cyrilzakka/clinical-trials huggingface dataset:
Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection

This is a multi-center, single arm, open-label, phase I study to determine the safety and effectiveness of EBV-TCR-T cell immunotherapy in treating EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) or EBV infection

Epstein-Barr virus (EBV) is a widely disseminated herpesvirus that is spread by intimate contact between susceptible persons and asymptomatic EBV shedders. The inability to control EBV infection can lead to some patients developing EBV-positive B-cell lymphomas, chronic active EBV infections, and hemophagocytic lymphohistiocytosis (HLH). In this prospective study, HLA-A\*02:01/11:01/24:02-restricted EBV-specific T cell receptor (TCR) will be introduced into the T cells of donors by ex vivo lentiviral transduction to generate EBV-TCR-T cells. An escalated dose ranging from 1×10\^6/kg to 1×10\^8/kg of EBV-TCR-T cells will be infused into patients with EBV-HLH or EBV infection. The safety, efficacy, pharmacokinetics and cytokine levels of allogenic EBV-TCR-T cell therapy will be evaluated.

Eligibility Criteria:
Inclusion Criteria:

* Age 1-60 years, gender unlimited.
* Diagnosed with EBV associated-hemophagocytic lymphohistiocytosis (HLH) or EBV infection.
* Fully understood and informed the study and signed the ICF.
* Karnofsky Score ≥ 70(age ≥16y) or Lansky Score ≥ 50(age\<16y).
* TCRT-T cell donor inclusion criteria: 1)Age \>=8 years, gender unlimited; 2) Understand and voluntarily sign informed consent and are willing to comply with laboratory tests and other research procedures; 3) ≥ 3/6 HLA match with TCR-T cell recipients enrolled; 4) Lymphocyte count = (0.8\~4) × 10\^9/L; 5) Have sufficient venous circulation, without any symptoms that do not allow blood cell isolation.

Exclusion Criteria:

* Patients with uncontrolled active aGVHD one day before TCR-T cell infusion.
* Patients with severe kidney disease (Cr \> 3×normal value), liver damage (TBIL \>2.5×upper limit of normal value, ALT and AST \> 3×upper limit of normal value) or heart failure (NYHA heart function grade IV or left ventricular ejection fraction\<50%) one week before TCR-T cell infusion.
* Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion.
* Use of immunosuppressive drugs or G-CSF within 2 weeks before PBMC blood collection.
* Have tumours, active and uncontrolled malignant diseases.
* Serologically positive for HIV-Ab or TAP-ab.
* Pregnant or lactating women.
* Men and their partners or women of childbearing potential refused contraception during the study period.
* Anticipated to have other cell therapies in 4 week post TCR-T cell infusion.
* Participated in any other clinical study of drugs and medical devices before 4 weeks of enrollment.
* Allergy to albumin.
* TCRT-T cell donor exclusion criteria: 1) pregnant woman; 2) Serologically positive for HBsAg, HCV-Ab, HIV-Ab or TAP-ab; 3) EBV-DNA or CMV-DNA positive; 4) other uncontrolled infection; 5) Use of immunosuppressive drugs or G-CSF within 2 weeks before PBMC blood collection.
Genetic Polymorphisms of Mannan-binding Lectin (MBL)and Serum Levels of MBL in Patients With Endometriosis

The purpose of the study is to investigate the possible association between low levels of MBL and the development of endometriosis

Endometriosis is a chronic, inflammatory disease, affecting approximately 10% of the female population. The pathogenesis of endometriosis is still unclear, but several studies have indicated that the immune system is involved. It has been suggested that endometriosis should be considered an autoimmune disease, considering the findings of elevated levels of cytokines, decreased cell apoptosis, increased incidence of autoantibodies and a higher frequency of other autoimmune diseases in endometriosis patients. MBL participates in the innate immune defence by activating complement on the surfaces of microorganisms, but several studies have suggested that MBL is also involved in autoimmune diseases. The individual MBL level is highly variable due to a number of polymorphic sites in the structural gene and in the promoter region, and approximately 12 % of the normal population have very low serum MBL levels (\<100 ng/ml).

The possible association between MBL and endometriosis has been investigated in two small studies, in which no association was found. The aim of the present study is to investigate the prevalence of individuals with low serum levels of MBL and with genotypes associated with low MBL production in a larger group of endometriosis patients.

