Stromal Vascular Fraction for Treatment of Xerostomia

Study Overview
=================
Brief Summary
-----------------
Prospective, single center, double armed, randomized treatment with observation only (standard of care) control group. Subjects receiving study treatment will have 6 months of study follow-up. Stromal vascular fraction (SVF), an adipose-derived tissue preparation, will be injected into salivary glands to determine safety and efficacy to restore saliva production in head and neck cancer patients with chronic xerostomia resulting from radiation therapy.

Official Title
-----------------
Evaluation of the Use of the Tissue Genesis® Icellator Cell Isolation System® (Icellator) Autologous Adipose Stromal Vascular Fraction Cells as a Treatment for Post-Irradiated Induced Xerostomia in Head and Neck Cancer Patients

Conditions
-----------------
Xerostomia Due to Radiotherapy (Disorder)

Intervention / Treatment
-----------------
* Biological: Stromal Vascular Fraction
* Other: Usual Care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and Female subjects are both eligible Subjects must be 21 years of age or older History of treated Head and Neck Cancer, no evidence of active cancer at the time of the study Original tumor not located adjacent to the parotid or sub-mandibular glands Diagnosis of radiation-induced xerostomia study is fully explained Females of child bearing potential agree to use acceptable methods of contraception through 6 month study follow-up. No current malignancy or history of previous malignancy within the last five years, other than the head and neck cancer, with the exception of adequately treated non-abdominal, non-melanoma cutaneous carcinoma (basal cell or squamous cell carcinoma of the skin) Willing to undergo a minor surgical procedure (small-volume liposuction, totaling approximately 60-120cc) and a single treatment of an injection of approximately 30ml of autologous Stromal Vascular Fraction taking approximately 10 minutes Abdominal area amenable to liposuction of at least 60-120cc of adipose tissue based on Investigator(s) examination Willing to be available for all baseline, treatment and follow-up examinations required by protocol Willing to forego participation in any other study throughout the duration of this study unless receiving prior approval by Investigator Exclusion Criteria: Patients taking immunosuppressive therapy in the prior 3 months Autoimmune disorders Patients who are pregnant or currently breast-feeding children Patients participating in a study of an experimental drug or medical device within 60 days of study entry Uncontrolled hypertension Reported unstable cardiovascular disease (e.g., unstable angina, myocardial infarction within past 6 months, cardiac failure or life-threatening arrhythmia, congestive heart failure) or symptomatic postural hypotension within 6 months before screening Hemoglobin A1c > 8% within 8 weeks prior to study treatment Current use of steroids or immunosuppressant therapies Any other condition, which, in the opinion of the Investigator, would contraindicate treatment, affect compliance, interfere with study evaluations, limit study participation, or confound the interpretation of study results History of Sjogren's Syndrome or related autoimmune disease. Taking medication for which xerostomia is a known major side effect

