cyrilzakka/clinical-trials huggingface dataset:
Ascending Dose Study of Genome Editing by Zinc Finger Nuclease Therapeutic SB-FIX in Subjects With Severe Hemophilia B

The purpose of the study is to evaluate the safety, tolerability and effect on FIX antigen and activity levels of ascending doses of SB-FIX. SB-FIX is an intravenously delivered Zinc Finger Nuclease (ZFN) Therapeutic for genome editing. It inserts a correct copy of the Factor 9 gene into the albumin locus in hepatocytes with the goal of lifelong therapeutic production of the Factor IX clotting factor.

The objective of the study is to provide long term expression of Factor IX in subjects with severe hemophilia B. SB-FIX is a therapeutic for ZFN-mediated genome editing which will be delivered by adeno-associated virus (AAV)-derived vectors. SB-FIX is intended to function by placement of a corrective copy of the Factor IX transgene into the genome of the subject's own hepatocytes, under the control of the highly expressed endogenous albumin locus, and is expected to provide permanent, liver-specific expression of Factor IX for the lifetime of a hemophilia B subject.

Eligibility Criteria:
Inclusion Criteria:

* Male \>18 years of age
* Severe hemophilia B (native circulating FIX activity \<1%, with or without cross reactive material)

Exclusion Criteria:

* Presence of neutralizing antibodies
* History of hypersensitivity response or an allergic reaction to FIX or FIX products
* Currently receiving long acting FIX replacement therapy
* FIX mutations known to be associated with FIX inhibitors
* Polymorphisms in the ZFN target region
* Presence of any liver mass on MRI, or elevated alpha-fetoprotein (AFP)
* Any contraindication to the use of corticosteroids for immunosuppression
* Currently receiving antiviral therapy for hepatitis B or C or with history or active hepatitis B or hepatitis C or HIV-1 or HIV1/2 antibody positive.
* Chronic anemia, leukopenia, or thrombocytopenia
* Past medical history of active tuberculosis or significant fungal disease
* Symptomatic cardiovascular disease as a co-morbid condition
* Markers of hepatic inflammation or overt or occult cirrhosis
* History of chronic renal disease or creatinine ≥ 1.5 mg/dL
* Systemic (iv or oral) immunomodulatory agent or steroid use (topical treatment is allowed)
* History of chronic infection or other chronic disorder considered an unacceptable risk
* History of malignancy except for treated basal cell or squamous cell carcinoma
* History of alcohol or substance abuse
* Previously received gene therapy product
* Participation in prior investigational drug or medical device study within the previous 3 months
* History of therapeutic non-adherence
* Any other reason that, in the opinion of the Investigator or Medical Monitor, would render the subject unsuitable for participation in the study
Systemic Chemotherapy Plus PD-1 for Metastasis ICC

This study were designed to verify the better method of survival for metastatic ICC.

Since the traditional method for metastatic ICC was GEMOX(recommended from NCCN guideline), our previous study found better results from Folfirinox over GEMOX.

Our current study were conducted for further investigation to verify the better method for metastatic ICC.

ICC(Intrahepatic CholangioCarcinoma) patients with metastasis has a short survival time and poor prognosis after diagnosis. Treatment methods was few and far from satisfaction. The treatment recommended from NCCN guideline was GEMOX(Systemic Chemotheray) and clinical trials. Our previous study has demonstrate Folfirinox(Systemic Chemotheray based on Oxaliplatin，5-fluorouracil and Irinotecan) has a survival and tumor response advantage of GEMOX.

Further study was needed to intensive confirmation of the result. We designed this study to demonstrate the hypothesis. Metastasis ICCs were recruited and screened by our criteria. All patients were treated with Folfirinox(Systemic Chemotheray based on Oxaliplatin，5-fluorouracil and Irinotecan) plus PD1(Sintilimab).

The progression free survival and overall survival were our primary and secondary endpoint.

Our study were designed to verify the better method of survival for metastatic ICC.