Eligibility Criteria:
Inclusion Criteria:

* histologically verified endometriosis
* ASRM stage 2-4

Exclusion Criteria:

* pregnancy
* actual treatment with GnRh analog
* autoimmune diseases
A Study Evaluating the Bioavailability of Two Formulations of Linifanib and Food Effect on Pharmacokinetics of Linifanib in Subjects With Advanced or Metastatic Solid Tumors

A pharmacokinetic study to compare 2 clinical formulations of linifanib and the effect of food on the pharmacokinetics of linifanib.

This study is designed to evaluate the bioavailability of linifanib from two formulations and the effect of food on the pharmacokinetics of the linifanib formulation intended for commercialization. Subjects may enroll in a separate extension study to continue receiving linifanib after completion of this study.

Eligibility Criteria:
Inclusion Criteria

1. Age is greater than or equal to 18 years.
2. Subject must have a histologically or cytologically confirmed non-hematologic malignancy other than Hepatocellular Carcinoma (HCC).
3. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
4. Subject must have adequate bone marrow, renal and hepatic function as follows:

   * Bone Marrow: Absolute neutrophil count (ANC) \>= 1,500/mm3 (1.5 X 109/L); Platelets \>= 75,000/mm3 (75 X 109/L); Hemoglobin \>= 9.0 g/dL (1.4 mmol/L)
   * Renal function: serum creatinine \<= 2.0 mg/dL (0.81 mmol/L);
   * Hepatic function: AST and ALT \<= 1.5 X ULN unless liver metastases are present, then AST and ALT \<= 5.0 X ULN; bilirubin \<= 1.5 mg/dL (0.026 mmol/L)
5. Subject must have Partial Thromboplastin Time (PTT) \</= 1.5 x Upper Limit of Normal ( ULN) and International Normalized Ratio (INR) \</= 1.5.

Exclusion Criteria

1. Subject has received anti-cancer therapy including investigational agents, cytotoxic chemotherapy, radiation therapy or biologic therapy within 21 days or within a period defined by 5 half lives, whichever is shorter, prior to study drug administration. In addition subject has not recovered to less than or equal to Grade 1 clinically significant adverse effects/toxicities of the previous therapy.
2. Subject has undergone major surgery within 21 days of Period 1, Study Day 1.
3. Subject has untreated brain or meningeal metastases. Subjects with treated brain metastases that are radiographically or clinically stable (for at least 4 weeks after therapy) and who have no evidence of cavitation or hemorrhage in the brain lesion, are eligible provided that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to Study Day 1, Period 1).
4. Current enrollment in another clinical trial.
Influence of Obesity on Oxalate Metabolism and Handling in Calcium Oxalate Stone Formers

The primary goals of this study are to determine the contribution of dietary oxalate absorption, renal oxalate handling, and endogenous oxalate synthesis to urinary oxalate excretion in normal Body Mass Index (BMI) and obese calcium oxalate kidney stone formers.


Eligibility Criteria:
Inclusion Criteria:

* Normal Body Mass Index (≥ 18.5 to \< 25); Obese Body Mass Index (≥ 30 to ≤ 45)
* Able to provide informed consent
* Willingness to consume controlled diet
* Composition of most recent stone \> 50% calcium oxalate, no uric acid component
* First time or recurrent calcium oxalate stone former
* 24-hour urine collections with creatinine values within 20% of appropriate ratio of creatinine (mg)/body weight (kg) for gender, and with creatinine values that are consistent between collections (within 20% of each other)
* Willingness to stop supplements \[vitamins, Ca (citrate or carbonate) and other minerals, herbal supplements, nutritional aids, probiotics\] for 14 days before start and during study
* Willingness to not undertake vigorous exercise during the controlled dietary study
* Normal fasting blood Comprehensive Metabolic Panel
* Hemoglobin A1c \< 6.5%
* No food allergies or intolerance to any of the food in study menus
* Permitted/willing to discontinue medications for kidney stone prevention, including thiazides, allopurinol, and febuxostat and citrate preparations, for 14 days before start and during the studies. They will be instructed to restart these medications at the conclusion of the study

Exclusion Criteria:

