cyrilzakka/clinical-trials huggingface dataset:
Sequential CAR-T Cells Targeting CD33/CD123 in Patients With Acute Myelocytic Leukemia AML

This is an open, single-arm, clinical study to evaluate the efficacy and safety of chimeric antigen receptor T cell immunotherapy (CAR-T) targeting CD33 or CD123 or both sequentially in the treatment of Acute Myelocytic Leukemia.

Chimeric antigen receptor (CAR)-modified T cells targeted against CD19 have demonstrated unprecedented successes in treating patients with hematopoietic and lymphoid malignancies. Besides CD19, many other molecules such as CD22, CD30,BCMA,CD123, etc. may have the potential to develop the corresponding CAR-T cells to treat patients whose tumors express those markers. In this study, investigators will evaluate the safety and efficacy of CAR-T targeting CD33/CD123 in patients with Acute Myelocytic Leukemia. The primary goal is safety assessment including cytokine storm response and any other adverse effects. In addition, disease status after treatment will also be evaluated.

The purpose of this clinical trial is to assess the feasibility, safety, and efficacy of multiple CAR T-cell therapy which combines CAR T cells against AML Cells with CAR T cells targeting CD123 or CD33 in patients with relapsed and refractory AML. The study also aims to learn more about the function of CAR T cells and their persistence in AML patients.

Eligibility Criteria:
Inclusion Criteria:

* Subjects with acute myeloid leukemia who voluntarily signed informed consent and met the following criteria:
* Age older than 6 months.
* Confirmed expression of CLL-1, CD123 and/or CD33 in blast AML by immuno-histochemical staining or flow cytometry.
* Karnofsky performance status (KPS) score is higher than 80 and life expectancy \> 3 months.
* Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: cardiac ejection fraction ≥ 50%, oxygen saturation ≥ 90%, creatinine ≤ 2.5 × upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal, total bilirubin ≤ 2.0mg/dL.
* Hgb≥80g/L.
* No cell separation contraindications.
* Abilities to understand and the willingness to provide written informed consent.

Exclusion Criteria:

* Severe illness or medical condition, which would not permit the patient to be managed according to the protocol, including active uncontrolled infection.
* Active bacterial, fungal or viral infection not controlled by adequate treatment.
* Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
* Pregnant or nursing women may not participate.
* Use of glucocorticoid for systemic therapy within one week prior to entering the trial.
* Patients, in the opinion of investigators, may not be able to comply with the study.
Applying an Osteopathic Intervention to Improve Mental Health Symptoms: a Mixed-methods Feasibility Study Protocol.

Applying an osteopathic intervention to improve mild to moderate mental health symptoms: a mixed-methods feasibility study protocol.

Introduction: Mental health services are stretched in the UK and in need of support. One approach that could improve mental health symptoms is osteopathy. Research suggests that osteopathy influences psychophysiological factors, which could lead to improvements in mental health. The first objective of this protocol is to investigate the feasibility and acceptability of four osteopathic interventions. A secondary aim is to evaluate the interventions' effectiveness in improving psychophysiological and mental health outcomes.

Methods and analysis: This study will be an explanatory mixed-methods design. Participants will be 30 adults who have mild to moderate mental health symptoms and not experiencing any issues with pain. The feasibility and acceptability of the interventions will be the first primary outcome. Secondary outcomes will be physiological measures including heart rate variability (HRV), interoceptive accuracy (IAc) and blood pressure (BP). Psychological outcomes will also be measured by standardised questionnaires. These are being collected pre-and post-intervention. Additional outcomes will include recruitment rates and any adverse events that occur during the study. Participants will be randomised to one of four interventions. These are: high-velocity and articulation techniques (HVAT), soft-tissue massage (STM), craniosacral therapy (CST), and a combination of these three approaches. Participants will be interviewed about their experiences of the study and interventions to aid in assessing the feasibility and acceptability.

Discussion: This study will assess the feasibility and acceptability of conducting osteopathic interventions for improving mental health outcomes. These results from this will help to inform the running of a future randomised controlled trial. The study will also be producing original data which could provide preliminary evidence whether osteopathic approaches are of benefit to individual's mental health, even if they are pain-free.