Eligibility Criteria:
Inclusion Criteria:

* The diagnosis of ICC
* With distant metastasis
* Patients must have at least one tumor lesion that can be accurately measured according to mRECIST criteria.
* With no previous treatment
* No Cirrhosis or cirrhotic status of Child-Pugh class A only
* Not amendable to surgical resection ,local ablative therapy and any other cured treatment
* The following laboratory parameters:

Platelet count ≥ 50,000/μL Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/ L Serum albumin ≥ 32 g/L ASL and AST ≤ 6 x upper limit of normal Serum creatinine ≤ 1.5 x upper limit of normal INR ≤ 1.5 or PT/APTT within normal limits Absolute neutrophil count (ANC) \>1,500/mm3

Exclusion Criteria:

* Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
* Known history of HIV
* History of organ allograft
* Known or suspected allergy to the investigational agents or any agent given in association with this trial.
* Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
* Evidence of bleeding diathesis.
* Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
Quality of Life and Participation of the Adult with Spinal Muscular Atrophy in France

Spinal muscular atrophy is a hereditary motorneuron disease caused by a mutation of the SMN1 gene, which is at the origin of a progressive limb and axial motor deficiency. It concerns 1200 individuals in France, including 700 adults in 2018. The main objective of this study is to assess the quality of life of SMA patients in France.

The secondary objectives are, in one hand, to compare the quality of life of SMA patients to a population of neuromuscular diseases patients. And on the other hand to evaluate the determinants of participation and the impact of participation on quality of life in adult SMA patients.


Eligibility Criteria:
Inclusion Criteria:

* Patient with SMA type 1, 2, 3 or 4
* ≥ 18 years old
* giving informed consent to participate to the study
* patients from the study of Dany et al "Construction of a Quality of Life Questionnaire for slowly progressive neuromuscular disease" (2015)

Exclusion Criteria:

* patients who do not complete ≥ 80% of the questionnaire)-
Interpersonal Therapy-Based Treatment to Prevent Postpartum Depression in Adolescent Mothers

This study will aim to prevent postpartum depression in pregnant teenagers through an interpersonal therapy-based program.

Postpartum depression is believed to be one of the most common complications after pregnancy. This type of depression often occurs within the first year after the baby is born and is most likely caused by dramatic changes in hormone levels after pregnancy. Pregnant teenagers are even more at risk for experiencing complications throughout pregnancy and parenting difficulties after delivery. Minimal research has been done on preventive ways to reduce postpartum depression in teenagers. Therefore, this study will evaluate the effectiveness of an interpersonal therapy-based program at preventing postpartum depression in financially disadvantaged pregnant teenagers.

Participants will first undergo a 15-minute interview about their background and emotions. Participants will undergo a second interview and then be randomly assigned to receive either interpersonal therapy-based treatment or standard care. Participants assigned to receive interpersonal therapy-based treatment will focus on the psychological aspects of pregnancy and factors that may play a role in the development of postpartum depression in teenage mothers, such as poor social support, role transitions, and life stressors. Participants assigned to receive standard care will focus more on the health issues associated with pregnancy and postpartum. Both groups will attend weekly 1-hour sessions for 5 weeks. Homework may be assigned to review topics discussed, and all participants will receive the book Baby Basics. Following treatment, participants will meet with researchers again when they are 34 to 36 weeks pregnant; in the hospital after the baby is born; and 6, 12, and 24 weeks after the baby is born.

Eligibility Criteria:
Inclusion Criteria:

* Less than 24 weeks pregnant
* Not currently being treated for depression
* Speaks and reads English fluently

Exclusion Criteria:

* Currently receiving mental health services from a health care provider
* Meets DSM-IV criteria for an affective disorder, substance use disorder, or psychosis
Cerebral NIRS Monitoring During Anesthesia in Neonates and Infants

The brain is a very vulnerable organ, especially in premature babies, newborns and infants. However, during anesthesia, the oxygenation of the brain can only be monitored indirectly and insufficiently. Near-infrared spectroscopy (NIRS) is an established monitoring method in other areas (e.g., neonatology, cardiac anesthesia), which provides non-invasive information about the regional oxygen supply of the brain. The integration of this monitoring device into the anaesthesiological care for neonates and infants could reduce the risk of cerebral hypoxia. The planned study investigates whether the use of NIRS in anesthetized children up to 6 months can prevent or influence the occurrence of cerebral hypoxia.