* Diabetes
* Abnormal fasting comprehensive metabolic panel (CMP)
* Hemoglobin A1c (HbA1c) result ≥ 6.5%
* Gout
* Estimated Glomerular Filtration Rate (eGFR) \<60 ml/min/1.73m\^2
* Primary hyperoxaluria
* Cystic fibrosis
* Cystinuria
* Uric acid stone former
* Utilization of immunosuppressive medication
* Nephrotic syndrome
* Enteric hyperoxaluria
* Gastrointestinal disorder that could impact oxalate transport
* Sarcoidosis
* Uncontrolled hypertension
* Renal tubular acidosis
* Primary hyperparathyroidism
* Liver disease
* Neurogenic bladder
* Urinary diversion
* Chronic diarrhea
* Bariatric surgery
* Active malignancy or treatment for malignancy within 12 months prior to screening
* Pregnancy
* Breast feeding/nursing
* Females of child bearing age who are not able to use an effective method of birth control during the study
* Mental/medical condition that is likely to impede successful study completion
* Illness including flu / common cold / fever 14 days before study and during study
* Diarrhea or other abnormal gastrointestinal event (e.g. abnormal bowel movements) 14 days before study or during study
* Antibiotic use within last 6 months (based on recommendations of the NIH Human Microbiome Project, Protocol A)
* Inability or unwillingness to undergo MRI
Detection of Herpesvirus DNA (CMV, EBV, HHV-6 and HSV) in Colonic Tissue: Impact on Ulcerative Colitis Flare-up

Flare-up of ulcerative colitis (UC) is characterized by the inflammation of colon mucosa that requires the use of immunosuppressive therapies. In previous studies, the active role of cytomegalovirus (CMV) has been demonstrated, with a correlation between the cytomegalovirus DNA ((deoxyribonucleic acid) load in the inflamed tissue and the resistance to successive lines of immunosuppressive therapy (Roblin et al., Am J Gastroenterol 2011). The main aim of this monocentric prospective study is to evaluate the DNA viral load by qPCR (Polymerase Chain Reaction) of 3 herpesviruses (Epstein-Barr virus, herpes virus 6 and herpes simplex) together with that of CMV in colonic mucosa depending of the local inflammation (endoscopically normal region, inflamed mucosa or ulcer) in patients suffering of moderate to severe UC flare-up (Mayo score \>6 with endoscopic score higher or equal than 2). The viral load will also be correlated to the Mayo endoscopic score and the response to immunosuppressive drugs (steroid and anti-TNF (Tumor Necrosis Factor) monoclonal antibodies).


Eligibility Criteria:
Inclusion Criteria:

* Age\>18 years
* Voluntary to participate to the study
* Flare-up of ulcerative colitis with Mayo score \>6
* Ability to receive steroid or anti-TNF therapy
* Agree the rectosigmoidoscopy and the therapies

Exclusion Criteria:

* Age \<18 years
* Pregnancy
* Disagree the rectosigmoidoscopy or the therapies
* Participation to the evaluation of a new therapy
* Colectomy (partial or total)
* Contraindication of steroid or anti-TNF therapy
* Anticoagulant drugs
Annexin Levels of Periodontal Inflammatory Regulation

ANXA1, a member of the annexin family, plays a role in the resolution of inflammation and the regulation of anti-inflammatory responses, while ANXA2 is involved in the initiation of the inflammatory responses. The aim of this study was to determine the effects of annexin family (ANXA1 and ANXA2) in periodontal disease.

Healthy participants (n:25) and stage III, grade B periodontitis (n:25) patients enrolled for this study. Clinical periodontal parameters and PISA levels were noted. Serum, saliva, and GCF samples were collected to measure the ANXA1, ANXA2 and IL-1β levels.

Eligibility Criteria:
Inclusion Criteria:

systemically healthy

* clinical diagnosis of periodontitis
* clinical diagnosis of periodontal health

Exclusion Criteria:

* • history of regular use of systemic antibiotics anti-inflammatory, or antioxidant drugs (previous 3 months)

  * nonsurgical periodontal treatment (previous 6 months)
  * surgical periodontal treatment (previous 12 months)
  * presence of\<10 teeth
  * current medications affecting gingival health (calcium channel blockers, phenytoin, cyclosporine, and hormone replacement therapy)
  * diabetes
  * diagnosis of rheumatoid arthritis
  * pregnancy
  * lactating
  * smoking
  * excessive alcohol consumption.
A Safety, Efficacy And Pharmacokinetics Study Of Tofacitinib In Pediatric Patients With sJIA

A randomized withdrawal study in which responders to open-label treatment with tofacitinib will be randomized in a 1:1 ratio to tofacitinib or placebo in a double-blind phase. In the double-blind phase "time to sJIA flare" will be evaluated as primary endpoint and subjects will be discontinued once they experience sJIA flare. An interim analysis for efficacy and futility will be conducted when at least 20 flares have been observed. If either criterion is met, the study will be stopped. If neither criterion is met, the study will continue until the requisite number of flares are observed as determined by the number of flares included in the interim analysis and a statistical penalty for conducting the interim analysis.


