD), Reflux
Hypersensitivity (RH), Functional Heartburn (FH) (Nikaki, Woodland and Sifrim, 2016). The
definition of these phenotype have evolved with the addition of diagnostic tests and methods
of their interpretation, the most recent being the Lyon Consensus Statement (Gyawali et al.,
2018). The majority of patients presenting with symptoms suggestive of GORD have no mucosal
lesion seen at endoscopy (Nikaki, Woodland and Sifrim, 2016). Studies have shown a relation
of increased IPCL numbers with GORD. This study aims to build a fully autmoated AI model
using Near-Focus NBI images on patients with symptoms suggestive of GORD phenotyped in
accordance with the Lyon Consensus.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Gastro-oesophageal reflux disease (GORD) is a chronic condition with symptoms arising
secondary to the reflux of stomach contents (Vakil et al., 2006). It is divided into four
phenotypes: Erosive Oesophagitis (EO), Non-Erosive Reflux Disease (NERD), Reflux
Hypersensitivity (RH), Functional Heartburn (FH) (Nikaki, Woodland and Sifrim, 2016). The
definition of these phenotype have evolved with the addition of diagnostic tests and methods
of their interpretation, the most recent being the Lyon Consensus Statement (Gyawali et al.,
2018). The majority of patients presenting with symptoms suggestive of GORD have no mucosal
lesion seen at endoscopy (Nikaki, Woodland and Sifrim, 2016). Complications of GORD, such as
peptic stricture and Barrett's oesophagus, can be readily diagnosed using WLE. The diagnosis
of reflux oesophagitis with standard-definition WLE is well described in the Los Angeles (LA)
classification (Armstrong et al., 1996) and validated (Lundell et al., 1999) with LA grades C
and D confirmatory of GORD (Gyawali et al., 2018). Furthermore, AET is demonstrated to
increase with LA classification A to D (Lundell et al., 1999). There is, however, only a
modest inter-observer agreement between LA grades (Kappa coefficient 0.4), especially A and
B. Furthermore LA grade A oesophagitis is detected in up to 17.0% of asymptomatic patients
(Nozu and Komiyama, 2008; Zagari et al., 2008). A diagnosis of GORD and decisions for
anti-reflux surgery cannot be made on this basis, mandating pH testing to confirm GORD.

Narrow Band Imaging

Imaging of the gastro-oesophageal junction using high definition Olympus H260 scope using the
LA classification of GORD with WLE and NBI demonstrated improvement in overall interobserver
reproducibility when used in a combination compared with WLE alone; k 0.62 vs 0.45
(<0.05)(Lee et al., 2007). Features identified using digital magnification NBI at the
squamo-columnar junction in cases of EO (n=41; LA grade A and B), NERD (n=36) and controls
(n=32) include micro-erosions (100% EO; 52.8% NERD; 23.3% controls), increased vascularity
(95.1% EO; 91.7% NERD; 36.7% controls) and round pit patterns (4.9% EO; 5.6% NERD; 70%
controls). Increased vascularity combined with absence of round pit pattern distinguishes
NERD from controls with sensitivity and specificity 86.1% and 83.3%. Inter-observer agreement
in this single centre study was good for increased vascularity (k=0.95) and micro erosions
(k=0.89) but low for pit pattern (k=0.59) (Fock et al., 2009).

Intra-papillary capillary loops (IPCLs) are mucosal capillaries arising from the submucosal
vein to the papilla, usually arranged in a regular 'dot' like fashion approximately
100micrometres apart (Inoue, 2001). The visualisation of oesophageal IPCLs with NBI is well
documented and form the basis of a NBI classification for squamous neoplasia (Inoue et al.,
2015). IPCL morphology changes have been proposed in patients being investigated for NERD, in
particular dilatation and elongation of IPCLs in patients with NERD with magnification NBI
(Kato et al., 2006).

NBI with optical magnification for the diagnosis of GORD has been evaluated in 2 studies
(Sharma et al., 2007; Lv et al., 2013). Sharma et al performed a feasibility trial with
Olympus Q240Z with quadrantic examination of the distal 5cm by WLE then NBI in n=50 GORD (EO
n=30; NERD n=20) and controls (n=30). Similar to Fock et al, the presence of microerosions
and hypervascularity was significantly higher amongst GORD. IPCL number and morphology of
tortuosity, dilatation were seen significantly more in GORD versus control. These findings
were consistent in independent comparison of EO and NERD versus controls. ROC analysis
thresholds for best sensitivity and specificity (respectively) for NERD were maximum
ipcl/field 131 (90%, 70%), min 99 (85%, 70%) and average 117 (90%, 70%) (Sharma et al.,
2007).

Lv et al used the Olympus GIF-H260Z to evaluate NERD (n=40), EO (n=40), Barrett's (n=40) and
healthy controls (n=40). IPCL number, morphology (prolonged/dilated/tortuous), microerosions,
round pit pattern above or below the SCJ, were recorded as features of reflux. Significant
differences were found with increased IPCL number, microerosions, non-round pit patterns
below the SCJ in GERD (NERD/EO and BE) patients compared to controls and fewer microerosions
in NERD patients compared to RE (Lv et al., 2013).

The definition of NERD in all studies to date, however, is variable and largely based on
symptom evaluation, response to PPI and the absence of mucosal lesions at endoscopic
examination without standardisation using pH studies.

Artificial Intelligence

To date there is one study evaluating the use of ANNs in predicting GORD based on 45
variables including demographics, medical history, health status, symptoms scores. All
patients underwent OGD, 24-pH studies performed in those with no mucosal lesion at endoscopy:
103 GORD patient (62 with reflux oesophagitis and 41 with AET>5%) and n=56 FH patients GORD.
The ANN demonstrated an accuracy of 100% compared to 78% using conventional statistical
regression analysis (Pace et al., 2005). While these are optimistic findings, the proportion
of training and test data used was not specified and further evaluation with larger datasets
is clearly warranted. There are no image-driven AI models for the diagnosis of GORD to date.
Machine learning with endoscopic images is a pathway of great interest as described in
section 1.7.7, with IPCLs as a potential target, based on previous studies of NBI for the
diagnosis of GORD. CNNs involving IPCL detection and morphology have been recently reported
in the context of a pilot study for the computer assisted diagnosis of oesophageal early
squamous cell cancer using segmentation technology with accuracy matching expert endoscopists
(Zhao et al., 2018). The image segmentation technique of Adaptive Local Thresholding has been
demonstrated to be useful in vessel detection in retinal photographs making this as
attractive technique for IPCLs (Jiang and Mojon, 2003).
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">November 23, 2017</start_date>
<completion_date type="Actual">November 30, 2018</completion_date>
<primary_completion_date type="Actual">July 26, 2018</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>To evaluate Intra-Papillary Capillary Loop (IPCL) changes secondary to oesophageal acid exposure.</measure>
<time_frame>6 weeks post completion of wireless capsule pH recording</time_frame>
<description>Parameters of IPCLs: IPCLs/region of interest, morphology: IPCL length, density correlated to oesophageal acid exposure</description>
</primary_outcome>
<primary_outcome>
<measure>To develop an accurate and reliable artificial intelligence model for the diagnosis of Gastro-Oesophageal Reflux Disease (GORD)</measure>
<time_frame>3 months after completion of all data collection</time_frame>
<description>Patient data split into training/validation and test dataset for computer assisted and deep learning model training and testing</description>
</primary_outcome>
<secondary_outcome>
<measure>To explore factors that may predict response to treatment.</measure>
<time_frame>6 weeks to include data of response to antacid treatment</time_frame>
<description>Statistical analysis of models for IPCL number/ROI and morphology features against response to an antacid medication challenge.</description>
</secondary_outcome>
<number_of_groups>2</number_of_groups>
<enrollment type="Actual">76</enrollment>
<condition>Gastro Esophageal Reflux</condition>
<arm_group>
<arm_group_label>Gastro-Esophageal Reflux Disease</arm_group_label>
<description>Patients defined as having GERD as per Lyon Consensus</description>
</arm_group>
<arm_group>
<arm_group_label>Non-acid Reflux</arm_group_label>
<description>Patient excluded for GERD as per Lyon Consensus</description>
</arm_group>
<intervention>
<intervention_type>Diagnostic Test</intervention_type>
<intervention_name>wireless pH capsule recording</intervention_name>
<description>wireless pH capsule recording for up to 96 hours</description>
<arm_group_label>Gastro-Esophageal Reflux Disease</arm_group_label>
<arm_group_label>Non-acid Reflux</arm_group_label>
</intervention>
<eligibility>
<study_pop>
<textblock>
Consecutive patients attending the Gastroenterology department for the investigation of
symptoms suggestive of Gastro-Oesophageal Reflux Disease (GORD) were approached for
recruitment. Patients had to have symptoms including heartburn, regurgitation or
chest/epigastric pain for a minimum of 3 months.
</textblock>
</study_pop>
<sampling_method>Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- Retaining capacity and medically fit for gastroscopy

- Requiring gastroscopy by current BSG guidelines for the investigation of acid reflux/
dyspepsia

Exclusion Criteria:

- Unable to give informed consent

- History of oesophageal or gastric surgery

- Allergy to proton-pump inhibitor

- Known Barrett's Oesophagus/ oesophageal carcinoma/ oesophageal stricture/ known
oesophageal dysmotility

- Portal Hypertension

- Pacemaker (BRAVO)
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>90 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<location>
<facility>
<name>Shraddha Gulati</name>
<address>
<city>London</city>
<zip>SE5 9RS</zip>
<country>United Kingdom</country>
</address>
</facility>
</location>
<location_countries>
<country>United Kingdom</country>
</location_countries>
<reference>
<citation>Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R; Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006 Aug;101(8):1900-20; quiz 1943. doi: 10.1111/j.1572-0241.2006.00630.x.</citation>
<PMID>16928254</PMID>
</reference>
<reference>
<citation>Nikaki K, Woodland P, Sifrim D. Adult and paediatric GERD: diagnosis, phenotypes and avoidance of excess treatments. Nat Rev Gastroenterol Hepatol. 2016 Sep;13(9):529-42. doi: 10.1038/nrgastro.2016.109. Epub 2016 Jul 27.</citation>
<PMID>27485786</PMID>
</reference>
<reference>
<citation>Gyawali CP, Kahrilas PJ, Savarino E, Zerbib F, Mion F, Smout AJPM, Vaezi M, Sifrim D, Fox MR, Vela MF, Tutuian R, Tack J, Bredenoord AJ, Pandolfino J, Roman S. Modern diagnosis of GERD: the Lyon Consensus. Gut. 2018 Jul;67(7):1351-1362. doi: 10.1136/gutjnl-2017-314722. Epub 2018 Feb 3.</citation>
<PMID>29437910</PMID>
</reference>
<reference>
<citation>Lundell LR, Dent J, Bennett JR, Blum AL, Armstrong D, Galmiche JP, Johnson F, Hongo M, Richter JE, Spechler SJ, Tytgat GN, Wallin L. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999 Aug;45(2):172-80. doi: 10.1136/gut.45.2.172.</citation>
<PMID>10403727</PMID>
</reference>
<reference>
<citation>Nozu T, Komiyama H. Clinical characteristics of asymptomatic esophagitis. J Gastroenterol. 2008;43(1):27-31. doi: 10.1007/s00535-007-2120-2. Epub 2008 Feb 24.</citation>
<PMID>18297432</PMID>
</reference>
<reference>
<citation>Zagari RM, Fuccio L, Wallander MA, Johansson S, Fiocca R, Casanova S, Farahmand BY, Winchester CC, Roda E, Bazzoli F. Gastro-oesophageal reflux symptoms, oesophagitis and Barrett's oesophagus in the general population: the Loiano-Monghidoro study. Gut. 2008 Oct;57(10):1354-9. doi: 10.1136/gut.2007.145177. Epub 2008 Apr 18.</citation>
<PMID>18424568</PMID>
</reference>
<reference>
<citation>Lee YC, Lin JT, Chiu HM, Liao WC, Chen CC, Tu CH, Tai CM, Chiang TH, Chiu YH, Wu MS, Wang HP. Intraobserver and interobserver consistency for grading esophagitis with narrow-band imaging. Gastrointest Endosc. 2007 Aug;66(2):230-6. doi: 10.1016/j.gie.2006.10.056.</citation>
<PMID>17643694</PMID>
</reference>
<reference>
<citation>Fock KM, Teo EK, Ang TL, Tan JY, Law NM. The utility of narrow band imaging in improving the endoscopic diagnosis of gastroesophageal reflux disease. Clin Gastroenterol Hepatol. 2009 Jan;7(1):54-9. doi: 10.1016/j.cgh.2008.08.030. Epub 2008 Sep 3.</citation>
<PMID>18852068</PMID>
</reference>
<reference>
<citation>Inoue H, Kaga M, Ikeda H, Sato C, Sato H, Minami H, Santi EG, Hayee B, Eleftheriadis N. Magnification endoscopy in esophageal squamous cell carcinoma: a review of the intrapapillary capillary loop classification. Ann Gastroenterol. 2015 Jan-Mar;28(1):41-48.</citation>
<PMID>25608626</PMID>
</reference>
<reference>
<citation>Kato M, Kaise M, Yonezawa J, Toyoizumi H, Yoshimura N, Yoshida Y, Kawamura M, Tajiri H. Magnifying endoscopy with narrow-band imaging achieves superior accuracy in the differential diagnosis of superficial gastric lesions identified with white-light endoscopy: a prospective study. Gastrointest Endosc. 2010 Sep;72(3):523-9. doi: 10.1016/j.gie.2010.04.041. Epub 2010 Jul 3.</citation>
<PMID>20598685</PMID>
</reference>
<reference>
<citation>Sharma P, Wani S, Bansal A, Hall S, Puli S, Mathur S, Rastogi A. A feasibility trial of narrow band imaging endoscopy in patients with gastroesophageal reflux disease. Gastroenterology. 2007 Aug;133(2):454-64; quiz 674. doi: 10.1053/j.gastro.2007.06.006. Epub 2007 Jun 8.</citation>
<PMID>17681166</PMID>
</reference>
<reference>
<citation>Lv J, Liu D, Ma SY, Zhang J. Investigation of relationships among gastroesophageal reflux disease subtypes using narrow band imaging magnifying endoscopy. World J Gastroenterol. 2013 Dec 7;19(45):8391-7. doi: 10.3748/wjg.v19.i45.8391.</citation>
<PMID>24363532</PMID>
</reference>
<reference>
<citation>Pace F, Buscema M, Dominici P, Intraligi M, Baldi F, Cestari R, Passaretti S, Bianchi Porro G, Grossi E. Artificial neural networks are able to recognize gastro-oesophageal reflux disease patients solely on the basis of clinical data. Eur J Gastroenterol Hepatol. 2005 Jun;17(6):605-10. doi: 10.1097/00042737-200506000-00003.</citation>
<PMID>15879721</PMID>
</reference>
<reference>
<citation>Zhao YY, Xue DX, Wang YL, Zhang R, Sun B, Cai YP, Feng H, Cai Y, Xu JM. Computer-assisted diagnosis of early esophageal squamous cell carcinoma using narrow-band imaging magnifying endoscopy. Endoscopy. 2019 Apr;51(4):333-341. doi: 10.1055/a-0756-8754. Epub 2018 Nov 23.</citation>
<PMID>30469155</PMID>
</reference>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 11, 2020</last_update_submitted>
<last_update_submitted_qc>February 11, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Gastroesophageal Reflux</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
<ipd_description>Protocol possible to obtain upon request</ipd_description>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Gastro-oesophageal reflux disease (GORD) is a chronic condition with symptoms arising
secondary to the reflux of stomach contents (Vakil et al., 2006). It is divided into four
phenotypes: Erosive Oesophagitis (EO), Non-Erosive Reflux Disease (NERD), Reflux
Hypersensitivity (RH), Functional Heartburn (FH) (Nikaki, Woodland and Sifrim, 2016). The
definition of these phenotype have evolved with the addition of diagnostic tests and methods
of their interpretation, the most recent being the Lyon Consensus Statement (Gyawali et al.,
2018). The majority of patients presenting with symptoms suggestive of GORD have no mucosal
lesion seen at endoscopy (Nikaki, Woodland and Sifrim, 2016). Studies have shown a relation
of increased IPCL numbers with GORD. This study aims to build a fully autmoated AI model
using Near-Focus NBI images on patients with symptoms suggestive of GORD phenotyped in
accordance with the Lyon Consensus.
Gastro-oesophageal reflux disease (GORD) is a chronic condition with symptoms arising
secondary to the reflux of stomach contents (Vakil et al., 2006). It is divided into four
phenotypes: Erosive Oesophagitis (EO), Non-Erosive Reflux Disease (NERD), Reflux
Hypersensitivity (RH), Functional Heartburn (FH) (Nikaki, Woodland and Sifrim, 2016). The
definition of these phenotype have evolved with the addition of diagnostic tests and methods
of their interpretation, the most recent being the Lyon Consensus Statement (Gyawali et al.,
2018). The majority of patients presenting with symptoms suggestive of GORD have no mucosal
lesion seen at endoscopy (Nikaki, Woodland and Sifrim, 2016). Complications of GORD, such as
peptic stricture and Barrett's oesophagus, can be readily diagnosed using WLE. The diagnosis
of reflux oesophagitis with standard-definition WLE is well described in the Los Angeles (LA)
classification (Armstrong et al., 1996) and validated (Lundell et al., 1999) with LA grades C
and D confirmatory of GORD (Gyawali et al., 2018). Furthermore, AET is demonstrated to
increase with LA classification A to D (Lundell et al., 1999). There is, however, only a
modest inter-observer agreement between LA grades (Kappa coefficient 0.4), especially A and
B. Furthermore LA grade A oesophagitis is detected in up to 17.0% of asymptomatic patients
(Nozu and Komiyama, 2008; Zagari et al., 2008). A diagnosis of GORD and decisions for
anti-reflux surgery cannot be made on this basis, mandating pH testing to confirm GORD.
Narrow Band Imaging
Imaging of the gastro-oesophageal junction using high definition Olympus H260 scope using the
LA classification of GORD with WLE and NBI demonstrated improvement in overall interobserver
reproducibility when used in a combination compared with WLE alone; k 0.62 vs 0.45
(<0.05)(Lee et al., 2007). Features identified using digital magnification NBI at the
squamo-columnar junction in cases of EO (n=41; LA grade A and B), NERD (n=36) and controls
(n=32) include micro-erosions (100% EO; 52.8% NERD; 23.3% controls), increased vascularity
(95.1% EO; 91.7% NERD; 36.7% controls) and round pit patterns (4.9% EO; 5.6% NERD; 70%
controls). Increased vascularity combined with absence of round pit pattern distinguishes
NERD from controls with sensitivity and specificity 86.1% and 83.3%. Inter-observer agreement
in this single centre study was good for increased vascularity (k=0.95) and micro erosions
(k=0.89) but low for pit pattern (k=0.59) (Fock et al., 2009).
Intra-papillary capillary loops (IPCLs) are mucosal capillaries arising from the submucosal
vein to the papilla, usually arranged in a regular 'dot' like fashion approximately
100micrometres apart (Inoue, 2001). The visualisation of oesophageal IPCLs with NBI is well
documented and form the basis of a NBI classification for squamous neoplasia (Inoue et al.,
2015). IPCL morphology changes have been proposed in patients being investigated for NERD, in
particular dilatation and elongation of IPCLs in patients with NERD with magnification NBI
(Kato et al., 2006).
NBI with optical magnification for the diagnosis of GORD has been evaluated in 2 studies
(Sharma et al., 2007; Lv et al., 2013). Sharma et al performed a feasibility trial with
Olympus Q240Z with quadrantic examination of the distal 5cm by WLE then NBI in n=50 GORD (EO
n=30; NERD n=20) and controls (n=30). Similar to Fock et al, the presence of microerosions
and hypervascularity was significantly higher amongst GORD. IPCL number and morphology of
tortuosity, dilatation were seen significantly more in GORD versus control. These findings
were consistent in independent comparison of EO and NERD versus controls. ROC analysis
thresholds for best sensitivity and specificity (respectively) for NERD were maximum
ipcl/field 131 (90%, 70%), min 99 (85%, 70%) and average 117 (90%, 70%) (Sharma et al.,
2007).
Lv et al used the Olympus GIF-H260Z to evaluate NERD (n=40), EO (n=40), Barrett's (n=40) and
healthy controls (n=40). IPCL number, morphology (prolonged/dilated/tortuous), microerosions,
round pit pattern above or below the SCJ, were recorded as features of reflux. Significant
differences were found with increased IPCL number, microerosions, non-round pit patterns
below the SCJ in GERD (NERD/EO and BE) patients compared to controls and fewer microerosions
in NERD patients compared to RE (Lv et al., 2013).
The definition of NERD in all studies to date, however, is variable and largely based on
symptom evaluation, response to PPI and the absence of mucosal lesions at endoscopic
examination without standardisation using pH studies.
Artificial Intelligence
To date there is one study evaluating the use of ANNs in predicting GORD based on 45
variables including demographics, medical history, health status, symptoms scores. All
patients underwent OGD, 24-pH studies performed in those with no mucosal lesion at endoscopy:
103 GORD patient (62 with reflux oesophagitis and 41 with AET>5%) and n=56 FH patients GORD.
The ANN demonstrated an accuracy of 100% compared to 78% using conventional statistical
regression analysis (Pace et al., 2005). While these are optimistic findings, the proportion
of training and test data used was not specified and further evaluation with larger datasets
is clearly warranted. There are no image-driven AI models for the diagnosis of GORD to date.
Machine learning with endoscopic images is a pathway of great interest as described in
section 1.7.7, with IPCLs as a potential target, based on previous studies of NBI for the
diagnosis of GORD. CNNs involving IPCL detection and morphology have been recently reported
in the context of a pilot study for the computer assisted diagnosis of oesophageal early
squamous cell cancer using segmentation technology with accuracy matching expert endoscopists
(Zhao et al., 2018). The image segmentation technique of Adaptive Local Thresholding has been
demonstrated to be useful in vessel detection in retinal photographs making this as
attractive technique for IPCLs (Jiang and Mojon, 2003).
Consecutive patients attending the Gastroenterology department for the investigation of
symptoms suggestive of Gastro-Oesophageal Reflux Disease (GORD) were approached for
recruitment. Patients had to have symptoms including heartburn, regurgitation or
chest/epigastric pain for a minimum of 3 months.
Inclusion Criteria:
- Retaining capacity and medically fit for gastroscopy
- Requiring gastroscopy by current BSG guidelines for the investigation of acid reflux/
dyspepsia
Exclusion Criteria:
- Unable to give informed consent
- History of oesophageal or gastric surgery
- Allergy to proton-pump inhibitor
- Known Barrett's Oesophagus/ oesophageal carcinoma/ oesophageal stricture/ known
oesophageal dysmotility
- Portal Hypertension
- Pacemaker (BRAVO)
|
NCT0426xxxx/NCT04268732.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268732</url>
</required_header>
<id_info>
<org_study_id>1284/19</org_study_id>
<nct_id>NCT04268732</nct_id>
</id_info>
<brief_title>Acute Undifferentiated Fever in Ethiopia</brief_title>
<official_title>Causes of Acute Undifferentiated Fever and the Utility of Biomarkers in Differentiating Bacterial From Viral Infection Among Acute Febrile Patients in Northwest Ethiopia</official_title>
<sponsors>
<lead_sponsor>
<agency>Institute of Tropical Medicine, Belgium</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>University of Gondar</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>Institute of Tropical Medicine, Belgium</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
A cross-sectional study on acute undifferentiated fever and the utility of biomarkers in
differentiating bacterial from viral infection among acute febrile patients in Gondar,
northwest Ethiopia.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
General objective:

To assess the causes of acute undifferentiated febrile illness and evaluation of biomarkers
for differentiation of bacterial and viral infections among outpatients at University of
Gondar (UOG) Hospital, Northwest Ethiopia

Specific objectives

1. To determine the number of malaria cases, bacterial infections (by blood culture and
polymearase chain reaction (PCR) for Rickettsia and Borrelia), and arboviral infections
(DENV, YFV, CHIKV) among all acute febrile patients

2. To evaluate the diagnostic performance different assays (RDT, RT-(reverse
transcriptase)PCR, ELISA) for the diagnosis of DENV

3. To evaluate the qualitative detection of C-reactive protein (CRP) and Myxovirus
resistance protein (MxA) (by FebriDx RDT) and quantitative CRP detection for
differentiating bacterial and viral infections

Study design, population, materials and methods: a cross-sectional cohort study on febrile
patients presenting with acute fever at the emergency ward of the UOG hospital from June to
August 2019. Clinical and epidemiological data will be recorded in a pseudo-anonymized and
collected using an electronic data collection tool (KoBoToolbox). Blood will be collected for
RDT testing, blood culture, PCR and serum for ELISA and RT-PCR.

Sample size: 200 acute febrile patients

Expected results and relevance: Evaluation of the causes of acute febrile illness and the
role of biomarkers in differentiating viral and bacterial infections will increase the
awareness of circulating pathogens and improve patient management. This evidence will
contribute to a more rational use of laboratory diagnostic tests, antibiotics and
antimalarial treatment.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">June 1, 2019</start_date>
<completion_date type="Actual">December 30, 2020</completion_date>
<primary_completion_date type="Actual">August 31, 2019</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Cross-Sectional</time_perspective>
</study_design_info>
<primary_outcome>
<measure>The differentiation of bacterial infections and viral infections among acute febrile patients with biomarkers</measure>
<time_frame>within 7 days after onset of fever</time_frame>
<description>CRP (bacterial biomarker) and MxA (viral biomarker) will be evaluated for differentiating confirmed bacterial and viral infections.</description>
</primary_outcome>
<secondary_outcome>
<measure>The number of malaria cases, bacterial infections, viral infections and unknown etiologies among acute febrile patients in Gondar</measure>
<time_frame>within 7 days after onset of fever</time_frame>
<description>Different diagnostic tools will be used for analysis of acute febrile patient samples to confirm malaria (by RDT), bacterial infection (by blood culture and PCR for Rickettsia and Borrelia) and for viral infections (by RT-PCR for DENV, CHIKV, YFV). Samples negative for all these tests are defined as unknown etiology.</description>
</secondary_outcome>
<secondary_outcome>
<measure>The comparison of different assays for diagnosis of DENV</measure>
<time_frame>within 7 days after onset of fever</time_frame>
<description>Different diagnostic tests will be evaluated for the detection of acute DENV infection (NS1 RDT, RT-PCR, ELISA IgM) and past DENV infection (ELISA IgG) among acute febrile patients.</description>
</secondary_outcome>
<secondary_outcome>
<measure>The comparison of the qualitative and qualitative detection of CRP for differentiating bacterial and viral infections</measure>
<time_frame>within 7 days after onset of fever</time_frame>
<description>Qualitative CRP levels will be measured by FebriDx test and quantitative CRP levels will be measured by QuikReadGo. The detection of > 20mg/L CRP will be used to evaluate the confirmed bacterial infections and to compare with antibiotic treatment.</description>
</secondary_outcome>
<enrollment type="Actual">200</enrollment>
<condition>Acute Febrile Illness</condition>
<biospec_retention>Samples With DNA</biospec_retention>
<biospec_descr>
<textblock>
whole blood serum blood culture bottles
</textblock>
</biospec_descr>
<eligibility>
<study_pop>
<textblock>
All patients ≥ 15 years old with acute undifferentiated fever and seeking health services
within 7 days after fever onset at the emergency ward of the university of Gondar hospital
(Ethiopia) during the study period.
</textblock>
</study_pop>
<sampling_method>Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- Patients presenting with acute fever (an axillary temperature of ≥37.5°C; symptom
duration ≤7 days)

- ≥ 15 years old

- signed informed consent

Exclusion Criteria:

- pregnant woman & children (<15 y)

- febrile patient suspected of urinary tract infection or acute respiratory tract
infection

- Individuals who had taken antimicrobial and antimalarial drug in the last 2 weeks

- Patients with acute injury or trauma or for which participation in the study implies
an unacceptable health risk as determined by the physicians
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>15 Years</minimum_age>
<maximum_age>N/A</maximum_age>
</eligibility>
<overall_official>
<last_name>Johan van Griensven, PhD, MD</last_name>
<role>Study Director</role>
<affiliation>Institute of Tropical Medicine</affiliation>
</overall_official>
<location>
<facility>
<name>Institute of Tropical Medicine</name>
<address>
<city>Antwerp</city>
<zip>2000</zip>
<country>Belgium</country>
</address>
</facility>
</location>
<location>
<facility>
<name>University of Gondar</name>
<address>
<city>Gondar</city>
<country>Ethiopia</country>
</address>
</facility>
</location>
<location_countries>
<country>Belgium</country>
<country>Ethiopia</country>
</location_countries>
<reference>
<citation>Bhargava A, Ralph R, Chatterjee B, Bottieau E. Assessment and initial management of acute undifferentiated fever in tropical and subtropical regions. BMJ. 2018 Nov 29;363:k4766. doi: 10.1136/bmj.k4766. No abstract available.</citation>
<PMID>30498133</PMID>
</reference>
<reference>
<citation>Mohammed Yusuf A, Abdurashid Ibrahim N. Knowledge, attitude and practice towards dengue fever prevention and associated factors among public health sector health-care professionals: in Dire Dawa, eastern Ethiopia. Risk Manag Healthc Policy. 2019 Jun 7;12:91-104. doi: 10.2147/RMHP.S195214. eCollection 2019.</citation>
<PMID>31239796</PMID>
</reference>
<reference>
<citation>Ferede G, Tiruneh M, Abate E, Wondimeneh Y, Damtie D, Gadisa E, Howe R, Aseffa A, Tessema B. A serologic study of dengue in northwest Ethiopia: Suggesting preventive and control measures. PLoS Negl Trop Dis. 2018 May 31;12(5):e0006430. doi: 10.1371/journal.pntd.0006430. eCollection 2018 May.</citation>
<PMID>29852020</PMID>
</reference>
<reference>
<citation>Lilay A, Asamene N, Bekele A, Mengesha M, Wendabeku M, Tareke I, Girmay A, Wuletaw Y, Adossa A, Ba Y, Sall A, Jima D, Mengesha D. Reemergence of yellow fever in Ethiopia after 50 years, 2013: epidemiological and entomological investigations. BMC Infect Dis. 2017 May 15;17(1):343. doi: 10.1186/s12879-017-2435-4.</citation>
<PMID>28506254</PMID>
</reference>
<reference>
<citation>Animut A, Mekonnen Y, Shimelis D, Ephraim E. Febrile illnesses of different etiology among outpatients in four health centers in Northwestern Ethiopia. Jpn J Infect Dis. 2009 Mar;62(2):107-10.</citation>
<PMID>19305049</PMID>
</reference>
<reference>
<citation>Kapasi AJ, Dittrich S, Gonzalez IJ, Rodwell TC. Host Biomarkers for Distinguishing Bacterial from Non-Bacterial Causes of Acute Febrile Illness: A Comprehensive Review. PLoS One. 2016 Aug 3;11(8):e0160278. doi: 10.1371/journal.pone.0160278. eCollection 2016.</citation>
<PMID>27486746</PMID>
</reference>
<reference>
<citation>Self WH, Rosen J, Sharp SC, Filbin MR, Hou PC, Parekh AD, Kurz MC, Shapiro NI. Diagnostic Accuracy of FebriDx: A Rapid Test to Detect Immune Responses to Viral and Bacterial Upper Respiratory Infections. J Clin Med. 2017 Oct 7;6(10):94. doi: 10.3390/jcm6100094.</citation>
<PMID>28991170</PMID>
</reference>
<verification_date>May 2021</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>May 10, 2021</last_update_submitted>
<last_update_submitted_qc>May 10, 2021</last_update_submitted_qc>
<last_update_posted type="Actual">May 11, 2021</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>biomarkers</keyword>
<keyword>bacterial infection</keyword>
<keyword>viral infection</keyword>
<keyword>malarial infection</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Hyperthermia</mesh_term>
<mesh_term>Fever</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>Undecided</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
A cross-sectional study on acute undifferentiated fever and the utility of biomarkers in
differentiating bacterial from viral infection among acute febrile patients in Gondar,
northwest Ethiopia.
General objective:
To assess the causes of acute undifferentiated febrile illness and evaluation of biomarkers
for differentiation of bacterial and viral infections among outpatients at University of
Gondar (UOG) Hospital, Northwest Ethiopia
Specific objectives
1. To determine the number of malaria cases, bacterial infections (by blood culture and
polymearase chain reaction (PCR) for Rickettsia and Borrelia), and arboviral infections
(DENV, YFV, CHIKV) among all acute febrile patients
2. To evaluate the diagnostic performance different assays (RDT, RT-(reverse
transcriptase)PCR, ELISA) for the diagnosis of DENV
3. To evaluate the qualitative detection of C-reactive protein (CRP) and Myxovirus
resistance protein (MxA) (by FebriDx RDT) and quantitative CRP detection for
differentiating bacterial and viral infections
Study design, population, materials and methods: a cross-sectional cohort study on febrile
patients presenting with acute fever at the emergency ward of the UOG hospital from June to
August 2019. Clinical and epidemiological data will be recorded in a pseudo-anonymized and
collected using an electronic data collection tool (KoBoToolbox). Blood will be collected for
RDT testing, blood culture, PCR and serum for ELISA and RT-PCR.
Sample size: 200 acute febrile patients
Expected results and relevance: Evaluation of the causes of acute febrile illness and the
role of biomarkers in differentiating viral and bacterial infections will increase the
awareness of circulating pathogens and improve patient management. This evidence will
contribute to a more rational use of laboratory diagnostic tests, antibiotics and
antimalarial treatment.
whole blood serum blood culture bottles
All patients ≥ 15 years old with acute undifferentiated fever and seeking health services
within 7 days after fever onset at the emergency ward of the university of Gondar hospital
(Ethiopia) during the study period.
Inclusion Criteria:
- Patients presenting with acute fever (an axillary temperature of ≥37.5°C; symptom
duration ≤7 days)
- ≥ 15 years old
- signed informed consent
Exclusion Criteria:
- pregnant woman & children (<15 y)
- febrile patient suspected of urinary tract infection or acute respiratory tract
infection
- Individuals who had taken antimicrobial and antimalarial drug in the last 2 weeks
- Patients with acute injury or trauma or for which participation in the study implies
an unacceptable health risk as determined by the physicians
|
NCT0426xxxx/NCT04268745.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268745</url>
</required_header>
<id_info>
<org_study_id>19-02-223</org_study_id>
<secondary_id>5P2CHD086851-05</secondary_id>
<nct_id>NCT04268745</nct_id>
</id_info>
<brief_title>Virtual Environments for Vestibular Rehabilitation</brief_title>
<official_title>Vestibular Rehabilitation Utilizing Virtual Environments to Train Sensory Integration for Postural Control in a Functional Context</official_title>
<sponsors>
<lead_sponsor>
<agency>New York University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Icahn School of Medicine at Mount Sinai</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
<agency_class>NIH</agency_class>
</collaborator>
</sponsors>
<source>New York University</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The specific aims of this pilot project are:

Aim #1: Determine the extent to which sensory integration strategies differ between 28
individuals with unilateral vestibular hypofunction and 28 age-matched peers. Participants'
postural sway will be recorded as they experience two levels of moving stars10 and white
noise, while standing on the floor or a compliant surface. Our working hypothesis is that
patients with vestibular hypofunction utilize substitution strategies such that they will
demonstrate greater visual and auditory reliance compared with controls, particularly when
somatosensory cues are reduced via the support surface. We will then explore whether these
mechanism changes after training.

Aim #2: Develop the protocol and establish the feasibility of a randomized controlled trial
(RCT) comparing C.S.I. training to standard vestibular rehabilitation. Following the
assessment, the 28 patients will be randomized into standard vestibular rehabilitation vs.
C.S.I. training. This pilot study will enable us to test the feasibility of our recruitment,
randomization procedures, establish attrition rate, and test the training protocol.

Aim #3: Generate pilot data for sample size calculation for a properly powered RCT. The
follow up RCT will test the effect of C.S.I. training on: Visual Vertigo Analog Scale (VVAS),
Functional Gait Analysis (primary); balance confidence, overall disability (descriptive). In
our preliminary study, 8 patients met the inclusion criteria for the current proposal.
Following the C.S.I. training, they had a large effect size of 1.17 on the VVAS. The current
study will allow us to identify the between-group effect size for the VVAS and for a
functional gait outcome.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
System: The testing platform runs at 120 frames per second with either HTC Vive or Oculus
Rift, on a Windows 10 laptop with 8GB RAM, Intel i7-7820HK CPU, Nvidia GTX 1080 Max-Q GPU,
and Bose SoundTrue around-ear headphones II. The software was developed in C# with Unity3D
2018.2.0f1(64-bit) (Unity Technologies, San Francisco, California). The system utilizes
SteamVR. Oculus Rift and HTC Vive both operate at 90 Hz refresh rate, 110 degrees field of
view, and a high-definition video of 1080x1200 resolution for each eye. The graphics of the
subway station, airport terminal building, and subway trains are modeled in Maya and imported
to Unity3D. The rest of the 3D objects are modeled in Unity3D. The subway station model and
airport model replicate a real subway station in New York City and a real airport terminal in
the US. The contents in the system are fully controllable by the user interface (see Figure
3). Three-dimensional sounds were implemented using Wwise middleware and Google Resonance
audio plugin. Using the head-tracking data, audio is modulated according to the position of
the listener's head. The technology allows for creation of a rich soundscape in all
directions around the listener. Audio assets used in the system are divided into two main
groups: sound objects and ambiances. Sound objects are attached to the visual objects in the
scene and their position is changing accordingly. Sounds include: footsteps, trains,
announcements, cars, balls, airplanes, etc. Ambiances are created from original recordings
from different locations in New York. These include different background sounds, i.e. sounds
of the crowd chatter, distant trains, wind, birds, traffic, and general room tone of each of
the spaces. All of the sounds used in the system are assigned to three different intensity
levels which relate to the increasing complexity of the soundscape.

Data Collection: The first assessment session will include a well-established postural
control assessment that the investigators had translated to a HMD paradigm and added an
auditory layer. The protocol will include all possible combinations of the following: 2
levels of visual perturbation (static stars; stars moving in the AP direction, 0.2 Hz,
0.032m); 2 levels of auditory perturbation (quiet room; white noise that cycles from 0 to 1
dB at 0.3Hz), and 2 levels of support surface (floor; memory foam). Each scene will be 60
seconds long, there are 8 combinations, and each will be repeated 3 times for a total of 24
trials. Power spectral density (PSD) of sway in 3 frequency segments will be derived from a
laboratory force plate and will serve to explore sensory integration mechanism. Participants
will also complete the FGA (primary), VVAS (primary), ABC (descriptive), and DHI
(descriptive).

Participants will complete the baseline assessment twice, one week apart, to assure stability
of the measures. Following the baseline assessments, participants will be randomized to a
C.S.I. experimental group (EG, n = 14) or a standard rehabilitation control group (CG, n =
14). The participants will commence the intervention program within a week of the second
assessment. The setting will be a vestibular rehabilitation clinic at the New York Eye and
Ear Infirmary of Mount Sinai.

Both groups: Eligible participants will be provided with patient education and a basic home
exercise program (gait, balance, no exercises with eyes closed) while they are considering
participation in the study.

Program Dose: 8 weeks, 1 visit per week, 30 minutes long EG: Progressive immersive training
with the C.S.I. app; Scenes: start from most salient to the patient, eventually do all
Duration: start at 60 seconds, increase over time up to 3 minutes per scene Complexity: start
minimal, gradually increase up to most complex Tasks: standing with diverse base of support
(BOS), head turns (progress with speed, planes); stepping, turning CG: Progressive gait, gaze
stability and balance exercises. Gait: walking with head turns, progress with range, speed
and planes of head movement; change of walking BOS: wide, normal, tandem Gaze: focus on a
target while moving head side to side / up down. Progress with speed, duration, busier
background, standing to walking.

Balance: standing balance tasks, progress with BOS (wide to narrow to tandem), support
surface, eyes closed, duration, head turns.

Both Groups Progression / Regression rule: The highest level of challenge that can be done
for 60 seconds with no loss of balance (LOB); No more than moderate symptoms in clinic based
on the Simulator Sickness Questionnaire; If symptoms persisted over 2 hours post-session,
scale the intensity back the next time. If symptoms improved immediately, repeat the task
with the same intensity and duration.

Home program for both groups: 8 weeks, 6 times per week, twice per day, 10 minutes long,
Highest level of challenge that is safe (no LOB, no increased symptoms) for 60 seconds per
task Home EG: Gait and balance exercises, No exercises with eyes closed Home CG: Gait, gaze
stability and balance exercises, including exercises with eyes closed

A post-assessment, identical to the baseline assessment, will be conducted within one week
from the completion of the 8th intervention session.

Sample Size: For Aim 1, the investigators will recruit 28 patients and 28 age and sex-matched
controls. For Aims 2 & 3, the 28 patients will be randomized into an experimental (N=14) and
control (N=14) groups. Assuming ~20% attrition during the course of the intervention, it is
expected to have 11-12 participants per intervention group. Given our history of recruitment,
this number is feasible for the duration and resources of the 12-month pilot grant. With that
the investigators will determine the sample size needed for a future, adequately powered,
study, as described below.

Internal Validity: To avoid selection bias and to balance potential confounders, the
investigators will use block-randomization strategy for participants using the blockrand
package in R.21 This procedure uses a two-stage process: first, the size of the block is
selected to 2, 4, 6, or 8; next, a block of that size is generated. Therefore, no researcher
will be able to predict which group a participant will be assigned to or change that
assignment (i.e. allocation concealment). Participants will only be randomized into groups
after the baseline assessment and consent to participate in the study have been completed.
Although, due to the nature of the intervention, participants and treating clinicians cannot
be blinded to group assignment, bias will be minimized by blinding the post-treatment
assessors to treatment status. To control for attrition bias, in addition to an
intent-to-treat approach, the investigators will ascertain whether any predictors of
missingness exist. If so, the investigators will use a pattern mixture model to multiply
impute (5 replications) any missing responses.

Consideration of Relevant Biological Variables: The eligibility criteria specified above
represent adult individuals with unilateral vestibular hypofunction of both sexes and of
diverse age range. The control group will be matched for age and sex with the vestibular
group. A wide age range (18 and up) will be recruited. Obesity is known to affect posture and
could alter postural control strategies. Should the sample include overweight individuals,
the model will be tested while adjusting for weight. Because the sample will include aging
individuals, the investigators anticipate additional health conditions that will be similar
between groups, e.g., age-related hearing loss. The exclusion criteria will eliminate health
conditions critical to postural control, such as: visual impairment, peripheral neuropathy,
and other neurological conditions.

Data Analysis: Aim 1: For each of the four measures of interest (PSD 1-3 and overall PSD),
the investigators will fit a linear mixed effects model to compare the age-matched controls
to patients with vestibular hypofunction while accounting for the inherent multi-level study
design (person, conditions, repetitions). The models will include main effects of group,
visual condition, auditory condition, surface condition, as well as their interactions, while
adjusting for age. P-values for the fixed effects will be calculated through the
Satterthwaite approximation for the degrees of freedom for the T-distribution. The analysis
will be repeated following the intervention, adjusting for group assignment and
pre-intervention values. ABC and DHI will be used to describe the sample.