Eligibility Criteria:
Inclusion Criteria:

* Expected duration of Anesthesia \>45 minutes
* Intervention/surgery in the operating room

Exclusion Criteria:

* Impossibility to place cerebral NIRS sensor
* Known cerebral pathology
* Missing parental consent
* Congenial cardiac condition with right to left shunt
* Cardiac surgery
Bespoke ctDNA Assay for Recurrence and Treatment Response Monitoring in Advanced Epithelial Ovarian Cancer

This prospective observational study is to assess the dynamics of circulating tumor DNA (ctDNA) in patients with advanced epithelial ovarian cancer (EOC) undergoing surgery, adjuvant chemotherapy, followed by poly adenosine diphosphate-ribose polymerase (PARP) inhibitors until disease progression or the end of the study. All patients will be closely monitored throughout the course of disease by a tumor-informed bespoke ctDNA assay as well as traditional methods of surveillance, such as CA125 and imaging. This study may provide preliminary evidence for ctDNA-guided treatment decisions in future clinical practice.

This observational study is designed for exploring prognostic and predictive values of the tumor-informed bespoke ctDNA assay in advanced EOC. Newly diagnosed patients who are eligible for radical surgery or relapsed patients from platinum-based adjuvant chemotherapy who are eligible for secondary cytoreductive surgery will be enrolled. The patients will be treated with SOC adjuvant therapies followed by PARP inhibitor for maintenance.

To evaluate ctDNA dynamics, tumor tissue collected from surgery will be sequenced with whole-exome sequencing (WES) to design patient-specific 16-plex panel. At planned monitoring timepoints, blood samples will be drawn, and ctDNA will be sequenced with ultra-deep ctDNA high-throughput sequencing methods.

Traditional surveillance methods will be applied as comparison, including but not limited to carbohydrate antigen 125 (CA-125)/ human epididymal protein 4 (HE4)/ carcinoembryonic antigen (CEA)/ carbohydrate antigen 199 (CA199), etc., as well as standard imaging.

Survival analyses will be conducted based on ctDNA status (positive/negative) after surgery. Recurrence rate of each subgroup, positive predictive values and negative predictive values etc. will be examined. Changes in ctDNA levels (ΔctDNA) during treatment will be used to evaluate the efficacy of maintenance therapy comparing traditional biomarkers,

Eligibility Criteria:
Inclusion Criteria:

1. Female, over 18 years of age;
2. Patients with advanced epithelial ovarian cancer who are eligible for radical surgery;
3. Patients with advanced epithelial ovarian cancer relapsed from platinum-based therapies and eligible for secondary cytoreductive surgery;
4. The subjects agree to sign the informed consent and agree to use their samples and data for related scientific research;
5. Subjects agree to collect tissue samples and peripheral blood samples for whole exon sequencing and ctDNA monitoring.

Exclusion Criteria:

1. Patients who are diagnosed, tested or treated for cancer other than ovarian cancer within 2 years (except for basal skin or squamous cell cancer that has been definitively treated);
2. Patients in pregnancy;
3. Patients with a history of blood transfusion within 3 months before enrollment;
4. Newly diagnosed patients who only received laparoscopic surgery;
5. Patients received chemotherapy or other anti-tumor therapy before surgery.
Melanocortin 4 Receptor Mutations and Obesity-associated Diseases

Mutations in the melanocortin 4 receptor (MC4R) are the most common form of monogenic obesity, and can explain 2-6% of severe obesity.

Studies have shown that mutations in MC4R are associated with increased fat mass, height-for-age, appetite and insulin resistance among children. In adults, mutations in MC4R are less penetrant for these phenotypes but it has been observed that individuals with MC4R mutations have a smaller than expected blood pressure for their degree of obesity.

The purpose of this study is to explore the association between functional MC4R mutations and obesity, insulin resistance and blood pressure.


Eligibility Criteria:
Inclusion Criteria:

* Age 18-70 years
* Men and women
* BMI \> 30 kg/m\^2

Exclusion Criteria:

* Uncontrolled type 2 diabetes
* Bariatric surgery
* Use of anti-obesity medication
Botulinum Toxin Type A for Treating Allodynic Pain in SCI and MS

This study will examine the efficacy of Botulinum Toxin Type A ("Botox") in treating Allodynic-type neuropathic pain in people with spinal cord injury or multiple sclerosis.

Neuropathic pain is pain initiated or caused by injury to or disease of the nervous system, and is common in spinal cord injury patients or people with multiple sclerosis.

Allodynia is a type of neuropathic pain caused by something that normally would not cause pain, such as light touch, pressure from clothing, or bed sheets brushing against the skin.

Botox has been used to treat the muscle overactivity that causes spasticity in spinal cord injured patients. It has been noticed to exert some analgesic(pain relieving) effect, and has recently been studied as a treatment for neuropathic pain.