Eligibility Criteria:
Inclusion Criteria:

* active sJIA disease according to ILAR criteria before screening and at baseline (Day 1);
* Treatment with stable doses of methotrexate (MTX) ≤25 mg/week or ≤20 mg/m2/week, whichever is lower, is permitted;
* Treatment with a stable dose of oral prednisone ≤1 mg/kg/day up to a maximum of 30 mg/day, or equivalent, for at least 1 week before the first study drug dose is permitted.

Exclusion Criteria:

* Previous juvenile idiopathic arthritis (JIA) treatment with tofacitinib.
* Current symptoms or findings of myocarditis, endocarditis or more than minimal pericardial effusion associated with systemic juvenile idiopathic arthritis (sJIA). Current symptoms or findings of more than minimal pleuritis with sJIA.
* Current infection or serious infection within 3 months of study enrollment.
Once Weekly Infant Corticosteroid Trial for DMD

The hypothesis tested here is that a lower dose of intermittent oral corticosteroids (5mg/kg/week) will be equally effective to the 10mg/kg/week dose.

The investigators know that the muscle destruction from Duchenne muscular dystrophy (DMD) begins in infancy and we previously demonstrated that motor decline in infancy compared to typically developing infants reflects that destruction. Because of the known side effects of daily corticosteroids, most physicians do not begin treatment until age 3-5 years. Most side effects (Cushingoid faces, linear growth arrest, and bone density loss) did not happen in infants and in ambulatory boys in two separate studies. However, in infants and young boys taking (10mg/kg/week), 56% of infants and young boys did have an increase in weight percentile compared to baseline. This study will test this lower dose of prednisolone (5mg/kg/week) in an unblinded study in infants and young DMD boys (ages 1 through 30 months) to determine if equal efficacy can be achieved with fewer side effects. The primary outcome for this study will be gross motor function. The study team will enroll boys from age 1 month through 30 months and follow each for two years. We will assess gross motor function using three outcome measures: the Bayley-4 Scales of Infant and Toddler Development (Bayley-4) and the newly developed Neuromuscular Gross Motor Outcomes (GRO) and the NorthStar Ambulatory Assessment (NSAA). The one-year outcome will be the change in the Bayley-4 Scaled Score and the two-year outcome will be the change in the GRO score. This study will determine if a lower dose is equally effective and if that dose may lessen the weight gain seen in about half of the infants in the first study. Both the Bayley-4 and the GRO allow assessment of gross motor function and are feasible in all boys with DMD under the age of 42 months. In addition, the GRO allows continued assessment of motor function across a wide age span which will allow this cohort to be followed for two full years.

Eligibility Criteria:
Inclusion Criteria:

* Subjects ages 1 month through 30 months
* Weakness consistent with Duchenne on exam, creatine kinase ≥ 20 times the upper limit of normal, and genetic mutation known to be causative for DMD.

Exclusion Criteria:

* Prior treatment with Glucocorticosteroids
Phase 2/3 Study of TLC590 for Postsurgical Pain Management

A phase 2/3 randomized, double-blind, 2-part, comparator- and placebo-controlled study to assess the safety, pharmacokinetics and efficacy of postsurgical local infiltration in adult subjects following inguinal hernia repair surgery.

This is a phase 2/3 randomized, double-blind, 2-part, comparator- and placebo-controlled study to assess the safety, pharmacokinetics and efficacy of postsurgical local infiltration in adult subjects following inguinal hernia repair surgery. This study includes 2 parts. An unblinded interim analysis will be performed after completion of part 1 (phase 2, approximately 115 subjects to be randomized for 2 different doses of TLC590, bupivacaine, ropivacaine, or placebo), for selecting a TLC590 dose for part 2 (phase 3, approximately 300 subjects to be randomized for TLC590, bupivacaine, or placebo).In this study, 2 doses of TLC590 24.5 mg/mL in inguinal hernia repair will be assessed in an initial phase 2 part before proceeding to a phase 3 pivotal evaluation.