Aim 2: No statistical analysis needed. Aim 3: First, following the intent-to-treat principle,
a linear regression model will be fit with the VVAS and FGA as the primary dependent
variable, on treatment group, controlling for baseline covariates (age and other
self-reported questionnaire measures) to improve the precision of the treatment effect
estimate, as well as pre-test scores. The potential efficacy of the intervention will be
assessed based on a significant coefficient for treatment status. Second, as described above,
the investigators will fit a pattern mixture model to multiply impute any missing values, and
use Rubin's rules to pool coefficients and their standard errors from the regression models
fit to each imputed dataset. Data generated from this pilot randomized trial will be used to
calculate the sample size needed for future, adequately powered, randomized controlled trials
by estimating the difference in means for the treatment groups (i.e. a future expected effect
size) as well as the variance of the primary outcomes and the values of other parameters
necessary to compute the power function.

Safety and Reporting: Preliminary work showed minimal to no cybersickness and no falls or
adverse reactions to the virtual reality training. Only 1 patient dropped out due to concern
about symptoms. Others dropped out due to anxiety, physician's request, cessation of therapy,
or other orthopaedic injuries that occurred after enrollment. In the current study, Dr. Maura
Cosetti, MD, will provide oversight and monitoring of the conduct of the trial as a
preliminary DSMB. This will ensure the safety of participants and the validity and integrity
of the data. The PI and Dr. Kelly will perform continuous monitoring of participant safety
(falls, symptoms on every session) with frequent reporting to Dr. Cosetti. The investigators
will follow the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement checklist
and diagram in reporting the results of the trial.
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">August 21, 2019</start_date>
<completion_date type="Actual">May 23, 2022</completion_date>
<primary_completion_date type="Actual">April 15, 2022</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>Single (Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>Visual Vertigo Analog Scale (VVAS)</measure>
<time_frame>8 weeks</time_frame>
<description>The Visual Vertigo Analogue Scale (VVAS) is a self-reported questionnaire where a participant rates their visual vertigo on a 10 cm line in 9 different visually challenging environments. A score of 0 indicates no dizziness. Maximal score is 100 (calculated as the measurement on each item X 9 divided by 10).</description>
</primary_outcome>
<primary_outcome>
<measure>Functional Gait Analysis (FGA)</measure>
<time_frame>8 weeks</time_frame>
<description>A functional test designed to assess individual's ability to perform various motor tasks, such as: walking with eyes closed, walking backwards, climbing stairs. There are 10 items, each is scored by a therapist on a scale of 0 (severe impairment) to 3 (normal). Maximal score is 30. Higher is better.</description>
</primary_outcome>
<secondary_outcome>
<measure>Power Spectral Density</measure>
<time_frame>8 weeks</time_frame>
<description>The postural sway signal (derived from a force platform) is decomposed into its frequency components. This technique allows for quantifying overall variability of COP sway (COP variance = sum of power at all frequency components) as well as specific components associated with pathological and/or physiological balance control. In our paradigm, PSD 1 (0.05 to 0.25 Hz) includes the visual frequency and will indicate visual weighting. PSD 2 (0.25 to 0.5 Hz) includes the auditory frequency and will indicate auditory weighting. PSD 3 (0.5 to 1 Hz) will indicate small corrective adjustments, and overall PSD will indicate destabilization induced by the stimulus.</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">31</enrollment>
<condition>Dizziness Chronic</condition>
<condition>Vertigo, Peripheral</condition>
<condition>Fall</condition>
<arm_group>
<arm_group_label>Virtual Reality</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Progressive immersive training with the virtual reality app Scenes: start from most salient to the patient, eventually do all Duration: start at 60 seconds, increase over time up to 3 minutes per scene Complexity: start minimal, gradually increase up to most complex Tasks: standing with diverse base of support (BOS), head turns (progress with speed, planes); stepping, turning 8 weeks, 1 visit per week, 30 minutes long In home: Gait and balance exercises, No exercises with eyes closed, 8 weeks, 6 times per week, twice per day, 10 minutes long</description>
</arm_group>
<arm_group>
<arm_group_label>Traditional Vestibular Rehabilitation</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Progressive gait, gaze stability and balance exercises Gait: walking with head turns, progress with range, speed and planes of head movement; change of walking BOS: wide, normal, tandem Gaze: focus on a target while moving head side to side / up down. Progress with speed, duration, busier background, standing to walking.
Balance: standing balance tasks, progress with BOS (wide to narrow to tandem), support surface, eyes closed, duration, head turns.
8 weeks, 1 visit per week, 30 minutes long In home: Gait, gaze stability and balance exercises, including exercises with eyes closed, 8 weeks, 6 times per week, twice per day, 10 minutes long</description>
</arm_group>
<intervention>
<intervention_type>Behavioral</intervention_type>
<intervention_name>Balance training</intervention_name>
<description>Progressive balance training within virtual environments</description>
<arm_group_label>Virtual Reality</arm_group_label>
<other_name>Virtual reality</other_name>
<other_name>Contextual sensory integration training</other_name>
<other_name>HTC Vive</other_name>
</intervention>
<intervention>
<intervention_type>Behavioral</intervention_type>
<intervention_name>Traditional Vestibular Rehabilitation</intervention_name>
<description>Progressive balance training and gaze stability exercises</description>
<arm_group_label>Traditional Vestibular Rehabilitation</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Adult patients (18 or older)

- Clinical diagnosis of chronic (3 months and longer) unilateral peripheral vestibular
hypofunction

- Patients will be included based on the presence of a positive head thrust test, head
shaking nystagmus, spontaneous nystagmus, and/or canal paresis > 25% if a caloric test
is available.

- Included patients must present with at least two positive items on the VVAS

Exclusion Criteria:

Patients will be excluded for prior vestibular rehab, bilateral or unstable vestibular loss
or another neurological condition, active benign paroxysmal positional vertigo, acute
orthopaedic injuries, peripheral neuropathy, hearing impairment, or visual impairment not
corrected with glasses.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Anat Lubetzky, PhD</last_name>
<role>Principal Investigator</role>
<affiliation>New York University</affiliation>
</overall_official>
<location>
<facility>
<name>New York Eye and Ear Infirmary of Mount Sinai</name>
<address>
<city>New York</city>
<state>New York</state>
<zip>10010</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>New York University Physical Therapy Department</name>
<address>
<city>New York</city>
<state>New York</state>
<zip>10010</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>May 2022</verification_date>
<study_first_submitted>January 24, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>May 23, 2022</last_update_submitted>
<last_update_submitted_qc>May 23, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">May 24, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Vertigo</mesh_term>
<mesh_term>Dizziness</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The specific aims of this pilot project are:
Aim #1: Determine the extent to which sensory integration strategies differ between 28
individuals with unilateral vestibular hypofunction and 28 age-matched peers. Participants'
postural sway will be recorded as they experience two levels of moving stars10 and white
noise, while standing on the floor or a compliant surface. Our working hypothesis is that
patients with vestibular hypofunction utilize substitution strategies such that they will
demonstrate greater visual and auditory reliance compared with controls, particularly when
somatosensory cues are reduced via the support surface. We will then explore whether these
mechanism changes after training.
Aim #2: Develop the protocol and establish the feasibility of a randomized controlled trial
(RCT) comparing C.S.I. training to standard vestibular rehabilitation. Following the
assessment, the 28 patients will be randomized into standard vestibular rehabilitation vs.
C.S.I. training. This pilot study will enable us to test the feasibility of our recruitment,
randomization procedures, establish attrition rate, and test the training protocol.
Aim #3: Generate pilot data for sample size calculation for a properly powered RCT. The
follow up RCT will test the effect of C.S.I. training on: Visual Vertigo Analog Scale (VVAS),
Functional Gait Analysis (primary); balance confidence, overall disability (descriptive). In
our preliminary study, 8 patients met the inclusion criteria for the current proposal.
Following the C.S.I. training, they had a large effect size of 1.17 on the VVAS. The current
study will allow us to identify the between-group effect size for the VVAS and for a
functional gait outcome.
System: The testing platform runs at 120 frames per second with either HTC Vive or Oculus
Rift, on a Windows 10 laptop with 8GB RAM, Intel i7-7820HK CPU, Nvidia GTX 1080 Max-Q GPU,
and Bose SoundTrue around-ear headphones II. The software was developed in C# with Unity3D
2018.2.0f1(64-bit) (Unity Technologies, San Francisco, California). The system utilizes
SteamVR. Oculus Rift and HTC Vive both operate at 90 Hz refresh rate, 110 degrees field of
view, and a high-definition video of 1080x1200 resolution for each eye. The graphics of the
subway station, airport terminal building, and subway trains are modeled in Maya and imported
to Unity3D. The rest of the 3D objects are modeled in Unity3D. The subway station model and
airport model replicate a real subway station in New York City and a real airport terminal in
the US. The contents in the system are fully controllable by the user interface (see Figure
3). Three-dimensional sounds were implemented using Wwise middleware and Google Resonance
audio plugin. Using the head-tracking data, audio is modulated according to the position of
the listener's head. The technology allows for creation of a rich soundscape in all
directions around the listener. Audio assets used in the system are divided into two main
groups: sound objects and ambiances. Sound objects are attached to the visual objects in the
scene and their position is changing accordingly. Sounds include: footsteps, trains,
announcements, cars, balls, airplanes, etc. Ambiances are created from original recordings
from different locations in New York. These include different background sounds, i.e. sounds
of the crowd chatter, distant trains, wind, birds, traffic, and general room tone of each of
the spaces. All of the sounds used in the system are assigned to three different intensity
levels which relate to the increasing complexity of the soundscape.
Data Collection: The first assessment session will include a well-established postural
control assessment that the investigators had translated to a HMD paradigm and added an
auditory layer. The protocol will include all possible combinations of the following: 2
levels of visual perturbation (static stars; stars moving in the AP direction, 0.2 Hz,
0.032m); 2 levels of auditory perturbation (quiet room; white noise that cycles from 0 to 1
dB at 0.3Hz), and 2 levels of support surface (floor; memory foam). Each scene will be 60
seconds long, there are 8 combinations, and each will be repeated 3 times for a total of 24
trials. Power spectral density (PSD) of sway in 3 frequency segments will be derived from a
laboratory force plate and will serve to explore sensory integration mechanism. Participants
will also complete the FGA (primary), VVAS (primary), ABC (descriptive), and DHI
(descriptive).
Participants will complete the baseline assessment twice, one week apart, to assure stability
of the measures. Following the baseline assessments, participants will be randomized to a
C.S.I. experimental group (EG, n = 14) or a standard rehabilitation control group (CG, n =
14). The participants will commence the intervention program within a week of the second
assessment. The setting will be a vestibular rehabilitation clinic at the New York Eye and
Ear Infirmary of Mount Sinai.
Both groups: Eligible participants will be provided with patient education and a basic home
exercise program (gait, balance, no exercises with eyes closed) while they are considering
participation in the study.
Program Dose: 8 weeks, 1 visit per week, 30 minutes long EG: Progressive immersive training
with the C.S.I. app; Scenes: start from most salient to the patient, eventually do all
Duration: start at 60 seconds, increase over time up to 3 minutes per scene Complexity: start
minimal, gradually increase up to most complex Tasks: standing with diverse base of support
(BOS), head turns (progress with speed, planes); stepping, turning CG: Progressive gait, gaze
stability and balance exercises. Gait: walking with head turns, progress with range, speed
and planes of head movement; change of walking BOS: wide, normal, tandem Gaze: focus on a
target while moving head side to side / up down. Progress with speed, duration, busier
background, standing to walking.
Balance: standing balance tasks, progress with BOS (wide to narrow to tandem), support
surface, eyes closed, duration, head turns.
Both Groups Progression / Regression rule: The highest level of challenge that can be done
for 60 seconds with no loss of balance (LOB); No more than moderate symptoms in clinic based
on the Simulator Sickness Questionnaire; If symptoms persisted over 2 hours post-session,
scale the intensity back the next time. If symptoms improved immediately, repeat the task
with the same intensity and duration.
Home program for both groups: 8 weeks, 6 times per week, twice per day, 10 minutes long,
Highest level of challenge that is safe (no LOB, no increased symptoms) for 60 seconds per
task Home EG: Gait and balance exercises, No exercises with eyes closed Home CG: Gait, gaze
stability and balance exercises, including exercises with eyes closed
A post-assessment, identical to the baseline assessment, will be conducted within one week
from the completion of the 8th intervention session.
Sample Size: For Aim 1, the investigators will recruit 28 patients and 28 age and sex-matched
controls. For Aims 2 & 3, the 28 patients will be randomized into an experimental (N=14) and
control (N=14) groups. Assuming ~20% attrition during the course of the intervention, it is
expected to have 11-12 participants per intervention group. Given our history of recruitment,
this number is feasible for the duration and resources of the 12-month pilot grant. With that
the investigators will determine the sample size needed for a future, adequately powered,
study, as described below.
Internal Validity: To avoid selection bias and to balance potential confounders, the
investigators will use block-randomization strategy for participants using the blockrand
package in R.21 This procedure uses a two-stage process: first, the size of the block is
selected to 2, 4, 6, or 8; next, a block of that size is generated. Therefore, no researcher
will be able to predict which group a participant will be assigned to or change that
assignment (i.e. allocation concealment). Participants will only be randomized into groups
after the baseline assessment and consent to participate in the study have been completed.
Although, due to the nature of the intervention, participants and treating clinicians cannot
be blinded to group assignment, bias will be minimized by blinding the post-treatment
assessors to treatment status. To control for attrition bias, in addition to an
intent-to-treat approach, the investigators will ascertain whether any predictors of
missingness exist. If so, the investigators will use a pattern mixture model to multiply
impute (5 replications) any missing responses.
Consideration of Relevant Biological Variables: The eligibility criteria specified above
represent adult individuals with unilateral vestibular hypofunction of both sexes and of
diverse age range. The control group will be matched for age and sex with the vestibular
group. A wide age range (18 and up) will be recruited. Obesity is known to affect posture and
could alter postural control strategies. Should the sample include overweight individuals,
the model will be tested while adjusting for weight. Because the sample will include aging
individuals, the investigators anticipate additional health conditions that will be similar
between groups, e.g., age-related hearing loss. The exclusion criteria will eliminate health
conditions critical to postural control, such as: visual impairment, peripheral neuropathy,
and other neurological conditions.
Data Analysis: Aim 1: For each of the four measures of interest (PSD 1-3 and overall PSD),
the investigators will fit a linear mixed effects model to compare the age-matched controls
to patients with vestibular hypofunction while accounting for the inherent multi-level study
design (person, conditions, repetitions). The models will include main effects of group,
visual condition, auditory condition, surface condition, as well as their interactions, while
adjusting for age. P-values for the fixed effects will be calculated through the
Satterthwaite approximation for the degrees of freedom for the T-distribution. The analysis
will be repeated following the intervention, adjusting for group assignment and
pre-intervention values. ABC and DHI will be used to describe the sample.
Aim 2: No statistical analysis needed. Aim 3: First, following the intent-to-treat principle,
a linear regression model will be fit with the VVAS and FGA as the primary dependent
variable, on treatment group, controlling for baseline covariates (age and other
self-reported questionnaire measures) to improve the precision of the treatment effect
estimate, as well as pre-test scores. The potential efficacy of the intervention will be
assessed based on a significant coefficient for treatment status. Second, as described above,
the investigators will fit a pattern mixture model to multiply impute any missing values, and
use Rubin's rules to pool coefficients and their standard errors from the regression models
fit to each imputed dataset. Data generated from this pilot randomized trial will be used to
calculate the sample size needed for future, adequately powered, randomized controlled trials
by estimating the difference in means for the treatment groups (i.e. a future expected effect
size) as well as the variance of the primary outcomes and the values of other parameters
necessary to compute the power function.
Safety and Reporting: Preliminary work showed minimal to no cybersickness and no falls or
adverse reactions to the virtual reality training. Only 1 patient dropped out due to concern
about symptoms. Others dropped out due to anxiety, physician's request, cessation of therapy,
or other orthopaedic injuries that occurred after enrollment. In the current study, Dr. Maura
Cosetti, MD, will provide oversight and monitoring of the conduct of the trial as a
preliminary DSMB. This will ensure the safety of participants and the validity and integrity
of the data. The PI and Dr. Kelly will perform continuous monitoring of participant safety
(falls, symptoms on every session) with frequent reporting to Dr. Cosetti. The investigators
will follow the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement checklist
and diagram in reporting the results of the trial.
Inclusion Criteria:
- Adult patients (18 or older)
- Clinical diagnosis of chronic (3 months and longer) unilateral peripheral vestibular
hypofunction
- Patients will be included based on the presence of a positive head thrust test, head
shaking nystagmus, spontaneous nystagmus, and/or canal paresis > 25% if a caloric test
is available.
- Included patients must present with at least two positive items on the VVAS
Exclusion Criteria:
Patients will be excluded for prior vestibular rehab, bilateral or unstable vestibular loss
or another neurological condition, active benign paroxysmal positional vertigo, acute
orthopaedic injuries, peripheral neuropathy, hearing impairment, or visual impairment not
corrected with glasses.
|
NCT0426xxxx/NCT04268758.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268758</url>
</required_header>
<id_info>
<org_study_id>Tulipon-HMO-CTIL</org_study_id>
<nct_id>NCT04268758</nct_id>
</id_info>
<brief_title>A Single-center Study Designed to Evaluate the Safety and Efficacy of Tulipon</brief_title>
<official_title>A Single-center Study Designed to Evaluate the Safety and Efficacy of a New Hygienic Device, Tulipon, in Adult Females With Normal Monthly Menstruation</official_title>
<sponsors>
<lead_sponsor>
<agency>Hadassah Medical Organization</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Gals Bio Ltd.</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>Hadassah Medical Organization</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Subjects who normally use tampons will use Tulipon device during one menstrual cycle.
Baseline and post usage clinical evaluation will be performed for safety testing.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Subjects use Tulipon device during one menstrual cycle. Baseline and post usage clinical
evaluation will be performed for safety testing.
</textblock>
</detailed_description>
<overall_status>Withdrawn</overall_status>
<why_stopped>
logistic and financial issues.
</why_stopped>
<start_date type="Anticipated">June 1, 2021</start_date>
<completion_date type="Anticipated">December 2021</completion_date>
<primary_completion_date type="Anticipated">December 2021</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>safety and efficacy of the Tulipon.</measure>
<time_frame>1 month</time_frame>
<description>We will take vaginal cultures to show no vaginal infection. By questionnaire we will find out about leakage of period blood from the Tulipon.</description>
</primary_outcome>
<enrollment type="Actual">0</enrollment>
<condition>Safety Issues</condition>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>tulipon</intervention_name>
<description>Tulipon is a new kind of hygienic device, used to collect the secreted menses during the bleeding phase of the menstruation.</description>
</intervention>
<eligibility>
<study_pop>
<textblock>
Adult females with normal monthly menstruation.
</textblock>
</study_pop>
<sampling_method>Non-Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

1. Women aged 18-45 years

2. Regular menstrual cycles (21-35 days)

3. Uses tampons every month for the last 2 months to handle their monthly bleeding.

4. Active Bleeding lasts at least 3 days

5. Willing not to change their feminine care or hygiene practices during their
participation in the study (except as directed by the protocol and instructions for
participants)

6. Non-pregnant, with no intentions to get pregnant during the clinical trial

7. Willing to use pads provided thought the study only for the duration of this study

8. Subject is able to comply with all the requirements of the study and agrees to
participate in all the activities of the study

9. Signed written informed consent form (ICF) to participate in the study

Exclusion Criteria:

1. Pregnant or lactating women

2. Gave birth less than a 12 month prior to the study.

3. Virgin

4. Using medications to manage pain during active bleeding

5. Using intrauterine device or intrauterine device with hormones (Mirena)

6. Had experienced Toxic shock syndrome (TSS)

7. Previous diagnosis of primary or secondary dysmenorrhea

8. Previous diagnosis of endometriosis

9. Experiences urinary incontinence

10. Suffers from uterus or urine prolapse

11. Abnormal findings following the gynecological exam

12. Subjects with a known or suspected sensitivity to any of the device materials
(Polyethylene, Polyurethane, Nylon, Cotton)

13. Been through a vaginal operation in the last 6 months prior to the study.

14. Participation in current or recent clinical trial within 30 days prior to baseline
visit
</textblock>
</criteria>
<gender>Female</gender>
<gender_based>Yes</gender_based>
<gender_description>women only.</gender_description>
<minimum_age>18 Years</minimum_age>
<maximum_age>45 Years</maximum_age>
</eligibility>
<verification_date>April 2020</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>August 2, 2022</last_update_submitted>
<last_update_submitted_qc>August 2, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">August 4, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<patient_data>
<sharing_ipd>Undecided</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Subjects who normally use tampons will use Tulipon device during one menstrual cycle.
Baseline and post usage clinical evaluation will be performed for safety testing.
Subjects use Tulipon device during one menstrual cycle. Baseline and post usage clinical
evaluation will be performed for safety testing.
Adult females with normal monthly menstruation.
Inclusion Criteria:
1. Women aged 18-45 years
2. Regular menstrual cycles (21-35 days)
3. Uses tampons every month for the last 2 months to handle their monthly bleeding.
4. Active Bleeding lasts at least 3 days
5. Willing not to change their feminine care or hygiene practices during their
participation in the study (except as directed by the protocol and instructions for
participants)
6. Non-pregnant, with no intentions to get pregnant during the clinical trial
7. Willing to use pads provided thought the study only for the duration of this study
8. Subject is able to comply with all the requirements of the study and agrees to
participate in all the activities of the study
9. Signed written informed consent form (ICF) to participate in the study
Exclusion Criteria:
1. Pregnant or lactating women
2. Gave birth less than a 12 month prior to the study.
3. Virgin
4. Using medications to manage pain during active bleeding
5. Using intrauterine device or intrauterine device with hormones (Mirena)
6. Had experienced Toxic shock syndrome (TSS)
7. Previous diagnosis of primary or secondary dysmenorrhea
8. Previous diagnosis of endometriosis
9. Experiences urinary incontinence
10. Suffers from uterus or urine prolapse
11. Abnormal findings following the gynecological exam
12. Subjects with a known or suspected sensitivity to any of the device materials
(Polyethylene, Polyurethane, Nylon, Cotton)
13. Been through a vaginal operation in the last 6 months prior to the study.
14. Participation in current or recent clinical trial within 30 days prior to baseline
visit
|
NCT0426xxxx/NCT04268771.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268771</url>
</required_header>
<id_info>
<org_study_id>RI-01-007</org_study_id>
<nct_id>NCT04268771</nct_id>
</id_info>
<brief_title>A Phase III Transition Study of DRL Rituximab to Reference Medicinal Products</brief_title>
<acronym>RI-01-007</acronym>
<official_title>A Randomized, Double-blind, Parallel Group, Multicenter Study to Assess the Immunogenicity and Safety of Transitioning Subjects With Rheumatoid Arthritis to Biosimilar Rituximab (DRL_RI) or Continued Treatment With Rituxan® or MabThera®</official_title>
<sponsors>
<lead_sponsor>
<agency>Dr. Reddy's Laboratories Limited</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
<collaborator>
<agency>PPD</agency>
<agency_class>Industry</agency_class>
</collaborator>
</sponsors>
<source>Dr. Reddy's Laboratories Limited</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The objective of the current study is to assess the immunogenicity and safety of
transitioning subjects with RA to DRL_RI from US-rituximab/EU-rituximab to continued
treatment with US-rituximab/EU-rituximab.

The primary objective of this study is to assess the immunogenicity of transitioning subjects
with RA to DRL_RI (biosimilar rituximab) from US-rituximab/EU-rituximab to continued
treatment with US-rituximab/EU-rituximab

To assess the safety of transitioning subjects with RA to DRL_RI from
US-rituximab/EU-rituximab to continued treatment with US-rituximab/EU-rituximab.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
This is a randomized, double-blind, parallel group, multicenter, Phase 3 transition study in
subjects with active RA who are eligible for the subsequent treatment course with
US-rituximab or EU-rituximab according to the clinical judgment of the investigator.

Subjects will then be randomized by interactive web response system (IWRS) to receive either
two 1000 mg infusions of DRL_RI (Arm A) or US-rituximab/EU-rituximab (Arm B) on Day 1 and Day
15.

Subjects randomized to Arm A will receive DRL_RI and subjects randomized to Arm B will
continue to receive either US-rituximab or EU-rituximab.

The study will consist of a screening period (Days -14 to 0) and a double-blind period (Day 1
to Week 12). Subjects will attend a screening visit followed by a visit at Weeks 0 (Day 1),
2, 4, 8, and 12 after randomization

It is planned that approximately 50 sites will be initiated for this study in up to 7
countries (including but not restricted to United States). There has been no randomization of
patients till date for this study.

The study endpoints include:

The immunogenicity endpoint is:

• The incidence of anti-drug antibodies (ADA), including titer and neutralizing antibodies
(NAb).

The primary safety endpoints are:

- Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events
(SAEs).

- Incidence of anaphylactic reactions, hypersensitivity reactions, and IRRs.
</textblock>
</detailed_description>
<overall_status>Active, not recruiting</overall_status>
<start_date type="Actual">April 8, 2020</start_date>
<completion_date type="Anticipated">April 29, 2022</completion_date>
<primary_completion_date type="Actual">January 26, 2022</primary_completion_date>
<phase>Phase 3</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>A randomized, double-blind, parallel group, multicenter study to assess the immunogenicity and safety of transitioning subjects with rheumatoid arthritis to biosimilar rituximab (DRL_RI) or continued treatment with Rituxan® or MabThera®</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>Incidence of ADA on Day 1</measure>
<time_frame>ADA will be obtained before the administration of study treatment on Day 1</time_frame>
<description>For Immunogenicity: Incidence of ADA, including titer and NAb</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of ADA on Day 15</measure>
<time_frame>ADA will be obtained before the administration of study treatment on Day 15</time_frame>
<description>For Immunogenicity: Incidence of ADA, including titer and NAb</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of ADA at Week 4</measure>
<time_frame>ADA will be obtained before the administration of study treatment at Week 4</time_frame>
<description>For Immunogenicity: Incidence of ADA, including titer and NAb</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of ADA at Week 8</measure>
<time_frame>ADA will be obtained before the administration of study treatment at Week 8</time_frame>
<description>For Immunogenicity: Incidence of ADA, including titer and NAb</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of ADA at Week 12 (EOS/ET) visits</measure>
<time_frame>ADA will be obtained before the administration of study treatment at Week 12 (EOS/ET) visits</time_frame>
<description>For Immunogenicity: Incidence of ADA, including titer and NAb</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of TEAEs on Day 1</measure>
<time_frame>Assessment of AE's will be carried out on Day 1</time_frame>
<description>For Safety: Incidence of TEAEs: Treatment-emergent AE are defined as any AE occurring or worsening on or after the first dose of study medication.</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of TEAEs on Day 15</measure>
<time_frame>Assessment of AE's will be carried out during Day 15</time_frame>
<description>For Safety: Incidence of TEAEs: Treatment-emergent AE are defined as any AE occurring or worsening on or after the first dose of study medication.</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of TEAEs at Week 4 ± 7 Days</measure>
<time_frame>Assessment of AE's will be carried out at Week 4 ± 7 Days</time_frame>
<description>For Safety: Incidence of TEAEs: Treatment-emergent AE are defined as any AE occurring or worsening on or after the first dose of study medication.</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of TEAEs at Week 8 ± 7 Days</measure>
<time_frame>Assessment of AE's will be carried out at Week 8 ± 7 Days</time_frame>
<description>For Safety: Incidence of TEAEs: Treatment-emergent AE are defined as any AE occurring or worsening on or after the first dose of study medication.</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of TEAEs at Week 12 ( EOS/ET) visits</measure>
<time_frame>Assessment of AE's will be carried out at Week 12 (EOS/ET) visits</time_frame>
<description>For Safety: Incidence of TEAEs: Treatment-emergent AE are defined as any AE occurring or worsening on or after the first dose of study medication.</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of SAEs during screening</measure>
<time_frame>Assessment of AE's will be carried out during screening</time_frame>
<description>For Safety: Incidence of SAEs: Results in death, is life-threatening, Requires in-subject hospitalization or prolongs existing hospitalization, Results in persistent or significant disability/incapacity.</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of SAEs on Day 1</measure>
<time_frame>Assessment of AE's will be carried out on Day 1</time_frame>
<description>For Safety: Incidence of SAEs: Results in death, is life-threatening, Requires in-subject hospitalization or prolongs existing hospitalization, Results in persistent or significant disability/incapacity.</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of SAEs on Day 15</measure>
<time_frame>Assessment of AE's will be carried out on Day 15</time_frame>
<description>For Safety: Incidence of SAEs: Results in death, is life-threatening, Requires in-subject hospitalization or prolongs existing hospitalization, Results in persistent or significant disability/incapacity.</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of SAEs at Week 4 ± 7 Days</measure>
<time_frame>Assessment of AE's will be carried out at Week 4 ± 7 Days</time_frame>
<description>For Safety: Incidence of SAEs: Results in death, Is life-threatening, Requires in-subject hospitalization or prolongs existing hospitalization, Results in persistent or significant disability/incapacity.</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of SAEs at Week 8 ± 7 Days</measure>
<time_frame>Assessment of AE's will be carried out at Week 8 ± 7 Days</time_frame>
<description>For Safety: Incidence of SAEs: Results in death, is life-threatening, Requires in-subject hospitalization or prolongs existing hospitalization, Results in persistent or significant disability/incapacity.</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of SAEs at Week 12 ( EOS/ET) Visits</measure>
<time_frame>Assessment of AE's will be carried out at Week 12 (EOS/ET) visits</time_frame>
<description>For Safety: Incidence of SAEs: Results in death, is life-threatening, Requires in-subject hospitalization or prolongs existing hospitalization, Results in persistent or significant disability/incapacity.</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Anaphylactic reactions during screening</measure>
<time_frame>Assessments of Anaphylactic reactions will be carried out during screening</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters anaphylactic reactions</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Anaphylactic reactions on Day 1</measure>
<time_frame>Assessments of Anaphylactic reactions will be carried out on Day 1</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters anaphylactic reactions</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Anaphylactic reactions on Day 15</measure>
<time_frame>Assessments of Anaphylactic reactions will be carried out on Day 15</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters anaphylactic reactions</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Anaphylactic reactions at Week 4 ± 7 Days</measure>
<time_frame>Assessments of Anaphylactic reactions will be carried out at Week 4 ± 7 Days</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters anaphylactic reactions</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Anaphylactic reactions at Week 8 ± 7 Days</measure>
<time_frame>Assessments of Anaphylactic reactions will be carried out at Week 8 ± 7 Days</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters anaphylactic reactions</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Anaphylactic reactions at Week 12 ( EOS/ET) visits</measure>
<time_frame>Assessments of Anaphylactic reactions will be carried out at Week 12 (EOS/ET) visits</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters anaphylactic reactions</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Hypersensitivity reactions during screening</measure>
<time_frame>Assessments of Hypersensitivity reactions will be carried out during screening</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters incidence of hypersensitivity reactions</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Hypersensitivity reactions on Day 1</measure>
<time_frame>Assessments of hypersensitivity reactions will be carried out on Day 1</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters incidence of hypersensitivity reactions</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Hypersensitivity reactions on Day 15</measure>
<time_frame>Assessments of hypersensitivity reactions will be carried out on Day 15</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters incidence of hypersensitivity reactions</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Hypersensitivity reactions at Week 4 ± 7 Days</measure>
<time_frame>Assessments of hypersensitivity reactions will be carried out at Week 4 ± 7 Days</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters incidence of hypersensitivity reactions</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Hypersensitivity reactions at Week 8 ± 7 Days</measure>
<time_frame>Assessments of hypersensitivity reactions will be carried out at at Week 8 ± 7 Days</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters incidence of hypersensitivity reactions</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Hypersensitivity reactions at Week 12 ( EOS/ET) visits</measure>
<time_frame>Assessments of hypersensitivity reactions will be carried out at Week 12 (EOS/ET) visits</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters incidence of hypersensitivity reactions</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Infusion-related reactions (IRRs) during screening</measure>
<time_frame>Assessments of IRRs will be carried out during screening</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters like IRRs</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Infusion-related reactions (IRRs) on Day 1</measure>
<time_frame>Assessments of IRRs will be carried out on Day 1</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters like IRRs</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Infusion-related reactions (IRRs) on Day 15</measure>
<time_frame>Assessments of IRRs will be carried out on Day 15</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters like IRRs</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Infusion-related reactions (IRRs) at Week 4 ± 7 Days</measure>
<time_frame>Assessment will be carried out at Week 4 ± 7 Days</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters like IRRs</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Infusion-related reactions (IRRs) at Week 8 ± 7 Days</measure>
<time_frame>Assessments of IRRs will be carried out at Week 8 ± 7 Days</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters like IRRs</description>
</primary_outcome>
<primary_outcome>
<measure>Incidence of Infusion-related reactions (IRRs) at Week 12 ( EOS/ET) visits</measure>
<time_frame>Assessments of IRRs will be carried out at Week 12 (EOS/ET) visits</time_frame>
<description>Safety assessment will be done by measuring primary safety parameters like IRRs</description>
</primary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">140</enrollment>
<condition>Rheumatoid Arthritis</condition>
<arm_group>
<arm_group_label>Arm A: DRL_RI</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Subjects who have already received at least 1 full course comprising two 1000 mg infusions of either US-rituximab or EU-rituximab and are candidates for re-treatment with Rituximab, will be enrolled. DRL_RI will be administrated in combination with MTX as two 1000 mg infusions on Day 1 and Day 15</description>
</arm_group>
<arm_group>
<arm_group_label>Arm B: US-Rituximab or EU-Rituximab</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Subjects who have already received at least 1 full course comprising two 1000 mg infusions of either US-rituximab or EU-rituximab and are candidates for re-treatment with rituximab, will be enrolled.
Patients enrolled in Arm -B will continue to receive US-rituximab or EU-rituximab. The rituximab reference product used (US-licensed rituximab [Rituxan] or EU-approved rituximab [MabThera]) should be the same in the prior and the randomized treatment course, respectively.</description>
</arm_group>
<intervention>
<intervention_type>Biological</intervention_type>
<intervention_name>Experimental: Arm A: DRL_RI</intervention_name>
<description>Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion</description>
<arm_group_label>Arm A: DRL_RI</arm_group_label>
</intervention>
<intervention>
<intervention_type>Biological</intervention_type>
<intervention_name>Arm B: Rituxan®/Mabthera®</intervention_name>
<description>Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion</description>
<arm_group_label>Arm B: US-Rituximab or EU-Rituximab</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Male or female subjects aged 18 years or older who have provided valid written
informed consent.

2. Subjects with a diagnosis of active RA who are eligible for the subsequent treatment
course with US-rituximab or EU-rituximab according to the clinical judgment of the
investigator.

3. Documented evidence that subject has received at least 1 full course comprising two
1000 mg infusions of either US-rituximab at least 16 weeks prior to the randomization
visit or EU-rituximab at least 24 weeks prior to the day of randomization visit.

4. Subjects receiving a stable dose of weekly methotrexate (MTX) for at least 4 weeks
prior to randomization (between 7.5 mg and 25 mg) and folic acid (at least 5 mg per
week.

EXCLUSION CRITERIA;

1. Subjects with RA in functional Class IV

2. Subjects with human immunodeficiency virus (positive HIV1Ab or HIV2Ab), hepatitis B
virus and/or hepatitis C virus infection, including those with positive results in the
viral disease screening.

3. Subjects with active tuberculosis. Subjects with evidence of latent TB or a history of
TB must have completed treatment or have initiated treatment for at least 1 month
before the first dose of study treatment (Day 1). TB testing is required only if it is
required by local regulations or practice.

4. Active systemic infection.

5. Severely immunocompromised.

6. History of severe hypersensitivity to either US-rituximab or EU-rituximab or any of
its excipients requiring drug discontinuation.

7. Any serious illness or uncontrolled medical condition, including but not limited to
severe infections, significant hepatic or renal disease, uncontrolled hypertension
despite treatment (defined as blood pressure ≥160/95 mmHg), congestive heart failure
(New York Heart Association [NYHA] Class III or IV), or other severe, uncontrolled
cardiac disease or uncontrolled diabetes with immediate risk of acute complications.

8. Any condition that in the opinion of the investigator represents an obstacle for study
conduct and/or represents a potential unacceptable risk for subjects.

9. Requires treatment with any biological medicinal product during the study other than
the study treatment.

10. Previous treatment with B-cell modulating or cell depleting biologic therapy except
US-rituximab or EU-rituximab.

11. Prior participation in this clinical trial or prior participation in any clinical
trial with any monoclonal antibody within 12 months of screening or prior
participation in any clinical trial within 3 months of screening or within 5
half-lives of the investigational drug or until the expected PD effect has returned to
baseline, whichever is longer.

12. Treatment with other biologic disease-modifying anti-rheumatic drugs, or Janus kinase
(JAK) inhibitors administered within 12 weeks before the first dose of rituximab of
the prior treatment course onwards till the date of randomization.

13. Subjects with the following laboratory abnormalities:

- Subjects with screening total white blood cell count <3000/μL, platelets
<100,000/μL, neutrophils <1,500/μL, or hemoglobin <8.5 g/dL

- Abnormal liver function tests such as aspartate aminotransferase, alanine
aminotransferase, or alkaline phosphatase >2 × upper limit of normal (ULN). A
single parameter >2 × ULN can be re-checked as soon as possible, at least prior
to randomization, if required as per the investigator's discretion.

- Creatinine clearance (Cockcroft & Gault formula) of less than 50 mL/min.

14. History of vaccination with live vaccines within 4 weeks of the first dose of study
treatment (Day 1) or known to require live vaccines during the study.

15. Lactating or pregnant female.

16. Women of childbearing potential who do not consent to use highly effective methods of
birth control (e.g., barrier contraceptives, oral contraceptives, intrauterine
devices, true abstinence if it allowed as per the country specific regulatory
requirement [periodic abstinence {e.g., calendar ovulation, symptothermal,
post-ovulation methods} and withdrawal are not acceptable methods of contraception],
or sterilization) during treatment and for at least 12 months after the last
administration of study treatment.

17. For men involved in any sexual intercourse that could lead to pregnancy, subjects must
agree to use 1 of the highly effective methods of birth control listed in Exclusion
Criterion #16 during treatment and for at least 12 months after the last
administration of study treatment.