Eligibility Criteria:
Inclusion Criteria:

* Mild to moderate mental health symptoms as measured by DASS
* Ability to read/write English.

Exclusion Criteria:

* No mental health symptoms or severe mental health symptoms (as measured by DASS)
* acute or chronic pain
Home Rehabilitation Improves Cardiac Effort in Pulmonary Arterial Hypertension

The purpose of this study is to evaluate whether a home rehabilitation program for patients diagnosed with Pulmonary Arterial Hypertension (PAH) will decrease Cardiac Effort (number of heart beats used during 6-minute walk test/walk distance) and improve quality of life. Ultimately, this information could help improve the management of patients with PAH.


Eligibility Criteria:
Inclusion Criteria:

* Follows at University of Rochester Medical Center Pulmonary Hypertension Clinic.
* Adult patients (\&gt;18 years old) with right heart catheterization confirmed pulmonary hypertension (PAH) on stable vasodilator dosing for at least 30 days. No planned titrations will occur during the 12-week study. If during the study, the treating physician feels it is necessary for safety reasons to adjust dosing, the subject will remain in their assigned group.
* Access to a smart phone or email to receive daily messages. If patients do not have access to either, we will offer a smartphone with cellular service for use during the study to receive daily messages.
* Clinically stable by the investigator (i.e., we will not enroll patients who endorse ongoing improvement or clinical worsening at enrollment).
* The treating investigator (Dr. Lachant or Dr. White) will review the clinical data of an eligible patient and establish them as safe to participate prior to approaching the patient for enrollment (i.e. not in decompensated heart failure or with recurrent pre-syncopal episodes prior to enrollment).

Exclusion Criteria:

* Pregnancy.
* Pulmonary Hypertension Groups 2-5.
* Resting tachycardia \&gt;120 beats/m during screening.
* Inability to walk.
* WHO Functional Class IV
* Lack of access to email or text messaging.
* Inability to follow daily instructions. including the two home 6-minute walk tests during the initial monitoring period. This is to show compliance with the protocol.
* Participating in a self-reported rehabilitation or exercise program.
* Oxygen therapy of more than 6 L/min at rest.
* Principal Investigator discretion
Clinical Pharmacology of 35/4 NEXThaler® in Children 5-11 Years Old

The study will be conducted in asthmatic children aged 5 to 11 years and is based on a single-dose, open-label, randomized, 2-way cross-over design where a Dry Powder Inhaler (DPI) fixed combination of beclometasone dipropionate (BDP) 35 μg plus formoterol fumarate (FF) 4 μg is compared with the free combination of licensed BDP DPI and FF DPI

This is a pharmacokinetic comparison of NEXThaler 35/4 μg versus the free combination of Beclomethasone DPI and Formoterol DPI in children (5 to 11 years old) of a formulation already approved in adults.

Eligibility Criteria:
Inclusion Criteria:

* Male/female children with asthma stable enough, according to paediatrician opinion, to allow a wash out period from steroids of 3 days before study treatments.
* Male/female children with asthma on regular treatment with ICS or using short-acting inhaled 2-agonist as reliever to control asthma symptoms.
* Age ≥ 5 \< 12 years (8 to 10 children in the age range 5-8 years old).
* Children with a forced expiratory volume in one second (FEV1)\>70% of predicted values (% pred) after withholding 2-agonists treatment for a minimum of 4 h prior to screening and to each study treatment.
* A cooperative attitude and ability to be trained about the proper use of DPI, ability to use correctly the medical devices and compliant to study procedures

Exclusion Criteria:

* Past or present diagnosis of cardiovascular, renal or liver disease.
* Known hypersensitivity to the active treatmen
* Exacerbation of asthma symptoms within 4 weeks prior to screening.
* Inability to perform the required breathing technique and blood sampling.
* Hospitalization due to exacerbation of asthma within 1 month prior to screening (Visit 1).
* Lower respiratory tract infection within 1 month prior to screening (Visit 1).
* Disease (other than asthma) which might influence the outcome of the study.
* Obesity, i.e. \> 97% weight percentile by local standards
Long-Term Behavioral and Cognitive Outcomes of Deep Brain Stimulation in Patients With Parkinson's Disease

The goal of this observational study is to evaluate the long-term effect of DBS-STN on cognitive and behavioral outcomes in Parkinson's disease (PD) patients.