We want to see if Botox, injected intradermally, will relieve the symptoms of allodynic-type neuropathic pain.

24 volunteers are to be enrolled, with 16 receiving active treatment, and 8 "controls" receiving placebo.


Eligibility Criteria:
Inclusion Criteria:

* Fulfills the criteria for neuropathic pain causing allodynia according to IASP pain terminology.
* Allodynia that is resistant to, or has failed, the standard level of care measures for more that six months.
* Allodynia pain on a daily basis.
* Allodynia pain that scores at least 4/10 on a pain numerical scale.
* Other pain medications(including antidepressants and anticonvulsants)have been maintained at a stable dose for at least 2 months prior to enrollment.
* Ability to communicate in English.

Exclusion Criteria:

* Presence of other pain syndromes (e.g.,fibromyalgia, ongoing peripheral neuropathic pain.
* Allergy to Botulinum Toxin Type A.
* Allergy to albumin.
* Use of Botulinum Toxin Type A for other treatment indications in the 3 months prior to enrollment.
* Renal failure.
* Hepatic failure.
* Neuromuscular junction disorders.
* Bleeding diathesis.
* Cognitive impairment, dementia, major depression or psychotic disorder.
* Pregnant or breastfeeding.
* Infection at the injection site.
* Active alchohol or substance abuse.
Treatment of Laryngotracheal Stenosis Using Mesenchymal Stem Cells

The trial evaluates the safety and efficacy of the olfactory mucosa-derived mesenchymal stem cells based therapy for the patients with chronic laryngeal and tracheal stenosis

Trial evaluating the safety and efficacy of olfactory mucosa-derived mesenchymal stem cells based therapy for the patients with chronic laryngeal and tracheal stenosis with/without cartilage defects

Mesenchymal stem cells are obtained from tissue biopsy of olfactory mucosa using explant method. Biomass of autologous mesenchymal stem cells in 10% human albumin solution is injected submucosally around and over the tissue after removal of a granuloma tissue during surgical intervention.

Eligibility Criteria:
Inclusion Criteria:

-confirmed diagnosis of chronic laryngeal or tracheal stenosis;

Exclusion Criteria:

* refuse of patient to participate in the trial;
* acute infectious diseases;
* chronic mental disorders with severe manifestations;
* pregnancy/lactation;
* intercurrent severe chronic diseases;
* HIV, Hepatites B/C;
* active tuberculosis;
* alcohol use disorder/drug addiction;
* cachexia of any origin;
* malignant neoplasms.
Effect of Intravenous Ketamine Infusion for Hemodynamic Stability in Patients Undergoing Caesarean Delivery.

Hypotension is the most frequent side effect of intrathecal anesthesia, with a found incidence of more than 80%. With a frequency of between 40% and 60% in patients undergoing surgery, Perioperative shivering is a serious consequence that frequently follows neuraxial anesthesia. This study aimed to determine the multiple advantages of intravenous minimal dose ketamine for intrathecal anesthesia in patients undergoing cesarean delivery

126 female patients undergoing cesarean deliveries, ASA-(II and III) and 21-40 ys old selected from an attendee of outpatient clinics of the Anesthesia Department. Two groups of patients were random to group K (63 patients): Received 0.3 mg/kg of ketamine IV diluted to 10 ml followed by infusion 0.1 mg/kg/hr. as 20 ml solution, group C (Controlled) (63 patients): Received 10 ml of normal saline followed by infusion of 0.1 ml/kg/hr. as 20 ml solution.

Eligibility Criteria:
Inclusion Criter

1. Female patients and full-term,
2. aged between (21 and 40) y. Old.
3. (ASA)-II or III, and undergoing a cesarean section.

Exclusion criteria:

1. Twins and preterm birth.
2. Hypertensive patients and preeclamptic patients.
3. Morbidly obese patients.
4. Spinal anesthesia contraindication as the patient refused, severe mitral or tricuspid stenosis and local sepsis.
A Phase II Multi-center Pilot Study of Concurrent Temozolomide and Whole Brain Irradiation in Lung Cancer and Breast Cancer Patients With Brain Metastases

Brain metastasis (BM) is among the most feared complications in cancer because even small tumors may cause incapacitating neurologic symptoms. It is observed in more than 50% of patients with lung cancer and 15% to 25% of patients with breast cancer. Temozolomide (TMZ) is an oral alkylating agent that crosses blood-brain barrier (BBB). This pilot study aims to evaluate the efficacy, safety and tolerability of whole-brain radiotherapy (WBRT) plus concomitant TMZ in lung cancer and breast cancer patients with BM.