18. Subject with serum IgG < lower limit of normal.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<location>
<facility>
<name>Arizona Arthritis and Rheumatology Research, PLLC</name>
<address>
<city>Phoenix</city>
<state>Arizona</state>
<zip>85032</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>California Allergy and Asthma Medical Group - CRN - PPDS 41230 11th Street West, Suite A</name>
<address>
<city>Palmdale</city>
<state>California</state>
<zip>93551</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Inland Rheumatology Clinical Trials Incorporated</name>
<address>
<city>Upland</city>
<state>California</state>
<zip>91786</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Rheumatology Consultant of Delaware dba Delaware Arthritis</name>
<address>
<city>Lewes</city>
<state>Delaware</state>
<zip>19958</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>MedBio Trials</name>
<address>
<city>Aventura</city>
<state>Florida</state>
<zip>33180</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Clinical Research of West Florida Inc - Clearwater</name>
<address>
<city>Clearwater</city>
<state>Florida</state>
<zip>33765</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Medical Research Center</name>
<address>
<city>Miami</city>
<state>Florida</state>
<zip>33144</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>AppleMed Research Group, LLC</name>
<address>
<city>Miami</city>
<state>Florida</state>
<zip>33155</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Integral Rheumatology and Immunology Specialist, 140 Southwest 84th Avenue, Suite B</name>
<address>
<city>Plantation</city>
<state>Florida</state>
<zip>33324.</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Vicis Clinical Research INC</name>
<address>
<city>Tampa</city>
<state>Florida</state>
<zip>33615</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Springfield Clinic (Clinic location)</name>
<address>
<city>Springfield</city>
<state>Illinois</state>
<zip>62702</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Bluegrass Community Research Inc,330 Waller Avenue, Suite 100,</name>
<address>
<city>Lexington</city>
<state>Kentucky</state>
<zip>40504.</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Arthritis and Osteoporosis Associates</name>
<address>
<city>Freehold</city>
<state>New Jersey</state>
<zip>07728</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Integrative Rheumatology</name>
<address>
<city>Charlotte</city>
<state>North Carolina</state>
<zip>28210</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Altoona Center For Clinical Research, 175 Meadowbrook Lane,</name>
<address>
<city>Duncansville</city>
<state>Pennsylvania</state>
<zip>16635</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Articularis Healthcare Group, Inc dba Low Country Rheumatology</name>
<address>
<city>Summerville</city>
<state>South Carolina</state>
<zip>29486</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Accurate Clinical Management, LLC</name>
<address>
<city>Baytown</city>
<state>Texas</state>
<zip>77521</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Trinity Clinical Research LLC, 2008 East Hebron Parkway, Suites 120/114/100,</name>
<address>
<city>Carrollton</city>
<state>Texas</state>
<zip>75010</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Abigail Neiman</name>
<address>
<city>Houston</city>
<state>Texas</state>
<zip>77084</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Accurate Clinical Management, LLC</name>
<address>
<city>Houston</city>
<state>Texas</state>
<zip>77084</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Laila A Hassan, MD, PA</name>
<address>
<city>Houston</city>
<state>Texas</state>
<zip>77084</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Accurate Clinical Research-Houston, 11003 Resource Parkway, Suite 102</name>
<address>
<city>Houston</city>
<state>Texas</state>
<zip>77089</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Houston Rheumatology & Arthritis Specialists</name>
<address>
<city>Katy</city>
<state>Texas</state>
<zip>77494</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Clinical Associates in Research Therapeutics of America, LLC</name>
<address>
<city>San Antonio</city>
<state>Texas</state>
<zip>78212</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Accurate Clinical Research, Inc.</name>
<address>
<city>San Antonio</city>
<state>Texas</state>
<zip>78229</zip>
<country>United States</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Accurate Clinical Research-League City</name>
<address>
<city>Texas City</city>
<state>Texas</state>
<zip>77034</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>April 2022</verification_date>
<study_first_submitted>January 31, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>April 6, 2022</last_update_submitted>
<last_update_submitted_qc>April 6, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">April 7, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Arthritis</mesh_term>
<mesh_term>Arthritis, Rheumatoid</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Rituximab</mesh_term>
</intervention_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The objective of the current study is to assess the immunogenicity and safety of
transitioning subjects with RA to DRL_RI from US-rituximab/EU-rituximab to continued
treatment with US-rituximab/EU-rituximab.
The primary objective of this study is to assess the immunogenicity of transitioning subjects
with RA to DRL_RI (biosimilar rituximab) from US-rituximab/EU-rituximab to continued
treatment with US-rituximab/EU-rituximab
To assess the safety of transitioning subjects with RA to DRL_RI from
US-rituximab/EU-rituximab to continued treatment with US-rituximab/EU-rituximab.
This is a randomized, double-blind, parallel group, multicenter, Phase 3 transition study in
subjects with active RA who are eligible for the subsequent treatment course with
US-rituximab or EU-rituximab according to the clinical judgment of the investigator.
Subjects will then be randomized by interactive web response system (IWRS) to receive either
two 1000 mg infusions of DRL_RI (Arm A) or US-rituximab/EU-rituximab (Arm B) on Day 1 and Day
15.
Subjects randomized to Arm A will receive DRL_RI and subjects randomized to Arm B will
continue to receive either US-rituximab or EU-rituximab.
The study will consist of a screening period (Days -14 to 0) and a double-blind period (Day 1
to Week 12). Subjects will attend a screening visit followed by a visit at Weeks 0 (Day 1),
2, 4, 8, and 12 after randomization
It is planned that approximately 50 sites will be initiated for this study in up to 7
countries (including but not restricted to United States). There has been no randomization of
patients till date for this study.
The study endpoints include:
The immunogenicity endpoint is:
• The incidence of anti-drug antibodies (ADA), including titer and neutralizing antibodies
(NAb).
The primary safety endpoints are:
- Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events
(SAEs).
- Incidence of anaphylactic reactions, hypersensitivity reactions, and IRRs.
Inclusion Criteria:
1. Male or female subjects aged 18 years or older who have provided valid written
informed consent.
2. Subjects with a diagnosis of active RA who are eligible for the subsequent treatment
course with US-rituximab or EU-rituximab according to the clinical judgment of the
investigator.
3. Documented evidence that subject has received at least 1 full course comprising two
1000 mg infusions of either US-rituximab at least 16 weeks prior to the randomization
visit or EU-rituximab at least 24 weeks prior to the day of randomization visit.
4. Subjects receiving a stable dose of weekly methotrexate (MTX) for at least 4 weeks
prior to randomization (between 7.5 mg and 25 mg) and folic acid (at least 5 mg per
week.
EXCLUSION CRITERIA;
1. Subjects with RA in functional Class IV
2. Subjects with human immunodeficiency virus (positive HIV1Ab or HIV2Ab), hepatitis B
virus and/or hepatitis C virus infection, including those with positive results in the
viral disease screening.
3. Subjects with active tuberculosis. Subjects with evidence of latent TB or a history of
TB must have completed treatment or have initiated treatment for at least 1 month
before the first dose of study treatment (Day 1). TB testing is required only if it is
required by local regulations or practice.
4. Active systemic infection.
5. Severely immunocompromised.
6. History of severe hypersensitivity to either US-rituximab or EU-rituximab or any of
its excipients requiring drug discontinuation.
7. Any serious illness or uncontrolled medical condition, including but not limited to
severe infections, significant hepatic or renal disease, uncontrolled hypertension
despite treatment (defined as blood pressure ≥160/95 mmHg), congestive heart failure
(New York Heart Association [NYHA] Class III or IV), or other severe, uncontrolled
cardiac disease or uncontrolled diabetes with immediate risk of acute complications.
8. Any condition that in the opinion of the investigator represents an obstacle for study
conduct and/or represents a potential unacceptable risk for subjects.
9. Requires treatment with any biological medicinal product during the study other than
the study treatment.
10. Previous treatment with B-cell modulating or cell depleting biologic therapy except
US-rituximab or EU-rituximab.
11. Prior participation in this clinical trial or prior participation in any clinical
trial with any monoclonal antibody within 12 months of screening or prior
participation in any clinical trial within 3 months of screening or within 5
half-lives of the investigational drug or until the expected PD effect has returned to
baseline, whichever is longer.
12. Treatment with other biologic disease-modifying anti-rheumatic drugs, or Janus kinase
(JAK) inhibitors administered within 12 weeks before the first dose of rituximab of
the prior treatment course onwards till the date of randomization.
13. Subjects with the following laboratory abnormalities:
- Subjects with screening total white blood cell count <3000/μL, platelets
<100,000/μL, neutrophils <1,500/μL, or hemoglobin <8.5 g/dL
- Abnormal liver function tests such as aspartate aminotransferase, alanine
aminotransferase, or alkaline phosphatase >2 × upper limit of normal (ULN). A
single parameter >2 × ULN can be re-checked as soon as possible, at least prior
to randomization, if required as per the investigator's discretion.
- Creatinine clearance (Cockcroft & Gault formula) of less than 50 mL/min.
14. History of vaccination with live vaccines within 4 weeks of the first dose of study
treatment (Day 1) or known to require live vaccines during the study.
15. Lactating or pregnant female.
16. Women of childbearing potential who do not consent to use highly effective methods of
birth control (e.g., barrier contraceptives, oral contraceptives, intrauterine
devices, true abstinence if it allowed as per the country specific regulatory
requirement [periodic abstinence {e.g., calendar ovulation, symptothermal,
post-ovulation methods} and withdrawal are not acceptable methods of contraception],
or sterilization) during treatment and for at least 12 months after the last
administration of study treatment.
17. For men involved in any sexual intercourse that could lead to pregnancy, subjects must
agree to use 1 of the highly effective methods of birth control listed in Exclusion
Criterion #16 during treatment and for at least 12 months after the last
administration of study treatment.
18. Subject with serum IgG < lower limit of normal.
|
NCT0426xxxx/NCT04268784.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268784</url>
</required_header>
<id_info>
<org_study_id>DNLI-F-0001</org_study_id>
<secondary_id>2019-004027-21</secondary_id>
<nct_id>NCT04268784</nct_id>
</id_info>
<brief_title>A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL343 in Healthy Volunteers</brief_title>
<official_title>A Phase 1, Single-Center, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL343 In Healthy Volunteers</official_title>
<sponsors>
<lead_sponsor>
<agency>Denali Therapeutics Inc.</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
</sponsors>
<source>Denali Therapeutics Inc.</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
<is_us_export>No</is_us_export>
</oversight_info>
<brief_summary>
<textblock>
This is a Phase 1 study carried out at a single site in 88 healthy male subjects and healthy
female subjects of non childbearing potential to investigate the safety, tolerability,
pharmacokinetics (PK) and pharmacodynamics (PD) of DNL343.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
This clinical trial information was submitted voluntarily under the applicable law and,
therefore, certain submission deadlines may not apply. (That is, clinical trial information
for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public
Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by
sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">February 20, 2020</start_date>
<completion_date type="Actual">August 3, 2021</completion_date>
<primary_completion_date type="Actual">August 3, 2021</primary_completion_date>
<phase>Phase 1</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Sequential Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>Double (Participant, Investigator)</masking>
</study_design_info>
<primary_outcome>
<measure>Incidence and severity of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs</measure>
<time_frame>Up to 20 days</time_frame>
</primary_outcome>
<primary_outcome>
<measure>PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma</measure>
<time_frame>Up to 20 days</time_frame>
</primary_outcome>
<primary_outcome>
<measure>PK parameter: The area under the concentration-time curve from zero to 12 or 24 hours for twice daily (BID) or once daily (QD) dosing, respectively (AUC0-τ) of DNL343 in plasma</measure>
<time_frame>Up to 20 days</time_frame>
</primary_outcome>
<primary_outcome>
<measure>PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma</measure>
<time_frame>Up to 20 days</time_frame>
</primary_outcome>
<primary_outcome>
<measure>PK parameter: Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC[0-last]) of DNL343 in plasma</measure>
<time_frame>Up to 20 days</time_frame>
</primary_outcome>
<primary_outcome>
<measure>PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma</measure>
<time_frame>Up to 20 days</time_frame>
</primary_outcome>
<primary_outcome>
<measure>PK parameter: Apparent terminal elimination rate constant (λz) with the respective t½ of DNL343 in plasma</measure>
<time_frame>Up to 20 days</time_frame>
</primary_outcome>
<secondary_outcome>
<measure>PK parameter: The amount of DNL343 excreted in urine from time zero to 48 hours postdose (Ae48)</measure>
<time_frame>Up to 20 days</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>PK parameter: Estimation of renal clearance (CLR)</measure>
<time_frame>Up to 20 days</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>PK parameter: Concentration of DNL343 in cerebrospinal fluid (CSF)</measure>
<time_frame>Up to 20 days</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>The PD of DNL343 in blood as measured by percent reduction of integrated stress response (ISR) protein levels measured by enzyme-linked immunosorbent assay (ELISA)</measure>
<time_frame>Up to 20 days</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>The PD of DNL343 in blood as measured by percent reduction in ISR gene expression levels measured by quantitative polymerase chain reaction (qPCR)</measure>
<time_frame>Up to 20 days</time_frame>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">96</enrollment>
<condition>Healthy Volunteers</condition>
<arm_group>
<arm_group_label>DNL343</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Cohort A: Single-ascending dose; Cohort B: Multiple-ascending doses</description>
</arm_group>
<arm_group>
<arm_group_label>Placebo</arm_group_label>
<arm_group_type>Placebo Comparator</arm_group_type>
<description>Cohort A: Single-ascending dose; Cohort B: Multiple-ascending doses</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>DNL343</intervention_name>
<description>Single and repeating oral dose(s)</description>
<arm_group_label>DNL343</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Placebo</intervention_name>
<description>Single and repeating oral dose(s)</description>
<arm_group_label>Placebo</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Key Inclusion Criteria:

- Women of non-childbearing potential and men; aged 18-50 years, inclusive

- BMI 18-32 kg/m², inclusive, and body weight of at least 50 kg

Key Exclusion Criteria:

- History of clinically significant neurologic, psychiatric, endocrine, pulmonary,
cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic,
immunologic, or allergic disease, or other major disorders
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>50 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Richard Tsai, MD</last_name>
<role>Study Director</role>
<affiliation>Denali Therapeutics Inc.</affiliation>
</overall_official>
<location>
<facility>
<name>Centre for Human Drug Research (CHDR)</name>
<address>
<city>Leiden</city>
<state>South Holland</state>
<zip>2333</zip>
<country>Netherlands</country>
</address>
</facility>
</location>
<location_countries>
<country>Netherlands</country>
</location_countries>
<verification_date>February 2022</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 3, 2022</last_update_submitted>
<last_update_submitted_qc>February 3, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">February 7, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This is a Phase 1 study carried out at a single site in 88 healthy male subjects and healthy
female subjects of non childbearing potential to investigate the safety, tolerability,
pharmacokinetics (PK) and pharmacodynamics (PD) of DNL343.
This clinical trial information was submitted voluntarily under the applicable law and,
therefore, certain submission deadlines may not apply. (That is, clinical trial information
for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public
Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by
sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
Key Inclusion Criteria:
- Women of non-childbearing potential and men; aged 18-50 years, inclusive
- BMI 18-32 kg/m², inclusive, and body weight of at least 50 kg
Key Exclusion Criteria:
- History of clinically significant neurologic, psychiatric, endocrine, pulmonary,
cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic,
immunologic, or allergic disease, or other major disorders
|
NCT0426xxxx/NCT04268797.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268797</url>
</required_header>
<id_info>
<org_study_id>TMS_negative symptoms</org_study_id>
<nct_id>NCT04268797</nct_id>
</id_info>
<brief_title>TMS in Treatment of Schizophrenia Negative Symptoms</brief_title>
<official_title>Efficacy and Safety of High-frequency Repetitive Transcranial Magnetic Stimulation With H7-coil in the Treatment of Schizophrenia Negative Symptoms; A Multicenter, Randomized, Sham Controlled, Triple Blind Trial</official_title>
<sponsors>
<lead_sponsor>
<agency>Sveti Ivan Psychiatric Hospital</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Sveti Ivan Psychiatric Hospital</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Primary objective: to examine the efficacy and safety of high frequency repetitive
transcranial magnetic stimulation (HF rTMS) with H7-coil applied once daily during the twenty
days, augmentative to the standard antipsychotic pharmacotherapy and other treatment of
negative symptoms in schizophrenia.

Targeted population: patients diagnosed with schizophrenia, 18-55 years old with predominant
negative symptoms, stable condition for >3 months and unchanged antipsychotic therapy for >1
months and no treatment with antidepressants.

Study design: industry independent, multicenter, prospective randomized sham-controlled,
two-arms, triple-blind superiority clinical trial with concealed allocation and masked
independent outcome assessment.

Primary outcome: adjusted median of differences in total SANS score. Adjustment for age,
gender, baseline total SANS score, duration of the disorder, and antipsychotic therapy.
</textblock>
</brief_summary>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">November 4, 2019</start_date>
<completion_date type="Anticipated">March 15, 2023</completion_date>
<primary_completion_date type="Anticipated">December 15, 2022</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>Adjusted median of differences in total SANS score</measure>
<time_frame>assessed up to 20 days of treatment</time_frame>
<description>Adjusted median of differences in total SANS score (Andreasen, 1989). We will adjust the medians for age, gender, baseline total SANS score, duration of the disorder, and antipsychotic therapy</description>
</primary_outcome>
<secondary_outcome>
<measure>Change in SNS score</measure>
<time_frame>assessed up to 20 days of treatment</time_frame>
<description>Change in Self-Evaluation of Negative Symptoms Scale (SNS) (Dollfus, Mach and Morello, 2016)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Change of BNSS score</measure>
<time_frame>assessed up to 20 days of treatment</time_frame>
<description>Change in Brief Negative Symptom Scale (BNSS), (Kirkpatrick et al., 2006)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Change in PANSS negative symptom subscale with items rescaled to 0-6 range</measure>
<time_frame>assessed up to 20 days of treatment</time_frame>
<description>Change in PANSS negative symptoms subscale with items rescaled to 0-6 range, (Kay, Fiszbein and Opler, 1987)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Change in CDSS score</measure>
<time_frame>assessed up to 20 days of treatment</time_frame>
<description>Change in depressive symptoms measured using Calgary Depression Scale for Schizophrenia (CDSS) (Addington, Addington and Schissel, 1990)</description>
</secondary_outcome>
<other_outcome>
<measure>The number of patients self-reported side effects during therapy, confirmed by the medical nurse</measure>
<time_frame>assessed up to 20 days of treatment</time_frame>
</other_outcome>
<other_outcome>
<measure>Change in verbal memory</measure>
<time_frame>assessed up to 20 days of treatment</time_frame>
<description>Change in verbal memory using Auditory Verbal Learning Test (AVLT), subtest from Wechsler Memory Scale (Revised)-Verbal-Logical Memory</description>
</other_outcome>
<other_outcome>
<measure>Change in visual memory</measure>
<time_frame>assessed up to 20 days of treatment</time_frame>
<description>Change in visual memory using Benton's visual retention test (BVRT)</description>
</other_outcome>
<other_outcome>
<measure>Change in numeric memory</measure>
<time_frame>assessed up to 20 days of treatment</time_frame>
<description>Change in numeric memory using subtest from Wechsler Memory Scale (Revised)-Digit Span</description>
</other_outcome>
<other_outcome>
<measure>Change in visual-spatial abilities and executive function</measure>
<time_frame>assessed up to 20 days of treatment</time_frame>
<description>Change in visual-spatial abilities and executive function using TMT (A/B) Trail Making Test, and subtest from Wechsler Intelligence Scale (Revised)-Block Design</description>
</other_outcome>
<other_outcome>
<measure>Change in psihomotor speed</measure>
<time_frame>assessed up to 20 days of treatment</time_frame>
<description>Change in psihomotor speed using subtest from Wechsler Intelligence Scale (Revised)-Digit Symbol Substitution Test</description>
</other_outcome>
<other_outcome>
<measure>Change in verbal fluency</measure>
<time_frame>assessed up to 20 days of treatment</time_frame>
<description>Change in verbal fluency using FAS Verbal Fluency Test</description>
</other_outcome>
<other_outcome>
<measure>Change in recognition of facial expressions of emotions</measure>
<time_frame>assessed up to 20 days of treatment</time_frame>
<description>Change in recognition of facial expressions of emotions using the Penn's Emotion Recognition Task test (ER40)</description>
</other_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">104</enrollment>
<condition>Schizophrenia</condition>
<arm_group>
<arm_group_label>HR rTMS H7-coil intervention group</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
</arm_group>
<arm_group>
<arm_group_label>sham control group</arm_group_label>
<arm_group_type>Sham Comparator</arm_group_type>
</arm_group>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>HR rTMS</intervention_name>
<description>high frequency repetitive transcranial magnetic stimulation (HF rTMS) with H7-coil applied once daily during the twenty days</description>
<arm_group_label>HR rTMS H7-coil intervention group</arm_group_label>
</intervention>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>sham</intervention_name>
<description>SHAM HF rTMS coil once daily x 20 days</description>
<arm_group_label>sham control group</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Confirmation diagnosis of schizophrenia (ICD-10 F20) using the Mini-International
Neuropsychiatric Interview (MINI) (Lecrubier et al., 1997; Sheehan et al., 1998),

2. Age 18-55 years,

3. Both genders,

4. PANSS negative symptoms subscale score >24,

5. PANSS positive symptoms subscale score <20,

6. Stable condition (no acute psychosis exacerbation, no psychiatric hospitalization
because of relapse or worsening of symptoms) during at least three months,

7. Stable antipsychotic therapy with no change of drugs or doses during the one months
before the enrollment.

Exclusion Criteria:

1. Antipsychotics dose change or change of antipsychotic drug,

2. Hospitalization for somatic illness in another institution,

3. Termination of treatment in a Psychiatric Hospital "Sveti Ivan",

4. Pregnancy,

5. Missed more than three consecutive interventions,

6. Withdrawal of consent to participate for the sake of intolerance of TMS or for other
reasons.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>55 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<location>
<facility>
<name>PB Sveti Ivan</name>
<address>
<city>Zagreb</city>
<zip>10000</zip>
<country>Croatia</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Ena Ivezic, MA</last_name>
<phone>38513430171</phone>
<email>ena.ivezic@pbsvi.hr</email>
</contact>
</location>
<location_countries>
<country>Croatia</country>
</location_countries>
<verification_date>May 2022</verification_date>
<study_first_submitted>February 7, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>May 18, 2022</last_update_submitted>
<last_update_submitted_qc>May 18, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">May 19, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Schizophrenia</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Primary objective: to examine the efficacy and safety of high frequency repetitive
transcranial magnetic stimulation (HF rTMS) with H7-coil applied once daily during the twenty
days, augmentative to the standard antipsychotic pharmacotherapy and other treatment of
negative symptoms in schizophrenia.
Targeted population: patients diagnosed with schizophrenia, 18-55 years old with predominant
negative symptoms, stable condition for >3 months and unchanged antipsychotic therapy for >1
months and no treatment with antidepressants.
Study design: industry independent, multicenter, prospective randomized sham-controlled,
two-arms, triple-blind superiority clinical trial with concealed allocation and masked
independent outcome assessment.
Primary outcome: adjusted median of differences in total SANS score. Adjustment for age,
gender, baseline total SANS score, duration of the disorder, and antipsychotic therapy.
Inclusion Criteria:
1. Confirmation diagnosis of schizophrenia (ICD-10 F20) using the Mini-International
Neuropsychiatric Interview (MINI) (Lecrubier et al., 1997; Sheehan et al., 1998),
2. Age 18-55 years,
3. Both genders,
4. PANSS negative symptoms subscale score >24,
5. PANSS positive symptoms subscale score <20,
6. Stable condition (no acute psychosis exacerbation, no psychiatric hospitalization
because of relapse or worsening of symptoms) during at least three months,
7. Stable antipsychotic therapy with no change of drugs or doses during the one months
before the enrollment.
Exclusion Criteria:
1. Antipsychotics dose change or change of antipsychotic drug,
2. Hospitalization for somatic illness in another institution,
3. Termination of treatment in a Psychiatric Hospital "Sveti Ivan",
4. Pregnancy,
5. Missed more than three consecutive interventions,
6. Withdrawal of consent to participate for the sake of intolerance of TMS or for other
reasons.
|
NCT0426xxxx/NCT04268810.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268810</url>
</required_header>
<id_info>
<org_study_id>S52212</org_study_id>
<secondary_id>Uracyst study</secondary_id>
<nct_id>NCT04268810</nct_id>
</id_info>
<brief_title>Prospective Trial Comparing Intravesical Chondroitin Sulphate 2% and DMSO in the Treatment of PBS/Interstitial Cystitis</brief_title>
<official_title>Prospective Randomised Trial Comparing Intravesical Chondroitin Sulphate 2% and DMSO in the Treatment of Painful Bladder Syndrome/ Interstitial Cystitis</official_title>
<sponsors>
<lead_sponsor>
<agency>National Multiple Sclerosis Center</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>National Multiple Sclerosis Center</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
</oversight_info>
<brief_summary>
<textblock>
Painful bladder syndrome/interstitial cystitis (PBS/IC)is a disease of unknown origin with a
significant impact on the quality of life. Next to oral treatment with tricyclic
antidepressants or pentosan polysulphate, intravesical treatment can be used as well. The
purpose of this treatment is to restore the protective lining of the bladder that consists of
glycan structures (GAG). Currently only dimethylsulfoxide (DMSO) is FDA approved for this.
Several other compounds have been introduced. We want to compare a solution of chondroitin
sulphate 2% with the standard DMSO solution. We will compare the patient perception of
benefit,but also pain scores, quality of life and micturition diaries.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
A. Introduction

Painful bladder syndrome(PBS) is a syndrome which is poorly understood. Patients usually
report suprapubic pain related to bladder filling and also report urinary urgency and
frequency. In a subgroup of patients, typical cystoscopic findings can be noted and this
defines this subgroup as interstitial cystitis. (Abrams et al. 116-26) The treatment of
PBS/IC is empirical. Bladder hydrodistension under anesthesia, tricyclic antidepressants,
antihistaminics and intravesical DMSO instillations are the only treatment for which some
evidence exists in the literature. More than 150 other treatment modalities have been
described . Most of them were poorly studied. (Fall et al. 1-99) Intravesical treatment with
DMSO has stood the test of time and is the only FDA approved intravesical treatment of
PBS/IC. DMSO however is also used as a solvent in the chemical industry and is in fact used '
off label' in this indication. (Erickson 333-43;Emerson and Perezmarrero A136;Perez-Marrero,
Emerson, and Feltis 36-39) One of the theories on which intravesical treatment is based,
claims that the glycosaminoglycan layer, which protects the urothelial cells is damaged.
DMSO, Chondroitin sulphate, hyaluronic acid and heparin have been used to repair the GAG
layer with variable clinical success. (Daha et al. 369-72;Daha et al. 987-90;Riedl et al.
717-21) Chondroitin sulphate seems to be promising, but comparative data are lacking.
(Gauruder-Burmester and Popken 355-59;Nickel et al. 56-60;Hauser et al. 2477-82;Nordling and
van Ophoven 328-35) Assessing the outcome of such treatments is difficult. Objective
parameters such as daytime and nighttime frequency may not always reflect the impact of the
condition on the life of the patient.

Patient reported outcome parameters are more frequently used to assess treatments in
overactive bladder disease and in painful bladder research. Several validated questionnaires
can be used to assess patients with PBS/IC. One of the most frequently used is the
O'Leary-Sant questionnaire ( see annex 1). Next to this questionnaire the Global Response
Assessment will be used. This is a validated 7 point Likert scale comparing the current
status of the patient to the pre-intervention status. This scale has been used in several
other studies on PBS/IC. (Nickel et al. 910-18;Baranowski et al. 33-36) Aim To compare the
clinical effectiveness of intravesical chondroitin sulphate 2% ( Uracyst ™) and DMSO 50% in
the treatment of patients with painful bladder syndrome

B. Randomization A central randomization will be used. Participating centers will have to
contact the trial office of the dept. of urology of the University Hospitals Leuven to
randomize the patient to one or the other treatment, either by telephone 016/346692 or
016/348345 or by mail elza.goossens@uzleuven.be or evelien.vankriekingen@uzleuven.be . A
block randomization per center will be done. The randomization list was generated on a web
application ( www.randomizer.org) to ensure an unbiased randomization schedule.

C. Protocol of administration Patients that are enrolled in the study will receive one
intravesical instillation of Uracyst or DMSO a week during 6 weeks. DMSO is prepared as a 50%
solution in 50cc physiologic serum. Uracyst will be prepared by the nurse or urologist
administering the product.

Uracyst is delivered as a 2% sterile solution in 20cc vials. The instillation is done by a
urethral catheterization. The catheter is withdrawn once the fluid has been instilled. The
solution is kept in the bladder for at least 30 minutes. A simple instillation protocol is
followed, meaning that the patient can move immediately after the instillation of the
product. The product is eliminated by spontaneous voiding after 30 minutes.

D. Safety Safety is assessed by monitoring adverse events at every visit. Anticipated adverse
events are hematuria, algiuria, urinary tract infection and garlic odor ( for DMSO)…

E. Statistics Comparison of the mean GRA by T-test will be used for the primary endpoint.
Appropriate statistical tests will be used for the secondary variables.

To detect a 0.75 difference on the 7 point Likert scale, with 80% power at 0.05% significance
45 patients will be needed in each group.
</textblock>
</detailed_description>
<overall_status>Terminated</overall_status>
<why_stopped>
too many side effect in the control arm (DMSO)
</why_stopped>
<start_date>March 2010</start_date>
<completion_date type="Actual">December 31, 2013</completion_date>
<primary_completion_date type="Actual">September 2013</primary_completion_date>
<phase>Phase 4</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>Single (Investigator)</masking>
</study_design_info>
<primary_outcome>
<measure>Global response assessment scale</measure>
<time_frame>4 weeks after last treatment</time_frame>
<description>Primary endpoint: Global response assessment scale.
This is a 7 point scale asking: As compared to when you started the current study, how would you rate your overall bladder symptoms now? Seven response options are given to the patient: Markedly worse, moderately worse, slightly worse, no change, slightly improved, moderately improved, markedly improved.</description>
</primary_outcome>
<secondary_outcome>
<measure>Urinary Frequency</measure>
<time_frame>4 weeks after last treatment</time_frame>
<description>Frequency measured as the mean frequency on a 3 day micturition diary
Nocturia episodes as the mean number of nocturia episodes on a 3 day micturition diary
Functional bladder capacity measured as the mean bladder capacity measured on a 3 day micturition diary
VAS pain scale
O'Leary -Sant scale</description>
</secondary_outcome>
<secondary_outcome>
<measure>Nocturia Episodes</measure>
<time_frame>4 weeks after last treatment</time_frame>
<description>Nocturia measured on 3 day micturition diary</description>
</secondary_outcome>
<secondary_outcome>
<measure>Functional bladder capacity</measure>
<time_frame>4 weeks after last treatment</time_frame>
<description>bladder capacity measured on 3 day micturition diary</description>
</secondary_outcome>
<secondary_outcome>
<measure>VAS pain scale</measure>
<time_frame>4 weeks after last treatment</time_frame>
<description>visual analogue pain scale</description>
</secondary_outcome>
<secondary_outcome>
<measure>O'Leary Sant</measure>
<time_frame>4 weeks after last treatment</time_frame>
<description>O'Leary Sant questionnaire score</description>
</secondary_outcome>
<other_outcome>
<measure>Drop-out</measure>
<time_frame>any time during study</time_frame>
<description>patients refusing further treatment because of intolerance to the intravesical treatment of by lack of improvement</description>
</other_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">36</enrollment>
<condition>Painful Bladder Syndrome</condition>
<condition>Interstitial Cystitis</condition>
<arm_group>
<arm_group_label>Chondroitin sulphate 2%</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>chondoritin sulphate 2% ( Uracyst) for bladder instillation. One bladeer instillation per week during 6 weeks.</description>
</arm_group>
<arm_group>
<arm_group_label>DMSO 50%</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>DMSO 50% in saline for bladder instillation. One bladder instillation per week during 6 weeks</description>
</arm_group>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>Bladder instillations</intervention_name>
<description>bladder instillations with either solution (DMSO or Uracyst)</description>
<arm_group_label>Chondroitin sulphate 2%</arm_group_label>
<arm_group_label>DMSO 50%</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Female and male patients from 18-75 years

2. A history of symptoms of bladder pain/discomfort described as suprapubic pain related
to bladder filling, accompanied by other symptoms such as daytime and/or nighttime
frequency in the absence of infection or other pathology, with or without the typical
cystoscopic findings of interstitial cystitis

3. Patients willing and able to complete the necessary questionnaires

Exclusion Criteria:

1. Patients with transitional cell carcinoma of the bladder or other significant
malignancy

2. Pregnant women

3. Breastfeading women

4. Patients with significant bacteriuria

5. Patients with hematuria

6. Neurogenic bladder

7. Patients with indwelling catheters

8. Chronic bacterial prostatitis

9. Currently receiving or having received investigational drugs thirty (30) days or less
prior to screening

10. Currently receiving or having had prior therapy with intravesical treatment (eg.
Uracyst, Cystistat®, heparin or BCG)

11. Receiving therapy for less than three months with antidepressants, antihistaminics,
hormonal agonists or antagonists; hence patient not stabilized on therapy. (Stable
therapy defined as continuous treatment for at least three months.)

12. IC symptoms relieved by antimicrobials, anticholinergics or antispasmodics

13. Functional Bladder capacity of greater than 400 ml

14. Neurologic disease affecting bladder function; any previous surgery or procedure
having affected bladder function

15. Current diagnosis of chemical, tuberculous or radiation cystitis

16. bladder or lower ureteral calculi

17. History of cancer within the last five years other than adequately treated
non-melanoma skin cancers

18. Active sexual transmitted disease

19. Current vaginitis

20. Endometriosis

21. Any condition/disease which in the opinion of the investigator could interfere with
patient compliance and/ or interfere with the interpretation of the treatment results
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>75 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Dirk JM De Ridder, MD, PhD</last_name>
<role>Principal Investigator</role>
<affiliation>University Hospitals KU Leuven</affiliation>
</overall_official>
<location>
<facility>
<name>Urology, University Hospitals KU Leuven</name>
<address>
<city>Leuven</city>
<zip>3000</zip>
<country>Belgium</country>
</address>
</facility>
</location>
<location_countries>
<country>Belgium</country>
</location_countries>
<reference>
<citation>Tutolo M, Ammirati E, Castagna G, Klockaerts K, Plancke H, Ost D, Van der Aa F, De Ridder D. A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroitin sulphate 2% for painful bladder syndrome/interstitial cystitis. Int Braz J Urol. 2017 Jan-Feb;43(1):134-141. doi: 10.1590/S1677-5538.IBJU.2016.0302.</citation>
<PMID>28124536</PMID>
</reference>
<verification_date>February 2020</verification_date>
<study_first_submitted>March 31, 2013</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 11, 2020</last_update_submitted>
<last_update_submitted_qc>February 11, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>painful bladder syndrome</keyword>
<keyword>interstitial cystitis</keyword>
<keyword>chondroitin sulphate</keyword>
<keyword>DMSO</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Cystitis</mesh_term>
<mesh_term>Cystitis, Interstitial</mesh_term>
<mesh_term>Syndrome</mesh_term>
<mesh_term>Pain</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Painful bladder syndrome/interstitial cystitis (PBS/IC)is a disease of unknown origin with a
significant impact on the quality of life. Next to oral treatment with tricyclic
antidepressants or pentosan polysulphate, intravesical treatment can be used as well. The
purpose of this treatment is to restore the protective lining of the bladder that consists of
glycan structures (GAG). Currently only dimethylsulfoxide (DMSO) is FDA approved for this.
Several other compounds have been introduced. We want to compare a solution of chondroitin
sulphate 2% with the standard DMSO solution. We will compare the patient perception of
benefit,but also pain scores, quality of life and micturition diaries.
A. Introduction
Painful bladder syndrome(PBS) is a syndrome which is poorly understood. Patients usually
report suprapubic pain related to bladder filling and also report urinary urgency and
frequency. In a subgroup of patients, typical cystoscopic findings can be noted and this
defines this subgroup as interstitial cystitis. (Abrams et al. 116-26) The treatment of
PBS/IC is empirical. Bladder hydrodistension under anesthesia, tricyclic antidepressants,
antihistaminics and intravesical DMSO instillations are the only treatment for which some
evidence exists in the literature. More than 150 other treatment modalities have been
described . Most of them were poorly studied. (Fall et al. 1-99) Intravesical treatment with
DMSO has stood the test of time and is the only FDA approved intravesical treatment of
PBS/IC. DMSO however is also used as a solvent in the chemical industry and is in fact used '
off label' in this indication. (Erickson 333-43;Emerson and Perezmarrero A136;Perez-Marrero,
Emerson, and Feltis 36-39) One of the theories on which intravesical treatment is based,
claims that the glycosaminoglycan layer, which protects the urothelial cells is damaged.
DMSO, Chondroitin sulphate, hyaluronic acid and heparin have been used to repair the GAG
layer with variable clinical success. (Daha et al. 369-72;Daha et al. 987-90;Riedl et al.
717-21) Chondroitin sulphate seems to be promising, but comparative data are lacking.
(Gauruder-Burmester and Popken 355-59;Nickel et al. 56-60;Hauser et al. 2477-82;Nordling and
van Ophoven 328-35) Assessing the outcome of such treatments is difficult. Objective
parameters such as daytime and nighttime frequency may not always reflect the impact of the
condition on the life of the patient.
Patient reported outcome parameters are more frequently used to assess treatments in
overactive bladder disease and in painful bladder research. Several validated questionnaires
can be used to assess patients with PBS/IC. One of the most frequently used is the
O'Leary-Sant questionnaire ( see annex 1). Next to this questionnaire the Global Response
Assessment will be used. This is a validated 7 point Likert scale comparing the current
status of the patient to the pre-intervention status. This scale has been used in several
other studies on PBS/IC. (Nickel et al. 910-18;Baranowski et al. 33-36) Aim To compare the
clinical effectiveness of intravesical chondroitin sulphate 2% ( Uracyst ™) and DMSO 50% in
the treatment of patients with painful bladder syndrome
B. Randomization A central randomization will be used. Participating centers will have to
contact the trial office of the dept. of urology of the University Hospitals Leuven to
randomize the patient to one or the other treatment, either by telephone 016/346692 or
016/348345 or by mail elza.goossens@uzleuven.be or evelien.vankriekingen@uzleuven.be . A
block randomization per center will be done. The randomization list was generated on a web
application ( www.randomizer.org) to ensure an unbiased randomization schedule.
C. Protocol of administration Patients that are enrolled in the study will receive one
intravesical instillation of Uracyst or DMSO a week during 6 weeks. DMSO is prepared as a 50%
solution in 50cc physiologic serum. Uracyst will be prepared by the nurse or urologist
administering the product.
Uracyst is delivered as a 2% sterile solution in 20cc vials. The instillation is done by a
urethral catheterization. The catheter is withdrawn once the fluid has been instilled. The
solution is kept in the bladder for at least 30 minutes. A simple instillation protocol is
followed, meaning that the patient can move immediately after the instillation of the
product. The product is eliminated by spontaneous voiding after 30 minutes.
D. Safety Safety is assessed by monitoring adverse events at every visit. Anticipated adverse
events are hematuria, algiuria, urinary tract infection and garlic odor ( for DMSO)…
E. Statistics Comparison of the mean GRA by T-test will be used for the primary endpoint.
Appropriate statistical tests will be used for the secondary variables.
To detect a 0.75 difference on the 7 point Likert scale, with 80% power at 0.05% significance
45 patients will be needed in each group.
Inclusion Criteria:
1. Female and male patients from 18-75 years
2. A history of symptoms of bladder pain/discomfort described as suprapubic pain related
to bladder filling, accompanied by other symptoms such as daytime and/or nighttime
frequency in the absence of infection or other pathology, with or without the typical
cystoscopic findings of interstitial cystitis
3. Patients willing and able to complete the necessary questionnaires
Exclusion Criteria:
1. Patients with transitional cell carcinoma of the bladder or other significant
malignancy
2. Pregnant women
3. Breastfeading women
4. Patients with significant bacteriuria
5. Patients with hematuria
6. Neurogenic bladder
7. Patients with indwelling catheters
8. Chronic bacterial prostatitis
9. Currently receiving or having received investigational drugs thirty (30) days or less
prior to screening
10. Currently receiving or having had prior therapy with intravesical treatment (eg.
Uracyst, Cystistat®, heparin or BCG)
11. Receiving therapy for less than three months with antidepressants, antihistaminics,
hormonal agonists or antagonists; hence patient not stabilized on therapy. (Stable
therapy defined as continuous treatment for at least three months.)
12. IC symptoms relieved by antimicrobials, anticholinergics or antispasmodics
13. Functional Bladder capacity of greater than 400 ml
14. Neurologic disease affecting bladder function; any previous surgery or procedure
having affected bladder function
15. Current diagnosis of chemical, tuberculous or radiation cystitis
16. bladder or lower ureteral calculi
17. History of cancer within the last five years other than adequately treated
non-melanoma skin cancers
18. Active sexual transmitted disease
19. Current vaginitis
20. Endometriosis
21. Any condition/disease which in the opinion of the investigator could interfere with
patient compliance and/ or interfere with the interpretation of the treatment results
|
NCT0426xxxx/NCT04268823.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268823</url>
</required_header>
<id_info>
<org_study_id>CQBW251B2202</org_study_id>
<nct_id>NCT04268823</nct_id>
</id_info>
<brief_title>Clinical Study to Assess the Mode of Action of QBW251 in Patients With Chronic Obstructive Pulmonary Disease (COPD)</brief_title>
<official_title>A Randomized, Subjects and Investigator Blinded, Placebo Controlled Parallel Group Study to Assess the Mode of Action of QBW251 in Patients With Chronic Obstructive Pulmonary Disease (COPD)</official_title>
<sponsors>
<lead_sponsor>
<agency>Novartis Pharmaceuticals</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
</sponsors>
<source>Novartis</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The purpose of this study is to determine whether potentiating the cystic fibrosis
transmembrane conductance regulator (CFTR) with QBW251 in subjects with COPD will be
efficacious with regards to reducing lung and systemic inflammation and bacterial
colonization as potential drivers of airway obstruction, airway destruction, remodeling and
exacerbations.

Furthermore, this study will provide supportive data to investigate the relationship of COPD
phenotype and the response in small airway structure, function, mucus load and spirometry
indices as well as in improvement of overall COPD symptoms and quality of life.
</textblock>
</brief_summary>
<overall_status>Completed</overall_status>
<start_date type="Actual">September 10, 2020</start_date>
<completion_date type="Actual">September 20, 2022</completion_date>
<primary_completion_date type="Actual">September 13, 2022</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>This is a randomized, subject and investigator blinded, parallel-group, placebo controlled study investigating the mode of action (MoA) and preliminary efficacy and safety of QBW251 administered orally twice daily (b.i.d.) for 12 weeks in subjects with moderate to severe COPD (GOLD 2-3).
Approximately 100 subjects will be randomized in a 1:1 ratio to receive either QBW251 or placebo treatment. Based on the assumption of a 15% drop-out rate (% drop out based on completed proof-of-concept COPD study CQBW251X2201), it is expected to have approximately 84 subjects to complete the study. A blinded interim analysis to re-assess the sample size is planned for when approximately 36 subjects have completed their Day 84 visit.
The study consists of the following periods: Screening, Baseline / Day 1, Treatment, and End of the Study followed by an additional post-treatment safety phone call. The total duration for each subject in the study is up to approximately 18 weeks.</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>Fibrinogen plasma concentration</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on fibrinogen</description>
</primary_outcome>
<secondary_outcome>
<measure>Total bacteria load of colony forming units (CFU/mL)</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>Change from baseline in total bacteria load of colony forming units (CFU/mL) of potentially pathogenic microorganisms in sputum.</description>
</secondary_outcome>
<secondary_outcome>
<measure>COPD Assessment Test (CAT) questionnaire.</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on COPD patients symptoms burden changes.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Euro Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) questionnaire.</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on health status and quality of patients life.</description>
</secondary_outcome>
<secondary_outcome>
<measure>St. George's Respiratory Questionnaire (SGRQ) total and domain scores.</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on changes in total and domain scores health-related quality of life.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Cough and Sputum Assessment Questionnaire (CASA-Q).</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on domain scores which evaluate clinical symptoms, cough and sputum.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Ctrough at pre-dose.</measure>
<time_frame>Day 1, Day 28, Day 56 and Day 84.</time_frame>
<description>To assess the effect of QBW251 compared to placebo during and after 12 weeks of treatment on pharmacokinetics, assessing drug exposure.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Trough FEV1.</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on spirometry (Forced Exploratory Volume in the first second).</description>
</secondary_outcome>
<secondary_outcome>
<measure>FVC.</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on spirometry (Forced Vital Capacity).</description>
</secondary_outcome>
<secondary_outcome>
<measure>FEV1/FVC.</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on spirometry</description>
</secondary_outcome>
<secondary_outcome>
<measure>Cmax at post-dose.</measure>
<time_frame>Post-dose (+3hr) at Day 1, Day 28, Day 56 and Day 84.</time_frame>
<description>To assess the effect of QBW251 compared to placebo during and after 12 weeks of treatment on pharmacokinetics, drug exposure.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Cmax in a subset of patient population</measure>
<time_frame>Post dose (+1hr, +2hr, +3hr, +4hr, +6hr, +8hr) at Day 1 and Day 28.</time_frame>
<description>To assess the effect of QBW251 compared to placebo during and after 12 weeks of treatment on pharmacokinetics, assessing drug exposure.</description>
</secondary_outcome>
<secondary_outcome>
<measure>AUC in a subset of patient population.</measure>
<time_frame>Post-dose (+1hr, +2hr, +3hr, +4hr, +6hr, +8hr) at Day 1 and Day 28.</time_frame>
<description>To assess the effect of QBW251 compared to placebo during and after 12 weeks of treatment on pharmacokinetics, assessing drug exposure.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Time to first COPD exacerbation.</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on COPD exacerbations, exacerbations defined by EXACT-PRO questionnaire.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Proportion of patients (percentage) with exacerbations.</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on COPD exacerbations , exacerbations defined by EXACT-PRO questionnaire.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Annualized rate of exacerbations.</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on COPD exacerbations, exacerbations defined by EXACT-PRO questionnaire.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Airway wall.</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on airway structure and function, measured by HRCT.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Airway extent of global and regional air trapping</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on airway structure and functions, measured by HRCT.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Airway lumen.</measure>
<time_frame>Change from baseline at 12 weeks.</time_frame>
<description>To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on airway structure and function measured by HRCT.</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">55</enrollment>
<condition>Chronic Obstructive Pulmonary Disease</condition>
<arm_group>
<arm_group_label>QBW251</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Oral use, one capsule twice daily.</description>
</arm_group>
<arm_group>
<arm_group_label>Placebo</arm_group_label>
<arm_group_type>Placebo Comparator</arm_group_type>
<description>Oral use, one capsule twice daily.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>QBW251</intervention_name>
<description>Capsule 300mg</description>
<arm_group_label>QBW251</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Placebo</intervention_name>
<description>Capsule 300mg</description>
<arm_group_label>Placebo</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Patients who have signed an Informed Consent Form prior to initiation of any
study-related procedure.

2. Male and female adults aged ≥40 years at screening.

3. Patients with stable COPD, stages GOLD 2-3, according to the current GOLD strategy
(GOLD 2019) at screening.

Patients with a post-bronchodilator FEV1/FVC < 0.70 at screening

4. Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥ 30% and
FEV1 < 80% of the predicted normal at Screening who must have had at least 2
documented moderate or at least 1 documented severe exacerbation(s) between January
2019 to study screening.

5. Patients with sputum positive (>0 CFU) for at least one strain of potentially
pathogenic microorganism at screening (H influenzae, H parainfluenzae, P aeruginosa, S
pneumoniae, S aureus, Moraxella catarrhalis, Enterobacteriaceae, Stenotrophomonas
maltophilia, Burkholderia species, and Achromobacter species or any potential
pathogenic bacteria measured by dilution/outgrowth. Any organism that is to be
included and that is not included in the list of the protocol defined pathogens will
be discussed case by case). Sputum samples may be re collected and re-tested once
during the screening period.