Eligibility Criteria:
Inclusion Criteria:

* Male or female at least 18 years old
* BMI 18-39 kg/m2
* Scheduled to undergo a primary, unilateral Lichtenstein inguinal hernia repair with mesh
* ASA Physical Status Classification of 1, 2 or 3

Exclusion Criteria:

* Clinically significant abnormal clinical laboratory test value
* Clinically significant 12-lead ECG
* History of orthostatic hypotension or syncope
* History of significant renal, hepatic, gastrointestinal, cardiovascular, metabolic, neurologic, psychiatric, or other condition
* History of seizure or currently taking anticonvulsants
* History of hypersensitivity to bupivacaine/ropivacaine, any other amide-type local anesthetic, propofol, oxycodone or morphine (or other opioids)
* History of severe or refractory post-operative nausea or vomiting (PONV)
* Abnormalities of laboratory parameters: HbA1c, platelet, hemoglobin, WBC, serun bilirubin/alanine aminotransferase/aspartate aminotrasferase, serum creatinine, PTT/INR
* Concurrent acute, or chronic painful restrictive/physical condition
* Received opioid therapy for longer than 4 days per week
* Prohibited medication: aspirin and other anti-platelet medication, anticoagulants, class III antiarrhythmic drugs, strong CYP1A2 inhibitors,systemic corticosteroids, NSAID, opioid, bupivacaine or ropivacaine, any investigational product
* History of drug abuse or alcohol abuse
* Positive results on the urine drug screen or alcohol breath test
* History of HIV; active HBV or HCV
* An inguinal hernia repair in the last 3 months or has undergone 3 or more surgeries within 12 months
* Malignancy in the last 2 years
* Documented sleep apnea or on home continuous positive airway pressure treatment (CPAP)
* Personal or family history of malignant hyperthermia.
Evaluation of Outcomes Following In-office Tympanostomy Using the Tula® System: a Prospective, Multi-center Registry

This prospective, single-arm, multicenter registry is being conducted to collect real world post-market data from patients aged from 6 months to 17 years of age who are undergoing an in-office ear tube placement procedure (tympanostomy) using the Tula® System. The Registry will include up to 20 centers in the US and up to 200 patients for the initial evaluation.

The FDA-approved Tula System includes the Tula Iontophoresis System (IPS) with TYMBION™ otic anesthetic for local anesthesia of the ear drum and the Tula Tube Delivery System (TDS) for ear tube placement. Clinical research established the safety, efficacy and tolerability of this system for in-office procedures in the pediatric population. Patients will be treated and evaluated according to standard medical care. Outcome data is collected up to 6 months following extrusion or removal of their tube(s).


Eligibility Criteria:
Inclusion Criteria:

* Patients ages 6 months through 17 years of age (inclusive) at time of tympanostomy in-office using the Tula® System
* Patients who are candidates for in-office tube placement using the Tula System according to the System Instructions For Use

Exclusion Criteria:

* Patients who are wards are not included
"Association of Proteinuria and Progression of Kidney Dysfunction in Sickle Cell Disease"Disease

To describe change in ACR and eGFR during study follow-up, and assesss the association of baseline and change in ACR and eGFR, with progression of kidney failure and/or all-cause mortality.

This is a retrospective, non-interventional, secondary use of the data coming from the single-center secondary GEN-MOD study cohort at the Henri Mondor Hospital (Creteil, France). The GEN-MOD cohort includes 355 SCD patients.

The GEN-MOD data are accessible through the center's clinical and laboratory database and will be extracted and analyzed for the purpose of this study.

The enrolment in the GEN-MOD cohort lasted from 01 December 2002 until 01 March 2014. Follow-up occurred every six months and ranged from five to seventeen years and ended on 31 December 2019. The index date (baseline) for this study is the time of inclusion of patients in GEN-MOD cohort study

Eligibility Criteria:
Inclusion Criteria:

* Adults aged ≥ 18 years old.
* Confirmed diagnosis of SCD by Hb electrophoresis or high performance liquid chromatography. SCD genotypes HbSS, HbSβ0-thal.
* Availability of ACR and eGFR baseline records.

Exclusion Criteria:

* Patients enrolled in a chronic transfusion program.
* Patients receiving hydroxyurea treatment at the time of study enrollment.