Eligibility Criteria:
Inclusion Criteria:

* Histologically or cytologically confirmed lung cancer or breast cancer at primary site
* Patient with inoperable brain metastases
* Female or male, ≥ 20 and \< 65 years of age
* Karnofsky performance status (KPS) ≥ 70%
* Life expectancy ≥ 12 weeks
* Adequate organ function
* Willing and able to provide a written informed consent

Exclusion Criteria:

* Female of childbearing potential\* who is pregnant/lactating or planning to be pregnant
* Male whose partner is planning to be pregnant
* Inability to swallow
* Meningeal carcinomatosis
* History of hypersensitivity to iodinated contrast media, temozolomide or any component of the study drugs
* Prior use of temozolomide
* Use of systemic chemotherapy within 2 weeks prior to the initiation of study treatment
* Prior surgery, chemotherapy or radiotherapy for a brain neoplasm
* Current use of valproic acid
* Use of any investigational product within 4 weeks prior to the initiation of study treatment
* Patient with any condition or disease which is considered not suitable for this study by investigator
Prevention of Fetal Alcohol Spectrum Disorder (FASD) by the Use of Technology

The Institute of Health Economics is conducting a study to determine how a breathalyzer linked to a cloud based alcohol monitoring system changes alcohol consumption during pregnancy in women with alcohol dependency issues.

IHE posits that the ability to self-monitor blood alcohol concentration and the ability to share sobriety via email or text with loved ones and counselors may reduce alcohol consumption and thus reduce the possibility of delivering a child with FASD.

The study will provide useful evidence for tailoring future optimal maternal and child healthcare for women, with the potential of decreasing healthcare utilization by prevention of FASD. Breathalyzer device usage plus secure document sobriety should improve patient monitoring convenience and demonstrate reductions in alcohol use outside of traditional office visits and patient self-reports.


Eligibility Criteria:
Inclusion Criteria:

* Pregnant, Alcoholic, actively in treatment for alcoholism addiction

Exclusion Criteria:

* Not pregnant, not in treatment/therapy for addiction
Cost Utility of Radical Surgery in Ovarian Cancer

The purpose of this study is to investigate the medico-economic impact of adherence to INCa (National Cancer Institute) guidelines in ovarian cancer surgery by assessment of outcome in cost per Quality Adjusted Life Years (QALY).

This is a prospective, multicenter, comparative and non-randomized study designed to investigate the medico-economic impact of adherence to INCa guidelines in ovarian cancer surgery by assessment of outcome in cost per Quality Adjusted Life Years (QALY).

A cost-utility study will be performed. It will primarily aim to assess the Incremental Cost-Utility Ratio (ICUR) at 3 years of the two treatment strategies of ovarian cancer surgery: adherence to INCa quality indicators versus non-adherence to INCa quality indicators.

Consecutive patients with stage IIIC and IV ovarian, tubal, and primary peritoneal malignancies will be recruited in different health care institutions, including comprehensive cancer centers, university hospitals and private hospitals.

Evaluation of adherence to quality indicators will be assessed retrospectively (once patients have completed the treatment) by two independent experts.

200 patients will be included over a period of 2 years and will be followed for a 3 years period after treatment (every 4 months the first two years and then every 6 months).

Eligibility Criteria:
Inclusion Criteria:

* 1. Woman with age ≥ 18 years.
* 2. Newly diagnosed ovarian, tubal or peritoneal malignancies.
* 3. Epithelial histology.
* 4. Stage IIIC or IVA with extrapelvic carcinomatosis according to FIGO classification 2014.
* 5. Patients undergoing primary surgery or neoadjuvant chemotherapy.
* 6. Performance Status ≤ 2.
* 7. Patient affiliated to a Social Health Insurance in France.
* 8. Patient information and informed consent form signed prior to any study specific procedures.

Exclusion Criteria:

* 1. Benign or borderline tumors.
* 2. Patients with extra-abdominal disease, except for pleural effusion with positive cytology.
* 3. Other malignancy diagnosed in the previous 5 years except skin cancer (other than melanoma).
* 4. Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure.
* 5. Patient who has forfeited his/her freedom by administrative or legal award or who is under guardianship.