6. Patients who have been treated with a combination of LABA/LAMA or LABA/ICS or
LABA/LAMA/ICS at a stable dose for the last 3 months prior to screening.

COPD patients are allowed to stay on macrolides as background therapy if they have
bronchiectasis as a secondary diagnosis and if they are treated with them at a stable
dose 3 months before screening.

7. Patients with plasma fibrinogen level ≥ 320 mg/dL at screening. Fibrinogen may be
re-tested once during the screening period.

8. A COPD Assessment Test (CAT) score of at least 10 at screening.

9. Current or ex-smokers who have a smoking history of at least 10 pack years (e.g. 10
pack years = 1 pack/day x 10 years, or 0.5 pack/day x 20 years) at screening.

10. Patients featuring chronic bronchitis, defined as productive cough that occurs on most
days (defined as >50% of days) during at least 3 consecutive months in the year prior
to screening, as assessed by documentation of patient recollection (anamnesis) or
documented in patients' records.

11. Able to communicate well with the investigator, to understand and comply with the
requirements of the study.

Exclusion Criteria:

1. Patients with a history of long-QT syndrome or whose QTcF interval at screening

2. Patients who have a clinically significant* ECG abnormality before randomization.
Note: Clinically significant abnormalities may include but are not limited to the
following: left bundle branch block, Wolff-Parkinson-White syndrome, clinically
significant arrhythmias (e.g., atrial fibrillation, ventricular tachycardia).

3. Clinical laboratory values abnormalities (including Gamma GT, AST, ALT, total
bilirubin or creatinine) considered as clinically significant in the opinion of the
Investigator at screening. For additional guidance on hepatic parameters see exclusion
criterion #5.

4. Patients who have clinically significant renal, cardiovascular (such as but not
limited to unstable ischemic heart disease, NYHA Class III/IV left ventricular
failure, myocardial infarction), neurological, endocrine, immunological, psychiatric,
gastrointestinal, or hematological abnormalities, which could interfere with the
assessment of the efficacy and safety of the study treatment, or patients with
uncontrolled Type II diabetes.

5. Patients with a history or current treatment for hepatic disease including but not
limited to acute hepatitis, cirrhosis or hepatic failure.

- Patients with stable chronic hepatitis may be included in the study by agreement
with Novartis Medical Expert on a case-by-case basis.

- A history of resolved Hepatitis A is not exclusionary.

- Patients with prothrombin time international normalized ratio (PT/INR) of more
than 1.5xULN at screening. Patients excluded for the PT/INR of more than 1.5xULN
can be re-screened when the values have returned to normal.

6. Patients with a history of malignancy of any organ system, treated or untreated,
within the past 5 years whether or not there is evidence of local recurrence or
metastases, with the exception of localized basal cell carcinoma of the skin. Patients
with a history of cancer and 5 years or more disease free survival time may be
included in the study by agreement with Novartis Medical Monitor on a case-by-case
basis.

7. Patients who develop a COPD exacerbation that required treatment with antibiotics
and/or oral corticosteroids and/or hospitalization during screening. Re-screening is
permitted after a minimum of 2 weeks after the resolution of the COPD exacerbation
(i.e 2 weeks after the stop of SOC therapy for exacerbation).

8. Patients who have had a respiratory tract infection within 4 weeks prior to screening.
If a respiratory tract infection occurs during screening, patients can be re-screened
after a minimum of 2 weeks after resolution of the respiratory tract infection.

9. Patients with history of asthma or any other clinically relevant lung diseases..

10. Patients with suspected active pulmonary tuberculosis or currently being treatment for
active pulmonary tuberculosis.

Note: Patients with a history of pulmonary tuberculosis can be enrolled if they meet
the following requirements: history of appropriate drug treatment followed by negative
imaging results within 12 months prior to screening suggesting low probability of
recurrent active tuberculosis.

11. Patients with pulmonary lobectomy, lung volume reduction surgery, bronchoscopic lung
volume reductions, or lung transplantation.

12. Patients participating in or planning to participate in the active phase of a
supervised pulmonary rehabilitation program during the trial. Participation in a
maintenance program is permitted. Note: the supervised pulmonary rehabilitation
program as a maintenance program has to be ongoing for at least 3 months at the time
of enrollment.

13. Patients with a body mass index (BMI) of more than 40 kg/m2.

14. Patients receiving any medications in the classes listed in Table 6-5.

15. Patients receiving any COPD related medications in the classes specified in Table 6-6,
unless they undergo the required washout period prior to screening and follow the
adjustment to treatment program.

16. Patients receiving medications in the classes listed in Table 6-2 should be excluded
unless the medication has been stabilized for the specified period and the stated
conditions have been met.

17. Use of other investigational drugs (approved or unapproved) within 30 days or 5
half-lives prior to screening, or until the expected pharmacodynamic effect has
returned to baseline (e.g., biologics), whichever is longer; or longer if required by
local regulations.

18. Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive human chorionic gonadotropin (hCG) laboratory test.

19. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using acceptable effective methods of contraception
during study participation.

20. Patients who have not achieved an acceptable spirometry result at screening in
accordance with American Thoracic Society (ATS)/ European Respiratory Society (ERS)
criteria for acceptability and repeatability.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>40 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Novartis Pharmaceuticals</last_name>
<role>Study Director</role>
<affiliation>Novartis Pharmaceuticals</affiliation>
</overall_official>
<location>
<facility>
<name>Novartis Investigative Site</name>
<address>
<city>Feldbach</city>
<zip>8330</zip>
<country>Austria</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Novartis Investigative Site</name>
<address>
<city>Heidelberg</city>
<state>Baden-Württemberg</state>
<zip>69126</zip>
<country>Germany</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Novartis Investigative Site</name>
<address>
<city>Berlin</city>
<zip>10119</zip>
<country>Germany</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Novartis Investigative Site</name>
<address>
<city>Berlin</city>
<zip>10969</zip>
<country>Germany</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Novartis Investigative Site</name>
<address>
<city>Frankfurt</city>
<zip>60596</zip>
<country>Germany</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Novartis Investigative Site</name>
<address>
<city>Mainz</city>
<zip>55128</zip>
<country>Germany</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Novartis Investigative Site</name>
<address>
<city>Witten</city>
<zip>58452</zip>
<country>Germany</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Novartis Investigative Site</name>
<address>
<city>Basel</city>
<zip>4031</zip>
<country>Switzerland</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Novartis Investigative Site</name>
<address>
<city>St Gallen</city>
<zip>9007</zip>
<country>Switzerland</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Novartis Investigative Site</name>
<address>
<city>Zurich</city>
<zip>8091</zip>
<country>Switzerland</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Novartis Investigative Site</name>
<address>
<city>Bradford</city>
<state>West Yorkshire</state>
<zip>BD9 6RJ</zip>
<country>United Kingdom</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Novartis Investigative Site</name>
<address>
<city>London</city>
<zip>SW3 6HP</zip>
<country>United Kingdom</country>
</address>
</facility>
</location>
<location_countries>
<country>Austria</country>
<country>Germany</country>
<country>Switzerland</country>
<country>United Kingdom</country>
</location_countries>
<verification_date>May 2023</verification_date>
<study_first_submitted>January 29, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>May 25, 2023</last_update_submitted>
<last_update_submitted_qc>May 25, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">May 26, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Lung Diseases</mesh_term>
<mesh_term>Lung Diseases, Obstructive</mesh_term>
<mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
</condition_browse>
<pending_results>
<submitted>September 7, 2023</submitted>
</pending_results>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The purpose of this study is to determine whether potentiating the cystic fibrosis
transmembrane conductance regulator (CFTR) with QBW251 in subjects with COPD will be
efficacious with regards to reducing lung and systemic inflammation and bacterial
colonization as potential drivers of airway obstruction, airway destruction, remodeling and
exacerbations.
Furthermore, this study will provide supportive data to investigate the relationship of COPD
phenotype and the response in small airway structure, function, mucus load and spirometry
indices as well as in improvement of overall COPD symptoms and quality of life.
Inclusion Criteria:
1. Patients who have signed an Informed Consent Form prior to initiation of any
study-related procedure.
2. Male and female adults aged ≥40 years at screening.
3. Patients with stable COPD, stages GOLD 2-3, according to the current GOLD strategy
(GOLD 2019) at screening.
Patients with a post-bronchodilator FEV1/FVC < 0.70 at screening
4. Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥ 30% and
FEV1 < 80% of the predicted normal at Screening who must have had at least 2
documented moderate or at least 1 documented severe exacerbation(s) between January
2019 to study screening.
5. Patients with sputum positive (>0 CFU) for at least one strain of potentially
pathogenic microorganism at screening (H influenzae, H parainfluenzae, P aeruginosa, S
pneumoniae, S aureus, Moraxella catarrhalis, Enterobacteriaceae, Stenotrophomonas
maltophilia, Burkholderia species, and Achromobacter species or any potential
pathogenic bacteria measured by dilution/outgrowth. Any organism that is to be
included and that is not included in the list of the protocol defined pathogens will
be discussed case by case). Sputum samples may be re collected and re-tested once
during the screening period.
6. Patients who have been treated with a combination of LABA/LAMA or LABA/ICS or
LABA/LAMA/ICS at a stable dose for the last 3 months prior to screening.
COPD patients are allowed to stay on macrolides as background therapy if they have
bronchiectasis as a secondary diagnosis and if they are treated with them at a stable
dose 3 months before screening.
7. Patients with plasma fibrinogen level ≥ 320 mg/dL at screening. Fibrinogen may be
re-tested once during the screening period.
8. A COPD Assessment Test (CAT) score of at least 10 at screening.
9. Current or ex-smokers who have a smoking history of at least 10 pack years (e.g. 10
pack years = 1 pack/day x 10 years, or 0.5 pack/day x 20 years) at screening.
10. Patients featuring chronic bronchitis, defined as productive cough that occurs on most
days (defined as >50% of days) during at least 3 consecutive months in the year prior
to screening, as assessed by documentation of patient recollection (anamnesis) or
documented in patients' records.
11. Able to communicate well with the investigator, to understand and comply with the
requirements of the study.
Exclusion Criteria:
1. Patients with a history of long-QT syndrome or whose QTcF interval at screening
2. Patients who have a clinically significant* ECG abnormality before randomization.
Note: Clinically significant abnormalities may include but are not limited to the
following: left bundle branch block, Wolff-Parkinson-White syndrome, clinically
significant arrhythmias (e.g., atrial fibrillation, ventricular tachycardia).
3. Clinical laboratory values abnormalities (including Gamma GT, AST, ALT, total
bilirubin or creatinine) considered as clinically significant in the opinion of the
Investigator at screening. For additional guidance on hepatic parameters see exclusion
criterion #5.
4. Patients who have clinically significant renal, cardiovascular (such as but not
limited to unstable ischemic heart disease, NYHA Class III/IV left ventricular
failure, myocardial infarction), neurological, endocrine, immunological, psychiatric,
gastrointestinal, or hematological abnormalities, which could interfere with the
assessment of the efficacy and safety of the study treatment, or patients with
uncontrolled Type II diabetes.
5. Patients with a history or current treatment for hepatic disease including but not
limited to acute hepatitis, cirrhosis or hepatic failure.
- Patients with stable chronic hepatitis may be included in the study by agreement
with Novartis Medical Expert on a case-by-case basis.
- A history of resolved Hepatitis A is not exclusionary.
- Patients with prothrombin time international normalized ratio (PT/INR) of more
than 1.5xULN at screening. Patients excluded for the PT/INR of more than 1.5xULN
can be re-screened when the values have returned to normal.
6. Patients with a history of malignancy of any organ system, treated or untreated,
within the past 5 years whether or not there is evidence of local recurrence or
metastases, with the exception of localized basal cell carcinoma of the skin. Patients
with a history of cancer and 5 years or more disease free survival time may be
included in the study by agreement with Novartis Medical Monitor on a case-by-case
basis.
7. Patients who develop a COPD exacerbation that required treatment with antibiotics
and/or oral corticosteroids and/or hospitalization during screening. Re-screening is
permitted after a minimum of 2 weeks after the resolution of the COPD exacerbation
(i.e 2 weeks after the stop of SOC therapy for exacerbation).
8. Patients who have had a respiratory tract infection within 4 weeks prior to screening.
If a respiratory tract infection occurs during screening, patients can be re-screened
after a minimum of 2 weeks after resolution of the respiratory tract infection.
9. Patients with history of asthma or any other clinically relevant lung diseases..
10. Patients with suspected active pulmonary tuberculosis or currently being treatment for
active pulmonary tuberculosis.
Note: Patients with a history of pulmonary tuberculosis can be enrolled if they meet
the following requirements: history of appropriate drug treatment followed by negative
imaging results within 12 months prior to screening suggesting low probability of
recurrent active tuberculosis.
11. Patients with pulmonary lobectomy, lung volume reduction surgery, bronchoscopic lung
volume reductions, or lung transplantation.
12. Patients participating in or planning to participate in the active phase of a
supervised pulmonary rehabilitation program during the trial. Participation in a
maintenance program is permitted. Note: the supervised pulmonary rehabilitation
program as a maintenance program has to be ongoing for at least 3 months at the time
of enrollment.
13. Patients with a body mass index (BMI) of more than 40 kg/m2.
14. Patients receiving any medications in the classes listed in Table 6-5.
15. Patients receiving any COPD related medications in the classes specified in Table 6-6,
unless they undergo the required washout period prior to screening and follow the
adjustment to treatment program.
16. Patients receiving medications in the classes listed in Table 6-2 should be excluded
unless the medication has been stabilized for the specified period and the stated
conditions have been met.
17. Use of other investigational drugs (approved or unapproved) within 30 days or 5
half-lives prior to screening, or until the expected pharmacodynamic effect has
returned to baseline (e.g., biologics), whichever is longer; or longer if required by
local regulations.
18. Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive human chorionic gonadotropin (hCG) laboratory test.
19. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using acceptable effective methods of contraception
during study participation.
20. Patients who have not achieved an acceptable spirometry result at screening in
accordance with American Thoracic Society (ATS)/ European Respiratory Society (ERS)
criteria for acceptability and repeatability.
|
NCT0426xxxx/NCT04268836.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268836</url>
</required_header>
<id_info>
<org_study_id>OAC #001</org_study_id>
<nct_id>NCT04268836</nct_id>
</id_info>
<brief_title>Vision Improvement for Patients With Age-Related Macular Degeneration</brief_title>
<acronym>AMD</acronym>
<official_title>Vision Improvement for Patients With Age-Related Macular Degeneration</official_title>
<sponsors>
<lead_sponsor>
<agency>Optimal Acuity Corporation</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
<collaborator>
<agency>Bochner Eye Institute</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>Optimal Acuity Corporation</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The purpose of this study is to determine whether the Optimal Acuity Clear-K® Low Vision Aid
System provides a safe and effective treatment to improve vision for patients with
age-related macular degeneration.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
The Optimal Acuity Clear-K® Low Vision Aid System treats corneas with near infrared light in
order to change the modulus of small volumes of anterior stromal corneal tissue. The change
of modulus produces a change of corneal stiffness and shape that modifies the distribution of
light onto the retina. Light rays are redirected from dysfunctional areas of the retina that
have been damaged by age-related macular degeneration (AMD) to functional areas of the
retina, thereby improving patient vision.

200 AMD patients meeting eligibility requirements will be treated. The study will record and
analyze pre-treatment (Tx) and post-Tx examinations with follow-up extending to 24 months
post-Tx. Analysis will include descriptive statistics and measures of correlation between
outcomes and patient baseline characteristics.

The primary objective of the study is to evaluate the safety and effectiveness of Clear-K®
treatment in providing vision improvement to AMD patients.
</textblock>
</detailed_description>
<overall_status>Not yet recruiting</overall_status>
<start_date type="Anticipated">January 9, 2024</start_date>
<completion_date type="Anticipated">May 1, 2025</completion_date>
<primary_completion_date type="Anticipated">May 31, 2024</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<intervention_model_description>Prospective, non-randomized, unmasked clinical study</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Best spectacle-corrected distance visual acuity (CDVA) changes from baseline to 24 months post-Tx</measure>
<time_frame>Through study completion, an average of 2 years</time_frame>
<description>CDVA will be measured using ETDRS letter scoring both pre-Tx and post-Tx with follow-up to 24 months post-Tx</description>
</primary_outcome>
<secondary_outcome>
<measure>Visual Function Questionnaire (VFQ)-25 quality of life assessment</measure>
<time_frame>Through study completion, an average of 2 years</time_frame>
<description>The VFQ-25 instrument will be used to assess patient quality of life measures.</description>
</secondary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Anticipated">200</enrollment>
<condition>Age-related Macular Degeneration</condition>
<arm_group>
<arm_group_label>Treatment arm</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Patients will be treated by the Optimal Acuity Clear-K Low Vision Aid System.</description>
</arm_group>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>Optimal Acuity Clear-K® Low Vision Aid System treatment</intervention_name>
<description>The treatment involves irradiation of the cornea with low energy light in a treatment pattern that produces corneal shape change.</description>
<arm_group_label>Treatment arm</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Male or Female

2. Any race

3. Patient is at least 50 years old.

4. Patient has diagnosed dry or wet age-related macular degeneration in one or both eyes,
as verified by a complete ocular examination by a retina specialist; the full ocular
examination, including optical coherence tomography (OCT) measurements, should be part
of the patient's file.

5. Wet AMD eyes should have an inactive disease state (i.e., there is no clinical or OCT
evidence of wet AMD disease activity).

6. Patient is pseudophakic or is phakic with no clinically significant cataract in eye(s)
to be treated..

7. Patient has manifest refraction, spherical equivalent (MRSE) between -1.50 D to 1.50 D
in eye(s) to be treated.

8. Patient has moderate to severe vision impairment due to dry age-related macular
degeneration with best spectacle-corrected distance visual acuity (CDVA) of 20/80 or
worse (decimal = 0.25 or less; logMAR ≥ 0.60) in the better eye.

9. Patient has CDVA of 20/400 or better (decimal = 0.05 or greater; logMAR ≤ 1.30) in the
worse eye.

10. Patient has normal corneal surface topography on videokeratography (i.e., without
distorted or unclear corneal mires) in both eyes.

11. Patient is not a contact lens (CL) wearer.

12. Patient is willing and able to comply with all examinations.

13. Patient must be competent to sign an informed consent form before study entry.

Exclusion Criteria:

1. Corneal disease or disorder in either eye;

2. Corneal topographic astigmatism greater than 2.00 D (mean value within 3.0 mm optical
zone);

3. Pathological retinal morphology in either eye that completely affects the entire 10°
(3 mm diameter) of the retina centered on the foveola (as evaluated by optical
coherence tomography);

4. Potential Visual Acuity (PVA) in both eyes that is not improved by at least three
lines compared to CDVA;

5. Increased intraocular pressure (above 20 mm Hg), glaucoma or history of glaucoma; and

6. Presence or history of any other condition or finding that, in the opinion of the
investigator, makes the patient unsuitable as a candidate for study participation or
that may confound the outcome of the study.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>50 Years</minimum_age>
<maximum_age>100 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Michael Berry, PhD</last_name>
<role>Study Director</role>
<affiliation>Optimal Acuity Corporation</affiliation>
</overall_official>
<overall_contact>
<last_name>Michael Berry, PhD</last_name>
<phone>8318691384</phone>
<email>mberry177@gmail.com</email>
</overall_contact>
<overall_contact_backup>
<last_name>Samuel Markowitz, MD, FRCSC</last_name>
<phone>4165315425</phone>
<email>snm1@rogers.com</email>
</overall_contact_backup>
<location>
<facility>
<name>1929 Bayview Ave., Suite 117</name>
<address>
<city>Toronto</city>
<state>Ontario</state>
<zip>M4G 3E8</zip>
<country>Canada</country>
</address>
</facility>
<contact>
<last_name>Samuel Markowitz, MD, FRCSC</last_name>
<phone>4165315425</phone>
<email>snm1@rogers.com</email>
</contact>
<investigator>
<last_name>Samuel N Markowitz, MD, FRCSC</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location_countries>
<country>Canada</country>
</location_countries>
<verification_date>April 2022</verification_date>
<study_first_submitted>January 16, 2018</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>March 21, 2023</last_update_submitted>
<last_update_submitted_qc>March 21, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">March 22, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>dry AMD</keyword>
<keyword>wet AMD</keyword>
<keyword>neovascular AMD</keyword>
<keyword>age-related macular degeneration</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Macular Degeneration</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The purpose of this study is to determine whether the Optimal Acuity Clear-K® Low Vision Aid
System provides a safe and effective treatment to improve vision for patients with
age-related macular degeneration.
The Optimal Acuity Clear-K® Low Vision Aid System treats corneas with near infrared light in
order to change the modulus of small volumes of anterior stromal corneal tissue. The change
of modulus produces a change of corneal stiffness and shape that modifies the distribution of
light onto the retina. Light rays are redirected from dysfunctional areas of the retina that
have been damaged by age-related macular degeneration (AMD) to functional areas of the
retina, thereby improving patient vision.
200 AMD patients meeting eligibility requirements will be treated. The study will record and
analyze pre-treatment (Tx) and post-Tx examinations with follow-up extending to 24 months
post-Tx. Analysis will include descriptive statistics and measures of correlation between
outcomes and patient baseline characteristics.
The primary objective of the study is to evaluate the safety and effectiveness of Clear-K®
treatment in providing vision improvement to AMD patients.
Inclusion Criteria:
1. Male or Female
2. Any race
3. Patient is at least 50 years old.
4. Patient has diagnosed dry or wet age-related macular degeneration in one or both eyes,
as verified by a complete ocular examination by a retina specialist; the full ocular
examination, including optical coherence tomography (OCT) measurements, should be part
of the patient's file.
5. Wet AMD eyes should have an inactive disease state (i.e., there is no clinical or OCT
evidence of wet AMD disease activity).
6. Patient is pseudophakic or is phakic with no clinically significant cataract in eye(s)
to be treated..
7. Patient has manifest refraction, spherical equivalent (MRSE) between -1.50 D to 1.50 D
in eye(s) to be treated.
8. Patient has moderate to severe vision impairment due to dry age-related macular
degeneration with best spectacle-corrected distance visual acuity (CDVA) of 20/80 or
worse (decimal = 0.25 or less; logMAR ≥ 0.60) in the better eye.
9. Patient has CDVA of 20/400 or better (decimal = 0.05 or greater; logMAR ≤ 1.30) in the
worse eye.
10. Patient has normal corneal surface topography on videokeratography (i.e., without
distorted or unclear corneal mires) in both eyes.
11. Patient is not a contact lens (CL) wearer.
12. Patient is willing and able to comply with all examinations.
13. Patient must be competent to sign an informed consent form before study entry.
Exclusion Criteria:
1. Corneal disease or disorder in either eye;
2. Corneal topographic astigmatism greater than 2.00 D (mean value within 3.0 mm optical
zone);
3. Pathological retinal morphology in either eye that completely affects the entire 10°
(3 mm diameter) of the retina centered on the foveola (as evaluated by optical
coherence tomography);
4. Potential Visual Acuity (PVA) in both eyes that is not improved by at least three
lines compared to CDVA;
5. Increased intraocular pressure (above 20 mm Hg), glaucoma or history of glaucoma; and
6. Presence or history of any other condition or finding that, in the opinion of the
investigator, makes the patient unsuitable as a candidate for study participation or
that may confound the outcome of the study.
|
NCT0426xxxx/NCT04268849.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268849</url>
</required_header>
<id_info>
<org_study_id>BariatricsProtocol100719</org_study_id>
<nct_id>NCT04268849</nct_id>
</id_info>
<brief_title>Trial of IV vs Oral Iron Treatment of Iron Deficiency Anemia in the Post-Operative Bariatric Surgical Patient</brief_title>
<official_title>A Randomized, Placebo-controlled Comparator Trial of IV vs Oral Iron Treatment of Iron Deficiency Anemia in the Post-Operative Bariatric Surgical Patient</official_title>
<sponsors>
<lead_sponsor>
<agency>Auerbach Hematology Oncology Associates P C</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>AMAG Pharmaceuticals, Inc.</agency>
<agency_class>Industry</agency_class>
</collaborator>
</sponsors>
<source>Auerbach Hematology Oncology Associates P C</source>
<oversight_info>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Given the limited long-term effectiveness of traditional weight loss methods, bariatric
surgery is increasingly becoming the preferred option for sustained weight loss. With the
ascendancy of the laparoscopic approach, the two most common procedures are the Roux-en-Y
gastric bypass (RYGB) and the vertical sleeve gastrectomy (VSG).

Because bariatric surgery decreases nutrient intake through restriction, malabsorption, or
both, and given that obese patients are often malnourished even before surgery, postoperative
micronutrient deficiency, particularly of iron, can be a serious complication and difficult
to treat. Iron deficiency anemia has been reported to be as high as 49% in the post-bariatric
surgical patient.

The current standard for correcting iron deficiency anemia in the post-operative bariatric
surgical patient is oral iron supplements. However, oral iron therapy is known for its
caustic effects on the gastric mucosa causing gastric irritation, nausea, epigastric
discomfort and constipation. These debilitating symptoms lead to poor adherence and lower
long and short-term efficacy. Furthermore, iron absorption from oral iron supplements when
taken with food in patients with low iron stores ranges from 2 to 13% and without food 5 to
28%. An alternative and more effective method of iron replenishment is the use of intravenous
iron. A litany of published trials, without contradiction, show marked superiority of
intravenous iron in improving hemoglobin concentrations and iron parameters when compared to
historical controls. Nonetheless, the current recommendations of the American Society of
Metabolic and Bariatric Surgery nutritional guidelines, state that oral iron supplementation
for IDA is the recommended first line of treatment. Studies are lacking that compare the
efficacy of oral versus intravenous (IV) iron therapy for the treatment of IDA in the
post-bariatric surgical patient.

The aim of our study is to compare two accepted treatments for iron deficiency anemia (oral
ferrous sulfate and intravenous ferumoxytol) for efficacy and speed of response in the
treatment of IDA in the post-operative bariatric surgical patient. In this study, 104
bariatric surgical post-operative patients will be randomly assigned 52 each to oral or 52 to
a single dose IV iron treatment using double-blind procedures.

The primary outcome will be determined at 6 weeks of treatment with a follow-up at 12 months
after treatment. Non-responders at 6 weeks after treatment may, if they qualify (based on
inclusion/exclusion criteria), have an open-label IV iron treatment and will be followed with
the same evaluations used after the first IV iron treatments.
</textblock>
</brief_summary>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">February 27, 2020</start_date>
<completion_date type="Anticipated">February 2024</completion_date>
<primary_completion_date type="Anticipated">November 2023</primary_completion_date>
<phase>Phase 3</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>Double blind, double dummy of oral versus intravenous iron for iron deficiency patients after bariatric surgery. All subjects will get either oral iron and intravenous saline, or oral vitamin C and intravenous iron.</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
<masking_description>Patients will wear sleep masks to blind intravenous intervention</masking_description>
</study_design_info>
<primary_outcome>
<measure>Change in Clinical Global Impression - improvement scale (CGI-2) score at 6 weeks after treatment begins.</measure>
<time_frame>6 weeks</time_frame>
<description>The CGI-2 is a measure of treatment response and the efficacy of the treatment based on a 1 to 7 scale where 1 is "very much better" and 7 "very much worse"</description>
</primary_outcome>
<primary_outcome>
<measure>Change in hemoglobin concentration</measure>
<time_frame>6 weeks</time_frame>
</primary_outcome>
<secondary_outcome>
<measure>Change in ferritin > 20%</measure>
<time_frame>6 weeks</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>Change in Transferrin saturation (TSAT) >19%</measure>
<time_frame>6 weeks</time_frame>
</secondary_outcome>
<secondary_outcome>
<measure>Quality of Life by visual linear analog scale (LASA)</measure>
<time_frame>6 weeks</time_frame>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">104</enrollment>
<condition>Iron Deficiency Anemia</condition>
<arm_group>
<arm_group_label>Oral Iron</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>The subject will receive one IV infusion of ferumoxytol administered as 1020 mg over 30 minutes or an equivalent volume of normal saline. At the time of the infusion, the patient will also be given an opaque bottle, containing either vitamin C tablets or ferrous sulfate 325 mg.</description>
</arm_group>
<arm_group>
<arm_group_label>IV Iron</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>The subject will receive one IV infusion of ferumoxytol administered as 1020 mg over 30 minutes or an equivalent volume of normal saline. At the time of the infusion, the patient will also be given an opaque bottle, containing either vitamin C tablets or ferrous sulfate 325 mg.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Ferumoxytol</intervention_name>
<description>Ferumoxytol (30 mg/mL) intravenous injection in single use vials.</description>
<arm_group_label>IV Iron</arm_group_label>
<arm_group_label>Oral Iron</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Saline</intervention_name>
<description>Placebo for Ferumoxytol</description>
<arm_group_label>IV Iron</arm_group_label>
<arm_group_label>Oral Iron</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Ferrous sulfate tablets</intervention_name>
<description>ferrous sulfate tablets containing 60 mg elemental iron</description>
<arm_group_label>IV Iron</arm_group_label>
<arm_group_label>Oral Iron</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Vitamin C</intervention_name>
<description>Placebo: Vitamin C, 250 mg, given in the same bottle as the oral iron</description>
<arm_group_label>IV Iron</arm_group_label>
<arm_group_label>Oral Iron</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion criteria:

1. Aged ≥ 18 years

2. Patients who have undergone a Roux-en Y Gastric Bypass or Vertical Sleeve Gastrectomy
and are at least 3 months or more out from surgery.

3. Iron deficiency anemia defined as iron deficient with either ferritin<30 mcg/l,
TSAT<20%, or anemia with Hgb<13 g/dL for both males and females.

4. Willingness to participate and signing the informed consent form.

Exclusion criteria:

1. Iron overload or disturbances in utilization of iron (e.g. hemochromatosis and
hemosiderosis)

2. Decompensated liver cirrhosis or active hepatitis (ALAT > 3 times upper limit of
normal)

3. Serum ferritin > 400 ng/mL or transferrin saturation >40 %

4. Active acute or chronic infections (assessed by clinical judgment that may be
indicated by White Blood Cells (WBC) and C-Reactive Protein (CRP) when these are
available)

5. Rheumatoid arthritis with symptoms or signs of active inflammation

6. Pregnant and nursing women

7. History of multiple allergies (two or more)

8. Known hypersensitivity to ferumoxytol or oral iron or any excipients in the drug
products

9. Previous IV iron treatment for IDA

10. Other iron treatment or blood transfusion within 4 weeks prior to the screening or
treatment visit

11. Planned elective surgery during the study

12. Any other medical condition that, in the opinion of Investigator, may cause the
subject to be unsuitable for the completion of the study or place the subject at
potential risk from being in the study, e.g. a malignancy, uncontrolled hypertension,
unstable ischemic heart disease, or uncontrolled diabetes mellitus
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_contact>
<last_name>Michael Auerbach, MD</last_name>
<phone>4107804050</phone>
<email>mauerbachmd@abhemonc.com</email>
</overall_contact>
<overall_contact_backup>
<last_name>Stella Rineer, RN</last_name>
<phone>410 7804050</phone>
<email>srineer@yahoo.com</email>
</overall_contact_backup>
<location>
<facility>
<name>Auerbach Hematology and Oncology</name>
<address>
<city>Baltimore</city>
<state>Maryland</state>
<zip>21237</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Michael Auerbach, MD</last_name>
<phone>410-780-4050</phone>
<email>mauerbachmd@abhemonc.com</email>
</contact>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>June 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>June 9, 2023</last_update_submitted>
<last_update_submitted_qc>June 9, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">June 12, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Auerbach Hematology Oncology Associates P C</investigator_affiliation>
<investigator_full_name>Michael Auerbach MD</investigator_full_name>
<investigator_title>Principal Investigator</investigator_title>
</responsible_party>
<keyword>Bariatric Surgery</keyword>
<keyword>Roux-en-Y gastric bypass (RYGB)</keyword>
<keyword>Vertical Sleeve Gastrectomy (VSG)</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Anemia</mesh_term>
<mesh_term>Anemia, Iron-Deficiency</mesh_term>
<mesh_term>Iron Deficiencies</mesh_term>
<mesh_term>Deficiency Diseases</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Ferrosoferric Oxide</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Given the limited long-term effectiveness of traditional weight loss methods, bariatric
surgery is increasingly becoming the preferred option for sustained weight loss. With the
ascendancy of the laparoscopic approach, the two most common procedures are the Roux-en-Y
gastric bypass (RYGB) and the vertical sleeve gastrectomy (VSG).
Because bariatric surgery decreases nutrient intake through restriction, malabsorption, or
both, and given that obese patients are often malnourished even before surgery, postoperative
micronutrient deficiency, particularly of iron, can be a serious complication and difficult
to treat. Iron deficiency anemia has been reported to be as high as 49% in the post-bariatric
surgical patient.
The current standard for correcting iron deficiency anemia in the post-operative bariatric
surgical patient is oral iron supplements. However, oral iron therapy is known for its
caustic effects on the gastric mucosa causing gastric irritation, nausea, epigastric
discomfort and constipation. These debilitating symptoms lead to poor adherence and lower
long and short-term efficacy. Furthermore, iron absorption from oral iron supplements when
taken with food in patients with low iron stores ranges from 2 to 13% and without food 5 to
28%. An alternative and more effective method of iron replenishment is the use of intravenous
iron. A litany of published trials, without contradiction, show marked superiority of
intravenous iron in improving hemoglobin concentrations and iron parameters when compared to
historical controls. Nonetheless, the current recommendations of the American Society of
Metabolic and Bariatric Surgery nutritional guidelines, state that oral iron supplementation
for IDA is the recommended first line of treatment. Studies are lacking that compare the
efficacy of oral versus intravenous (IV) iron therapy for the treatment of IDA in the
post-bariatric surgical patient.
The aim of our study is to compare two accepted treatments for iron deficiency anemia (oral
ferrous sulfate and intravenous ferumoxytol) for efficacy and speed of response in the
treatment of IDA in the post-operative bariatric surgical patient. In this study, 104
bariatric surgical post-operative patients will be randomly assigned 52 each to oral or 52 to
a single dose IV iron treatment using double-blind procedures.
The primary outcome will be determined at 6 weeks of treatment with a follow-up at 12 months
after treatment. Non-responders at 6 weeks after treatment may, if they qualify (based on
inclusion/exclusion criteria), have an open-label IV iron treatment and will be followed with
the same evaluations used after the first IV iron treatments.
Inclusion criteria:
1. Aged ≥ 18 years
2. Patients who have undergone a Roux-en Y Gastric Bypass or Vertical Sleeve Gastrectomy
and are at least 3 months or more out from surgery.
3. Iron deficiency anemia defined as iron deficient with either ferritin<30 mcg/l,
TSAT<20%, or anemia with Hgb<13 g/dL for both males and females.
4. Willingness to participate and signing the informed consent form.
Exclusion criteria:
1. Iron overload or disturbances in utilization of iron (e.g. hemochromatosis and
hemosiderosis)
2. Decompensated liver cirrhosis or active hepatitis (ALAT > 3 times upper limit of
normal)
3. Serum ferritin > 400 ng/mL or transferrin saturation >40 %
4. Active acute or chronic infections (assessed by clinical judgment that may be
indicated by White Blood Cells (WBC) and C-Reactive Protein (CRP) when these are
available)
5. Rheumatoid arthritis with symptoms or signs of active inflammation
6. Pregnant and nursing women
7. History of multiple allergies (two or more)
8. Known hypersensitivity to ferumoxytol or oral iron or any excipients in the drug
products
9. Previous IV iron treatment for IDA
10. Other iron treatment or blood transfusion within 4 weeks prior to the screening or
treatment visit
11. Planned elective surgery during the study
12. Any other medical condition that, in the opinion of Investigator, may cause the
subject to be unsuitable for the completion of the study or place the subject at
potential risk from being in the study, e.g. a malignancy, uncontrolled hypertension,
unstable ischemic heart disease, or uncontrolled diabetes mellitus
|
NCT0426xxxx/NCT04268862.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268862</url>
</required_header>
<id_info>
<org_study_id>RA HM-2019-003</org_study_id>
<nct_id>NCT04268862</nct_id>
</id_info>
<brief_title>Metabolic Defects in Prediabetic Kuwaiti Arabs and Indians</brief_title>
<official_title>Ethnic Dependence of the Metabolic Defects in Prediabetic Individuals: Kuwaiti Arabs Versus Indians</official_title>
<sponsors>
<lead_sponsor>
<agency>Dasman Diabetes Institute</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Dasman Diabetes Institute</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Insulin resistance and beta cell dysfunction are the major core defects responsible for the
development of type 2 diabetes (T2DM). Although insulin resistance is the early metabolic
defect detected in subjects destined to develop T2DM, it is the beta cell failure which is
responsible for the development of hyperglycemia.

Longitudinal and cross-sectional studies have demonstrated that, initially, the compensatory
hyperinsulinemia is sufficient to offset the insulin resistance and maintain normal glucose
tolerance. However, when the beta cell fails to adequately compensate for the insulin
resistance, glucose homeostasis deteriorates. Initially, this is manifest as impaired glucose
tolerance (IGT) and later as overt diabetes. It follows that the level of beta cell failure
at which hyperglycemia becomes evident depends upon the prevailing level of insulin
resistance. A more severe insulin resistance results in development of overt hyperglycemia at
lower level of beta cell failure. The investigators previously have shown that the severity
of insulin resistance varies amongst different ethnic groups (Arabs versus Indians). Thus,
the level of beta cell failure at which overt hyperglycemia becomes evident amongst each
ethnic group also varies. Thus, individuals/ethnic groups with more severe insulin
resistance, overt hyperglycemia becomes evident at lower level of beta cell dysfunction.
Conversely, severe beta cell dysfunction is required for evert hyperglycemia to develop in
individuals/ethnicities with less severe insulin resistance.

In the present study, the investigators aim to quantitate beta cell function with the gold
standard technique (i.e. hyperglycemic clamp) in Arab and Indian non-diabetic individuals and
relate the level of beta cell function to the prevailing level of insulin resistance measured
as the glucose infusion rate divided by the mean plasma insulin concentration during the
clamp.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Insulin resistance and the accompanying hyperinsulinemia also lead to the development of
multiple metabolic abnormalities which are responsible, at least in part, for the excessive
risk of coronary heart disease in T2DM , non-alcoholic steatohepatitis (NASH), and impaired
diastolic left ventricular (LV) function. Thus, insulin resistance contributes, not only to
increased T2DM risk, but also to the morbidity and mortality associated with the disease.

Etiology of Insulin Resistance Insulin resistance is closely related to obesity. Multiple
mechanisms contribute to insulin resistance in obese individuals. Accumulation of fat in
insulin target tissues (i.e. ectopic fat), e.g. in myocytes and hepatocytes, plays a central
role in the pathogenesis of insulin resistance. When energy intake exceeds energy
expenditure, the energy excess is stored in subcutaneous adipocytes in the form of
triglycerides. However, under conditions of persistent positive energy balance, subcutaneous
fat stores become filled and the excess energy spills over into the circulation in the form
of FFA, leading to increased fat content in lean tissues, i.e. ectopic fat. Many studies have
documented the important role of ectopic fat content in the pathogenesis of insulin
resistance in obese individuals. The severity of insulin resistance in skeletal muscle and
liver strongly correlates with ectopic fat content in myocytes and hepatocytes, respectively.
Further, therapies that deplete ectopic fat, e.g. weight loss and pioglitazone, significantly
improve insulin sensitivity.

Fat spill over and the subsequent increase in ectopic fat content in lean tissues could
result from subcutaneous fat cells that are filled to capacity or the inability of the
subcutaneous fat stores to expand. Consistent with this hypothesis, several studies have
demonstrated increased fat cell size in subcutaneous fat in insulin resistant obese
individuals compared to insulin sensitive controls. Moreover, large fat cells have a higher
rate of lipolysis and decreased rate of FFA esterification compared to small fat cells,
suggesting decreased ability of large fat cells to further store fat in subcutaneous adipose
tissue in obese individuals. Of note, large fat cell size is a strong predictor of future
T2DM risk in non-diabetic individuals, independent of insulin resistance. Collectively, these
results have led to the hypothesis that inability of subcutaneous fat tissue to expand
results in fat spill over into muscle, liver, heart, etc and the subsequent development of
insulin resistance.
</textblock>
</detailed_description>
<overall_status>Unknown status</overall_status>
<last_known_status>Recruiting</last_known_status>
<start_date type="Actual">March 1, 2020</start_date>
<completion_date type="Anticipated">December 31, 2021</completion_date>
<primary_completion_date type="Anticipated">July 15, 2021</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Cross-Sectional</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Insulin Resistance</measure>
<time_frame>15 months</time_frame>
<description>Insulin Resistance measured as total glucose disposal TGD with the Insulin Clamp</description>
</primary_outcome>
<primary_outcome>
<measure>Insulin Secretion</measure>
<time_frame>15 months</time_frame>
<description>First phase and second phase insulin secretion measured with the hyperglycemic clamp</description>
</primary_outcome>
<primary_outcome>
<measure>Beta Cell function</measure>
<time_frame>15 months</time_frame>
<description>Beta cell function for the first phase and second phase measured as ∆C-Pep/(1/TGD)</description>
</primary_outcome>
<primary_outcome>
<measure>Comparison of genetic markers</measure>
<time_frame>15 months</time_frame>
<description>Genetic markers that correlate with the metabolic phenotype measured using GWAS</description>
</primary_outcome>
<primary_outcome>
<measure>GLP1 Action</measure>
<time_frame>15 months</time_frame>
<description>GLP1 Action measured as increase in C-peptide during the hyperglycemic clamp caused by exenatide infusion</description>
</primary_outcome>
<enrollment type="Anticipated">120</enrollment>
<condition>Pathophysiology</condition>
<condition>Metabolic Glucose Disorders</condition>
<biospec_retention>Samples With DNA</biospec_retention>
<biospec_descr>
<textblock>
Insulin and C-peptide will be measured in plasma samples
</textblock>
</biospec_descr>
<eligibility>
<study_pop>
<textblock>
Subjects from two ethnic groups will participate in the present study: (1) 60 Kuwaiti Arab
subjects and (2) 60 subjects of Indian ethnicity. Each ethnic group will include 30
subjects with normal glucose tolerance (NGT), and 30 subjects with impaired glucose
tolerance (IGT) according to the American Diabetes Association criteria.

Subjects in each ethnic group will be matched for age, sex, BMI and family history of type
2 diabetes.
</textblock>
</study_pop>
<sampling_method>Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

1. age 21-65 years

2. BMI=18-45 kg/m2

3. NGT (FPG<100 mg/dl and 2-hour PG <140 mg/dl) or IGT (FPG < 125 mg/dl, and 2-hour
PG=140-199 mg/dl) according to the ADA criteria.

4. Good general health as determined by physical exam, medical history, blood
chemistries, CBC, TSH, T4, lipid profile.

5. Stable body weight (± 3 lbs) over the preceding three months

6. Not participate in an excessively heavy exercise program.

Exclusion Criteria:

Subjects with

- Haematocrit < 34.0

- Diabetes, Thyroid disorders, Cardiovascular Diseases, Cancer, Bronchial Asthma and any
autoimmune disease.