PD patients will be assessed over time using tests, questionnaires and standardized clinical scales. An initial assessment (T0) and annual follow-up assessments will be carried out for 5 years.

Researchers will compare data collected from patients with DBS versus patients with best medical therapy.


Eligibility Criteria:
Inclusion Criteria:

* Parkinson's disease patients candidates for DBS of the subthalamic nucleus
* Parkinson's disease patients with best medical treatment

Exclusion Criteria:

* patients unable to complete study assessments
Evaluation of a Nutritional Technology for Vitamin D Absorption

This is a prospective, 2-group crossover, randomized, double-blind study to evaluate nutrient absorption.


Eligibility Criteria:
Inclusion Criteria:

* Adult participants (18-55 years of age)
* Body mass index (BMI) \<30 kg/m2
* Males and nonpregnant, nonlactating females
* Free of gastrointestinal disorders that my impact nutrient absorption in the small intestine, endocrine, hepatic, renal, or bone diseases

Exclusion Criteria:

* Use of vitamin D or calcium supplements within 3 weeks prior to the Screening Visit.
* Use of a tanning booth/lamp within 3 weeks prior to the Screening Visit.
* Travel to sunny location within 3 weeks prior to the Screening Visit.
* Consumption of more than 3 alcoholic drinks per day starting 48 hours before the Screening Visit.
* Has an allergy or intolerance to any ingredient in the study product.
* Participating in another study that has not been approved as a concomitant study by Abbott Nutrition.
* Use of the following medications that may have interactions with vitamin D absorption or metabolism:

  * Aluminum-containing phosphate binders
  * Anticonvulsants
  * Atorvastatin
  * Calcipotriene
  * Cholestyramine
  * Cytochrome P-450 3A4 substrates
  * Digoxin
  * Diltiazem
  * Orlistat
  * Thiazide diuretics
  * Corticosteroids
  * Stimulant laxatives
  * Verapamil
Multi-center Phase II Study Assessing the Safety and Efficacy of DE-117 Ophthalmic Solution in Subjects With Primary Open-angle Glaucoma or Ocular Hypertension

The purpose of this study is to investigate the safety and efficacy of five concentrations of DE-117 ophthalmic solution.

This is a 90-day randomized, observer-masked, active-controlled, parallel-group, multi-center, study assessing the safety and efficacy of five concentrations of DE-117 ophthalmic solution when compared to latanoprost (0.005% latanoprost) in subjects with primary open-angle glaucoma or ocular hypertension.

Eligibility Criteria:
Inclusion Criteria:

* Current diagnosis of primary open-angle glaucoma or ocular hypertension in both eyes
* Qualifying intraocular pressure in at least one eye at Baseline
* Qualifying corrected ETDRS visual acuity in each eye
* Qualifying central cornea thickness in each eye

Exclusion Criteria:

* Closed/barely open anterior chamber angle or a history of acute angle closure in either eye
* Diagnosis of primary open-angle glaucoma or ocular hypertension due to etiology known to be non-responsive to conventional drug therapy
* Evidence of advanced glaucoma, visual field defect or progressive visual field loss that that do not meet the study criteria
* History of ocular surgery specifically intended to lower IOP
* History of any ocular or systemic abnormality or condition that may put the subject at significant risk, may confound study results, or may interfere significantly with the subject's participation in the study
* Intended or current use of any ocular medications other than study medications during the study
* Use of contact lenses within one week prior to Baseline (Day 1) until end of treatment
* Known allergy or sensitivity to any components of the study medications
* Use of steroids (systemic) within 30 days prior to Visit 1 (Screening)
* Anticipate the need to initiate or modify an existing chronic therapy that could substantially affect IOP or the study outcomes during the study period
* Females who are pregnant, nursing or planning a pregnancy
ARQ 501 in Combination With Gemcitabine in Subjects With Pancreatic Cancer

The study will document the safety and efficacy of the combination of ARQ 501 and gemcitabine in patients with treatment-naïve, unresectable, metastatic pancreatic adenocarcinoma.