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomly assigned to usual care (palliation of symptoms) or injection of stromal vascular fraction.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Usual Care<br>Subjects in the Usual Care arm will receive typical therapies to manage the symptoms of dry mouth including but not limited to: chewing gum, sucking sugar-free candy, sipping water, mouth rinses and over-the-counter artificial saliva preparations. | Other: Usual Care<br>* Usual care will include over-the-counter and prescription methods to treat xerostomia.<br>* Other names: Standard of Care;|
| Experimental: Stromal Vascular Fraction<br>Subjects in the Stromal Vascular Fraction arm will receive single injections into each of the six (6) peri-oral salivary glands (parotid, submandibular, sublingual). | Biological: Stromal Vascular Fraction<br>* Stromal Vascular Fraction will be produced from the subject's own adipose tissue by the Tissue Genesis Icellator device.<br>* Other names: Adipose-Derived Stem Cells;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Safety Profile (Reported Adverse Events graded according to CTCAE guidelines) | Reported Adverse Events graded according to CTCAE guidelines will be recorded starting at or after the time of injection and at or before 72 hours post injection. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic Safety Profile (Reported Adverse Events graded according to Common Terminology Criteria for Adverse Events (CTCAE) guidelines) | Reported Adverse Events graded according to Common Terminology Criteria for Adverse Events (CTCAE) guidelines will be recorded starting on Day 0 (day of SVF injection) and ending at 12 months. | Months 3, 6 and 12 after Day 0 (date of injection) | 
| Unstimulated Saliva Production | Rate of saliva production over a 5-minute period. (g/minute) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| Stimulated Saliva Production | Rate of saliva production while chewing gum over a 5-minute period. (g/minute) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire- How severe is your dry mouth problem? | Mean score calculated from patient-reported survey (Likert Scale; 1 = Normal; 2 = somewhat more complaints than before radiation therapy; 3 = considerable more complaints than before radiation therapy; and 4 = Permanent complaints of a very dry mouth) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Under which circumstances does the dry mouth problem occur? (In the open air) | Incidence of each indication calculated from categorical patient-reported survey (Yes, No, Not Applicable) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Under which circumstances does the dry mouth problem occur? (In the open air in case of wind and cold) | Incidence of each indication calculated from categorical patient-reported survey (Yes, No, Not Applicable) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Under which circumstances does the dry mouth problem occur? (In air-conditioned spaces) | Incidence of each indication calculated from categorical patient-reported survey (Yes, No, Not Applicable) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Under which circumstances does the dry mouth problem occur? (Especially dry mouth during daytime) | Incidence of each indication calculated from categorical patient-reported survey (Yes, No, Not Applicable) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Under which circumstances does the dry mouth problem occur? (Especially dry mouth at nighttime) | Incidence of each indication calculated from categorical patient-reported survey (Yes, No, Not Applicable) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Under which circumstances does the dry mouth problem occur? (Always dry mouth night and day) | Incidence of each indication calculated from categorical patient-reported survey (Yes, No, Not Applicable) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Under which circumstances does the dry mouth problem occur? (Especially bother of the dry mouth during meals) | Incidence of each indication calculated from categorical patient-reported survey (Yes, No, Not Applicable) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire- How often do you wake up at night because of a dry mouth? | Number of events as reported by patient (Number) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - How would you describe the quality of your saliva? | Mean score calculated from patient-reported survey (Likert Scale; 1 = Normal, watery fluid; 2 = Normal watery but too little volume; 3 = Sticky saliva; and 4 = No saliva at all) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Do you have difficulties with speech because of the dry mouth? | Mean score calculated from patient-reported survey (Likert Scale; 1 = No problems; unchanged with respect to situation before radiation therapy; 2 = Occasionally some difficulty with speech; 3 = Frequently speech problems; 4 = always difficulties with speech; and 5= always major speech problems) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Do you need to sip water to facilitate speech? | Mean score calculated from patient-reported survey (Likert Scale; 1 = Never; 2 = Occasionally; 3 = Frequently; 4 = Always; and 5= Even have to interrupt speaking to take a sip of water) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Is swallowing changed because of the dry mouth problem? | Mean score calculated from patient-reported survey (Likert Scale; 1 = No problems; unchanged with respect to situation before radiation therapy; 2 = Occasionally some difficulty with swallowing; 3 = Frequently problems with swallowing; 4 = Always swallowing difficulties; and 5 = Swallowing is seriously impaired because of the dry mouth problem) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Has the dry mouth a negative influence on chewing? | Mean score calculated from patient-reported survey (Likert Scale; 1 = No change in chewing capability; 2 = Some difficulty with chewing; 3 = Frequently difficulties with chewing; 4 = Always difficulties with chewing; 5 = Chewing is seriously hampered because of the dry mouth problem) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Do you need to sip water to facilitate eating? | Mean score calculated from patient-reported survey (Likert Scale; 1 = No never; 2 = Sometimes, depending on the quality of the food; 3 = Frequently; more often than before radiation therapy; and 4 = Always need to take a sip of water/ fluid with every bite of food) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Did you change your feeding habits? | Mean score calculated from patient-reported survey (Likert Scale; 1 = No change; 2 = Minor changes, such as avoiding some products; 3 = Can eat only mashed food; 4 = Can eat only liquid food; and 5= Tube feeding) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Do you have painful, dry, or crusted lips? | Mean score calculated from patient-reported survey (Likert Scale; 1 = Never; 2 = Sometimes, depending on the weather and environmental circumstances; 3 = Frequently; and 4 = Always, day and night) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Do you need to carry a bottle of fluid with you when leaving home? | Mean score calculated from patient-reported survey (Likert Scale; 1 = Never 2 = Occasionally; 3 = Frequently; 4 = Very often; and 5 = Always) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Do you have a sore or painful mouth? | Mean score calculated from patient-reported survey (Likert Scale; 1 = Never 2 = Occasionally; 3 = Frequently; 4 = Very often; and 5 = Always) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Did your taste change? | Mean score calculated from patient-reported survey (Likert Scale; 1 = No change; normal taste sensation; 2 = Some reduction in taste discrimination and sensation; 3 = Considerable change in taste; 4 = No taste sensation at all; and 5 = Always a bad taste in the mouth) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Do you often have an infected oral mucosa or irritated gums? | Incidence of each indication calculated from categorical patient-reported survey (Yes, No, Not Applicable) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Did your teeth deteriorate after radiation therapy? | Mean score calculated from patient-reported survey (Likert Scale; 1 = never; 2 = Occasionally; 3 = Frequently; and 4 = Very often) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Rotterdam Hospital Xerostomia Questionnaire - Overall Xerostomia Index | Overall Xerostomia Index is calculated from the first three questions of the Questionnaire [I = (Q1 x 15.8) + (Q2 x 8.5) + (Q3 x 5.9) - 33.2; where Qn = score of that question.] | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Michigan Xerostomia-Related Quality of Life Scale - Physical Functioning | Mean score calculated from patient-reported survey (Likert Scale; 0=Best Functioning to 4=Worst Functioning) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Michigan Xerostomia-Related Quality of Life Scale - Pain/Discomfort | Mean score calculated from patient-reported survey (Likert Scale; 0=No Pain to 4=Worst Pain) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Michigan Xerostomia-Related Quality of Life Scale - Personal/Psychological Functioning | Mean score calculated from patient-reported survey (Likert Scale; 0=Best Functioning to 4=Worst Functioning) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| University of Michigan Xerostomia-Related Quality of Life Scale - Social Functioning | Mean score between Baseline and 3 months calculated from patient-reported survey (Likert Scale; 0=Best Functioning to 4=Worst Functioning) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline | 
| Late Effects Normal Tissue-Subjective Objective Management Analytica (LENT-SOMA) survey | Mean score calculated from patient-reported survey (Likert Scale; 1=Best Functioning to 4=Worst Functioning) | Assessed at Baseline and 3 months, 6 months and 12 months after Baseline |