- Subjects who receive medications which affect glucose tolerance, e.g. Steroids

- Subjects who participate in excessively heavy exercise programs, e.g. Athletes
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>21 Years</minimum_age>
<maximum_age>65 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Ebaa AlOzairi, MD, PhD</last_name>
<role>Principal Investigator</role>
<affiliation>Dasman Diabetes Institute</affiliation>
</overall_official>
<overall_contact>
<last_name>Ebaa AlOzairi, Md, PhD</last_name>
<phone>+965 22242999</phone>
<phone_ext>3111</phone_ext>
<email>ebaa.alozairi@dasmaninstitute.org</email>
</overall_contact>
<overall_contact_backup>
<last_name>Smitha Abraham</last_name>
<phone>+965 22260005</phone>
<email>smitha.abraham@dasmaninstitute.org</email>
</overall_contact_backup>
<location>
<facility>
<name>Dasman Diabetes Institute</name>
<address>
<city>Kuwait</city>
<zip>15462</zip>
<country>Kuwait</country>
</address>
</facility>
<status>Recruiting</status>
</location>
<location_countries>
<country>Kuwait</country>
</location_countries>
<reference>
<citation>Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009 Apr;58(4):773-95. doi: 10.2337/db09-9028. No abstract available.</citation>
<PMID>19336687</PMID>
</reference>
<reference>
<citation>Abdul-Ghani MA, DeFronzo RA. Pathophysiology of prediabetes. Curr Diab Rep. 2009 Jun;9(3):193-9. doi: 10.1007/s11892-009-0032-7.</citation>
<PMID>19490820</PMID>
</reference>
<reference>
<citation>DeFronzo RA. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia. 2010 Jul;53(7):1270-87. doi: 10.1007/s00125-010-1684-1. Epub 2010 Apr 2.</citation>
<PMID>20361178</PMID>
</reference>
<reference>
<citation>Clarke GD, Solis-Herrera C, Molina-Wilkins M, Martinez S, Merovci A, Cersosimo E, Chilton RJ, Iozzo P, Gastaldelli A, Abdul-Ghani M, DeFronzo RA. Pioglitazone Improves Left Ventricular Diastolic Function in Subjects With Diabetes. Diabetes Care. 2017 Nov;40(11):1530-1536. doi: 10.2337/dc17-0078. Epub 2017 Aug 28.</citation>
<PMID>28847910</PMID>
</reference>
<reference>
<citation>Abdul-Ghani MA, DeFronzo RA. Pathogenesis of insulin resistance in skeletal muscle. J Biomed Biotechnol. 2010;2010:476279. doi: 10.1155/2010/476279. Epub 2010 Apr 26.</citation>
<PMID>20445742</PMID>
</reference>
<reference>
<citation>Eckel RH, Kahn SE, Ferrannini E, Goldfine AB, Nathan DM, Schwartz MW, Smith RJ, Smith SR. Obesity and type 2 diabetes: what can be unified and what needs to be individualized? J Clin Endocrinol Metab. 2011 Jun;96(6):1654-63. doi: 10.1210/jc.2011-0585.</citation>
<PMID>21602457</PMID>
</reference>
<reference>
<citation>Lettner A, Roden M. Ectopic fat and insulin resistance. Curr Diab Rep. 2008 Jun;8(3):185-91. doi: 10.1007/s11892-008-0032-z.</citation>
<PMID>18625114</PMID>
</reference>
<reference>
<citation>Sabag A, Way KL, Keating SE, Sultana RN, O'Connor HT, Baker MK, Chuter VH, George J, Johnson NA. Exercise and ectopic fat in type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab. 2017 Jun;43(3):195-210. doi: 10.1016/j.diabet.2016.12.006. Epub 2017 Feb 2.</citation>
<PMID>28162956</PMID>
</reference>
<reference>
<citation>Lundgren M, Svensson M, Lindmark S, Renstrom F, Ruge T, Eriksson JW. Fat cell enlargement is an independent marker of insulin resistance and 'hyperleptinaemia'. Diabetologia. 2007 Mar;50(3):625-33. doi: 10.1007/s00125-006-0572-1. Epub 2007 Jan 10.</citation>
<PMID>17216279</PMID>
</reference>
<reference>
<citation>Weyer C, Foley JE, Bogardus C, Tataranni PA, Pratley RE. Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance. Diabetologia. 2000 Dec;43(12):1498-506. doi: 10.1007/s001250051560.</citation>
<PMID>11151758</PMID>
</reference>
<reference>
<citation>McLaughlin T, Craig C, Liu LF, Perelman D, Allister C, Spielman D, Cushman SW. Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive Humans. Diabetes. 2016 May;65(5):1245-54. doi: 10.2337/db15-1213. Epub 2016 Feb 16.</citation>
<PMID>26884438</PMID>
</reference>
<reference>
<citation>Badoud F, Perreault M, Zulyniak MA, Mutch DM. Molecular insights into the role of white adipose tissue in metabolically unhealthy normal weight and metabolically healthy obese individuals. FASEB J. 2015 Mar;29(3):748-58. doi: 10.1096/fj.14-263913. Epub 2014 Nov 19.</citation>
<PMID>25411437</PMID>
</reference>
<reference>
<citation>Arner P, Engfeldt P, Ostman J. Relationship between lipolysis, cyclic AMP, and fat-cell size in human adipose tissue during fasting and in diabetes mellitus. Metabolism. 1979 Mar;28(3):198-209. doi: 10.1016/0026-0495(79)90065-9.</citation>
<PMID>216883</PMID>
</reference>
<reference>
<citation>Scherer PE. The Multifaceted Roles of Adipose Tissue-Therapeutic Targets for Diabetes and Beyond: The 2015 Banting Lecture. Diabetes. 2016 Jun;65(6):1452-61. doi: 10.2337/db16-0339.</citation>
<PMID>27222389</PMID>
</reference>
<reference>
<citation>Bays H, Mandarino L, DeFronzo RA. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab. 2004 Feb;89(2):463-78. doi: 10.1210/jc.2003-030723. No abstract available.</citation>
<PMID>14764748</PMID>
</reference>
<verification_date>July 2020</verification_date>
<study_first_submitted>October 20, 2019</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>July 19, 2020</last_update_submitted>
<last_update_submitted_qc>July 19, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">July 22, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Dasman Diabetes Institute</investigator_affiliation>
<investigator_full_name>Dr. Ebaa Al Ozairi</investigator_full_name>
<investigator_title>Chief Medical Officer</investigator_title>
</responsible_party>
<keyword>Beta cell function</keyword>
<keyword>Insulin Resistance</keyword>
<keyword>Arabs</keyword>
<keyword>Asian Indians</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Glucose Metabolism Disorders</mesh_term>
</condition_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Insulin resistance and beta cell dysfunction are the major core defects responsible for the
development of type 2 diabetes (T2DM). Although insulin resistance is the early metabolic
defect detected in subjects destined to develop T2DM, it is the beta cell failure which is
responsible for the development of hyperglycemia.
Longitudinal and cross-sectional studies have demonstrated that, initially, the compensatory
hyperinsulinemia is sufficient to offset the insulin resistance and maintain normal glucose
tolerance. However, when the beta cell fails to adequately compensate for the insulin
resistance, glucose homeostasis deteriorates. Initially, this is manifest as impaired glucose
tolerance (IGT) and later as overt diabetes. It follows that the level of beta cell failure
at which hyperglycemia becomes evident depends upon the prevailing level of insulin
resistance. A more severe insulin resistance results in development of overt hyperglycemia at
lower level of beta cell failure. The investigators previously have shown that the severity
of insulin resistance varies amongst different ethnic groups (Arabs versus Indians). Thus,
the level of beta cell failure at which overt hyperglycemia becomes evident amongst each
ethnic group also varies. Thus, individuals/ethnic groups with more severe insulin
resistance, overt hyperglycemia becomes evident at lower level of beta cell dysfunction.
Conversely, severe beta cell dysfunction is required for evert hyperglycemia to develop in
individuals/ethnicities with less severe insulin resistance.
In the present study, the investigators aim to quantitate beta cell function with the gold
standard technique (i.e. hyperglycemic clamp) in Arab and Indian non-diabetic individuals and
relate the level of beta cell function to the prevailing level of insulin resistance measured
as the glucose infusion rate divided by the mean plasma insulin concentration during the
clamp.
Insulin resistance and the accompanying hyperinsulinemia also lead to the development of
multiple metabolic abnormalities which are responsible, at least in part, for the excessive
risk of coronary heart disease in T2DM , non-alcoholic steatohepatitis (NASH), and impaired
diastolic left ventricular (LV) function. Thus, insulin resistance contributes, not only to
increased T2DM risk, but also to the morbidity and mortality associated with the disease.
Etiology of Insulin Resistance Insulin resistance is closely related to obesity. Multiple
mechanisms contribute to insulin resistance in obese individuals. Accumulation of fat in
insulin target tissues (i.e. ectopic fat), e.g. in myocytes and hepatocytes, plays a central
role in the pathogenesis of insulin resistance. When energy intake exceeds energy
expenditure, the energy excess is stored in subcutaneous adipocytes in the form of
triglycerides. However, under conditions of persistent positive energy balance, subcutaneous
fat stores become filled and the excess energy spills over into the circulation in the form
of FFA, leading to increased fat content in lean tissues, i.e. ectopic fat. Many studies have
documented the important role of ectopic fat content in the pathogenesis of insulin
resistance in obese individuals. The severity of insulin resistance in skeletal muscle and
liver strongly correlates with ectopic fat content in myocytes and hepatocytes, respectively.
Further, therapies that deplete ectopic fat, e.g. weight loss and pioglitazone, significantly
improve insulin sensitivity.
Fat spill over and the subsequent increase in ectopic fat content in lean tissues could
result from subcutaneous fat cells that are filled to capacity or the inability of the
subcutaneous fat stores to expand. Consistent with this hypothesis, several studies have
demonstrated increased fat cell size in subcutaneous fat in insulin resistant obese
individuals compared to insulin sensitive controls. Moreover, large fat cells have a higher
rate of lipolysis and decreased rate of FFA esterification compared to small fat cells,
suggesting decreased ability of large fat cells to further store fat in subcutaneous adipose
tissue in obese individuals. Of note, large fat cell size is a strong predictor of future
T2DM risk in non-diabetic individuals, independent of insulin resistance. Collectively, these
results have led to the hypothesis that inability of subcutaneous fat tissue to expand
results in fat spill over into muscle, liver, heart, etc and the subsequent development of
insulin resistance.
Insulin and C-peptide will be measured in plasma samples
Subjects from two ethnic groups will participate in the present study: (1) 60 Kuwaiti Arab
subjects and (2) 60 subjects of Indian ethnicity. Each ethnic group will include 30
subjects with normal glucose tolerance (NGT), and 30 subjects with impaired glucose
tolerance (IGT) according to the American Diabetes Association criteria.
Subjects in each ethnic group will be matched for age, sex, BMI and family history of type
2 diabetes.
Inclusion Criteria:
1. age 21-65 years
2. BMI=18-45 kg/m2
3. NGT (FPG<100 mg/dl and 2-hour PG <140 mg/dl) or IGT (FPG < 125 mg/dl, and 2-hour
PG=140-199 mg/dl) according to the ADA criteria.
4. Good general health as determined by physical exam, medical history, blood
chemistries, CBC, TSH, T4, lipid profile.
5. Stable body weight (± 3 lbs) over the preceding three months
6. Not participate in an excessively heavy exercise program.
Exclusion Criteria:
Subjects with
- Haematocrit < 34.0
- Diabetes, Thyroid disorders, Cardiovascular Diseases, Cancer, Bronchial Asthma and any
autoimmune disease.
- Subjects who receive medications which affect glucose tolerance, e.g. Steroids
- Subjects who participate in excessively heavy exercise programs, e.g. Athletes
|
NCT0426xxxx/NCT04268875.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268875</url>
</required_header>
<id_info>
<org_study_id>RBHP 2019 SOUTEYRAND</org_study_id>
<secondary_id>2019-A02305-52</secondary_id>
<nct_id>NCT04268875</nct_id>
</id_info>
<brief_title>Morphological Parameters of In-stent RESTenosis Assessed and Identified by OCT</brief_title>
<acronym>RESTO</acronym>
<official_title>Morphological Parameters of In-stent RESTenosis Assessed and Identified by OCT</official_title>
<sponsors>
<lead_sponsor>
<agency>University Hospital, Clermont-Ferrand</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Abbott</agency>
<agency_class>Industry</agency_class>
</collaborator>
<collaborator>
<agency>Corelab ISIT</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>University Hospital, Clermont-Ferrand</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The statistical risk of intrastent stenosis has fallen considerably with the emergence of
latest generation coated stents (drug-eluting stents: DES). The number and clinical lifespan
of stents implanted over the last twenty-five years, however, explain the fact that
restenosis remains a not unusual clinical problem which is expressed as a recurrence of
angina or of an acute coronary syndrome (ACS).

The mechanisms involved in this restenosis are multifactorial in nature and differ depending
on the type of stent and the time since the restenosis occurred. In symptomatic stent
restenosis (angina or acute coronary syndrome), a further angioplasty is usually required,
occasionally on an emergency basis. Coronary angiography is often not capable of explaining
the mechanical causes of this complication.

Optical coherence tomography (OCT), a high-resolution endocoronary imaging technique can
assist in the understanding of the mechanism of restenosis and guide treatment. OCT during
angiography provides a detailed analysis of the stents and potential complications: the
presence of neoatherosclerosis with or without plaque rupture, intimal hyperplasia, stent
under-deployment, stent fracture and distal or proximal progression of the atherosclerosis.

The investigators propose a prospective, multicentre study of all cases of intrastent
restenosis, examined by angiography, causing clinical features involving stable angina and
acute coronary syndrome. The coronary artery involved will be routinely studied by OCT for a
mechanical cause of the intrastent restenosis. The routine use of intrastent OCT may assist
in the understanding of causes of restenosis and in the decision on appropriate treatment.
There are several possible treatments for restenosis, including balloon angioplasty, coated
balloon angioplasty, stenting or aorto-coronary bypass graft surgery.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
All stented coronary artery patients hospitalised for stable angina or an ACS requiring a
further coronary angiogram (regardless of time since implantation or type of the initial
stent) identified to have intrastent restenosis during coronary angiography will be included
after being informed and obtaining their informed written consent.

- For cases of stable angina the OCT the will be performed immediately with insertion of
the probe distal to the area being studied and then automatic retraction of the fibre
during injection of the contrast medium.

- For ACS, the OCT will be performed immediately or on a deferred basis at the discretion
of the operator.

- For critical lesions which prevent the OCT fibre passing across the lesion, "soft"
predilatation with a 2 mm or smaller balloon is permitted.

- Practical conduct of the OCT:

- Pullback at baseline state and analysis of the stent with a 5 mm margin proximal
and distal to the lesion.

- OCT analysis: under-deployment of the stent (expansion < 80% of the reference mean
surface area), neoatherosclerosis with or without rupture, homogeneous or
non-homogeneous hyperplasia, stent fracture and proximal or distal progression of
the atherosclerosis.

- Final pullback in cases of a new angioplasty (balloon angioplasty, angioplasty with
a coated balloon or stenting).

- The OCT investigations will be anonymised and registered in their original format with a
view to centralised reading (Corelab ISIT, UMR 6284-CNRS, Clermont-Ferrand University).

- The angiography records will be submitted for reading by a panel blinded to the OCT for
the purposes of demonstrating the added value of OCT in the fine details of diagnosis
and the impact of a treatment decision. The angiograms will be reviewed in a centralised
analytical laboratory, which will re-read the procedures blind.

- Patients will be followed up via telephone contact or visit one year after inclusion
into the study to record any complications which have developed (possible myocardial
infarction, reason, any new revascularisation of the target lesion or another artery and
reason for this, any deaths and their causes).
</textblock>
</detailed_description>
<overall_status>Completed</overall_status>
<start_date type="Actual">December 11, 2019</start_date>
<completion_date type="Actual">December 6, 2022</completion_date>
<primary_completion_date type="Actual">December 6, 2022</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<primary_purpose>Diagnostic</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Characteristics of morphological abnormalities, seen on OCT on millimetre sections of the whole stented segment (5 mm proximally and distally to the stent), potentially responsible for the intrastent restenosis</measure>
<time_frame>day 0</time_frame>
<description>Under-deployment of the stent with percentage under-deployment is defined when the minimum intrastent surface area is less than 80% of the reference surface area.</description>
</primary_outcome>
<primary_outcome>
<measure>Characteristics of morphological abnormalities, seen on OCT on millimetre sections of the whole stented segment (5 mm proximally and distally to the stent), potentially responsible for the intrastent restenosis</measure>
<time_frame>day 0</time_frame>
<description>Homogeneous or non-homogeneous intimal hyperplasia.</description>
</primary_outcome>
<primary_outcome>
<measure>Characteristics of morphological abnormalities, seen on OCT on millimetre sections of the whole stented segment (5 mm proximally and distally to the stent), potentially responsible for the intrastent restenosis</measure>
<time_frame>day 0</time_frame>
<description>Presence of neoatherosclerosis, with or without rupture.</description>
</primary_outcome>
<primary_outcome>
<measure>Characteristics of morphological abnormalities, seen on OCT on millimetre sections of the whole stented segment (5 mm proximally and distally to the stent), potentially responsible for the intrastent restenosis</measure>
<time_frame>day 0</time_frame>
<description>Stent fracture .</description>
</primary_outcome>
<primary_outcome>
<measure>Characteristics of morphological abnormalities, seen on OCT on millimetre sections of the whole stented segment (5 mm proximally and distally to the stent), potentially responsible for the intrastent restenosis</measure>
<time_frame>day 0</time_frame>
<description>Progression of the proximal or distal atherosclerosis .</description>
</primary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>time to onset of intrastent restenosis</description>
</secondary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>sex</description>
</secondary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>age</description>
</secondary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>past history of angioplasty</description>
</secondary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>myocardial infarction</description>
</secondary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>coronary artery bypass grafting</description>
</secondary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>multi-vessel disease</description>
</secondary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>prosthetic valve</description>
</secondary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>heart failure</description>
</secondary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>chronic renal failure</description>
</secondary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>atrial fibrillation</description>
</secondary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>valve disease</description>
</secondary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>vascular disease</description>
</secondary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>CVA</description>
</secondary_outcome>
<secondary_outcome>
<measure>Clinical data</measure>
<time_frame>day 0</time_frame>
<description>TIA</description>
</secondary_outcome>
<secondary_outcome>
<measure>Cardiovascular risk factors</measure>
<time_frame>day 0</time_frame>
<description>hypertension</description>
</secondary_outcome>
<secondary_outcome>
<measure>Cardiovascular risk factors</measure>
<time_frame>day 0</time_frame>
<description>dyslipidaemia</description>
</secondary_outcome>
<secondary_outcome>
<measure>Cardiovascular risk factors</measure>
<time_frame>day 0</time_frame>
<description>diabetes</description>
</secondary_outcome>
<secondary_outcome>
<measure>Cardiovascular risk factors</measure>
<time_frame>day 0</time_frame>
<description>family history</description>
</secondary_outcome>
<secondary_outcome>
<measure>Cardiovascular risk factors</measure>
<time_frame>day 0</time_frame>
<description>overweight (BMI > 25)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Cardiovascular risk factors</measure>
<time_frame>day 0</time_frame>
<description>smoking habit</description>
</secondary_outcome>
<secondary_outcome>
<measure>Blood sample</measure>
<time_frame>day 0, day 365</time_frame>
<description>Measure of LDL cholesterol</description>
</secondary_outcome>
<secondary_outcome>
<measure>Blood sample</measure>
<time_frame>day 0, day 365</time_frame>
<description>Measure of HDL cholesterol</description>
</secondary_outcome>
<secondary_outcome>
<measure>Blood sample</measure>
<time_frame>day 0, day 365</time_frame>
<description>Measure of triglycerides</description>
</secondary_outcome>
<secondary_outcome>
<measure>Blood sample</measure>
<time_frame>day 0, day 365</time_frame>
<description>Measure of HbA1c</description>
</secondary_outcome>
<secondary_outcome>
<measure>Blood sample</measure>
<time_frame>day 0, day 365</time_frame>
<description>Measure of creatinine</description>
</secondary_outcome>
<secondary_outcome>
<measure>Blood sample</measure>
<time_frame>day 0, day 365</time_frame>
<description>Measure of renal clearance</description>
</secondary_outcome>
<secondary_outcome>
<measure>New revascularisation events</measure>
<time_frame>day 365</time_frame>
<description>new revascularisation event in the target lesion or another artery, myocardial infarctions, deaths and causes of events</description>
</secondary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Actual">307</enrollment>
<condition>In-stent Restenosis</condition>
<arm_group>
<arm_group_label>OCT</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Patient witch coronary artery disease who has been stented and is hospitalised for stable angina or acute coronary syndrome requiring a further coronary angiogram (regardless of time since implantation or type of the initial stent.
- Identification of intrastent restenosis during coronary angiography and realisation of an immediate or deferred OCT.</description>
</arm_group>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>Optical Coherence Tomography (OCT)</intervention_name>
<description>The OCT fibre is an optical fibre catheter containing a lens located at its extremity and positioned distal to the arterial segment to be examined. This is an intracoronary, very high-resolution section technique based on absorption and reflection of close infrared light by stents and tissues.
OCT analysis is performed during a usual coronary angiography procedure. It is a common technique already used and recommended for intrastent restenosis to establish the mechanism of the process. No new product is being tested. The examination performed is the same.</description>
<arm_group_label>OCT</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Men or women, aged 18 years and over.

- Uncoated, coated or bioresorbable stent restenosis, defined by lumen obstruction of
over 50% in the stent and/or within 5 mm proximal or distal to the stent found on
coronary angiography.

- Patients treated for an acute coronary syndrome in which restenosis is suspected. It
is recommended that OCT be performed after restoring TIMI grade 3 coronary flow in the
initial investigation or in a later review at < 7 days.

- Patient informed consent.

- Subscription to a social security system.

Exclusion Criteria:

- Technical inability to perform the OCT (distal lesions, severe chronic renal failure).

- Contraindication to the use of ABBOTT systems when insertion of any type of catheter
represents a risk to the patient. The contraindications include the following:

- Bacteraemia or septicaemia

- Significant coagulation system abnormalities

- Patients in whom coronary artery spasm has been diagnosed

- Patients who do not meet the criteria for coronary artery bypass grafting

- Patients who do not meet the criteria for percutaneous coronary angioplasty

- Severe haemodynamic shock or instability

- Total occlusion

- Life expectancy of under one year for non-cardiac reasons.

- Pregnant or breast-feeding women or women who are fertile and not taking appropriate
contraceptives.

- Patients under legal protection or guardianship
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Géraud Souteyrand</last_name>
<role>Principal Investigator</role>
<affiliation>University Hospital, Clermont-Ferrand</affiliation>
</overall_official>
<location>
<facility>
<name>Université- Hôpital Leuven</name>
<address>
<city>Leuven</city>
<country>Belgium</country>
</address>
</facility>
</location>
<location>
<facility>
<name>CHU Clermont Ferrand</name>
<address>
<city>Clermont-Ferrand</city>
<state>Auvergne</state>
<zip>63000</zip>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Clinique la Roseraie</name>
<address>
<city>Aubervilliers</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>CH Avignon</name>
<address>
<city>Avignon</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>CHRU Besançon</name>
<address>
<city>Besançon</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>CHU Bordeaux</name>
<address>
<city>Bordeaux</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>CHRU Morvan</name>
<address>
<city>Brest</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Hôpital privé saint Martin</name>
<address>
<city>Cauro</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Centre Hospitalier les Hôpitaux de Chartres</name>
<address>
<city>Chartres</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>CHRU Grenoble Alpes</name>
<address>
<city>Grenoble</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Centre Hospitalier Départemental Vendée</name>
<address>
<city>La Roche-sur-Yon</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>CHRU Lille</name>
<address>
<city>Lille</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Centre Hospitalier Saint Joseph Saint Luc</name>
<address>
<city>Lyon</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Hospices Civiles Lyon</name>
<address>
<city>Lyon</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>AP-HM</name>
<address>
<city>Marseille</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>CHRU Nîmes</name>
<address>
<city>Nîmes</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Polyclinique les fleurs</name>
<address>
<city>Ollioules</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>AP-HP</name>
<address>
<city>Paris</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Hôpital Privé Institut Mutualiste Montsouris</name>
<address>
<city>Paris</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>CHRU Poitiers</name>
<address>
<city>Poitiers</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Clinique Saint Hilaire</name>
<address>
<city>Rouen</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>CHRU Strasbourg</name>
<address>
<city>Strasbourg</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Clinique Pasteur Toulouse</name>
<address>
<city>Toucy</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>CHRU Toulouse</name>
<address>
<city>Toulouse</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>CHRU Hôpitaux de Tours</name>
<address>
<city>Tours</city>
<country>France</country>
</address>
</facility>
</location>
<location>
<facility>
<name>CH de Bern</name>
<address>
<city>Bern</city>
<country>Switzerland</country>
</address>
</facility>
</location>
<location>
<facility>
<name>CHUV de Lausanne</name>
<address>
<city>Lausanne</city>
<country>Switzerland</country>
</address>
</facility>
</location>
<location_countries>
<country>Belgium</country>
<country>France</country>
<country>Switzerland</country>
</location_countries>
<verification_date>April 2023</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>April 14, 2023</last_update_submitted>
<last_update_submitted_qc>April 14, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">April 18, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>In-stent restenosis</keyword>
<keyword>optical coherence tomography (OCT)</keyword>
<keyword>coronary angiography</keyword>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The statistical risk of intrastent stenosis has fallen considerably with the emergence of
latest generation coated stents (drug-eluting stents: DES). The number and clinical lifespan
of stents implanted over the last twenty-five years, however, explain the fact that
restenosis remains a not unusual clinical problem which is expressed as a recurrence of
angina or of an acute coronary syndrome (ACS).
The mechanisms involved in this restenosis are multifactorial in nature and differ depending
on the type of stent and the time since the restenosis occurred. In symptomatic stent
restenosis (angina or acute coronary syndrome), a further angioplasty is usually required,
occasionally on an emergency basis. Coronary angiography is often not capable of explaining
the mechanical causes of this complication.
Optical coherence tomography (OCT), a high-resolution endocoronary imaging technique can
assist in the understanding of the mechanism of restenosis and guide treatment. OCT during
angiography provides a detailed analysis of the stents and potential complications: the
presence of neoatherosclerosis with or without plaque rupture, intimal hyperplasia, stent
under-deployment, stent fracture and distal or proximal progression of the atherosclerosis.
The investigators propose a prospective, multicentre study of all cases of intrastent
restenosis, examined by angiography, causing clinical features involving stable angina and
acute coronary syndrome. The coronary artery involved will be routinely studied by OCT for a
mechanical cause of the intrastent restenosis. The routine use of intrastent OCT may assist
in the understanding of causes of restenosis and in the decision on appropriate treatment.
There are several possible treatments for restenosis, including balloon angioplasty, coated
balloon angioplasty, stenting or aorto-coronary bypass graft surgery.
All stented coronary artery patients hospitalised for stable angina or an ACS requiring a
further coronary angiogram (regardless of time since implantation or type of the initial
stent) identified to have intrastent restenosis during coronary angiography will be included
after being informed and obtaining their informed written consent.
- For cases of stable angina the OCT the will be performed immediately with insertion of
the probe distal to the area being studied and then automatic retraction of the fibre
during injection of the contrast medium.
- For ACS, the OCT will be performed immediately or on a deferred basis at the discretion
of the operator.
- For critical lesions which prevent the OCT fibre passing across the lesion, "soft"
predilatation with a 2 mm or smaller balloon is permitted.
- Practical conduct of the OCT:
- Pullback at baseline state and analysis of the stent with a 5 mm margin proximal
and distal to the lesion.
- OCT analysis: under-deployment of the stent (expansion < 80% of the reference mean
surface area), neoatherosclerosis with or without rupture, homogeneous or
non-homogeneous hyperplasia, stent fracture and proximal or distal progression of
the atherosclerosis.
- Final pullback in cases of a new angioplasty (balloon angioplasty, angioplasty with
a coated balloon or stenting).
- The OCT investigations will be anonymised and registered in their original format with a
view to centralised reading (Corelab ISIT, UMR 6284-CNRS, Clermont-Ferrand University).
- The angiography records will be submitted for reading by a panel blinded to the OCT for
the purposes of demonstrating the added value of OCT in the fine details of diagnosis
and the impact of a treatment decision. The angiograms will be reviewed in a centralised
analytical laboratory, which will re-read the procedures blind.
- Patients will be followed up via telephone contact or visit one year after inclusion
into the study to record any complications which have developed (possible myocardial
infarction, reason, any new revascularisation of the target lesion or another artery and
reason for this, any deaths and their causes).
Inclusion Criteria:
- Men or women, aged 18 years and over.
- Uncoated, coated or bioresorbable stent restenosis, defined by lumen obstruction of
over 50% in the stent and/or within 5 mm proximal or distal to the stent found on
coronary angiography.
- Patients treated for an acute coronary syndrome in which restenosis is suspected. It
is recommended that OCT be performed after restoring TIMI grade 3 coronary flow in the
initial investigation or in a later review at < 7 days.
- Patient informed consent.
- Subscription to a social security system.
Exclusion Criteria:
- Technical inability to perform the OCT (distal lesions, severe chronic renal failure).
- Contraindication to the use of ABBOTT systems when insertion of any type of catheter
represents a risk to the patient. The contraindications include the following:
- Bacteraemia or septicaemia
- Significant coagulation system abnormalities
- Patients in whom coronary artery spasm has been diagnosed
- Patients who do not meet the criteria for coronary artery bypass grafting
- Patients who do not meet the criteria for percutaneous coronary angioplasty
- Severe haemodynamic shock or instability
- Total occlusion
- Life expectancy of under one year for non-cardiac reasons.
- Pregnant or breast-feeding women or women who are fertile and not taking appropriate
contraceptives.
- Patients under legal protection or guardianship
|
NCT0426xxxx/NCT04268888.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268888</url>
</required_header>
<id_info>
<org_study_id>CA209-9Y9</org_study_id>
<nct_id>NCT04268888</nct_id>
</id_info>
<brief_title>Nivolumab in Combination With TACE/TAE for Patients With Intermediate Stage HCC</brief_title>
<acronym>TACE-3</acronym>
<official_title>A Two-arm Multi-stage (TAMS) Seamless Phase II/III Randomised Trial of Nivolumab in Combination With TACE/TAE for Patients With Intermediate Stage HCC</official_title>
<sponsors>
<lead_sponsor>
<agency>The Clatterbridge Cancer Centre NHS Foundation Trust</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>The Clatterbridge Cancer Centre NHS Foundation Trust</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
<is_us_export>Yes</is_us_export>
</oversight_info>
<brief_summary>
<textblock>
This study evaluates the addition of nivolumab to TACE/TAE in the treatment of patients with
intermediate stage hepatocellular carcinoma. All patients will receive TACE/TAE and half will
receive nivolumab.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
A significant proportion of HCC patients present with, or progress to, intermediate stage
disease and these patients are typically treated with transarterial chemo-embolisation (TACE)
or transarterial embolisation (TAE).

However, since TACE/TAE is generally a palliative therapy, it provides a potential backbone
for the addition of effective systemic therapies with the aim of improving survival outcomes.
Since TACE may liberate an abundance of tumour antigens and 'danger' signals, it may lend
itself to combination with immunotherapeutic strategies.

Nivolumab is a human monoclonal antibody. Nivolumab targets the programmed death-1 PD-1)
cluster of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative
regulatory molecule expressed by activated T and B lymphocytes.
</textblock>
</detailed_description>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">May 8, 2019</start_date>
<completion_date type="Anticipated">June 2026</completion_date>
<primary_completion_date type="Anticipated">June 2025</primary_completion_date>
<phase>Phase 2/Phase 3</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>Patients shall be randomised on a 1:1 basis throughout the study and allocated using pre-generated lists produced by the study statistician. List shall be produced using permuted blocks algorithm with random block sizes of 2 and 4. Stratification factors used in the study are randomising centre, baseline HAP score (A vs. B vs. C) and vascular invasion (No vs. Yes).</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Overall Survival - phase III primary outcome</measure>
<time_frame>The time until death. Patients discontinuing the study, lost to follow-up or still alive at the end of the study will be censored at the last know date alive, this can be assessed up until 2 years after the last patient.</time_frame>
<description>Measured in days</description>
</primary_outcome>
<primary_outcome>
<measure>Time to TACE Progression (TTTP) - phase II primary outcome</measure>
<time_frame>The time to confirmatory scan 4 weeks after progression this can be assessed up until 2 years after the last patient is randomised</time_frame>
<description>Measured in days</description>
</primary_outcome>
<secondary_outcome>
<measure>Time to Progression</measure>
<time_frame>Time to date of progression confirmed by RECIST1.1 assessed up until 2 years after the last patient is randomised</time_frame>
<description>Measured in days</description>
</secondary_outcome>
<secondary_outcome>
<measure>Radiological response rate</measure>
<time_frame>Through study completion</time_frame>
<description>RECIST 1.1</description>
</secondary_outcome>
<secondary_outcome>
<measure>Safety and Toxicity: the number and percentage of patients reporting a Serious Adverse Event (SAE) and Grade 3 or higher Adverse Event (AE)</measure>
<time_frame>Through study completion</time_frame>
<description>the number and percentage of patients reporting a Serious Adverse Event (SAE) and Grade 3 or higher Adverse Event (AE), measured and categorised based on CTCAE (version 4).</description>
</secondary_outcome>
<secondary_outcome>
<measure>Progression Free Survival</measure>
<time_frame>Time to progression or death. Assessed up until 2 years.</time_frame>
<description>Measured in days</description>
</secondary_outcome>
<secondary_outcome>
<measure>QOL: EORTC QLQ-C30</measure>
<time_frame>baseline, pre - TACE (first treatment) and 12 weekly thereafter until end of treatment. Assessed up until 2 years after the last patient is randomised</time_frame>
<description>QoL will be scored according to the EORTC QLQ-C30 manual and guidelines.</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">522</enrollment>
<condition>Hepatocellular Carcinoma</condition>
<arm_group>
<arm_group_label>TACE/TAE Alone</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Transarterial Chemoembolisation (TACE) and/or Transarterial Embolisation (TAE) Alone.</description>
</arm_group>
<arm_group>
<arm_group_label>TACE/TAE and Nivolumab</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>As above for TACE/TAE. Nivolumab adminstered as a flat dose of 480mg IV.</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Nivolumab and TACE/TAE</intervention_name>
<description>Immunotherapy and TACE/TAE</description>
<arm_group_label>TACE/TAE and Nivolumab</arm_group_label>
</intervention>
<intervention>
<intervention_type>Procedure</intervention_type>
<intervention_name>TACE/TAE</intervention_name>
<description>TACE/TAE (as per local practice)</description>
<arm_group_label>TACE/TAE Alone</arm_group_label>
<arm_group_label>TACE/TAE and Nivolumab</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Histological diagnosis of HCC and at least one uni-dimensional lesion measurable
according to RECIST 1.1 criteria by CT-scan or MRI.

2. Not a candidate for surgical resection or liver transplantation

3. Aged ≥16 years and estimated life expectancy >3 months

4. ECOG performance status 0-1

5. Adequate haematological function:

- Hb ≥9g/L

- Absolute neutrophil count ≥1.0x109/L

- Platelet count ≥60x109/L

6. Bilirubin ≤50 μmol/L, AST,ALT and ALP ≤5 x ULN

7. Adequate renal function; Creatinine ≤ 1.5ULN (Using Cockcroft-Gault Formula)

8. INR ≤1.6

9. Child-Pugh A (score ≤6) (Appendix D)

10. HAP score A, B or C (Appendix E)

11. No contra-indications to T-cell checkpoint inhibitor therapy (use of immunosuppressive
drugs including steroids at dose equivalent to prednisolone >10mg/day unless used as
replacement therapy; organ transplantation; subjects with an active, known or
suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism
only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or
alopecia) not requiring systemic treatment, lichen planus or other conditions not
expected to recur in the absence of an external trigger are permitted to enrol).

12. Women of child-bearing potential should have a negative pregnancy test prior to study
entry. Both men and women must be using an adequate contraception method, which must
be continued for 5 months after completion of treatment for women and 7 months for men

13. Written informed consent

Exclusion Criteria:

1. Extrahepatic metastasis

2. Prior embolisation, systemic or radiation therapy for HCC

3. Any contraindications for hepatic embolisation procedures including portosystemic
shunt, hepatofugal blood flow, known severe atheromatosis

4. Investigational therapy or major surgery within 4 weeks of trial entry

5. History of variceal bleeding within the past 4 weeks

6. Child-Pugh cirrhosis B or C (score ≥7)

7. HAP score D

8. Hepatic encephalopathy

9. Ascites refractory to diuretic therapy

10. Documented occlusion of the hepatic artery or main portal vein5

11. Hypersensitivity to intravenous contrast agents

12. Active clinically serious infection > Grade 2 NCI-CTC

13. Pregnant or lactating women

14. Known history of HIV infection

15. HBV chronic infection with HBV DNA > 500IU/mL or without antiviral therapy; HBV
patients with cirrhosis should be treated.