This is a single-arm, non-randomized study of ARQ 501 in combination with gemcitabine in adult patients with treatment-naïve, unresectable, metastatic pancreatic adenocarcinoma. The study objectives are:

Primary Objective:

* Assess the overall response rate (ORR) of patients treated with ARQ 501 in combination with gemcitabine.

Secondary Objectives:

* Determine time to tumor progression (TTP) of patients treated with ARQ 501 in combination with gemcitabine
* Further characterize the safety of ARQ 501 in combination with gemcitabine

Eligibility Criteria:
Inclusion Criteria:

* Have a pathologically confirmed diagnosis of unresectable, metastatic pancreatic adenocarcinoma
* Be treatment-naïve.
* Have measurable disease per RECIST Criteria.
* Be ≥18 years old.
* Have a Karnofsky Performance Status (KPS) of ≥70%.
* Have an estimated life expectancy of ≥12 weeks.
* Be male or a non-pregnant, non-lactating female patient. Patients who are fertile agree to use an effective barrier method of birth control (e.g., latex condom, diaphragm, or cervical cap) to avoid pregnancy.
* Have a negative serum or urine pregnancy test within 7 days prior to the first dose of study drug (if patient is a female of childbearing potential).
* Sign a written informed consent form.
* Have adequate organ function as indicated by acceptable laboratory values obtained within 7 days prior to the first dose of study drug.

Exclusion Criteria:

* Have received any prior therapy for the treatment of their pancreatic malignancy (including chemotherapy, immunotherapy, vaccines, monoclonal antibodies, major surgery, or irradiation, whether conventional or investigational).
* Have an active, uncontrolled systemic infection considered opportunistic, life threatening or clinically significant at the time of treatment.
* Are pregnant or lactating.
* Have a psychiatric disorder(s) that would interfere with consent, study participation, or follow-up.
* Have any other severe concurrent disease, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
* Have symptomatic or untreated central nervous system (CNS) metastases.
* Have a known hypersensitivity to gemcitabine.
School-Based Living in Families with Emotions Training

The overall purpose of this study is to identify adolescents who are at-risk for psychosis, as evidenced by endorsement of mild-to-moderate, sub-syndromal symptoms, and provide them with a potentially preventive intervention aimed at enhancing resilience.


Eligibility Criteria:
Inclusion Criteria:

1. Male and female adolescents from the Boston area who are in middle school at the time of enrollment;
2. Enrolled in a school where study screening is taking place;
3. Have a parent or legal guardian who is able and willing to provide written informed consent;
4. Competent and willing to provide written informed assent;
5. English language proficiency of parent/guardian and participant;
6. Response of "yes, definitely" or "maybe" to auditory hallucinations, visual hallucinations, or paranoia on the Adult Psychotic-like Symptom Checker (APSS);
7. Able to safely participate in the protocol and appropriate for outpatient level of care, in the opinion of the investigator.

Exclusion Criteria:

1. Current DSM-V diagnosis with serious active symptoms (such as active psychotic symptoms, current suicidality, serious active alcohol or substance use, marked deterioration in functioning over the prior month) that necessitates close monitoring or individual therapy and/or inpatient or partial hospitalization;
2. Current enrollment in psychological or behavioral health treatment;
3. Current use of psychotropic medications (other than stimulants) prescribed by a physician;
4. Severe developmental delays (including, but not limited to, Autism Spectrum Disorder, Intellectual Disability, and Down Syndrome).
AZD1152 in Patients With Advanced Solid Malignancies

The primary purpose of this protocol is to investigate the safety and tolerability of AZD1152 when given as a continuous 48-hour infusion every 14 days and as a 2-hour infusion for 2 consecutive days every 14 days in patients with advanced solid malignancies.