17. History of second malignancy except those treated with curative intent more than three
years previously without relapse and non-melanotic skin cancer or cervical carcinoma in
situ 18. Evidence of severe or uncontrolled systemic disease, or laboratory finding that in
the view of the Investigator makes it undesirable for the patient to participate in the
trial 19. Psychiatric or other disorder likely to impact on informed consent 20. Patient is
unable and/or unwilling to comply with treatment and study instructions 20. Interstitial
lung disease that is symptomatic or may interfere with the detection or management of
suspected treatment-related pulmonary toxicity

21. Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial,
anti-viral or antifungal therapy within 7 days prior to administration of study medication

22. Positive test for latent TB or evidence of active TB

23. Hypersensitivity to any of the active substances or excipients

24. Patients who have received a live vaccine within 30 days prior to the first dose of
trial treatment

25. Subjects with a condition requiring systemic treatment with either corticosteroids (>
10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of
the first dose of study drug administration

26. Any uncontrolled inflammatory GI disease including Crohn's Disease and ulcerative
colitis

27. Participants with an active, known or suspected autoimmune disease. Participants with
type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders
(such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions
not expected to recur in the absence of an external trigger are permitted to enrol
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>16 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Daniel Palmer, PhD, MD</last_name>
<role>Study Director</role>
<affiliation>Clatterbridge Cancer Centre</affiliation>
</overall_official>
<overall_contact>
<last_name>Maria Maguire, PhD</last_name>
<phone>0151 556</phone>
<email>maria.maguire2@nhs.net</email>
</overall_contact>
<overall_contact_backup>
<last_name>David Price</last_name>
<phone>0151 556</phone>
<email>david.price9@nhs.net</email>
</overall_contact_backup>
<location>
<facility>
<name>University of Liverpool</name>
<address>
<city>Liverpool</city>
<zip>L69 7ZB</zip>
<country>United Kingdom</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Louise Handley</last_name>
<phone>0151 794 8935</phone>
<email>louise.handley@liverpool.ac.uk</email>
</contact>
<investigator>
<last_name>Daniel Palmer, PhD, MD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location_countries>
<country>United Kingdom</country>
</location_countries>
<verification_date>July 2020</verification_date>
<study_first_submitted>June 5, 2019</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>July 14, 2020</last_update_submitted>
<last_update_submitted_qc>July 14, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">July 16, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Intermediate Stage</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Carcinoma, Hepatocellular</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Nivolumab</mesh_term>
<mesh_term>Chlorotrianisene</mesh_term>
</intervention_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This study evaluates the addition of nivolumab to TACE/TAE in the treatment of patients with
intermediate stage hepatocellular carcinoma. All patients will receive TACE/TAE and half will
receive nivolumab.
A significant proportion of HCC patients present with, or progress to, intermediate stage
disease and these patients are typically treated with transarterial chemo-embolisation (TACE)
or transarterial embolisation (TAE).
However, since TACE/TAE is generally a palliative therapy, it provides a potential backbone
for the addition of effective systemic therapies with the aim of improving survival outcomes.
Since TACE may liberate an abundance of tumour antigens and 'danger' signals, it may lend
itself to combination with immunotherapeutic strategies.
Nivolumab is a human monoclonal antibody. Nivolumab targets the programmed death-1 PD-1)
cluster of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative
regulatory molecule expressed by activated T and B lymphocytes.
Inclusion Criteria:
1. Histological diagnosis of HCC and at least one uni-dimensional lesion measurable
according to RECIST 1.1 criteria by CT-scan or MRI.
2. Not a candidate for surgical resection or liver transplantation
3. Aged ≥16 years and estimated life expectancy >3 months
4. ECOG performance status 0-1
5. Adequate haematological function:
- Hb ≥9g/L
- Absolute neutrophil count ≥1.0x109/L
- Platelet count ≥60x109/L
6. Bilirubin ≤50 μmol/L, AST,ALT and ALP ≤5 x ULN
7. Adequate renal function; Creatinine ≤ 1.5ULN (Using Cockcroft-Gault Formula)
8. INR ≤1.6
9. Child-Pugh A (score ≤6) (Appendix D)
10. HAP score A, B or C (Appendix E)
11. No contra-indications to T-cell checkpoint inhibitor therapy (use of immunosuppressive
drugs including steroids at dose equivalent to prednisolone >10mg/day unless used as
replacement therapy; organ transplantation; subjects with an active, known or
suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism
only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or
alopecia) not requiring systemic treatment, lichen planus or other conditions not
expected to recur in the absence of an external trigger are permitted to enrol).
12. Women of child-bearing potential should have a negative pregnancy test prior to study
entry. Both men and women must be using an adequate contraception method, which must
be continued for 5 months after completion of treatment for women and 7 months for men
13. Written informed consent
Exclusion Criteria:
1. Extrahepatic metastasis
2. Prior embolisation, systemic or radiation therapy for HCC
3. Any contraindications for hepatic embolisation procedures including portosystemic
shunt, hepatofugal blood flow, known severe atheromatosis
4. Investigational therapy or major surgery within 4 weeks of trial entry
5. History of variceal bleeding within the past 4 weeks
6. Child-Pugh cirrhosis B or C (score ≥7)
7. HAP score D
8. Hepatic encephalopathy
9. Ascites refractory to diuretic therapy
10. Documented occlusion of the hepatic artery or main portal vein5
11. Hypersensitivity to intravenous contrast agents
12. Active clinically serious infection > Grade 2 NCI-CTC
13. Pregnant or lactating women
14. Known history of HIV infection
15. HBV chronic infection with HBV DNA > 500IU/mL or without antiviral therapy; HBV
patients with cirrhosis should be treated.
17. History of second malignancy except those treated with curative intent more than three
years previously without relapse and non-melanotic skin cancer or cervical carcinoma in
situ 18. Evidence of severe or uncontrolled systemic disease, or laboratory finding that in
the view of the Investigator makes it undesirable for the patient to participate in the
trial 19. Psychiatric or other disorder likely to impact on informed consent 20. Patient is
unable and/or unwilling to comply with treatment and study instructions 20. Interstitial
lung disease that is symptomatic or may interfere with the detection or management of
suspected treatment-related pulmonary toxicity
21. Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial,
anti-viral or antifungal therapy within 7 days prior to administration of study medication
22. Positive test for latent TB or evidence of active TB
23. Hypersensitivity to any of the active substances or excipients
24. Patients who have received a live vaccine within 30 days prior to the first dose of
trial treatment
25. Subjects with a condition requiring systemic treatment with either corticosteroids (>
10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of
the first dose of study drug administration
26. Any uncontrolled inflammatory GI disease including Crohn's Disease and ulcerative
colitis
27. Participants with an active, known or suspected autoimmune disease. Participants with
type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders
(such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions
not expected to recur in the absence of an external trigger are permitted to enrol
|
NCT0426xxxx/NCT04268901.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268901</url>
</required_header>
<id_info>
<org_study_id>CHLA-15-00549</org_study_id>
<nct_id>NCT04268901</nct_id>
</id_info>
<brief_title>VR to Reduce Pain/Anxiety During Painful Procedures</brief_title>
<official_title>Effectiveness of Virtual Reality to Reduce Pain/Anxiety During Routine Painful Procedures</official_title>
<sponsors>
<lead_sponsor>
<agency>Children's Hospital Los Angeles</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>AppliedVR Inc.</agency>
<agency_class>Industry</agency_class>
</collaborator>
</sponsors>
<source>Children's Hospital Los Angeles</source>
<oversight_info>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>Yes</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This study aims to test the effectiveness of virtual reality (VR) as a non-pharmaceutical
intervention to reduce pain and anxiety in children undergoing painful procedures in
Phlebotomy, Radiology, Infusion, Orthopedics, Gastroenterology, and Immunology, amongst
others, at CHLA, as measured by self- and proxy-report. Examples of the painful procedures
include IV sticks, cast removals, allergy testing, and anorectal manometries.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Distraction is a form of non pharmacological intervention for reducing pain and anxiety in
children during painful medical procedures (e.g., venipuncture, IV placement). Recent
technological developments in the area of virtual reality (VR) provide new and potentially
more effective ways of distracting children from the pain and anxiety associated with medical
procedures. While initial studies of VR pain distraction are promising, few have studied the
effectiveness of the technology in children, using a multi-method approach. The current study
aims to recruit 240 children ages 7-21 and their caregivers who arrive at the hospital for an
outpatient painful medical procedure. Children and their parents will be randomly assigned to
one of two treatment conditions: 1) existing hospital standard of care or 2) standard of care
plus distraction via VR. Children and caregivers will be asked to complete measures assessing
pain and anxiety both before and after the procedure. In addition, objective measures of
child pain and distress during the medical procedure will be taken using coding of
behavioral/verbal expressions. Univariate Analysis of Variance (ANOVA) will be used to
compare differences in primary and secondary outcome variables in VR + standard of care to
standard of care only conditions when pre and post-operative measures are available.
Univariate ANOVA will be used to compare conditions on post-operative variables.
</textblock>
</detailed_description>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">February 19, 2016</start_date>
<completion_date type="Anticipated">December 6, 2025</completion_date>
<primary_completion_date type="Anticipated">December 6, 2025</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Supportive Care</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>VAS</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>VAS anticipatory anxiety measure: The VAS anticipatory anxiety measure is a vertical VAS, anchored with 0 at the bottom indicating the least amount and 10 at the top indicating the greatest amount, in response to the instruction to rate "how nervous, afraid, or worried" they were about the upcoming task. The scale also has color cues, graded from yellow at the bottom to dark red at the top, as well as a neutral face at the bottom and a face showing a negative expression at the top. Prior research used the VAS to rate anticipatory anxiety and pain in children.</description>
</primary_outcome>
<primary_outcome>
<measure>Faces Pain Scale (FPS-R)</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>Revised is an updated version of the Wong-Baker Faces Pain Rating Scale depicting no pain as a neutral expression as compared with the smiling face of the original measure. The child is asked to point to the face cartoon that depicts how they are currently feeling because of their pain. Face measures are thought to measure pain intensity, and the Wong-Baker Faces measure has demonstrated good reliability and validity.</description>
</primary_outcome>
<primary_outcome>
<measure>Facial Affective Scale</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>A faces scale to predict pediatric pain unpleasantness.</description>
</primary_outcome>
<primary_outcome>
<measure>Child State Anxiety Index (CASI) or Anxiety Sensitivity Index (ASI) if 18 and older</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>CASI is an 18-item scale that measures the tendency to view anxiety-related bodily sensations as dangerous (e.g., ''It scares me when my heart beats fast''). Items are scored on a 3-point scale (none, some, a lot), and total scores are calculated by summing all items. The CASI has demonstrated high internal consistency and adequate test-retest reliability. The CASI correlates well with measures of trait anxiety but also accounts for variance in fear not attributable to trait anxiety measures</description>
</primary_outcome>
<primary_outcome>
<measure>Malaise Scale</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>The MS is a six-point scale indicating level of nausea from (1) no symptoms to (6) being sick The MS is completed before and after administration of the VR game to monitor for any signs of nausea. Instructions to the child are as follows: "This is a scale from one to six. One means that you feel fine and no different to how you normally feel. Two means that you feel a little bit different or funny but not sick in the tummy. Three means that you feel a little bit sick and four means that you feel more than a little bit sick but not really sick. Five means that you feel really sick, like you are going to throw up or vomit and six means that you are being sick or vomiting. I'm going to ask you every few minutes how you feel. I want you to tell me which number from one to six best describes how you feel at that time."</description>
</primary_outcome>
<primary_outcome>
<measure>Child Presence Questionnaire</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The Child Presence Questionnaire was developed out of a content analysis of the entire domain of adult presence items and selection and adaptation of appropriate items for assessing the child's sense of believability of their experience. This 16-item measure is verbally administered to children and asks them to respond according to a 3-point Likert-like format. Items assess the child's sense of involvement, realism, and transportation into the experience. Patients in the VR condition will complete the Child Presence Questionnaire post-procedure to assess level of VR immersion.</description>
</primary_outcome>
<primary_outcome>
<measure>Child Satisfaction Survey</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The child survey is 13-item, Likert-like survey to assess child estimates of pain reduction, fear reduction, decreased behavioral distress, and overall satisfaction; it mirrors the parent survey. There are two versions, one for each treatment condition. Two versions of the survey exist, to account for condition (VR vs. standard of care).</description>
</primary_outcome>
<primary_outcome>
<measure>Parent Satisfaction Survey</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The parent survey is 16-item, Likert-like survey to assess parent estimates of pain reduction, fear reduction, decreased behavioral distress, and overall satisfaction. Two versions of the survey exist, to account for condition (VR vs. standard of care).</description>
</primary_outcome>
<primary_outcome>
<measure>Healthcare Provider Survey</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The healthcare provider survey is a 7-item Likert-like investigator-developed survey to assess their estimates of pain and anxiety management, cooperation, and satisfaction with the procedure. Healthcare providers are also invited to write comments about the use of VR (if applicable) during the IV placement procedure.</description>
</primary_outcome>
<primary_outcome>
<measure>VAS</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>VAS anticipatory anxiety measure: The VAS anticipatory anxiety measure is a vertical VAS, anchored with 0 at the bottom indicating the least amount and 10 at the top indicating the greatest amount, in response to the instruction to rate "how nervous, afraid, or worried" they were about the upcoming task. The scale also has color cues, graded from yellow at the bottom to dark red at the top, as well as a neutral face at the bottom and a face showing a negative expression at the top. Prior research used the VAS to rate anticipatory anxiety and pain in children.</description>
</primary_outcome>
<primary_outcome>
<measure>Faces Pain Scale (FPS-R)</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>Revised is an updated version of the Wong-Baker Faces Pain Rating Scale depicting no pain as a neutral expression as compared with the smiling face of the original measure. The child is asked to point to the face cartoon that depicts how they are currently feeling because of their pain. Face measures are thought to measure pain intensity, and the Wong-Baker Faces measure has demonstrated good reliability and validity.</description>
</primary_outcome>
<primary_outcome>
<measure>Facial Affective Scale</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>A faces scale to predict pediatric pain unpleasantness.</description>
</primary_outcome>
<primary_outcome>
<measure>Malaise Scale</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The MS is a six-point scale indicating level of nausea from (1) no symptoms to (6) being sick The MS is completed before and after administration of the VR game to monitor for any signs of nausea. Instructions to the child are as follows: "This is a scale from one to six. One means that you feel fine and no different to how you normally feel. Two means that you feel a little bit different or funny but not sick in the tummy. Three means that you feel a little bit sick and four means that you feel more than a little bit sick but not really sick. Five means that you feel really sick, like you are going to throw up or vomit and six means that you are being sick or vomiting. I'm going to ask you every few minutes how you feel. I want you to tell me which number from one to six best describes how you feel at that time."</description>
</primary_outcome>
<secondary_outcome>
<measure>CAMPIS-R</measure>
<time_frame>Peri-procedure</time_frame>
<description>The CAMPIS-R is a standardized rating scale that codes videotaped verbal interactions in the pediatric treatment room. The CAMPIS-R codes the subject, speaker, phase of medical procedure, verbal content, affective tone, and to whom vocalizations are directed. Adult vocalizations are coded as coping-promoting (nonprocedural talk or humor directed to the child, commands to engage in coping strategies), distress-promoting (reassuring comments, apologies, giving control to the child, criticism, and empathetic statements), or neutral (humor to adults, nonprocedural talk to adults, child's condition talk, commands for procedural activity, praise, notification of procedure to come, behavioral commands to child, checking child's status). Two independent study team coders will complete the CAMPIS-R while reviewing the videotape from each of the I&D of abscess procedures.</description>
</secondary_outcome>
<other_outcome>
<measure>Demographic Survey</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>A brief demographic survey will be administered to parent regarding their child's age, ethnicity, grade in school, and any medical conditions or learning problems they may have.</description>
</other_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">700</enrollment>
<condition>Phlebotomy</condition>
<condition>Orthopedics</condition>
<condition>Radiology</condition>
<condition>Pain</condition>
<condition>Anxiety</condition>
<condition>Virtual Reality</condition>
<condition>Allergy</condition>
<condition>Gastroenterology</condition>
<arm_group>
<arm_group_label>Standard of Care (No VR) Randomization</arm_group_label>
<arm_group_type>No Intervention</arm_group_type>
<description>In the standard of care treatment condition, participants will receive the standard CHLA treatment protocol for the medical procedure.</description>
</arm_group>
<arm_group>
<arm_group_label>VR Randomization</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Children in the VR condition will undergo the invasive procedure while distracted by interaction with an immersive virtual environment (VE) presented via a head mounted display (HMD). The intervention group will receive standard CHLA treatment with VR distraction.</description>
</arm_group>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>Samsung Gear VR</intervention_name>
<description>Participants 13 -21 years old can use the Samsung Gear VR. The VE to be used in this study is mobile based (Samsung with the Gear VR) and has active matrix LCDs with high pixel resolution, creating a bright, vibrant color and a quality image. The VR game is equipped with a head-tracking system, enabling the player to look around the virtual environment. In addition, there is the option to interact with the VR environment using a tap pad located on the side of the helmet. Therefore, the child will be receiving distraction via 3-D visual and auditory sensory, and tactile feedback, thus supplying a multi-sensory immersive experience. While wearing these glasses, the children only can see the HMD screen so that the immersion and presence will be increased. The VR glasses will be sanitized before every use so that the chance of infection will be minimized.</description>
<arm_group_label>VR Randomization</arm_group_label>
</intervention>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>Merge VR</intervention_name>
<description>Participants 10-21 years can use the Merge. The VE to be used in this study is mobile based (Pixel with the Merge) and has active matrix LCDs with high pixel resolution, creating a bright, vibrant color and a quality image. The VR game is equipped with a head-tracking system, enabling the player to look around the virtual environment. In addition, there is the option to interact with the VR environment using a tap pad located on the side of the helmet. Therefore, the child will be receiving distraction via 3-D visual and auditory sensory, and tactile feedback, thus supplying a multi-sensory immersive experience. While wearing these glasses, the children only can see the HMD screen so that the immersion and presence will be increased. The VR glasses will be sanitized before every use so that the chance of infection will be minimized.</description>
<arm_group_label>VR Randomization</arm_group_label>
</intervention>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>Oculus Go</intervention_name>
<description>Participants 7-21 years can use the Oculus Go. The visual a bright, vibrant color and a quality image. The VR game is equipped with a head-tracking system, enabling the player to look around the virtual environment. In addition, there is the option to interact with the VR environment using a handheld remote. Therefore, the child will be receiving distraction via 3-D visual and auditory sensory, and tactile feedback, thus supplying a multi-sensory immersive experience. While wearing these glasses, the children only can see the HMD screen so that the immersion and presence will be increased. The VR glasses will be sanitized before every use so that the chance of infection will be minimized.</description>
<arm_group_label>VR Randomization</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

Inclusion Criteria for Children:

1. Children who are 7-21 years old

2. Children who are English speaking (caregivers may be Spanish English speaking or
Spanish speaking)

3. Children who are undergoing a painful medical procedure (e.g., venipuncture, IV
placement, PICC lines, wound care, cast removal, botox injections) are eligible to
participate in this project.

4. Only children who are in the normal range of development will be recruited for this
study. This will be assessed by report from the parents. The rationale for excluding
patients with developmental delay is that due to their cognitive impairments, such
children react to the stressors of surgery differently than do children without such
developmental delay. It is unclear how such children would use the interventions
included in this study, and it is likely that their responses on baseline and outcome
measures will differ from children of normal developmental parameters.

Inclusion criteria for healthcare providers:

1. Healthcare providers must be 18 years old or older

2. Healthcare providers must be Children's Hospital Los Angeles staff

3. Healthcare providers may participate if they have witnessed and/or administered the
medical procedure

Exclusion Criteria:

1. Children who are currently taking pain medication or anxiolytic medication will be
excluded from this study.

2. Children with a psychiatric disorder, organic brain syndrome, mental retardation, or
other known cognitive/neurological disorders

3. Children with visual, auditory, or tactile deficits that would interfere with the
ability to complete the experimental tasks

4. Children with a history of seizure disorder.

5. Children currently sick with flu-like symptoms or experiencing a headache or earache.

6. Children with known or suspected motion sickness
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>7 Years</minimum_age>
<maximum_age>21 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Jeffrey I Gold, PhD</last_name>
<role>Principal Investigator</role>
<affiliation>Children's Hospital Los Angeles</affiliation>
</overall_official>
<overall_contact>
<last_name>Nhat Ngo, BS, BA</last_name>
<phone>3233616244</phone>
<email>nngo@chla.usc.edu</email>
</overall_contact>
<location>
<facility>
<name>Children's Hospital Los Angeles</name>
<address>
<city>Los Angeles</city>
<state>California</state>
<zip>90027</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Jeffrey I Gold, PhD</last_name>
<phone>323-361-6341</phone>
<email>jgold@chla.usc.edu</email>
</contact>
</location>
<location_countries>
<country>United States</country>
</location_countries>
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<verification_date>March 2022</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>March 28, 2022</last_update_submitted>
<last_update_submitted_qc>March 28, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">March 29, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Children's Hospital Los Angeles</investigator_affiliation>
<investigator_full_name>Jeffrey I Gold, PhD</investigator_full_name>
<investigator_title>Professor of Anesthesiology, Pediatrics, and Psychiatry & Behavioral Sciences</investigator_title>
</responsible_party>
<keyword>phlebotomy</keyword>
<keyword>radiology</keyword>
<keyword>orthopedics</keyword>
<keyword>infusion</keyword>
<keyword>IV stick</keyword>
<keyword>cast removal</keyword>
<keyword>pain</keyword>
<keyword>anxiety</keyword>
<keyword>virtual reality</keyword>
<keyword>allergy</keyword>
<keyword>gastroenterology</keyword>
<keyword>anorectal manometry</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Anxiety Disorders</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This study aims to test the effectiveness of virtual reality (VR) as a non-pharmaceutical
intervention to reduce pain and anxiety in children undergoing painful procedures in
Phlebotomy, Radiology, Infusion, Orthopedics, Gastroenterology, and Immunology, amongst
others, at CHLA, as measured by self- and proxy-report. Examples of the painful procedures
include IV sticks, cast removals, allergy testing, and anorectal manometries.
Distraction is a form of non pharmacological intervention for reducing pain and anxiety in
children during painful medical procedures (e.g., venipuncture, IV placement). Recent
technological developments in the area of virtual reality (VR) provide new and potentially
more effective ways of distracting children from the pain and anxiety associated with medical
procedures. While initial studies of VR pain distraction are promising, few have studied the
effectiveness of the technology in children, using a multi-method approach. The current study
aims to recruit 240 children ages 7-21 and their caregivers who arrive at the hospital for an
outpatient painful medical procedure. Children and their parents will be randomly assigned to
one of two treatment conditions: 1) existing hospital standard of care or 2) standard of care
plus distraction via VR. Children and caregivers will be asked to complete measures assessing
pain and anxiety both before and after the procedure. In addition, objective measures of
child pain and distress during the medical procedure will be taken using coding of
behavioral/verbal expressions. Univariate Analysis of Variance (ANOVA) will be used to
compare differences in primary and secondary outcome variables in VR + standard of care to
standard of care only conditions when pre and post-operative measures are available.
Univariate ANOVA will be used to compare conditions on post-operative variables.
Inclusion Criteria:
Inclusion Criteria for Children:
1. Children who are 7-21 years old
2. Children who are English speaking (caregivers may be Spanish English speaking or
Spanish speaking)
3. Children who are undergoing a painful medical procedure (e.g., venipuncture, IV
placement, PICC lines, wound care, cast removal, botox injections) are eligible to
participate in this project.
4. Only children who are in the normal range of development will be recruited for this
study. This will be assessed by report from the parents. The rationale for excluding
patients with developmental delay is that due to their cognitive impairments, such
children react to the stressors of surgery differently than do children without such
developmental delay. It is unclear how such children would use the interventions
included in this study, and it is likely that their responses on baseline and outcome
measures will differ from children of normal developmental parameters.
Inclusion criteria for healthcare providers:
1. Healthcare providers must be 18 years old or older
2. Healthcare providers must be Children's Hospital Los Angeles staff
3. Healthcare providers may participate if they have witnessed and/or administered the
medical procedure
Exclusion Criteria:
1. Children who are currently taking pain medication or anxiolytic medication will be
excluded from this study.
2. Children with a psychiatric disorder, organic brain syndrome, mental retardation, or
other known cognitive/neurological disorders
3. Children with visual, auditory, or tactile deficits that would interfere with the
ability to complete the experimental tasks
4. Children with a history of seizure disorder.
5. Children currently sick with flu-like symptoms or experiencing a headache or earache.
6. Children with known or suspected motion sickness
|
NCT0426xxxx/NCT04268914.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268914</url>
</required_header>
<id_info>
<org_study_id>CHLA-15-00461</org_study_id>
<nct_id>NCT04268914</nct_id>
</id_info>
<brief_title>VR to Reduce Pre-Operative Anxiety</brief_title>
<official_title>Effectiveness of Virtual Reality to Reduce Pre-Operative Anxiety</official_title>
<sponsors>
<lead_sponsor>
<agency>Children's Hospital Los Angeles</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>AppliedVR Inc.</agency>
<agency_class>Industry</agency_class>
</collaborator>
</sponsors>
<source>Children's Hospital Los Angeles</source>
<oversight_info>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>Yes</is_fda_regulated_device>
<is_us_export>No</is_us_export>
</oversight_info>
<brief_summary>
<textblock>
This study aims to test the effectiveness of virtual reality (VR) as a non-pharmaceutical
intervention to reduce pain and anxiety in children undergoing various procedures in the
Ambulatory Surgery Center (ASC) at CHLA, as measured by self- and proxy-report.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
4 million children undergo surgery in the US each year and up to 65% of these children
experience significant anxiety and distress before surgery. High anxiety can be traumatic,
but it can also lead to postoperative adverse outcomes, such as increased pain and analgesics
requirements, delayed hospital discharge, and maladaptive behavioral changes, in children
after the surgery. Non-pharmacological intervention, complementary and alternative medicine
(CAM) interventions, such as virtual reality, has been shown to decrease anxiety and distress
in other medical procedures (e.g., burn care, phlebotomy). Yet to date, no clinical trial has
been conducted to examine the effectiveness of virtual reality (VR) to reduce anxiety and
distress prior to outpatient surgeries in the operating room setting.

The current study aims to: 1) Determine if VR is more effective than standard care for
preventing anxiety, distress, and pain before surgery among children undergoing anesthesia
induction, 2) To evaluate healthcare provider's and caregiver's assessment of patient
cooperation and caregiver's distress and satisfaction with VR compared to standard of care,
and 3) to explore the influence of patient and caregiver characteristics on the effectiveness
of VR in preventing pre-operative anxiety and distress and subsequent post-operative
outcomes.

Study Population: Children (age 10 - 21 years) and their parents who are scheduled to undergo
outpatient surgery, whose health status is American Society of Anesthesiologists (ASA)
physical status I-III, and are in the normal range of development are eligible to be in the
study.

Study Methodology: The study is a randomized, controlled trial designed to examine the
effects of VR on the level of preoperative pain, anxiety and distress of children undergoing
surgery.

Statistical Analyses: Univariate Analysis of Variance (ANOVA) will be used to compare
differences in primary and secondary outcome variables in VR + standard of care to standard
of care only conditions when pre and post-operative measures are available. Univariate ANOVA
will be used to compare conditions on post-operative variables. Multiple regression analyses
will be used to examine the influence of patient and caregiver variables on patient outcomes
in the VR group only.
</textblock>
</detailed_description>
<overall_status>Active, not recruiting</overall_status>
<start_date type="Actual">December 4, 2015</start_date>
<completion_date type="Anticipated">October 6, 2022</completion_date>
<primary_completion_date type="Anticipated">October 6, 2022</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Supportive Care</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>VAS anticipatory anxiety measure</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>The VAS anticipatory anxiety measure is a vertical VAS, anchored with 0 at the bottom indicating the least amount and 10 at the top indicating the greatest amount, in response to the instruction to rate "how nervous, afraid, or worried" they were about the upcoming task. The scale also has color cues, graded from yellow at the bottom to dark red at the top, as well as a neutral face at the bottom and a face showing a negative expression at the top. Prior research used the VAS to rate anticipatory anxiety and pain in children.</description>
</primary_outcome>
<primary_outcome>
<measure>STAI-C (if elementary or junior high aged), STAI-Y (if in high school or college)</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>The STAIC is a self-administered measure of anxiety in children. It is comprised of separate, self-report scales for measuring two distinct anxiety concepts: state anxiety (A-State) and trait anxiety (A-Trait). The STAI-C distinguishes between a general proneness to anxious behavior rooted in the personality and anxiety as a fleeting emotional state. The instrument consists of two 20-item scales. In the current study, the measure will be used to measure both state and trait anxiety. The STAI is the validated instrument for measuring anxiety in in elementary and junior high aged children.</description>
</primary_outcome>
<primary_outcome>
<measure>Child State Anxiety Index (CASI) or Anxiety Sensitivity Index (ASI) if 18 and older</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>The Childhood Anxiety Sensitivity Index (CASI): CASI is an 18-item scale that measures the tendency to view anxiety-related bodily sensations as dangerous (e.g., ''It scares me when my heart beats fast''). Items are scored on a 3-point scale (none, some, a lot), and total scores are calculated by summing all items. The CASI has demonstrated high internal consistency and adequate test-retest reliability. The CASI correlates well with measures of trait anxiety but also accounts for variance in fear not attributable to trait anxiety measures.</description>
</primary_outcome>
<primary_outcome>
<measure>The Faces Pain Scale (FPS-R)</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>Revised is an updated version of the Wong-Baker Faces Pain Rating Scale depicting no pain as a neutral expression as compared with the smiling face of the original measure. The child is asked to point to the face cartoon that depicts how they are currently feeling because of their pain. Face measures are thought to measure pain intensity, and the Wong-Baker Faces measure has demonstrated good reliability and validity.</description>
</primary_outcome>
<primary_outcome>
<measure>Child Satisfaction Questionnaire</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The child survey is 13-item, Likert-like survey to assess child estimates of pain reduction, fear reduction, decreased behavioral distress, and overall satisfaction; it mirrors the parent survey. There are two versions, one for each treatment condition. Two versions of the survey exist, to account for condition (VR vs. standard of care).</description>
</primary_outcome>
<primary_outcome>
<measure>CAMPIS-R</measure>
<time_frame>Peri-procedure</time_frame>
<description>The CAMPIS-R is a standardized rating scale that codes videotaped verbal interactions in the pediatric treatment room. The CAMPIS-R codes the subject, speaker, phase of medical procedure, verbal content, affective tone, and to whom vocalizations are directed. Adult vocalizations are coded as coping-promoting (nonprocedural talk or humor directed to the child, commands to engage in coping strategies), distress-promoting (reassuring comments, apologies, giving control to the child, criticism, and empathetic statements), or neutral (humor to adults, nonprocedural talk to adults, child's condition talk, commands for procedural activity, praise, notification of procedure to come, behavioral commands to child, checking child's status).</description>
</primary_outcome>
<primary_outcome>
<measure>Yale Preoperative Anxiety Scale (m-YPAS; Kain et al., 1995; Kain et al., 1997)</measure>
<time_frame>Peri-procedure</time_frame>
<description>The YPAS consists of 27 items in five domains of behavior indicating anxiety in young children (Activity, Emotional expressivity, State of arousal, Vocalization and Use of parents). This measure takes approximately 5-10 minutes to complete. The 'adjusted YPAS total score' ranges from 0 to 100 with higher scores indicating greater anxiety. The YPAS was developed originally to measure the anxiety of children while undergoing induction of anesthesia. Recently, we validated the YPAS against a self-report measure, the State Trait Anxiety Inventory for Children (Kain et al., 1997; STAIC). Data Obtained: Standard scores for the anxiety level of children during the perioperative period.</description>
</primary_outcome>
<primary_outcome>
<measure>Parent Anxiety Scale</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>The parent is asked to indicate "how nervous, afraid, or worried" they believe their child was about the task on a scale of 1 to 10, from least to most anxious. (See description of Child Anticipatory/Procedural Anxiety)</description>
</primary_outcome>
<primary_outcome>
<measure>STAI</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>The STAI is a self-administered measure of anxiety in adults. It is comprised of separate, self-report scales for measuring two distinct anxiety concepts: state anxiety (A-State) and trait anxiety (A-Trait). The STAI-Y distinguishes between a general proneness to anxious behavior rooted in the personality and anxiety as a fleeting emotional state. The instrument consists of two 20-item scales. In the current study, the measure will be used to measure trait and state anxiety. The STAI is the validated instrument for measuring anxiety in working adults, and in young adults in high school and college.</description>
</primary_outcome>
<primary_outcome>
<measure>Parent Pain Scale</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>Parents/Caregivers will be asked to report on their child's pain on a faces pain scale of 1 to 6, from least to most pain, during 1) the IV start procedure and 2) the mask induction. (See description of Child Pain - POST)</description>
</primary_outcome>
<primary_outcome>
<measure>7-item self-report measure of healthcare provider's perceptions about the child's cooperation, pain, distress, and anxiety</measure>
<time_frame>Peri-procedure</time_frame>
<description>The healthcare provider survey is a 7-item Likert-like investigator-developed survey to assess their estimates of pain and anxiety management, cooperation, and satisfaction with the procedure. Healthcare providers are also invited to write comments about the use of VR (if applicable) during the IV placement procedure.</description>
</primary_outcome>
<primary_outcome>
<measure>6-item self-report measure of healthcare provider's perceptions about the child's cooperation, distress, and anxiety</measure>
<time_frame>Peri-procedure</time_frame>
<description>The healthcare provider survey is a 6-item Likert-like investigator-developed survey to assess their estimates of fear reduction, decreased behavioral distress, and overall satisfaction related to the procedure they just performed with the child/adolescent. Healthcare providers are also asked about sedative use and are invited to write comments about the use of VR (if applicable) during the mask induction procedure.</description>
</primary_outcome>
<primary_outcome>
<measure>VAS anticipatory anxiety measure</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The VAS anticipatory anxiety measure is a vertical VAS, anchored with 0 at the bottom indicating the least amount and 10 at the top indicating the greatest amount, in response to the instruction to rate "how nervous, afraid, or worried" they were about the upcoming task. The scale also has color cues, graded from yellow at the bottom to dark red at the top, as well as a neutral face at the bottom and a face showing a negative expression at the top. Prior research used the VAS to rate anticipatory anxiety and pain in children.</description>
</primary_outcome>
<primary_outcome>
<measure>STAI-C (if elementary or junior high aged), STAI-Y (if in high school or college)</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The STAIC is a self-administered measure of anxiety in children. It is comprised of separate, self-report scales for measuring two distinct anxiety concepts: state anxiety (A-State) and trait anxiety (A-Trait). The STAI-C distinguishes between a general proneness to anxious behavior rooted in the personality and anxiety as a fleeting emotional state. The instrument consists of two 20-item scales. In the current study, the measure will be used to measure both state and trait anxiety. The STAI is the validated instrument for measuring anxiety in in elementary and junior high aged children.</description>
</primary_outcome>
<primary_outcome>
<measure>The Faces Pain Scale (FPS-R)</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>Revised is an updated version of the Wong-Baker Faces Pain Rating Scale depicting no pain as a neutral expression as compared with the smiling face of the original measure. The child is asked to point to the face cartoon that depicts how they are currently feeling because of their pain. Face measures are thought to measure pain intensity, and the Wong-Baker Faces measure has demonstrated good reliability and validity.</description>
</primary_outcome>
<primary_outcome>
<measure>Parent Anxiety Scale</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The parent is asked to indicate "how nervous, afraid, or worried" they believe their child was about the task on a scale of 1 to 10, from least to most anxious. (See description of Child Anticipatory/Procedural Anxiety)</description>
</primary_outcome>
<primary_outcome>
<measure>STAI</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The STAI is a self-administered measure of anxiety in adults. It is comprised of separate, self-report scales for measuring two distinct anxiety concepts: state anxiety (A-State) and trait anxiety (A-Trait). The STAI-Y distinguishes between a general proneness to anxious behavior rooted in the personality and anxiety as a fleeting emotional state. The instrument consists of two 20-item scales. In the current study, the measure will be used to measure trait and state anxiety. The STAI is the validated instrument for measuring anxiety in working adults, and in young adults in high school and college.</description>
</primary_outcome>
<secondary_outcome>
<measure>Malaise Scale (MS)</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>The MS is a six-point scale indicating level of nausea from (1) no symptoms to (6) being sick The MS is completed before and after administration of the VR game to monitor for any signs of nausea. Instructions to the child are as follows: "This is a scale from one to six. One means that you feel fine and no different to how you normally feel. Two means that you feel a little bit different or funny but not sick in the tummy. Three means that you feel a little bit sick and four means that you feel more than a little bit sick but not really sick. Five means that you feel really sick, like you are going to throw up or vomit and six means that you are being sick or vomiting. I'm going to ask you every few minutes how you feel. I want you to tell me which number from one to six best describes how you feel at that time."</description>
</secondary_outcome>
<secondary_outcome>
<measure>Blood pressure and heart rate (BP/ HR)</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>Blood pressure and heart rate assessed intraoperatively and in the operating room will be ascertained via chart review.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Child Presence Questionnaire</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The Child Presence Questionnaire was developed out of a content analysis of the entire domain of adult presence items and selection and adaptation of appropriate items for assessing the child's sense of believability of their experience. This 16-item measure is verbally administered to children and asks them to respond according to a 3-point Likert-like format. Items assess the child's sense of involvement, realism, and transportation into the experience. Patients in the VR condition will complete the Child Presence Questionnaire post-procedure to assess level of VR immersion.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Behavior Assessment System for Children (BASC-2)</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>The BASC-2 is a multi-dimensional approach to evaluate behavior (problem behavior as well as adaptive behavior) of children 8 to 18 years old. The parent-report measure has good internal consistency and test-retest reliability. It has been validated in English and Spanish.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Parent Satisfaction Questionnaire</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The parent survey is 16-item, Likert-like survey to assess parent estimates of pain reduction, fear reduction, decreased behavioral distress, and overall satisfaction. Two versions of the survey exist, to account for condition (VR vs. standard of care).</description>
</secondary_outcome>
<secondary_outcome>
<measure>Pediatric Anesthesia Emergence Delirium (Sikich, 2004; PAED)</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The PAED rating scale consists of five psychometric items ("child makes eye contact with the caregiver", "child's actions are purposeful", child is aware of the surroundings", child is restless", "child is inconsolable") for the measurement of ED in children. A decreased ability of the child to make eye contact with the caregiver and a declined awareness of his surroundings reflect disturbances in consciousness with a reduced ability to focus, sustain, or shift attention. Less purposeful actions suggest cognitive changes that include perception and memory impairment as well as disorganized thinking patterns. The two other items reflect a disturbance in psychomotor behavior and emotion, although they may also suggest pain or apprehension.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Watcha Scale (Watcha et al., 1992)</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The Watcha Scale is a four point scale that is used to assess emergence delirium (ED). A child with a score of 3 or 4 can be considered to have emergence delirium. The Watcha Scale demonstrates reliability and validity in pediatric populations (Reduque & Verghese 2012).</description>
</secondary_outcome>
<secondary_outcome>
<measure>Analgesic Requirements</measure>
<time_frame>Peri-procedure</time_frame>
<description>Frequency and dose of analgesic administered intraoperatively and in the operating room will be ascertained via chart review. Data Obtained: Frequency and dose of analgesic received in the operating room.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Malaise Scale (MS)</measure>
<time_frame>Approximately 5-15 minutes after procedure</time_frame>
<description>The MS is a six-point scale indicating level of nausea from (1) no symptoms to (6) being sick The MS is completed before and after administration of the VR game to monitor for any signs of nausea. Instructions to the child are as follows: "This is a scale from one to six. One means that you feel fine and no different to how you normally feel. Two means that you feel a little bit different or funny but not sick in the tummy. Three means that you feel a little bit sick and four means that you feel more than a little bit sick but not really sick. Five means that you feel really sick, like you are going to throw up or vomit and six means that you are being sick or vomiting. I'm going to ask you every few minutes how you feel. I want you to tell me which number from one to six best describes how you feel at that time."</description>
</secondary_outcome>
<other_outcome>
<measure>Demographic Survey</measure>
<time_frame>Approximately 5 minutes to one hour before procedure</time_frame>
<description>A brief demographic survey will be administered to parent regarding their child's age, ethnicity, grade in school, and any medical conditions or learning problems they may have.</description>
</other_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">450</enrollment>
<condition>Virtual Reality</condition>
<condition>Augmented Reality</condition>
<condition>IV Stick</condition>
<condition>Mask Induction</condition>
<condition>Ambulatory Surgery</condition>
<condition>Pain</condition>
<condition>Anxiety</condition>
<arm_group>
<arm_group_label>Standard of Care (No VR) Randomization</arm_group_label>
<arm_group_type>No Intervention</arm_group_type>
<description>In the standard of care treatment condition, participants will receive the standard CHLA treatment protocol for IV placement and induction of anesthesia. Current standard of care practices at CHLA for outpatient surgery induction will include the following steps. Children may receive midazolam, parental presence during induction and any other intervention or medication chosen by the HCP. The research team will have no input to the decision regarding the use of any therapy.</description>
</arm_group>
<arm_group>
<arm_group_label>VR Randomization</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>When a child is assigned to the VR condition s/he will have the added component of VR distraction during pre-surgical preparation. Children in the VR condition will interact with an immersive 3D virtual environment presented via a HMD (head-mounted display), a helmet with computer screens for each eye. This study will use two HMDs at two possible time points: (1) Prior to and during IV placement, participants will play using the Oculus Go; (2) Prior to and during anesthesia induction, participants will play using the Mira Prism.</description>
</arm_group>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>Oculus Go VR</intervention_name>
<description>The Oculus Go is a standalone headset with built-in speakers that runs independently of a smartphone. Via the Oculus Go, participants will engage with BearBlast (developed by AppliedVR). Throughout the world, plush moles play the role of antagonist, standing in for the nuisance and distraction of pain. The VR game is equipped with a head-tracking system, enabling the player to look around the virtual environment. In addition, there is the option to interact with the VR environment using a tap pad located on the side of the helmet. Therefore, the child will be receiving distraction via 3-D visual and auditory sensory, and tactile feedback, thus supplying a multi-sensory immersive experience. The VR HMD runs independently of a smartphone and has active matrix LCDs with high pixel resolution, creating a bright, vibrant color and a quality image.</description>
<arm_group_label>VR Randomization</arm_group_label>
</intervention>
<intervention>
<intervention_type>Device</intervention_type>
<intervention_name>Mira Prism VR</intervention_name>
<description>The Mira Prism is a portable, augmented reality (AR) HMD powered by iPhone. When paired with the iPhone, the Mira Prism goggles can superimpose computer-generated images on the user's view of the real world. Unlike the full immersion of VR, AR allows users to view the outside world while interacting with digital content. In this study, the patient will interact with Magic Mallet (developed by Miney Moe) until falling asleep during the anesthesia induction process. Magic Mallet is a distraction game designed for pain management and communication during procedures. The game automatically adjusts cognitive load for optimal effect for users. Study team iPhones specifically loaded with Magic Mallet, and without cellular capability, will be used with the Mira Prism.</description>
<arm_group_label>VR Randomization</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Children who are 10-21 years old

2. Children who are English speaking (parents may be Spanish English speaking or Spanish
speaking)

3. Children who are scheduled to undergo outpatient surgery are eligible to participate
in this project.

4. Children whose health status is American Society of Anesthesiologists (ASA) physical
status I-III will be recruited for this study. ASA status I refers to patients who are
normal and healthy with no known systemic disease. ASA status II refers to patients
who have mild or well-controlled systemic diseases, such as non-insulin dependent
diabetes, upper respiratory conditions, well-controlled asthma or allergies.

4. Only children who are in the normal range of development will be recruited for this
study. This will be assessed by report from the parents. The rationale for excluding
patients with developmental delay is that due to their cognitive impairments, such children
react to the stressors of surgery differently than do children without such developmental
delay. It is unclear how such children would use the preparation programs and interventions
included in this study, and it is likely that their responses on baseline and outcome
measures will differ from children of normal developmental parameters.

Exclusion Criteria:

1. Children with health status defined by ASA status IV-V will be excluded from this
study. ASA status IV refers to patients with an incapacitating systemic disease that
is a constant threat to life. ASA status V patients are considered moribund.

2. Children who are taking psychotropic medications that affect emotion modulation will
be excluded from this study.

3. Children with organic brain syndrome, mental retardation, or other known
cognitive/neurological disorders

4. Children with visual, auditory, or tactile deficits that would interfere with the
ability to complete the experimental tasks or use the technological devices

5. Children with a history of seizure disorder.

6. Children currently sick with flu-like symptoms or experiencing a headache or earache
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>10 Years</minimum_age>
<maximum_age>21 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Jeffrey I Gold, PhD</last_name>
<role>Principal Investigator</role>
<affiliation>Children's Hospital Los Angeles</affiliation>
</overall_official>
<location>
<facility>
<name>Children's Hospital Los Angeles</name>
<address>
<city>Los Angeles</city>
<state>California</state>
<zip>90027</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<reference>
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<verification_date>March 2022</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>March 28, 2022</last_update_submitted>
<last_update_submitted_qc>March 28, 2022</last_update_submitted_qc>
<last_update_posted type="Actual">March 29, 2022</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Children's Hospital Los Angeles</investigator_affiliation>
<investigator_full_name>Jeffrey I Gold, PhD</investigator_full_name>
<investigator_title>Professor of Anesthesiology, Pediatrics, and Psychiatry & Behavioral Sciences</investigator_title>
</responsible_party>
<keyword>virtual reality</keyword>
<keyword>augmented reality</keyword>
<keyword>IV stick</keyword>
<keyword>mask induction</keyword>
<keyword>tonsillectomy</keyword>
<keyword>adenoidectomy</keyword>
<keyword>arthroscopy</keyword>
<keyword>hernia</keyword>
<keyword>circumcision</keyword>
<keyword>orchiopexy</keyword>
<keyword>hymenectomy</keyword>
<keyword>esophagogastroduodenoscopy</keyword>
<keyword>colonoscopy</keyword>
<keyword>tymanoplasty</keyword>
<keyword>myringotomy</keyword>
<keyword>pilondial cyst excision</keyword>
<keyword>pain</keyword>
<keyword>anxiety</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Anxiety Disorders</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This study aims to test the effectiveness of virtual reality (VR) as a non-pharmaceutical
intervention to reduce pain and anxiety in children undergoing various procedures in the
Ambulatory Surgery Center (ASC) at CHLA, as measured by self- and proxy-report.
4 million children undergo surgery in the US each year and up to 65% of these children
experience significant anxiety and distress before surgery. High anxiety can be traumatic,
but it can also lead to postoperative adverse outcomes, such as increased pain and analgesics
requirements, delayed hospital discharge, and maladaptive behavioral changes, in children
after the surgery. Non-pharmacological intervention, complementary and alternative medicine
(CAM) interventions, such as virtual reality, has been shown to decrease anxiety and distress
in other medical procedures (e.g., burn care, phlebotomy). Yet to date, no clinical trial has
been conducted to examine the effectiveness of virtual reality (VR) to reduce anxiety and
distress prior to outpatient surgeries in the operating room setting.
The current study aims to: 1) Determine if VR is more effective than standard care for
preventing anxiety, distress, and pain before surgery among children undergoing anesthesia
induction, 2) To evaluate healthcare provider's and caregiver's assessment of patient
cooperation and caregiver's distress and satisfaction with VR compared to standard of care,
and 3) to explore the influence of patient and caregiver characteristics on the effectiveness
of VR in preventing pre-operative anxiety and distress and subsequent post-operative
outcomes.
Study Population: Children (age 10 - 21 years) and their parents who are scheduled to undergo
outpatient surgery, whose health status is American Society of Anesthesiologists (ASA)
physical status I-III, and are in the normal range of development are eligible to be in the
study.
Study Methodology: The study is a randomized, controlled trial designed to examine the
effects of VR on the level of preoperative pain, anxiety and distress of children undergoing
surgery.
Statistical Analyses: Univariate Analysis of Variance (ANOVA) will be used to compare
differences in primary and secondary outcome variables in VR + standard of care to standard
of care only conditions when pre and post-operative measures are available. Univariate ANOVA
will be used to compare conditions on post-operative variables. Multiple regression analyses
will be used to examine the influence of patient and caregiver variables on patient outcomes
in the VR group only.
Inclusion Criteria:
1. Children who are 10-21 years old
2. Children who are English speaking (parents may be Spanish English speaking or Spanish
speaking)
3. Children who are scheduled to undergo outpatient surgery are eligible to participate
in this project.
4. Children whose health status is American Society of Anesthesiologists (ASA) physical
status I-III will be recruited for this study. ASA status I refers to patients who are
normal and healthy with no known systemic disease. ASA status II refers to patients
who have mild or well-controlled systemic diseases, such as non-insulin dependent
diabetes, upper respiratory conditions, well-controlled asthma or allergies.
4. Only children who are in the normal range of development will be recruited for this
study. This will be assessed by report from the parents. The rationale for excluding
patients with developmental delay is that due to their cognitive impairments, such children
react to the stressors of surgery differently than do children without such developmental
delay. It is unclear how such children would use the preparation programs and interventions
included in this study, and it is likely that their responses on baseline and outcome
measures will differ from children of normal developmental parameters.
Exclusion Criteria:
1. Children with health status defined by ASA status IV-V will be excluded from this
study. ASA status IV refers to patients with an incapacitating systemic disease that
is a constant threat to life. ASA status V patients are considered moribund.
2. Children who are taking psychotropic medications that affect emotion modulation will
be excluded from this study.
3. Children with organic brain syndrome, mental retardation, or other known
cognitive/neurological disorders
4. Children with visual, auditory, or tactile deficits that would interfere with the
ability to complete the experimental tasks or use the technological devices
5. Children with a history of seizure disorder.
6. Children currently sick with flu-like symptoms or experiencing a headache or earache
|
NCT0426xxxx/NCT04268927.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268927</url>
</required_header>
<id_info>
<org_study_id>letrozole/ GnRH ant</org_study_id>
<nct_id>NCT04268927</nct_id>
</id_info>
<brief_title>Extended Letrozole Regimen Co-treatment With Gonadotropin Releasing Hormone Antagonist Protocol Versus Gonadotropin Releasing Hormone Antagonist Protocol in Poor Responders Undergoing IVF-ET</brief_title>
<official_title>Extended Letrozole Regimen Co-treatment With Gonadotropin Releasing Hormone Antagonist Protocol Versus Gonadotropin Releasing Hormone Antagonist Protocol in Poor Responders Undergoing IVF-ET. A Randomized Controlled Trial</official_title>
<sponsors>
<lead_sponsor>
<agency>Cairo University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Cairo University</source>
<oversight_info>
<has_dmc>Yes</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
<is_us_export>No</is_us_export>
</oversight_info>
<brief_summary>
<textblock>
The object of this study is to evaluate the efficacy of extended letrozole co-treatment with
GnRH-antagonist protocol in ovarian stimulation of poor responder patients undergoing IVF-ET.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Poor response to controlled ovarian stimulation (COH) is estimated to occur in 9-24 % of all
IVF cycles. Although there is no consensus on the definition of poor response to COH,
inability to produce adequate number of mature follicles( ≤ 2-5) or to recruit adequate
number of oocytes ( ≤ 3 oocytes ) in response to standard stimulation protocols are the main
criteria used for diagnosis of poor responders .

Patients with poor response to COH usually have higher cyclical cancelation rate , poor
embryo quality and less number of embryos suitable for transfer or cryopreservation .

During the past decade gonadotropin releasing hormone antagonists (GnRHant) were widely used
in the treatment of patients with poor response to standard gonadotropin releasing hormone
agonist (GnRHa) protocols .In contrast to GnRHa, GnRHant is administered at the late
follicular phase and therefore don't suppress the early follicular phase endogenous
gonadotropins and has no suppressive effect on ovarian function at the stage of follicular
recruitment.Several studies comparing GnRHant protocol with the standard GnRHa long protocol
revealed a reduction in the duration of stimulation , dose of required gonadotropins , and
the costs of IVF cycle with GnRHant as well as equivalent pregnancy rates .

In 2001, Mitwally and Casper introduced letrozole ( a third generation non steroidal
aromatase inhibitor licensed for treatment of hormonally-responsive breast cancer after
surgery ) as new ovulation induction agent in clomiphene citrate resistant patients with
polycystic ovary syndrome (PCOS) . Subsequent studies confirmed the effectiveness of
letrozole in induction of ovulation in women with PCOS and in superovulation (either alone or
in combination with gonadotropins ) .

In patients with poor response undergoing IVF, several studies revealed that the combination
of letrozole ( 2.5 mg or 5 mg/day for 5 consecutive days in early follicular phase ) with
GnRHant protocol improved the ovarian response and reduced the gonadotrophin dose required.
On the other hand , Schoolcraft et al reported that letrozole(2.5 mg/day from cycle day 3 to
7)/GnRHant protocol has no advantages over microdose flare GnRHa protocol.

The ideal dose and duration of letrozole administration for ovulation and superovulation is
still not clear. Several studies comparing two doses of letrozole (2.5 mg or 5 mg) in
superovulation suggested that the higher dose might be associated with more follicles
developing.

In almost all studies to date , letrozole was administered for five consecutive days in early
follicular phase . In only one study , letrozole (2.5 mg/day) was administered for ten
consecutive days starting on day 1 of menstrual cycle . In that study , prolonged
administration of letrozole produced more mature follicles and pregnancies than short
letrozole therapy regimen in patients with clomiphene citrate resistant polycystic ovary
syndrome .

The investigators designed this randomized controlled trial to evaluate the efficacy of
extended letrozole co-treatment with GnRH-antagonist protocol in ovarian stimulation of poor
responder patients undergoing IVF-ET
</textblock>
</detailed_description>
<overall_status>Unknown status</overall_status>
<last_known_status>Recruiting</last_known_status>
<start_date type="Actual">April 1, 2018</start_date>
<completion_date type="Anticipated">April 20, 2020</completion_date>
<primary_completion_date type="Anticipated">March 20, 2020</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
</study_design_info>
<primary_outcome>
<measure>Number of oocytes retrieved</measure>
<time_frame>Three weeks after start of ovarian stimulation</time_frame>
<description>Oocytes aspirated during ovum pickup</description>
</primary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">106</enrollment>
<condition>Infertility</condition>
<arm_group>
<arm_group_label>GnRH ant/letrozole</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Letrozole (Femara; Novertis pharma AG, Basle, Switzerland) is administered starting on cycle day one for 8 consecutive days . The dose of letrozole is 5mg /day during the first 5 days of cycle and 2.5 mg/day during the subsequent 3 days .
Highly purified urinary FSH (HP-uFSH) (Fostimon, IBSA) 300 IU/day is started on cycle day 5 and is continued until and including the day of HCG administration. Starting from cycle day 8 , the dose of HP-uFSH is adjusted individually according to ovarian response which is monitored using transvaginal ultrasound and serum estradiol.
GnRH antagonist (cetrorelix acetate)(Cetrotide®) 0.25 mg S.C once daily is started when the leading follicle is 14 mm in mean diameter and is continued until and including the day of HCG administration .</description>
</arm_group>
<arm_group>
<arm_group_label>GnRH ant</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>Highly purified urinary FSH (HP-uFSH) (Fostimon, IBSA) 300 IU/day is started on cycle day 5 and is continued until and including the day of HCG administration. Starting from cycle day 8 , the dose of HP-uFSH is adjusted individually according to ovarian response which is monitored using transvaginal ultrasound and serum estradiol.
GnRH antagonist (cetrorelix acetate)(Cetrotide®) 0.25 mg S.C once daily is started when the leading follicle is 14 mm in mean diameter and is continued until and including the day of HCG administration .</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>GnRH ant/letrozole</intervention_name>
<description>Letrozole (Femara; Novertis pharma AG, Basle, Switzerland) is administered starting on cycle day one for 8 consecutive days . The dose of letrozole is 5mg /day during the first 5 days of cycle and 2.5 mg/day during the subsequent 3 days .
Highly purified urinary FSH (HP-uFSH) (Fostimon, IBSA) 300 IU/day is started on cycle day 5 and is continued until and including the day of HCG administration. Starting from cycle day 8 , the dose of HP-uFSH is adjusted individually according to ovarian response which is monitored using transvaginal ultrasound and serum estradiol.
GnRH antagonist (cetrorelix acetate)(Cetrotide®) 0.25 mg S.C once daily is started when the leading follicle is 14 mm in mean diameter and is continued until and including the day of HCG administration .</description>
<arm_group_label>GnRH ant/letrozole</arm_group_label>
</intervention>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>GnRH ant</intervention_name>
<description>Highly purified urinary FSH (HP-uFSH) (Fostimon, IBSA) 300 IU/day is started on cycle day 5 and is continued until and including the day of HCG administration. Starting from cycle day 8 , the dose of HP-uFSH is adjusted individually according to ovarian response which is monitored using transvaginal ultrasound and serum estradiol.
GnRH antagonist (cetrorelix acetate)(Cetrotide®) 0.25 mg S.C once daily is started when the leading follicle is 14 mm in mean diameter and is continued until and including the day of HCG administration .</description>
<arm_group_label>GnRH ant</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Poor responders according to the ESHRE Bologna criteria

Exclusion Criteria:

Age > 42 years FSH> 12 IU/L Irregular menstrual cycles Unilateral ovary Polycystic ovary
syndrome Endometriosis Male factor of infertility requiring ICSI History of recurrent
miscarriage Endocrinologic disorders Systemic disease contraindicating pregnancy
</textblock>
</criteria>
<gender>Female</gender>
<gender_based>Yes</gender_based>
<minimum_age>30 Years</minimum_age>
<maximum_age>42 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Usama M Fouda, Prof</last_name>
<role>Study Chair</role>
<affiliation>Cairo University</affiliation>
</overall_official>
<overall_official>
<last_name>Usama M Fouda, Prof</last_name>
<role>Study Chair</role>
<affiliation>Riyadh Fertility and Reproductive Health center</affiliation>
</overall_official>
<overall_contact>
<last_name>Usama M Fouda, Prof</last_name>
<phone>+201095401375</phone>
<email>umfrfouda@yahoo.com</email>
</overall_contact>
<location>
<facility>
<name>Obstetrics &Gynecology Department , Faculty of medicine ,Cairo university</name>
<address>
<city>Cairo</city>
<country>Egypt</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Usama M Fouda, M.D,PhD</last_name>
<phone>01095401375</phone>
<email>umfrfouda@yahoo.com</email>
</contact>
<investigator>
<last_name>Usama M Fouda, M.D,PhD</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location>
<facility>
<name>Riyadh Fertility and Reproductive Health center</name>
<address>
<city>Giza</city>
<country>Egypt</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Usama M Fouda, Prof</last_name>
<phone>+20123595106</phone>
<email>umfrfouda@yahoo.com</email>
</contact>
<investigator>
<last_name>Usama M Fouda, Prof</last_name>
<role>Principal Investigator</role>
</investigator>
</location>
<location_countries>
<country>Egypt</country>
</location_countries>
<reference>
<citation>Badawy A, Mosbah A, Tharwat A, Eid M. Extended letrozole therapy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a novel protocol. Fertil Steril. 2009 Jul;92(1):236-9. doi: 10.1016/j.fertnstert.2008.04.065. Epub 2008 Aug 15.</citation>
<PMID>18706549</PMID>
</reference>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 12, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 12, 2020</last_update_submitted>
<last_update_submitted_qc>February 12, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 13, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Cairo University</investigator_affiliation>
<investigator_full_name>Usama M Fouda</investigator_full_name>
<investigator_title>Prof.</investigator_title>
</responsible_party>
<keyword>Letrozole ,IVF, poor responders , GnRH antagonist</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Infertility</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Letrozole</mesh_term>
<mesh_term>LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-</mesh_term>
<mesh_term>Prolactin Release-Inhibiting Factors</mesh_term>
</intervention_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The object of this study is to evaluate the efficacy of extended letrozole co-treatment with
GnRH-antagonist protocol in ovarian stimulation of poor responder patients undergoing IVF-ET.
Poor response to controlled ovarian stimulation (COH) is estimated to occur in 9-24 % of all
IVF cycles. Although there is no consensus on the definition of poor response to COH,
inability to produce adequate number of mature follicles( ≤ 2-5) or to recruit adequate
number of oocytes ( ≤ 3 oocytes ) in response to standard stimulation protocols are the main
criteria used for diagnosis of poor responders .
Patients with poor response to COH usually have higher cyclical cancelation rate , poor
embryo quality and less number of embryos suitable for transfer or cryopreservation .
During the past decade gonadotropin releasing hormone antagonists (GnRHant) were widely used
in the treatment of patients with poor response to standard gonadotropin releasing hormone
agonist (GnRHa) protocols .In contrast to GnRHa, GnRHant is administered at the late
follicular phase and therefore don't suppress the early follicular phase endogenous
gonadotropins and has no suppressive effect on ovarian function at the stage of follicular
recruitment.Several studies comparing GnRHant protocol with the standard GnRHa long protocol
revealed a reduction in the duration of stimulation , dose of required gonadotropins , and
the costs of IVF cycle with GnRHant as well as equivalent pregnancy rates .
In 2001, Mitwally and Casper introduced letrozole ( a third generation non steroidal
aromatase inhibitor licensed for treatment of hormonally-responsive breast cancer after
surgery ) as new ovulation induction agent in clomiphene citrate resistant patients with
polycystic ovary syndrome (PCOS) . Subsequent studies confirmed the effectiveness of
letrozole in induction of ovulation in women with PCOS and in superovulation (either alone or
in combination with gonadotropins ) .
In patients with poor response undergoing IVF, several studies revealed that the combination
of letrozole ( 2.5 mg or 5 mg/day for 5 consecutive days in early follicular phase ) with
GnRHant protocol improved the ovarian response and reduced the gonadotrophin dose required.
On the other hand , Schoolcraft et al reported that letrozole(2.5 mg/day from cycle day 3 to
7)/GnRHant protocol has no advantages over microdose flare GnRHa protocol.
The ideal dose and duration of letrozole administration for ovulation and superovulation is
still not clear. Several studies comparing two doses of letrozole (2.5 mg or 5 mg) in
superovulation suggested that the higher dose might be associated with more follicles
developing.
In almost all studies to date , letrozole was administered for five consecutive days in early
follicular phase . In only one study , letrozole (2.5 mg/day) was administered for ten
consecutive days starting on day 1 of menstrual cycle . In that study , prolonged
administration of letrozole produced more mature follicles and pregnancies than short
letrozole therapy regimen in patients with clomiphene citrate resistant polycystic ovary
syndrome .
The investigators designed this randomized controlled trial to evaluate the efficacy of
extended letrozole co-treatment with GnRH-antagonist protocol in ovarian stimulation of poor
responder patients undergoing IVF-ET
Inclusion Criteria:
- Poor responders according to the ESHRE Bologna criteria
Exclusion Criteria:
Age > 42 years FSH> 12 IU/L Irregular menstrual cycles Unilateral ovary Polycystic ovary
syndrome Endometriosis Male factor of infertility requiring ICSI History of recurrent
miscarriage Endocrinologic disorders Systemic disease contraindicating pregnancy
|
NCT0426xxxx/NCT04268940.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268940</url>
</required_header>
<id_info>
<org_study_id>19-5121</org_study_id>
<nct_id>NCT04268940</nct_id>
</id_info>
<brief_title>Thrombo-Elastography Guided Management of ECMO</brief_title>
<acronym>TEGMO</acronym>
<official_title>Thrombo-Elastography Guided Management of ECMO</official_title>
<sponsors>
<lead_sponsor>
<agency>Damian Ratano</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>The PSI Foundation, Ontario</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>University Health Network, Toronto</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Anticoagulation and coagulation management during ECMO is a challenge. Bleeding and clotting
are major sources of morbidity and mortality. The currently used strategies are of poor
evidence. This observational study wants to evaluate the use of automated thromboelastography
(TEG 6s) to guide the management of coagulation and anticoagulation in patients supported by
ECMO
</textblock>
</brief_summary>
<detailed_description>
<textblock>
ECMO induces both a risk of clotting and bleeding. Therapeutic anticoagulation is recommended
during ECMO. While preventing clotting, anticoagulation triggers a higher risk of bleeding.
However, anticoagulation does not completely avoid clotting due to complex interactions
between the circuit, the patients' blood and the anticoagulant. Unfractionated heparin (UFH)
is the most commonly used anticoagulant and requires monitoring. No clear recommendation
exists. The activated partial thromboplastin time (aPTT) as well as the anti-factor Xa
activity (anti-Xa) are plasma-based tests used to monitor UFH. The evidence for their use is
poor and they do no correlate well. Moreover, these two tests do not take into account all
the elements of blood and do not reflect the entire coagulation process.

Thromboelastography is a whole-blood point-of-care test that describes each phases of the
clotting process from the activation of coagulation factors to the later lysis to the
thrombus. TEG is also sensitive to UFH and can be used to quantify its effect. The use of
heparinase during TEG also permits to evaluate the coagulation process during the use of
heparin. This could give an important understanding of the effect of the ECMO itself on the
circuit and help to develop a strategy to prevent bleeding and clotting as well as monitor
heparin treatment.

The hypothesis for this study is that the use of thromboelastography will identify situations
with high risk of bleeding and allow interventions to reduce hemorrhagic events and blood
products transfusions. It is also hypothesized that the monitoring of unfractionated heparin
(UFH) with TEG is feasible and could lead to the use of less UFH during the course of ECMO.

The objectives of this study are 1) to determine and calibrate the TEG R-time values
corresponding to aPTT therapeutic range for patients under therapeutic UFH during ECMO
course, 2) to determine the level of correlation of TEG parameters with other anticoagulation
tests [Prothrombin Time (PT), anti-Xa, activated clotting time (ACT)], fibrinogen level,
platelets count and d-dimers, 3) to determine the TEG values that are associated with the
administration of blood-derived coagulation products in clinical practice 4) to identify TEG
cutoff points that are associated with an increased risk of bleeding/clotting in ECMO
patients 5) use these observational data to develop a TEG-based algorithm for anticoagulation
management and blood products replacement that could be tested in a future study.

This study will you the last version of TEG, TEG-6s which is a fully automated point-of-care
device.
</textblock>
</detailed_description>
<overall_status>Unknown status</overall_status>
<last_known_status>Active, not recruiting</last_known_status>
<start_date type="Actual">June 3, 2020</start_date>
<completion_date type="Anticipated">September 1, 2021</completion_date>
<primary_completion_date type="Anticipated">August 1, 2021</primary_completion_date>
<study_type>Observational</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<observational_model>Cohort</observational_model>
<time_perspective>Prospective</time_perspective>
</study_design_info>
<primary_outcome>
<measure>Correlation between TEG (R-time K-TEG) and aPTT</measure>
<time_frame>0-10 days</time_frame>
</primary_outcome>
<primary_outcome>
<measure>Correlation of TEG parameters with "classical" coagulation tests</measure>
<time_frame>0-10 days</time_frame>
</primary_outcome>
<primary_outcome>
<measure>Ability of TEG data to identify patients at higher risk of bleeding (or clotting) during the course of ECMO</measure>
<time_frame>0-10 days</time_frame>
</primary_outcome>
<enrollment type="Actual">61</enrollment>
<condition>Extracorporeal Circulation of Blood; Thrombocytopenia</condition>
<intervention>
<intervention_type>Diagnostic Test</intervention_type>
<intervention_name>Thromboelastography</intervention_name>
<description>Thromboelastography (TEG 6s, global hemostasis cartridge) will be performed before ECMO insertion and at different time-points during the course of ECMO. In parallel a full coagulation work-up (aPTT, prothrombin time [PT], anti-Xa, activated clotting time[ACT], platelets count, d-dimers, von Willebrand panel and fibrinogen) will be measured simultaneously with each TEG.</description>
</intervention>
<eligibility>
<study_pop>
<textblock>
Adult patients suffering from cardiorespiratory failure and needing Extracorporeal Membrane
Oxygenation
</textblock>
</study_pop>
<sampling_method>Probability Sample</sampling_method>
<criteria>
<textblock>
Inclusion Criteria:

- Consecutive patients admitted in Toronto General Hospital Medical Surgical ICU (MSICU)
supported with ECMO. Patients cannulated before admission (ECMO retrieval) can also be
included

Exclusion Criteria:

- Refusal of consent, unavailability or impossibility to process blood samples before
ECMO cannulation
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Damian Ratano, MD</last_name>
<role>Principal Investigator</role>
<affiliation>University Health Network, Toronto</affiliation>
</overall_official>
<overall_official>
<last_name>Eddy Fan, MD, PhD</last_name>
<role>Principal Investigator</role>
<affiliation>University Health Network, Toronto</affiliation>
</overall_official>
<location>
<facility>
<name>University Health Network</name>
<address>
<city>Toronto</city>
<state>Ontario</state>
<zip>M5G2N2</zip>
<country>Canada</country>
</address>
</facility>
</location>
<location_countries>
<country>Canada</country>
</location_countries>
<link>
<url>https://www.elso.org/Portals/0/Files/elsoanticoagulationguideline8-2014-table-contents.pdf</url>
<description>Extracorporeal life support organisation (ELSO) anticoagulation guidelines</description>
</link>
<link>
<url>https://teg.haemonetics.com/en-gb/teg-6s-hemostasis-analyzer</url>
<description>TEG 6s description</description>
</link>
<reference>
<citation>Sauer CM, Yuh DD, Bonde P. Extracorporeal membrane oxygenation use has increased by 433% in adults in the United States from 2006 to 2011. ASAIO J. 2015 Jan-Feb;61(1):31-6. doi: 10.1097/MAT.0000000000000160.</citation>
<PMID>25303799</PMID>
</reference>
<reference>
<citation>Gorbet MB, Sefton MV. Biomaterial-associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes. Biomaterials. 2004 Nov;25(26):5681-703. doi: 10.1016/j.biomaterials.2004.01.023.</citation>
<PMID>15147815</PMID>
</reference>
<reference>
<citation>Annich GM. Extracorporeal life support: the precarious balance of hemostasis. J Thromb Haemost. 2015 Jun;13 Suppl 1:S336-42. doi: 10.1111/jth.12963.</citation>
<PMID>26149045</PMID>
</reference>
<reference>
<citation>Zangrillo A, Landoni G, Biondi-Zoccai G, Greco M, Greco T, Frati G, Patroniti N, Antonelli M, Pesenti A, Pappalardo F. A meta-analysis of complications and mortality of extracorporeal membrane oxygenation. Crit Care Resusc. 2013 Sep;15(3):172-8.</citation>
<PMID>23944202</PMID>
</reference>
<reference>
<citation>Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e24S-e43S. doi: 10.1378/chest.11-2291. Erratum In: Chest. 2012 May;141(5):1369. Dosage error in article text. Chest. 2013 Aug;144(2):721. Dosage error in article text.</citation>
<PMID>22315264</PMID>
</reference>
<reference>
<citation>Kreyer S, Muders T, Theuerkauf N, Spitzhuttl J, Schellhaas T, Schewe JC, Guenther U, Wrigge H, Putensen C. Hemorrhage under veno-venous extracorporeal membrane oxygenation in acute respiratory distress syndrome patients: a retrospective data analysis. J Thorac Dis. 2017 Dec;9(12):5017-5029. doi: 10.21037/jtd.2017.11.05.</citation>
<PMID>29312706</PMID>
</reference>
<reference>
<citation>Ratano D, Alberio L, Delodder F, Faouzi M, Berger MM. Agreement between activated partial thromboplastin time and anti-Xa activity in critically ill patients receiving therapeutic unfractionated heparin. Thromb Res. 2019 Mar;175:53-58. doi: 10.1016/j.thromres.2019.01.002. Epub 2019 Jan 7.</citation>
<PMID>30708169</PMID>
</reference>
<reference>
<citation>Basu D, Gallus A, Hirsh J, Cade J. A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time. N Engl J Med. 1972 Aug 17;287(7):324-7. doi: 10.1056/NEJM197208172870703. No abstract available.</citation>
<PMID>5041701</PMID>
</reference>
<reference>
<citation>Levine MN, Hirsh J, Gent M, Turpie AG, Cruickshank M, Weitz J, Anderson D, Johnson M. A randomized trial comparing activated thromboplastin time with heparin assay in patients with acute venous thromboembolism requiring large daily doses of heparin. Arch Intern Med. 1994 Jan 10;154(1):49-56.</citation>
<PMID>8267489</PMID>
</reference>
<reference>
<citation>Atallah S, Liebl M, Fitousis K, Bostan F, Masud F. Evaluation of the activated clotting time and activated partial thromboplastin time for the monitoring of heparin in adult extracorporeal membrane oxygenation patients. Perfusion. 2014 Sep;29(5):456-61. doi: 10.1177/0267659114524264. Epub 2014 Feb 25.</citation>
<PMID>24570077</PMID>
</reference>
<reference>
<citation>Panigada M, E Iapichino G, Brioni M, Panarello G, Protti A, Grasselli G, Occhipinti G, Novembrino C, Consonni D, Arcadipane A, Gattinoni L, Pesenti A. Thromboelastography-based anticoagulation management during extracorporeal membrane oxygenation: a safety and feasibility pilot study. Ann Intensive Care. 2018 Jan 16;8(1):7. doi: 10.1186/s13613-017-0352-8.</citation>
<PMID>29340875</PMID>
</reference>
<reference>
<citation>Henderson N, Sullivan JE, Myers J, Wells T, Calhoun A, Berkenbosch J, Tzanetos DT. Use of Thromboelastography to Predict Thrombotic Complications in Pediatric and Neonatal Extracorporeal Membranous Oxygenation. J Extra Corpor Technol. 2018 Sep;50(3):149-154.</citation>
<PMID>30250340</PMID>
</reference>
<reference>
<citation>Riley JB, Schears GJ, Nuttall GA, Oliver WC Jr, Ereth MH, Dearani JA. Coagulation Parameter Thresholds Associated with Non-Bleeding in the Eighth Hour of Adult Cardiac Surgical Post-Cardiotomy Extracorporeal Membrane Oxygenation. J Extra Corpor Technol. 2016 Jun;48(2):71-8.</citation>
<PMID>27578897</PMID>
</reference>
<reference>
<citation>Gurbel PA, Bliden KP, Tantry US, Monroe AL, Muresan AA, Brunner NE, Lopez-Espina CG, Delmenico PR, Cohen E, Raviv G, Haugen DL, Ereth MH. First report of the point-of-care TEG: A technical validation study of the TEG-6S system. Platelets. 2016 Nov;27(7):642-649. doi: 10.3109/09537104.2016.1153617. Epub 2016 Apr 11.</citation>
<PMID>27809712</PMID>
</reference>
<reference>
<citation>Delmas C, Jacquemin A, Vardon-Bounes F, Georges B, Guerrero F, Hernandez N, Marcheix B, Seguin T, Minville V, Conil JM, Silva S. Anticoagulation Monitoring Under ECMO Support: A Comparative Study Between the Activated Coagulation Time and the Anti-Xa Activity Assay. J Intensive Care Med. 2020 Jul;35(7):679-686. doi: 10.1177/0885066618776937. Epub 2018 May 16.</citation>
<PMID>29768983</PMID>
</reference>
<verification_date>April 2021</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>April 23, 2021</last_update_submitted>
<last_update_submitted_qc>April 23, 2021</last_update_submitted_qc>
<last_update_posted type="Actual">April 26, 2021</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor-Investigator</responsible_party_type>
<investigator_affiliation>University Health Network, Toronto</investigator_affiliation>
<investigator_full_name>Damian Ratano</investigator_full_name>
<investigator_title>Principal investigator</investigator_title>
</responsible_party>
<keyword>Unfractionated heparin</keyword>
<keyword>Extracorporeal Membrane Oxygenation (ECMO)</keyword>
<keyword>Thromboelastography</keyword>
<keyword>Anticoagulation monitoring</keyword>
<keyword>aPTT</keyword>
<keyword>Anti-factor Xa</keyword>
<keyword>Point-of-care</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Thrombocytopenia</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Anticoagulation and coagulation management during ECMO is a challenge. Bleeding and clotting
are major sources of morbidity and mortality. The currently used strategies are of poor
evidence. This observational study wants to evaluate the use of automated thromboelastography
(TEG 6s) to guide the management of coagulation and anticoagulation in patients supported by
ECMO
ECMO induces both a risk of clotting and bleeding. Therapeutic anticoagulation is recommended
during ECMO. While preventing clotting, anticoagulation triggers a higher risk of bleeding.
However, anticoagulation does not completely avoid clotting due to complex interactions
between the circuit, the patients' blood and the anticoagulant. Unfractionated heparin (UFH)
is the most commonly used anticoagulant and requires monitoring. No clear recommendation
exists. The activated partial thromboplastin time (aPTT) as well as the anti-factor Xa
activity (anti-Xa) are plasma-based tests used to monitor UFH. The evidence for their use is
poor and they do no correlate well. Moreover, these two tests do not take into account all
the elements of blood and do not reflect the entire coagulation process.
Thromboelastography is a whole-blood point-of-care test that describes each phases of the
clotting process from the activation of coagulation factors to the later lysis to the
thrombus. TEG is also sensitive to UFH and can be used to quantify its effect. The use of
heparinase during TEG also permits to evaluate the coagulation process during the use of
heparin. This could give an important understanding of the effect of the ECMO itself on the
circuit and help to develop a strategy to prevent bleeding and clotting as well as monitor
heparin treatment.
The hypothesis for this study is that the use of thromboelastography will identify situations
with high risk of bleeding and allow interventions to reduce hemorrhagic events and blood
products transfusions. It is also hypothesized that the monitoring of unfractionated heparin
(UFH) with TEG is feasible and could lead to the use of less UFH during the course of ECMO.
The objectives of this study are 1) to determine and calibrate the TEG R-time values
corresponding to aPTT therapeutic range for patients under therapeutic UFH during ECMO
course, 2) to determine the level of correlation of TEG parameters with other anticoagulation
tests [Prothrombin Time (PT), anti-Xa, activated clotting time (ACT)], fibrinogen level,
platelets count and d-dimers, 3) to determine the TEG values that are associated with the
administration of blood-derived coagulation products in clinical practice 4) to identify TEG
cutoff points that are associated with an increased risk of bleeding/clotting in ECMO
patients 5) use these observational data to develop a TEG-based algorithm for anticoagulation
management and blood products replacement that could be tested in a future study.
This study will you the last version of TEG, TEG-6s which is a fully automated point-of-care
device.
Adult patients suffering from cardiorespiratory failure and needing Extracorporeal Membrane
Oxygenation
Inclusion Criteria:
- Consecutive patients admitted in Toronto General Hospital Medical Surgical ICU (MSICU)
supported with ECMO. Patients cannulated before admission (ECMO retrieval) can also be
included
Exclusion Criteria:
- Refusal of consent, unavailability or impossibility to process blood samples before
ECMO cannulation
|
NCT0426xxxx/NCT04268953.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268953</url>
</required_header>
<id_info>
<org_study_id>AC-20-021</org_study_id>
<nct_id>NCT04268953</nct_id>
</id_info>
<brief_title>Study to Compare the Pharmacokinetics of Daily Administration of Tricaprilin on Ketone Body Production</brief_title>
<official_title>A Phase 1, Single-centre, Multiple-dose, Open-label Study to Assess the Safety, Tolerability, and Pharmacokinetics of the AC-SD-03 Formulation of Tricaprilin in Healthy Older Volunteers</official_title>
<sponsors>
<lead_sponsor>
<agency>Cerecin</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
</sponsors>
<source>Cerecin</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>Yes</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This is a Phase I, single center, open label, multiple dose, pharmacokinetic (PK) study
recruiting healthy older subjects.
</textblock>
</brief_summary>
<overall_status>Completed</overall_status>
<start_date type="Actual">February 27, 2020</start_date>
<completion_date type="Actual">May 1, 2020</completion_date>
<primary_completion_date type="Actual">March 26, 2020</primary_completion_date>
<phase>Phase 1</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<intervention_model>Sequential Assignment</intervention_model>
<primary_purpose>Basic Science</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Safety and tolerability of multiple-dose administrations of tricaprilin formulated as AC-SD-03 administered using a titration scheme in healthy older volunteers</measure>
<time_frame>32 days</time_frame>
<description>TEAE incidence rate</description>
</primary_outcome>
<secondary_outcome>
<measure>Pharmacokinetics (PK) parameters of Total Ketones levels after multiple dose of AC-SD-03 using AUC(0-t)</measure>
<time_frame>28 days</time_frame>
<description>AUC(0-t) will be calculated from PK concentrations of Total Ketones (B-hydroxybutyrate and Acetoacetate) Levels. AUC (0-t) = Area under the concentration-time curve from 0 to last quantifiable concentration. Summary statistics will be generated for each PK parameter.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Pharmacokinetics (PK) parameters of Total Ketones levels after multiple dose of AC-SD-03 using Cmax</measure>
<time_frame>28 days</time_frame>
<description>Cmax will be calculated from PK concentrations of Total Ketones (B-hydroxybutyrate and Acetoacetate) Levels. Cmax = Cmax is maximum concentration, determined directly from individual concentration-time data.Summary statistics will be generated for each PK parameter.</description>
</secondary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Actual">12</enrollment>
<condition>Alzheimer Disease</condition>
<arm_group>
<arm_group_label>AC-SD-03</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Study drug administered concurrently with a standard meal</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Tricaprilin</intervention_name>
<description>Tricaprilin formulated as AC-SD-03 mixed in 300mL water</description>
<arm_group_label>AC-SD-03</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

1. Healthy, adult, males or females, age 50 years and above, at Screening.

2. Subject must be in reasonably good health as determined by the investigator based on a
detailed medical history, full physical examination (including blood pressure and
pulse rate measurement), 12 lead ECG and clinical laboratory tests. Subjects with
mild, chronic, stable disease (e.g., controlled hypertension, Type 2 diabetes, etc)
will be permitted to enrol.

3. Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at Screening.

4. Agrees to comply with study procedures including the confinement period of 28 days.

5. Subject is able and willing to consume a prescribed full breakfast, lunch and dinner
while confined in the CRU. Subject does not have specific dietary requirements
(vegetarian, vegan, lactose-free, low-fat, etc.).

6. Subject is not consuming a ketogenic diet (defined by consumption of < 50 gm
carbohydrates per day).

7. A non vasectomized male subject must agree to use a condom or abstain from sexual
intercourse during the study and for 90 days following last dose of AC-SD 03. No
restrictions are required for a vasectomized male provided his vasectomy has been
performed 4 months or more prior to Screening. A subject who has been vasectomized
less than 4 months prior to Screening must follow the same restrictions as a non
vasectomized male.

8. Female subjects must be either surgically sterile or 2 or more years post-menopause.

9. Has given voluntary, written informed consent to participate in the study.

Exclusion Criteria:

1. History or presence of alcoholism or substance abuse disorder within the last year.

2. Positive urine drug screen at Screening or Check-In.

3. Subject is currently actively using MCTs, ketone esters, or other ketogenic products
or is following a ketogenic diet.

4. Clinically significant abnormal laboratory results at Screening that in the opinion of
the PI preclude participating in this study

5. Participation in another clinical trial within 30 days prior to Check-In.

6. Subject has a known allergy to the study drug's active or inactive ingredients.

7. Subject has been following a ketogenic diet (or other diet incompatible with the
on-study diet), in the opinion of the investigator.

8. Unable to refrain from, or anticipates the use of drugs other than allowed products,
including prescription and non-prescription medications, beginning 14 days prior to
the first dose and throughout the study.

1. Allowed medications include anti-hypertensive agents, statins, aspirin in a dose
of 100 mg or less per day for prophylaxis.

2. Paracetamol (acetaminophen), up to 4 g per 24 hour period, or ibuprofen (up to
1200 mg per 24-hour period) may be permitted during the study.

3. Herbal remedies and vitamin supplements are permitted in usual doses (not hyper
supplementation) so long as subject has been on stable amounts for at least 6
weeks.

4. Agents being taken to improve memory or cognition are not allowed, whether
herbal, 'natural' or pharmaceutical.

9. Subject is known HIV, HBV or HCV positive, or has a positive test at Screening.

10. Any other condition which, in the investigator's opinion may adversely affect the
subject's ability to complete the study or its measures or which may pose significant
risk to the subject.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>50 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<location>
<facility>
<name>Celerion</name>
<address>
<city>Tempe</city>
<state>Arizona</state>
<zip>85283</zip>
<country>United States</country>
</address>
</facility>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>July 2020</verification_date>
<study_first_submitted>February 12, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>July 7, 2020</last_update_submitted>
<last_update_submitted_qc>July 7, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">July 8, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Alzheimer Disease</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>No</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This is a Phase I, single center, open label, multiple dose, pharmacokinetic (PK) study
recruiting healthy older subjects.
Inclusion Criteria:
1. Healthy, adult, males or females, age 50 years and above, at Screening.
2. Subject must be in reasonably good health as determined by the investigator based on a
detailed medical history, full physical examination (including blood pressure and
pulse rate measurement), 12 lead ECG and clinical laboratory tests. Subjects with
mild, chronic, stable disease (e.g., controlled hypertension, Type 2 diabetes, etc)
will be permitted to enrol.
3. Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at Screening.
4. Agrees to comply with study procedures including the confinement period of 28 days.
5. Subject is able and willing to consume a prescribed full breakfast, lunch and dinner
while confined in the CRU. Subject does not have specific dietary requirements
(vegetarian, vegan, lactose-free, low-fat, etc.).
6. Subject is not consuming a ketogenic diet (defined by consumption of < 50 gm
carbohydrates per day).
7. A non vasectomized male subject must agree to use a condom or abstain from sexual
intercourse during the study and for 90 days following last dose of AC-SD 03. No
restrictions are required for a vasectomized male provided his vasectomy has been
performed 4 months or more prior to Screening. A subject who has been vasectomized
less than 4 months prior to Screening must follow the same restrictions as a non
vasectomized male.
8. Female subjects must be either surgically sterile or 2 or more years post-menopause.
9. Has given voluntary, written informed consent to participate in the study.
Exclusion Criteria:
1. History or presence of alcoholism or substance abuse disorder within the last year.
2. Positive urine drug screen at Screening or Check-In.
3. Subject is currently actively using MCTs, ketone esters, or other ketogenic products
or is following a ketogenic diet.
4. Clinically significant abnormal laboratory results at Screening that in the opinion of
the PI preclude participating in this study
5. Participation in another clinical trial within 30 days prior to Check-In.
6. Subject has a known allergy to the study drug's active or inactive ingredients.
7. Subject has been following a ketogenic diet (or other diet incompatible with the
on-study diet), in the opinion of the investigator.
8. Unable to refrain from, or anticipates the use of drugs other than allowed products,
including prescription and non-prescription medications, beginning 14 days prior to
the first dose and throughout the study.
1. Allowed medications include anti-hypertensive agents, statins, aspirin in a dose
of 100 mg or less per day for prophylaxis.
2. Paracetamol (acetaminophen), up to 4 g per 24 hour period, or ibuprofen (up to
1200 mg per 24-hour period) may be permitted during the study.
3. Herbal remedies and vitamin supplements are permitted in usual doses (not hyper
supplementation) so long as subject has been on stable amounts for at least 6
weeks.
4. Agents being taken to improve memory or cognition are not allowed, whether
herbal, 'natural' or pharmaceutical.
9. Subject is known HIV, HBV or HCV positive, or has a positive test at Screening.
10. Any other condition which, in the investigator's opinion may adversely affect the
subject's ability to complete the study or its measures or which may pose significant
risk to the subject.
|
NCT0426xxxx/NCT04268966.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268966</url>
</required_header>
<id_info>
<org_study_id>CMX001-206</org_study_id>
<nct_id>NCT04268966</nct_id>
</id_info>
<brief_title>An Open-Label Study , Safety and Tolerability of Brincidofovir for Post Exposure Prophylaxis of Ebola</brief_title>
<acronym>BCV EBOV</acronym>
<official_title>An Open-Label, Multicenter Study of the Safety and Tolerability of Brincidofovir (CMX001) for Post-Exposure Prophylaxis of Ebola Virus Disease</official_title>
<sponsors>
<lead_sponsor>
<agency>Chimerix</agency>
<agency_class>Industry</agency_class>
</lead_sponsor>
<collaborator>
<agency>Food and Drug Administration (FDA)</agency>
<agency_class>U.S. Fed</agency_class>
</collaborator>
</sponsors>
<source>Chimerix</source>
<brief_summary>
<textblock>
The purpose of this study is to determine how safe and tolerable Brincidofovir (BCV) is when
given for post exposure prophylaxis of Ebola virus disease.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
The primary objective of this study is to evaluate the safety and tolerability of BCV when
administered for post-exposure prophylaxis of EVD
</textblock>
</detailed_description>
<overall_status>Withdrawn</overall_status>
<start_date>October 2014</start_date>
<completion_date type="Anticipated">December 2015</completion_date>
<primary_completion_date type="Anticipated">November 2015</primary_completion_date>
<phase>Phase 2</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>N/A</allocation>
<intervention_model>Single Group Assignment</intervention_model>
<primary_purpose>Treatment</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>The primary objective of this study is to evaluate the safety and tolerability of BCV when administered for post-exposure prophylaxis of EVD</measure>
<time_frame>8 weeks</time_frame>
</primary_outcome>
<secondary_outcome>
<measure>To assess the effect of BCV treatment on development of EVD in subjects through 21 days post-initiation of BCV therapy</measure>
<time_frame>8 weeks</time_frame>
</secondary_outcome>
<number_of_arms>1</number_of_arms>
<enrollment type="Actual">0</enrollment>
<condition>Ebola Virus Disease</condition>
<arm_group>
<arm_group_label>CMX001</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Initial dose of 200mg followed by 4 doses of 100mg</description>
</arm_group>
<intervention>
<intervention_type>Drug</intervention_type>
<intervention_name>Brincidofovir</intervention_name>
<arm_group_label>CMX001</arm_group_label>
<other_name>CMX001</other_name>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Individuals have high-risk exposure to Ebola Virus based on CDC definitions

- Must be able to ingest, absorb and tolerate oral medication

- As appropriate, must be willing to use adequate methods of contraception during the
study and at least 6 months after their last dose of BCV

Exclusion Criteria:

-
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>85 Years</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 12, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 24, 2020</last_update_submitted>
<last_update_submitted_qc>February 24, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 26, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Virus Diseases</mesh_term>
<mesh_term>Hemorrhagic Fever, Ebola</mesh_term>
</condition_browse>
<intervention_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Brincidofovir</mesh_term>
</intervention_browse>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The purpose of this study is to determine how safe and tolerable Brincidofovir (BCV) is when
given for post exposure prophylaxis of Ebola virus disease.
The primary objective of this study is to evaluate the safety and tolerability of BCV when
administered for post-exposure prophylaxis of EVD
Inclusion Criteria:
- Individuals have high-risk exposure to Ebola Virus based on CDC definitions
- Must be able to ingest, absorb and tolerate oral medication
- As appropriate, must be willing to use adequate methods of contraception during the
study and at least 6 months after their last dose of BCV
Exclusion Criteria:
-
|
NCT0426xxxx/NCT04268979.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268979</url>
</required_header>
<id_info>
<org_study_id>MCC 19731</org_study_id>
<nct_id>NCT04268979</nct_id>
</id_info>
<brief_title>Electronic Social Network Assessment Program (eSNAP) + Caregiver Navigator</brief_title>
<official_title>Electronic Social Network Assessment Program (eSNAP) + Caregiver Navigator Intervention for Neuro-Oncology Couples</official_title>
<sponsors>
<lead_sponsor>
<agency>H. Lee Moffitt Cancer Center and Research Institute</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>H. Lee Moffitt Cancer Center and Research Institute</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
The purpose of the study is to determine if family caregivers of neuro-oncology patients feel
less burdened by utilizing the Electronic Social Network Assessment Program (eSNAP) + the
Caregiver Navigator.
</textblock>
</brief_summary>
<overall_status>Recruiting</overall_status>
<start_date type="Actual">February 13, 2020</start_date>
<completion_date type="Anticipated">June 30, 2024</completion_date>
<primary_completion_date type="Anticipated">February 1, 2024</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<primary_purpose>Supportive Care</primary_purpose>
<masking>None (Open Label)</masking>
</study_design_info>
<primary_outcome>
<measure>Family Caregiver Well-Being Using GAD-7 Scale</measure>
<time_frame>8 weeks per participant</time_frame>
<description>Caregiver well being will be measured using the Generalized Anxiety Disorder 7 Item Scale (GAD-7). The GAD-7 measures anxiety scoring 0-3 points per item, with a total score range 0-21,with a higher score meaning more anxiety.</description>
</primary_outcome>
<primary_outcome>
<measure>Family Caregiver Well-Being using PHQ-8 Scale</measure>
<time_frame>8 weeks per participant</time_frame>
<description>Caregiver well being will be measured using the Personal Health Questionnaire Depression 8 Item Scale Scale (PHQ 8). The PHQ 8 measures depression scoring 0-3 points per item, with a total score range of 0-24, with the higher score meaning more depression.</description>
</primary_outcome>
<primary_outcome>
<measure>Family Caregiver Well-Being Using Zarit Burden Interview</measure>
<time_frame>8 weeks per participant</time_frame>
<description>Caregiver well being will be measured using the Zarit Burden Interview. The Zarit Burden Interview measures burden scoring 0-4 points per item, with a total score range of 0-48, with the higher score meaning more burden.</description>
</primary_outcome>
<primary_outcome>
<measure>Neuro Patients Well-Being Using GAD-7 Scale</measure>
<time_frame>8 weeks per participant</time_frame>
<description>Neuro patients well being will be measured using the Generalized Anxiety Disorder 7 Item Scale (GAD-7). The GAD-7 measures anxiety scoring 0-3 points per item, with a total score range 0-21,with a higher score meaning more anxiety.</description>
</primary_outcome>
<primary_outcome>
<measure>Neuro Patients Well-Being using PHQ-8 Scale</measure>
<time_frame>8 weeks per participant</time_frame>
<description>Neuro patients well being will be measured using the Personal Health Questionnaire Depression 8 Item Scale Scale (PHQ 8). The PHQ 8 measures depression scoring 0-3 points per item, with a total score range of 0-24, with the higher score meaning more depression.</description>
</primary_outcome>
<primary_outcome>
<measure>Neuro Patients Well-Being using NeuroQol</measure>
<time_frame>8 weeks per participant</time_frame>
<description>Neuro patients well being will be measured using Neuro-Qol (Neuro Quality of Life) which will be using T scores where the lower values represent worse outcomes.</description>
</primary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">225</enrollment>
<condition>Brain Cancer</condition>
<arm_group>
<arm_group_label>eSNAP & Caregiver Navigator</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>eSNAP intervention plus questionnaires</description>
</arm_group>
<arm_group>
<arm_group_label>Waitlist Control Condition</arm_group_label>
<arm_group_type>No Intervention</arm_group_type>
<description>Participants randomly assigned to the waitlist control condition will only complete questionnaires during the 8-week study period. After the 8 weeks, they will then have access to the eSNAP, including completion of questionnaires and 8 weeks of Caregiver Navigator sessions as needed.</description>
</arm_group>
<intervention>
<intervention_type>Behavioral</intervention_type>
<intervention_name>eSNAP</intervention_name>
<description>eSNAP is a web based tool that quickly collects and organizes social support information entered by Family Caregivers (FCGs) into visualizations of the size, quality, and function of support networks. Visualizations can help FCGs catalogue support resources and present them in a new way, which may make them more salient and remind FCGs of their availability.</description>
<arm_group_label>eSNAP & Caregiver Navigator</arm_group_label>
<other_name>Electronic Social Network Assessment Program</other_name>
</intervention>
<intervention>
<intervention_type>Behavioral</intervention_type>
<intervention_name>Caregiver Navigator</intervention_name>
<description>The Caregiver Navigator will have social work training and will help Family Caregivers (FCGs) identify and leverage informal and formal social support, including enrolling or directing FCGs to services.</description>
<arm_group_label>eSNAP & Caregiver Navigator</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- English-speaking/reading/writing

- Able to complete questionnaires (including by proxy)

- Family Caregivers (FCGs) must self-identify as being a primary FCG of a patient with a
primary brain tumor, secondary (metastatic) brain tumor, or leptomeningeal disease
diagnosis. A primary caregiver is a family member, friend, or other unpaid person who
provides at least some care for a patient at home.