Eligibility Criteria:
Inclusion Criteria:

* Histological or cytological confirmation of a solid, malignant tumour
* At least one measurable or non-measurable site of disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

Exclusion Criteria:

* Participation in an investigational drug study within the 21 days prior to therapy or those who have not recovered from the effects of an investigational study drug
* Recent major surgery within 4 weeks prior to entry into the study
Biomechanical Effects of Three Types of Foot Orthoses in Individuals With Posterior Tibialis Tendon Dysfunction

Background :

Posterior tibialis tendon dysfunction (PTTD) is characterized by a loss of function of the muscle caused by the degeneration of the tendon leading to a flattening of the arch. FOs can be used as a treatment option, but their biomechanical effects are not yet fully understood. The aim of this study was to investigate the effects of three different types of foot orthoses (FOs) on gait biomechanics in individuals suffering from PTTD.

Methods :

Fourteen individuals were recruited with painful stage 1 or 2 PTTD based on the Johnson and Strom's classification. Quantitative gait analysis of the affected limb was performed in four conditions: shoed condition (Shoe), prefabricated FOs condition (PFO), neutral custom FOs condition (CFO) and five degrees varus (medial wedge) with a 4 mm medial heel skive custom FOs condition (CVFO). A curve analysis, using 1D statistical parametric mapping (SMP), was used to assess differences in lower limb joint motion, joint moments and muscle activity over the stance phase of gait across conditions.


Eligibility Criteria:
Inclusion Criteria:

* Symptoms located to the medial ankle or foot Pain on palpation to the posterior tibialis muscle tendon Positive single or double heel-rise test Foot flattening and ''too many toes" sign

Exclusion Criteria:

* Rigidity of those deformities Pain on palpation of the peroneal muscles Wearing any type of foot and/or ankle orthoses one month prior to the study onset History of corticosteroid injection in the tendon one month prior to the study onset Having a neurological disease or past history of surgery to the affected ankle
Investigation of the Safety and Efficacy of Renzapride in Constipation Predominant Irritable Bowel Syndrome (IBS)

The purpose of the study is to investigate whether renzapride will help alleviate the symptoms associated with constipation predominant irritable bowel syndrome in female patients.

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by recurrent symptoms of abdominal pain/discomfort accompanied by disturbed bowel function.

In this study female patients with constipation predominant IBS will receive one of two dosing regimens of renzapride or placebo for 12 weeks. Patients will record the severity of their symptoms throughout the study. The results will be analysed to see if those patients who received renzapride had greater relief of their symptoms than did the patients who received placebo.

Eligibility Criteria:
Inclusion Criteria:

* Females with constipation predominant IBS as defined by the Rome II criteria
* Colonoscopy or sigmoidoscopy in previous 5 years showed no significant disease

Exclusion Criteria:

* Patients who have diarrhoea predominant or alternating symptom IBS
* Other gastrointestinal diseases that affect bowel transit
Platelet Function in Patients With Hemophilia A

Abnormalities in the gene encoding Factor VIII (FVIII) results in hemophilia A, an X-linked recessive bleeding disorder with a prevalence of 1 in 5000 males. Hemophilia A patients are classified into 3 different categories based on residual FVIII activity compared to normal: mild (6-40%), moderate (1-5%) and severe (\<1%). This categorization correlates to some degree with bleeding phenotype, but does not completely define it. Some patients with hemophilia A bleed less often than others despite identical plasma FVIII levels. The cause(s) of this phenotype heterogeneity in hemophilia A remains largely unknown, despite a number of studies of possible factors.

Activated platelets, in addition to their role in primary hemostasis, play a major role in secondary hemostasis (coagulation) by providing a phospholipid surface to which coagulation factors bind. A role for platelets in the hemorrhagic propensity of hemophilia A has been suggested in the past, but only a small number of studies have been performed with limitations in assays performed and numbers of patients. The purpose of the present study is to determine whether platelet reactivity in severe hemophilia A patients is associated with past bleeding frequency and/or predicts future bleeding frequency.


Eligibility Criteria:
Inclusion Criteria:

* Patients with severe hemophilia A who are being prophylactically treated with FVIII.
* Age of at least 2 years.
* Bleeding history of at least 6 months.
* IRB-approved informed consent.

Exclusion Criteria:

* Presence of FVIII inhibitors.
* Greater than 7 days since active bleeding.