- Patients must be diagnosed with new or recurrent primary brain tumor, a secondary
(metastatic) brain tumor or leptominingeal disease within the last 9 months, receiving
at least some evaluation and/or care at Moffitt (i.e. at least one appointment), have
a prognosis of at least 9 months

Exclusion Criteria:

- Patients may not participate without a consenting FCG, but FCGs may participate
without a consenting patient

- Patients and FCGs who are experiencing acute distress will be excluded from enrollment
and referred directly to social work, per Moffitt policy.
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>21 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Margaret Byrne, PhD</last_name>
<role>Principal Investigator</role>
<affiliation>Moffitt Cancer Center</affiliation>
</overall_official>
<overall_contact>
<last_name>Margaret Byrne, PhD</last_name>
<phone>813-745-5569</phone>
<email>Margaret.Byrne@moffitt.org</email>
</overall_contact>
<location>
<facility>
<name>Moffitt Cancer Center</name>
<address>
<city>Tampa</city>
<state>Florida</state>
<zip>33612</zip>
<country>United States</country>
</address>
</facility>
<status>Recruiting</status>
<contact>
<last_name>Margaret Byrne, PhD</last_name>
<phone>813-745-5569</phone>
<email>Margaret.Byrne@moffitt.org</email>
</contact>
<investigator>
<last_name>Margaret Byrne, PhD</last_name>
<role>Principal Investigator</role>
</investigator>
<investigator>
<last_name>Peter Forsyth, MD</last_name>
<role>Sub-Investigator</role>
</investigator>
</location>
<location_countries>
<country>United States</country>
</location_countries>
<verification_date>June 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>June 16, 2023</last_update_submitted>
<last_update_submitted_qc>June 16, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">June 22, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>Neuro Oncology</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Brain Neoplasms</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>Undecided</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
The purpose of the study is to determine if family caregivers of neuro-oncology patients feel
less burdened by utilizing the Electronic Social Network Assessment Program (eSNAP) + the
Caregiver Navigator.
Inclusion Criteria:
- English-speaking/reading/writing
- Able to complete questionnaires (including by proxy)
- Family Caregivers (FCGs) must self-identify as being a primary FCG of a patient with a
primary brain tumor, secondary (metastatic) brain tumor, or leptomeningeal disease
diagnosis. A primary caregiver is a family member, friend, or other unpaid person who
provides at least some care for a patient at home.
- Patients must be diagnosed with new or recurrent primary brain tumor, a secondary
(metastatic) brain tumor or leptominingeal disease within the last 9 months, receiving
at least some evaluation and/or care at Moffitt (i.e. at least one appointment), have
a prognosis of at least 9 months
Exclusion Criteria:
- Patients may not participate without a consenting FCG, but FCGs may participate
without a consenting patient
- Patients and FCGs who are experiencing acute distress will be excluded from enrollment
and referred directly to social work, per Moffitt policy.
|
NCT0426xxxx/NCT04268992.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04268992</url>
</required_header>
<id_info>
<org_study_id>1-16-02-408-19</org_study_id>
<nct_id>NCT04268992</nct_id>
</id_info>
<brief_title>Effect of Long-term Exercise on Haemostasis and Inflammation in Patients With Coronary Artery Disease</brief_title>
<official_title>Effect of Long-term Exercise on Haemostasis and Inflammation Compared With Standard Care in Patients With Stable Coronary Artery Disease: a Randomised Clinical Trial</official_title>
<sponsors>
<lead_sponsor>
<agency>Aarhus University Hospital</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>National Hospital of the Faroe Islands</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>Aarhus University Hospital</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Introduction: Regular exercise training improves prognosis in patients with coronary artery
disease (CAD). This study investigates whether the beneficial effects of exercise can be
partly explained by favourable changes in haemostasis and inflammation.

Methods: 150 CAD patients are randomised to a supervised long-term exercise program (3
months) or usual care. Blood samples are obtained at baseline, 1.5 months, and 3 months after
randomisation.

Results: The investigators will evaluate platelet turnover and aggregation, coagulation,
fibrinolysis, and inflammatory markers before and after short- and long-term exercise, and
the two randomised groups will be compared.

Perspectives: The present study will increase our knowledge of the beneficial mechanisms
underlying the effect of exercise in CAD patients, potentially paving the way for improved
exercise recommendations.
</textblock>
</brief_summary>
<overall_status>Completed</overall_status>
<start_date type="Actual">July 3, 2020</start_date>
<completion_date type="Actual">January 16, 2023</completion_date>
<primary_completion_date type="Actual">June 4, 2021</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>A randomized controlled trial</intervention_model_description>
<primary_purpose>Treatment</primary_purpose>
<masking>Single (Participant)</masking>
</study_design_info>
<primary_outcome>
<measure>Changes in fibrinolytic biomarkers: tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1).</measure>
<time_frame>3 months</time_frame>
<description>Changes in fibrinolytic biomarkers in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare fibrinolytic biomarkers assessed at baseline and after three months of supervised exercise for every patient.</description>
</primary_outcome>
<primary_outcome>
<measure>Changes in clot maximum absorbance using the clot lysis assay.</measure>
<time_frame>3 months</time_frame>
<description>Changes in maximum absorbance in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare clot maximum absorbance assessed at baseline and after three months of supervised exercise for every patient.</description>
</primary_outcome>
<primary_outcome>
<measure>Changes in clot lysis time using the clot lysis assay.</measure>
<time_frame>3 months</time_frame>
<description>Changes in clot lysis time in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare clot lysis time assessed at baseline and after three months of supervised exercise for every patient.</description>
</primary_outcome>
<primary_outcome>
<measure>Changes in area under the curve using the clot lysis assay.</measure>
<time_frame>3 months</time_frame>
<description>Changes in area under the curve in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare area under the curve assessed at baseline and after three months of supervised exercise for every patient.</description>
</primary_outcome>
<secondary_outcome>
<measure>Changes in platelet aggregation using arachidonic acid (ASPI) as agonist.</measure>
<time_frame>3 months</time_frame>
<description>Changes in platelet aggregation with ASPI as agonist in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare the results assessed at baseline and after three months of supervised exercise for every patient.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Changes in platelet aggregation using adenosine diphosphate (ADP) as agonist.</measure>
<time_frame>3 months</time_frame>
<description>Changes in platelet aggregation with ADP as agonist in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare the results assessed at baseline and after three months of supervised exercise for every patient.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Changes in platelet aggregation using thrombin receptor activating peptide-6 (TRAP) as agonist.</measure>
<time_frame>3 months</time_frame>
<description>Changes in platelet aggregation with TRAP as agonist in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare the results assessed at baseline and after three months of supervised exercise for every patient.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Changes in thrombin generation assessing lag-time until initial thrombin generation.</measure>
<time_frame>3 months</time_frame>
<description>Changes in lag-time until initial thrombin generation in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare the results assessed at baseline and after three months of supervised exercise for every patient.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Changes in thrombin generation assessing maximum concentration of thrombin.</measure>
<time_frame>3 months</time_frame>
<description>Changes in maximum concentration of thrombin in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare the results assessed at baseline and after three months of supervised exercise for every patient.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Changes in thrombin generation assessing time to peak.</measure>
<time_frame>3 months</time_frame>
<description>Changes in time to peak in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare the results assessed at baseline and after three months of supervised exercise for every patient.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Changes in thrombin generation assessing endogenous thrombin potential.</measure>
<time_frame>3 months</time_frame>
<description>Changes in endogenous thrombin potential in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare the results assessed at baseline and after three months of supervised exercise for every patient.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Changes in coagulation biomarkers: APTT, INR, Factor VIII, vWF.</measure>
<time_frame>3 months</time_frame>
<description>Changes in coagulation biomarkers in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare coagulation biomarkers assessed at baseline and after three months of supervised exercise for every patient.</description>
</secondary_outcome>
<secondary_outcome>
<measure>Changes in inflammatory biomarkers: CRP, multiple interleukins, tumor necrosis factor alpha (TNF-α), interferon gamma (INF-γ) and more.</measure>
<time_frame>3 months</time_frame>
<description>Changes in inflammatory biomarkers in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare inflammatory biomarkers assessed at baseline and after three months of supervised exercise for every patient.</description>
</secondary_outcome>
<other_outcome>
<measure>Changes in cardiorespiratory performance: maximal oxygen uptake</measure>
<time_frame>3 months</time_frame>
<description>Changes in maximal oxygen uptake in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group).</description>
</other_outcome>
<other_outcome>
<measure>Changes in cardiorespiratory performance: maximal power output</measure>
<time_frame>3 months</time_frame>
<description>Changes in maximal power output in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group).</description>
</other_outcome>
<other_outcome>
<measure>Changes in physical health and mental health (quality of life) assessed by the SF-36v2 questionnaire.</measure>
<time_frame>3 months</time_frame>
<description>Changes in physical and mental health in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group).</description>
</other_outcome>
<other_outcome>
<measure>Incidence of adverse events associated with the exercise intervention.</measure>
<time_frame>3 months</time_frame>
<description>Number of adverse events (severe, moderate or mild) and training related injuries in coronary artery disease patients who are randomised to long-term exercise.</description>
</other_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Actual">142</enrollment>
<condition>Coronary Artery Disease</condition>
<condition>Exercise</condition>
<condition>Inflammation</condition>
<condition>Hemostasis</condition>
<arm_group>
<arm_group_label>Long-term exercise</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>Supervised exercise training three times a week for three months.</description>
</arm_group>
<arm_group>
<arm_group_label>Usual care</arm_group_label>
<arm_group_type>No Intervention</arm_group_type>
<description>Patients are not offered supervised exercise.</description>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Long-term exercise</intervention_name>
<description>All patients randomised to long-term exercise will perform exercise training at least three times a week for three months. The exercise is supervised and individualised.</description>
<arm_group_label>Long-term exercise</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- Age ≥ 18 years

- Angiographically verified coronary artery disease with stenosis of at least 50% or
previous percutaneous coronary intervention (PCI)/coronary artery bypass graft (CABG)
surgery.

- Diagnosis or revascularisation have been made at least 12 months prior to inclusion.

Exclusion Criteria:

- Inability to perform strenuous exercise

- Anticoagulant treatment

- Heart failure (ejection fraction <30% or NYHA >2)

- Implanted implantable cardioverter defibrillator (ICD) or cardiac resynchronization
therapy (CRT)

- Serious arrhythmia requiring hospitalisation within the last 6 months

- Severe valvular heart disease

- Chronic obstructive pulmonary disease GOLD IV
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<location>
<facility>
<name>National Hospital of the Faroe Islands</name>
<address>
<city>Tórshavn</city>
<zip>100</zip>
<country>Faroe Islands</country>
</address>
</facility>
</location>
<location_countries>
<country>Faroe Islands</country>
</location_countries>
<verification_date>August 2023</verification_date>
<study_first_submitted>February 10, 2020</study_first_submitted>
<study_first_submitted_qc>February 12, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>August 2, 2023</last_update_submitted>
<last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">August 4, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Aarhus University Hospital</investigator_affiliation>
<investigator_full_name>Jacobina Kristiansen</investigator_full_name>
<investigator_title>M.D., PhD-student</investigator_title>
</responsible_party>
<keyword>Cardiovascular Diseases</keyword>
<keyword>Exercise</keyword>
<keyword>Hemostasis</keyword>
<keyword>Inflammation</keyword>
<condition_browse>
<!-- CAUTION: The following MeSH terms are assigned with an imperfect algorithm -->
<mesh_term>Coronary Artery Disease</mesh_term>
<mesh_term>Myocardial Ischemia</mesh_term>
<mesh_term>Coronary Disease</mesh_term>
<mesh_term>Inflammation</mesh_term>
</condition_browse>
<patient_data>
<sharing_ipd>Undecided</sharing_ipd>
</patient_data>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Introduction: Regular exercise training improves prognosis in patients with coronary artery
disease (CAD). This study investigates whether the beneficial effects of exercise can be
partly explained by favourable changes in haemostasis and inflammation.
Methods: 150 CAD patients are randomised to a supervised long-term exercise program (3
months) or usual care. Blood samples are obtained at baseline, 1.5 months, and 3 months after
randomisation.
Results: The investigators will evaluate platelet turnover and aggregation, coagulation,
fibrinolysis, and inflammatory markers before and after short- and long-term exercise, and
the two randomised groups will be compared.
Perspectives: The present study will increase our knowledge of the beneficial mechanisms
underlying the effect of exercise in CAD patients, potentially paving the way for improved
exercise recommendations.
Inclusion Criteria:
- Age ≥ 18 years
- Angiographically verified coronary artery disease with stenosis of at least 50% or
previous percutaneous coronary intervention (PCI)/coronary artery bypass graft (CABG)
surgery.
- Diagnosis or revascularisation have been made at least 12 months prior to inclusion.
Exclusion Criteria:
- Inability to perform strenuous exercise
- Anticoagulant treatment
- Heart failure (ejection fraction <30% or NYHA >2)
- Implanted implantable cardioverter defibrillator (ICD) or cardiac resynchronization
therapy (CRT)
- Serious arrhythmia requiring hospitalisation within the last 6 months
- Severe valvular heart disease
- Chronic obstructive pulmonary disease GOLD IV
|
NCT0426xxxx/NCT04269005.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04269005</url>
</required_header>
<id_info>
<org_study_id>2019-01724; me19Schaefert</org_study_id>
<nct_id>NCT04269005</nct_id>
</id_info>
<brief_title>SomPsyNet - Prevention of Psychosocial Distress Consequences in Somatic Medicine: a Model for Collaborative Care</brief_title>
<acronym>SomPsyNet</acronym>
<official_title>SomPsyNet - Prevention of Psychosocial Distress Consequences in Somatic Medicine: a Model for Collaborative Care</official_title>
<sponsors>
<lead_sponsor>
<agency>University Hospital, Basel, Switzerland</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
<collaborator>
<agency>Gesundheitsförderung Schweiz, GFCH</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>Bethesda Krankenhaus</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>University Department of Geriatric Medicine FELIX PLATTER</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>Gesundheitsdepartement Basel-Stadt</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>Swiss Tropical & Public Health Institute</agency>
<agency_class>Other</agency_class>
</collaborator>
<collaborator>
<agency>Institute of Pharmaceutical Medicine (ECPM), University of Basel</agency>
<agency_class>Other</agency_class>
</collaborator>
</sponsors>
<source>University Hospital, Basel, Switzerland</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
This study is to evaluate the impact of the "stepped and collaborative care model" (SCCM) on
health-related quality of life in somatic hospital patients with psychosocial distress.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
Given the burden of psychosocial distress, the public health relevance, and the current
standard of health care, new approaches to a model of care for patients with mental-somatic
multimorbidity are urgently needed. SomPsyNet is a comprehensive healthcare project for
patients from somatic hospitals that promotes the prevention of psychosocial distress by
establishing a stepped and collaborative care network in Basel-Stadt, Switzerland and may
therefore help to counteract against the described lack of care.

SomPsyNet is a "stepped and collaborative care model" (SCCM) including a
Psychosomatic-psychiatric consultation and liaison Service (CL Service) and post hospital
intervention supported by a collaborative network structure. It aims to identify patients
with psychosocial distress at an early stage during their hospital stay in a standardized
way.

Implementation of the SCCM within this study using the stepped-wedge cluster randomized trial
(SW-CRT) design will take place in phases:

- SomPsyNet phase 0: treatment as usual (TAU) in combination with the baseline and
follow-up survey in a distressed focus sample.

- SomPsyNet phase 1: TAU in combination with the baseline survey, implementation of
screening questions stage 1 ('baseline distress information from professionals', without
consequence) in hospital routine and follow-up survey in a distressed focus sample.

- SomPsyNet phase 2 refers to the implementation of the SCCM: baseline survey, assessment
of screening questions stage 1 (with consequence), screening questions stage 2 (with
consequence) and if necessary psychosomatic-psychiatric consultation and liaison service
including if applicable post hospital intervention and a follow-up survey in a
distressed focus sample.
</textblock>
</detailed_description>
<overall_status>Active, not recruiting</overall_status>
<start_date type="Actual">June 8, 2020</start_date>
<completion_date type="Anticipated">June 30, 2026</completion_date>
<primary_completion_date type="Anticipated">July 31, 2023</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Sequential Assignment</intervention_model>
<primary_purpose>Health Services Research</primary_purpose>
<masking>Single (Outcomes Assessor)</masking>
<masking_description>Hospital employees who will assign patients to the wards and clusters are blinded to randomization. Blinding of staff involved in the recruitment process is limited as phase 1 and phase 2 will consist of different study information and consent sheets. Trained staff will perform the follow-up assessment, and we intend to blind them regarding study phase allocation of the patients (if procedural aspects allow it).</masking_description>
</study_design_info>
<primary_outcome>
<measure>Change in health related quality of life</measure>
<time_frame>Baseline to 6 months follow-up</time_frame>
<description>Health related quality of life will be assessed with the 'Mental Health Component Summary score' of the Short Form-36 (SF-36). The SF-36 consists of 36-Items to measure health-related quality of life using eight concepts (physical functioning (PF, 10 items), physical role functioning (RP, 4 items), bodily pain (BP, 2 items), general health perception (GH, 5 items), vitality (VT, 4 items), social role functioning (SF, 2 items), emotional role functioning (RE, 3 items) and mental health (MH, 5 items) to measure the 'Mental Health Component Summary score'</description>
</primary_outcome>
<secondary_outcome>
<measure>Change in Depression</measure>
<time_frame>Baseline to 6 months follow-up</time_frame>
<description>Current depressive disorders assessed by the eight-item Patient Health Questionnaire depression scale (PHQ-8)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Change in Generalized Anxiety Disorder</measure>
<time_frame>Baseline to 6 months follow-up</time_frame>
<description>Generalized Anxiety Disorder assessed by the 7-item Generalized Anxiety Disorder Scale (GAD-7)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Change in Somatic symptom disorder</measure>
<time_frame>Baseline to 6 months follow-up</time_frame>
<description>Psychological features of Somatic Symptom Disorder (SSD) assessed by the 12-item Somatic Symptom Disorder Scale (SSD-12)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Change in Somatic symptom burden</measure>
<time_frame>Baseline to 6 months follow-up</time_frame>
<description>Somatic symptom severity assessed by the 8-item Somatic Symptom Scale-8 (SSS-8)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Change in Quality of life</measure>
<time_frame>Baseline to 6 months follow-up</time_frame>
<description>"Health-related quality of life assessed by the 5-level EuroQol 5-dimensional questionnaire (EQ-5D- 5L)"</description>
</secondary_outcome>
<secondary_outcome>
<measure>Change in health related quality of life</measure>
<time_frame>Baseline to 6 months follow-up</time_frame>
<description>Health-related quality of life assessed by the Physical Health Component Summary score of the SF-36</description>
</secondary_outcome>
<secondary_outcome>
<measure>Health economics</measure>
<time_frame>6 months to 3 years following initiation of the SCCM in a given patient</time_frame>
<description>total costs of hospital treatment including additional medical, psychiatric or physiotherapeutic treatment during patient's hospital stay; follow-up costs at treating hospitals; healthcare costs, relevant sub-categories of costs and medical resource use based on health insurance claims data; indirect costs due to reduced productivity</description>
</secondary_outcome>
<secondary_outcome>
<measure>Resilience</measure>
<time_frame>6 months follow-up</time_frame>
<description>Resilience assessed by the Resilience Scale for Adults (RSA)</description>
</secondary_outcome>
<secondary_outcome>
<measure>Social support</measure>
<time_frame>6 months follow-up</time_frame>
<description>Social support assessed by the Oslo social support scale (OSSS-3)</description>
</secondary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">2500</enrollment>
<condition>Psychosocial Distress</condition>
<arm_group>
<arm_group_label>Treatment as usual</arm_group_label>
<arm_group_type>No Intervention</arm_group_type>
<description>phase 0: Treatment as usual in combination with baseline and follow-up Survey but without any screening procedures (facilitating the study as a run-in phase to establish study procedures).
phase 1: randomized and main control condition with TAU + collection of information on psychosocial distress in the baseline
Intervention effects will be estimated, using the distressed focus sample, contrasting Phase 2 vs. Phase 1.
We intend to conduct additional statistical analyses to compare data from phases 2 and 1 vs. phase 0 to estimate potential effects of introducing parts of the screening 1 without consequences.</description>
</arm_group>
<arm_group>
<arm_group_label>Intervention condition</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>phase 2: implementation of the SCCM
The intervention (SSCM) will be implemented step-wise in predefined sections at all three sites using a stepped-wedge cluster randomized trial design. Clusters will be randomized to different sequences that dictate the timing at which each cluster will switch from the control to the intervention condition.</description>
</arm_group>
<intervention>
<intervention_type>Other</intervention_type>
<intervention_name>Implementation of the SCCM</intervention_name>
<description>Implementation of the SCCM includes a baseline survey, assessment of screening questions stage 1 (with consequence), screening questions stage 2 (with consequence) and if necessary psychosomatic-psychiatric consultation and liaison service including if applicable post hospital intervention and a follow-up survey in a distressed focus sample.</description>
<arm_group_label>Intervention condition</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- patients from selected wards (i. e., somatic diseases treated at these wards from
three somatic hospitals)

Exclusion Criteria:

- Inability to understand and speak German or any other language at which study is
tailored at that point in time

- Inability to give informed consent by himself / herself

- Inability to follow the procedures of the study, e.g. due to severe medical / clinical
limitations

- Need for immediate support as indicated by the risk of current suicidality or
attempted suicide

- Oncological condition

- Already participated in the SomPsyNet project on the occasion of a previous
hospitalization

- Confirmed current COVID-19 disease at time of screening for exclusion criteria

- Being hospitalized under the medical supervision of services of a ward that is not
part of one of the SomPsyNet study clusters ('original ward'), but physically located
in rooms of a ward contributing to one of the study clusters only because of lack of
space in the original ward
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>N/A</maximum_age>
<healthy_volunteers>No</healthy_volunteers>
</eligibility>
<overall_official>
<last_name>Gunther Meinlschmidt, Prof. Dr. rer. nat.</last_name>
<role>Principal Investigator</role>
<affiliation>Department of Psychosomatic Medicine, University Hospital Basel</affiliation>
</overall_official>
<location>
<facility>
<name>Universitäre Altersmedizin Felix Platter</name>
<address>
<city>Basel</city>
<zip>4002</zip>
<country>Switzerland</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Department of Psychosomatics/ Division of Medicine; University Hospital of Basel</name>
<address>
<city>Basel</city>
<zip>4031</zip>
<country>Switzerland</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Universitätsspital Basel - Frauenklinik</name>
<address>
<city>Basel</city>
<zip>4031</zip>
<country>Switzerland</country>
</address>
</facility>
</location>
<location>
<facility>
<name>Bethesda Spital AG</name>
<address>
<city>Basel</city>
<zip>4052</zip>
<country>Switzerland</country>
</address>
</facility>
</location>
<location_countries>
<country>Switzerland</country>
</location_countries>
<reference>
<citation>Aebi NJ, Caviezel S, Schaefert R, Meinlschmidt G, Schwenkglenks M, Fink G, Riedo L, Leyhe T, Wyss K; SomPsyNet Consortium. A qualitative study to investigate Swiss hospital personnel's perceived importance of and experiences with patient's mental-somatic multimorbidities. BMC Psychiatry. 2021 Jul 12;21(1):349. doi: 10.1186/s12888-021-03353-5.</citation>
<PMID>34253168</PMID>
</reference>
<reference>
<citation>Aebi NJ, Fink G, Wyss K, Schwenkglenks M, Baenteli I, Caviezel S, Studer A, Trost S, Tschudin S, Schaefert R, Meinlschmidt G; SomPsyNet Consortium. Association of Different Restriction Levels With COVID-19-Related Distress and Mental Health in Somatic Inpatients: A Secondary Analysis of Swiss General Hospital Data. Front Psychiatry. 2022 May 3;13:872116. doi: 10.3389/fpsyt.2022.872116. eCollection 2022.</citation>
<PMID>35592378</PMID>
</reference>
<verification_date>June 2023</verification_date>
<study_first_submitted>February 11, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>June 14, 2023</last_update_submitted>
<last_update_submitted_qc>June 14, 2023</last_update_submitted_qc>
<last_update_posted type="Actual">June 18, 2023</last_update_posted>
<responsible_party>
<responsible_party_type>Sponsor</responsible_party_type>
</responsible_party>
<keyword>mental health</keyword>
<keyword>mental disorder</keyword>
<keyword>mental comorbidity</keyword>
<keyword>mental-somatic multimorbidity</keyword>
<keyword>"stepped and collaborative care model" (SCCM)</keyword>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
This study is to evaluate the impact of the "stepped and collaborative care model" (SCCM) on
health-related quality of life in somatic hospital patients with psychosocial distress.
Given the burden of psychosocial distress, the public health relevance, and the current
standard of health care, new approaches to a model of care for patients with mental-somatic
multimorbidity are urgently needed. SomPsyNet is a comprehensive healthcare project for
patients from somatic hospitals that promotes the prevention of psychosocial distress by
establishing a stepped and collaborative care network in Basel-Stadt, Switzerland and may
therefore help to counteract against the described lack of care.
SomPsyNet is a "stepped and collaborative care model" (SCCM) including a
Psychosomatic-psychiatric consultation and liaison Service (CL Service) and post hospital
intervention supported by a collaborative network structure. It aims to identify patients
with psychosocial distress at an early stage during their hospital stay in a standardized
way.
Implementation of the SCCM within this study using the stepped-wedge cluster randomized trial
(SW-CRT) design will take place in phases:
- SomPsyNet phase 0: treatment as usual (TAU) in combination with the baseline and
follow-up survey in a distressed focus sample.
- SomPsyNet phase 1: TAU in combination with the baseline survey, implementation of
screening questions stage 1 ('baseline distress information from professionals', without
consequence) in hospital routine and follow-up survey in a distressed focus sample.
- SomPsyNet phase 2 refers to the implementation of the SCCM: baseline survey, assessment
of screening questions stage 1 (with consequence), screening questions stage 2 (with
consequence) and if necessary psychosomatic-psychiatric consultation and liaison service
including if applicable post hospital intervention and a follow-up survey in a
distressed focus sample.
Inclusion Criteria:
- patients from selected wards (i. e., somatic diseases treated at these wards from
three somatic hospitals)
Exclusion Criteria:
- Inability to understand and speak German or any other language at which study is
tailored at that point in time
- Inability to give informed consent by himself / herself
- Inability to follow the procedures of the study, e.g. due to severe medical / clinical
limitations
- Need for immediate support as indicated by the risk of current suicidality or
attempted suicide
- Oncological condition
- Already participated in the SomPsyNet project on the occasion of a previous
hospitalization
- Confirmed current COVID-19 disease at time of screening for exclusion criteria
- Being hospitalized under the medical supervision of services of a ward that is not
part of one of the SomPsyNet study clusters ('original ward'), but physically located
in rooms of a ward contributing to one of the study clusters only because of lack of
space in the original ward
|
NCT0426xxxx/NCT04269018.xml | <clinical_study>
<!-- This xml conforms to an XML Schema at:
https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
<required_header>
<download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
<link_text>Link to the current ClinicalTrials.gov record.</link_text>
<url>https://clinicaltrials.gov/ct2/show/NCT04269018</url>
</required_header>
<id_info>
<org_study_id>24</org_study_id>
<nct_id>NCT04269018</nct_id>
</id_info>
<brief_title>The Effect of Mobile Text Message on Behavioral Risks of Cancer: A Randomized Controlled Trial</brief_title>
<official_title>The Effect of Mobile Text Message on Behavioral Risks of Cancer Among College Students, Northeast Ethiopia: A Randomized Controlled Trial</official_title>
<sponsors>
<lead_sponsor>
<agency>Wollo University</agency>
<agency_class>Other</agency_class>
</lead_sponsor>
</sponsors>
<source>Wollo University</source>
<oversight_info>
<has_dmc>No</has_dmc>
<is_fda_regulated_drug>No</is_fda_regulated_drug>
<is_fda_regulated_device>No</is_fda_regulated_device>
</oversight_info>
<brief_summary>
<textblock>
Summary Background: Cancer is a public health problem in Ethiopia. A third of cancer deaths
are preventable. Its effects can be significantly reduced if effective interventions are put
in place to control risk factors. Text-messaging has been currently targeted as a simple tool
for providing people with health information. Thus this study aimed to measure the
effectiveness of text message in behavioral risk factors that is helpful to raise cancer
awareness and promote cancer prevention and control in this country.

Methods: A randomized control trial will be used to measure the effectiveness of mobile text
message in behavioral risk factor of cancer among Governmental Collage students in Dessie
City and utilize quantitative method of data collection. Data will be collected on a total of
80 intervention and 80 controls using structured questionnaire. Socio-demographic, health
belief variables and behavioral risk factor of cancer will be collected before and after
intervention. Text message will be provided based on health belief model. Data will be
entered using Epidata version 3.1 and will be exported to STATA version 13.0 for cleaning and
analysis. Liner regression will be applied to identify predictors of behavioral risk factor
of cancer. Student's paired samples t-test will be used to test changes in terms of HBM
variables and behavioural outcomes. Analysis of Covariance will be used to test over group
comparison.
</textblock>
</brief_summary>
<detailed_description>
<textblock>
The study will be a single blind randomized controlled trial, which utilize quantitative
method of data collection. College students who will receive a mobile text message about the
behavioral risks of cancer and prevention mechanism will be considered as intervention groups
while controls will be those who receive a text message related with general health once a
week. A total of 160 (80 interventions and 80 controls) students will be included in the
study using simple random sampling technique. After the baseline assessment, participants
will be randomized to either usual care (control) or the text message intervention group in a
uniform 1:1 (control: intervention) allocation ratio, using computer-based randomization
service.

Self-administered questionnaire will be used to assess baseline and end line data of
behavioral risk factors and other variables. Participants in the control group will receive
an initial text message welcoming them to the study, but they will not receive the text
message support program. The intervention group will receive a text message support program,
where they will receive seven messages per week at random times and days for two months. The
text message will be prepared and delivered based on health belief model (HBM), the items of
this subscale will be measured on a Likert scale ranging from 1= "Strongly disagree" to 5 =
"Strongly agree". Tobacco use, harmful use of alcohol, unhealthy diet and physical inactivity
with a series of items will be used to measure the behavioral outcomes the items in this
subscale will be measured on a Likert scale.

Validity of the items will be measured by an expert panel of specialists in health education
and nutrition. They will judge about the necessity and relevance of the scale items. To
control the data quality all data collectors will be trained for two days. Supervisors will
monitor data collection process and the principal investigator will visit frequently. The
questionnaire will be first prepared in English language and translated to Amharic and again
re-translated in to English by another person to check for consistency. About 10% of the
questionnaire will be pretested and internal consistency will be checked. Completeness of the
collected data will be checked during data collection.

The data will be checked for completeness and consistency, then categorized, coded and
entered using Epidata version 3.1 to minimize error. Then, the clean data will be exported to
Stata version 14 for analysis. Normality of the data will be checked through
Kolmogorov-Smirnov test. Student's paired samples t-test will be used to test within-group
changes in terms of health belief model (HBM) variables and behavioral outcomes. The analysis
of Covariance will be used to make over-group comparisons. Data will be reported as mean ±
standard deviation. The significance level for all of the results will be presented at the
P<0.05 level.
</textblock>
</detailed_description>
<overall_status>Unknown status</overall_status>
<last_known_status>Not yet recruiting</last_known_status>
<start_date type="Anticipated">March 1, 2020</start_date>
<completion_date type="Anticipated">May 15, 2020</completion_date>
<primary_completion_date type="Anticipated">April 30, 2020</primary_completion_date>
<phase>N/A</phase>
<study_type>Interventional</study_type>
<has_expanded_access>No</has_expanded_access>
<study_design_info>
<allocation>Randomized</allocation>
<intervention_model>Parallel Assignment</intervention_model>
<intervention_model_description>Participants will be randomly assigned to intervention and control group, the intervention group will be received daily text message while the controls will receive general health messages once a week.</intervention_model_description>
<primary_purpose>Prevention</primary_purpose>
<masking>Single (Participant)</masking>
<masking_description>To maintain blinding, randomization will occur after the baseline assessment and both groups will receive welcome message for participating in the study. Then motivational and general healthy related texts will be delivered to controls one times per week.</masking_description>
</study_design_info>
<primary_outcome>
<measure>Physical activity level</measure>
<time_frame>on average 6 months</time_frame>
<description>For measuring physical activity International Physical Activity Questionnaires (IPAQ) will be used. The questions will ask the time study participants spent being physically active in the last 7 days. Then, it will be summarized as Metabolic Equivalents (METs).</description>
</primary_outcome>
<primary_outcome>
<measure>Health dietary score</measure>
<time_frame>on average 6 months</time_frame>
<description>Healthy diet score will be assessed the health diet score adapted from the WHO list of healthy diet foods, which is a Likert scale ranged from 1 to 6.</description>
</primary_outcome>
<primary_outcome>
<measure>Tobacco use</measure>
<time_frame>on average 6 months</time_frame>
<description>Tobacco smoking will be assessed using a series of questions adopted from the World Health Organization (WHO), which used to assess the duration, quantity and frequency of smoking within one month.</description>
</primary_outcome>
<primary_outcome>
<measure>Alcohol intake</measure>
<time_frame>on average 6 months</time_frame>
<description>Alcohol consumption will be assessed using a tool adopted from National Institute on Alcohol Abuse and Alcoholism (NIAAA), which used to assess participants consumption in the past 1 month.</description>
</primary_outcome>
<primary_outcome>
<measure>Risk perception</measure>
<time_frame>on average 6 months</time_frame>
<description>Risk perception will be measured using health belief model variables: perceived susceptibility towards cancer, perceived severity of cancer, perceived benefits of adopting behaviors, perceived barriers to adopting behaviors, perceived self-efficacy for adopting dietary behaviors and internal cues for adopting dietary behaviors, the items of this subscale will be measured on a Likert scale ranging from 1= "Strongly disagree" to 5 = "Strongly agree".</description>
</primary_outcome>
<number_of_arms>2</number_of_arms>
<enrollment type="Anticipated">160</enrollment>
<condition>Behavioral Risks of Cancer</condition>
<arm_group>
<arm_group_label>Cancer specific Mobile text message</arm_group_label>
<arm_group_type>Experimental</arm_group_type>
<description>This arm will receive daily mobile text message related with cancer risks and prevention</description>
</arm_group>
<arm_group>
<arm_group_label>general health messages</arm_group_label>
<arm_group_type>Active Comparator</arm_group_type>
<description>This arm will receive general health message once a week</description>
</arm_group>
<intervention>
<intervention_type>Behavioral</intervention_type>
<intervention_name>Cancer specific Mobile text message</intervention_name>
<description>The intervention is cancer specific lifestyle mobile text messages daily for 2 months</description>
<arm_group_label>Cancer specific Mobile text message</arm_group_label>
</intervention>
<intervention>
<intervention_type>Behavioral</intervention_type>
<intervention_name>General health messages</intervention_name>
<description>Daily text related with general health message</description>
<arm_group_label>general health messages</arm_group_label>
</intervention>
<eligibility>
<criteria>
<textblock>
Inclusion Criteria:

- College students aged 18 to 35

Exclusion Criteria:

- Mental and physical disability, those who already have diagnosed cancer
</textblock>
</criteria>
<gender>All</gender>
<minimum_age>18 Years</minimum_age>
<maximum_age>35 Years</maximum_age>
<healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
</eligibility>
<overall_contact>
<last_name>Foziya Hussien, MPH</last_name>
<phone>+251913714985</phone>
<email>foziyamohammed2018@gmail.com</email>
</overall_contact>
<verification_date>February 2020</verification_date>
<study_first_submitted>February 9, 2020</study_first_submitted>
<study_first_submitted_qc>February 11, 2020</study_first_submitted_qc>
<study_first_posted type="Actual">February 13, 2020</study_first_posted>
<last_update_submitted>February 19, 2020</last_update_submitted>
<last_update_submitted_qc>February 19, 2020</last_update_submitted_qc>
<last_update_posted type="Actual">February 21, 2020</last_update_posted>
<responsible_party>
<responsible_party_type>Principal Investigator</responsible_party_type>
<investigator_affiliation>Wollo University</investigator_affiliation>
<investigator_full_name>Foziya Mohammed Hussien</investigator_full_name>
<investigator_title>lecturer</investigator_title>
</responsible_party>
<!-- Results have not yet been posted for this study -->
</clinical_study>
|
Summary Background: Cancer is a public health problem in Ethiopia. A third of cancer deaths
are preventable. Its effects can be significantly reduced if effective interventions are put
in place to control risk factors. Text-messaging has been currently targeted as a simple tool
for providing people with health information. Thus this study aimed to measure the
effectiveness of text message in behavioral risk factors that is helpful to raise cancer
awareness and promote cancer prevention and control in this country.
Methods: A randomized control trial will be used to measure the effectiveness of mobile text
message in behavioral risk factor of cancer among Governmental Collage students in Dessie
City and utilize quantitative method of data collection. Data will be collected on a total of
80 intervention and 80 controls using structured questionnaire. Socio-demographic, health
belief variables and behavioral risk factor of cancer will be collected before and after
intervention. Text message will be provided based on health belief model. Data will be
entered using Epidata version 3.1 and will be exported to STATA version 13.0 for cleaning and
analysis. Liner regression will be applied to identify predictors of behavioral risk factor
of cancer. Student's paired samples t-test will be used to test changes in terms of HBM
variables and behavioural outcomes. Analysis of Covariance will be used to test over group
comparison.
The study will be a single blind randomized controlled trial, which utilize quantitative
method of data collection. College students who will receive a mobile text message about the
behavioral risks of cancer and prevention mechanism will be considered as intervention groups
while controls will be those who receive a text message related with general health once a
week. A total of 160 (80 interventions and 80 controls) students will be included in the
study using simple random sampling technique. After the baseline assessment, participants
will be randomized to either usual care (control) or the text message intervention group in a
uniform 1:1 (control: intervention) allocation ratio, using computer-based randomization
service.
Self-administered questionnaire will be used to assess baseline and end line data of
behavioral risk factors and other variables. Participants in the control group will receive
an initial text message welcoming them to the study, but they will not receive the text
message support program. The intervention group will receive a text message support program,
where they will receive seven messages per week at random times and days for two months. The
text message will be prepared and delivered based on health belief model (HBM), the items of
this subscale will be measured on a Likert scale ranging from 1= "Strongly disagree" to 5 =
"Strongly agree". Tobacco use, harmful use of alcohol, unhealthy diet and physical inactivity
with a series of items will be used to measure the behavioral outcomes the items in this
subscale will be measured on a Likert scale.
Validity of the items will be measured by an expert panel of specialists in health education
and nutrition. They will judge about the necessity and relevance of the scale items. To
control the data quality all data collectors will be trained for two days. Supervisors will
monitor data collection process and the principal investigator will visit frequently. The
questionnaire will be first prepared in English language and translated to Amharic and again
re-translated in to English by another person to check for consistency. About 10% of the
questionnaire will be pretested and internal consistency will be checked. Completeness of the
collected data will be checked during data collection.
The data will be checked for completeness and consistency, then categorized, coded and
entered using Epidata version 3.1 to minimize error. Then, the clean data will be exported to
Stata version 14 for analysis. Normality of the data will be checked through
Kolmogorov-Smirnov test. Student's paired samples t-test will be used to test within-group
changes in terms of health belief model (HBM) variables and behavioral outcomes. The analysis
of Covariance will be used to make over-group comparisons. Data will be reported as mean ±
standard deviation. The significance level for all of the results will be presented at the
P<0.05 level.
Inclusion Criteria:
- College students aged 18 to 35
Exclusion Criteria:
- Mental and physical disability, those who already have diagnosed cancer
|