cyrilzakka/clinical-trials huggingface dataset:
Validation of Therapeutic Efficacy Targeting the Splicing Variants in Cystic Fibrosis and CFTR Pathologies

Cystic Fibrosis, an inherited autosomal recessive disease, arises from mutations in the CFTR gene. For intronic mutations affecting splicing events, oligonucleotides therapy has the potential to restore the production of the full length CFTR protein. Recent scientific research has demonstrated the potential of this approach to restore full length mRNA CFTR in in vitro human airway cells. The study aims to validate the therapeutic efficacy of oligonucleotide blockers (ONB) that target splicing defects associated to splicing variants in epithelia obtained from patients with Cystic Fibrosis and CFTR-related disorders.

The study will include patients with various CFTR genotypes. The assessment of ONB (named ONB-CFTR) will be performed using an air-liquid interface model of airway epithelium, developed from nasal cells of patients, without or with a combination of existing CFTR modulators, depending on the patient' genotype.

This study will also aim to build a local biobank of rectal organoids from patients (only from Montpellier, France) carrying rare CFTR disease-causing variants.

Eligibility Criteria:
Inclusion Criteria:

* The subject must have given their free and informed consent and signed the consent
* The subject must be affiliated or beneficiary of a health insurance plan Women and men are included
* The patient is at least 12 years old.
* The patient has cystic fibrosis or a CFTR pathology and therefore carries two mutations (with at least one mutation affecting splicing) in the CFTR gene.
* Patients who volunteer for rectal biopsy collection (only from Montpellier University Hospital) must be at least 18 years old.

Exclusion Criteria:

* The subject is in a period of exclusion determined by a previous study.
* The subject is under judicial protection, under guardianship or under curatorship
* The subject does not accept to sign consent
* It turns out to be impossible to give informed information to the subject
* The subject does not read the French language fluently
* The subject is a pregnant or breastfeeding woman
* The subject has porphyria, or has hepatic insufficiency, or suffers from epilepsy, or suffers from conduction disorders, or suffers from severe heart failure, has a cons-indication to the use of a local anesthetic spray.

Specific non-inclusion criteria for rectal sampling:

* the subject has thrombocytopenia
* the subject has a bleeding disorder
* The patient has severe inflammation of the rectum.
Comparison of the Efficacy & Safety of Resusix With FP24 in Patients With Acquired Coagulopathy

Phase 2a study to assess the safety and efficacy of IV infused spray-dried solvent/detergent -treated plasma (Resusix) when compared with an equal volume of plasma frozen within 24 hours after phlebotomy (FP24) in patients with liver disease who are actively bleeding or who require prophylaxis for surgical bleeding


Eligibility Criteria:
Inclusion Criteria:

* SBP 90-150 mm Hg
* acquired coagulopathy due to hepatic disease
* INR \>1.4
* Order for 1-4 units of plasma for active bleeding or prophylaxis for bleeding prior to surgery or invasive procedure
* Written informed consent
* MELD score: 25 or less (1st cohort), 35 or less (2nd cohort)

Exclusion Criteria:

* Pregnant women
* Incarcerated patients
* Life expectancy less than 72 hours
* Severe bleeding at time of enrollment
* HIV, sepsis, intracranial bleeding, congenital disorder, anti-phospholipid antibody syndrome or known lupus anticoagulant antibodies
* Receipt of plasma products, coagulation factor concentrates or anti-platelets within 3 days of enrollment
* Specific factor inhibitor activity or history of hypersensitivity to plasma-derived products
* Receipt of iv heparin within 24 hours of enrollment
* Use of a continuous infusion of an intravenous vasoactive medication
* Thrombocytopenia
* BMI greater than or equal to 40 kg/m2
* Participation in another clinical trial within 30 days of enrollment and received investigational product that may impact safety or efficacy of this study
* West Haven Hepatic Encephalopathy Grade 3 or 4 (cohort 1) and Grade 4 (cohort 2)
A Study Of PF-03732010 In Patients With Advanced Solid Tumors

P-cadherin may play a part in tumor growth; PF-03732010 is a new drug that inhibits P-cadherin. This study will test how well the drug is tolerated, and what effects there might be. Blood will also be taken to measure the amount of drug in blood.


Eligibility Criteria:
Inclusion Criteria:

* Advanced solid tumors refractory to (or intolerant of) established therapy known to provide clinical benefit, or for which there is no standard therapy
* Age \>= 18 years of age
* Adequate bone marrow function as defined by: absolute neutrophil count (ANC) ≥1500/uL, hemoglobin ≥ 9 g/dL, platelets \> 100,000/uL
* Adequate liver function as defined by: bilirubin \< 1.5 x ULN, AST, ALT and ALP \< 2.5 x ULN, or \< 5 x ULN with documented liver and/or bone metastases
* Serum creatinine \< 1.5 x ULN
* ECOG status 0-1
* Availability of biopsy tumor tissue (or fine needle aspirate) for testing of P-cadherin expression
* Tumor tissue (or fine needle aspirate) showing over-expression of P-cadherin
* Must be able to give written informed consent
* Be able to comply with scheduled study visits, treatment plans, laboratory tests and other procedures

Exclusion Criteria:

* Chemotherapy, radiotherapy, or any investigational cancer therapy within 4 weeks of study entry
* Patients with carcinomatous meningitis or untreated brain metastases.
* History of significant low platelet count, and/or bleeding disorders, requiring medical or surgical intervention
* History of significant bleeding episodes within 6 months, unless the source of bleeding has been resected
Cardiac Magnetic Resonance Assessment for Heart Failure With Preserved Ejection Fraction

This is a prospective study that aims to define the utility of cardiac magnetic resonance feature tracking (CMR-FT) as a non-invasive quantification tool to assess diastolic functionality in patients with Heart Failure with preserved ejection fraction.

Despite the increasing prevalence and poor prognosis of HFpEF worldwide, it is facing diagnostic challenges due to its non-specific clinical manifestations. Currently, echocardiography serves as the main diagnostic tool, but alternatives are limited to less preferred invasive procedures in most clinical situations.

It is therefore proposed to investigate HFpEF using cardiovascular magnetic resonance imaging (CMR), as an alternative non-invasive diagnostic tool which carries lower risk than invasive procedures.

The study aims to: (1) access the utility of CMR-FT as a new indicator to diagnose diastolic dysfunction by differentiating HFpEF patients from non-HFpEF patient and normal volunteers. (2) Compare accuracy of CMR-FT to CMR tagging and phase contrast imaging.

Eligibility Criteria:
Inclusion Criteria:

* Patients presenting with symptoms and signs suggestive of HFpEF
* Patients undergoing coronary catheterisation for stable chest pain with no evidence of diastolic dysfunction, heart failure, infarct, left ventricular ejection fraction \<50% or significant coronary artery disease (ie. \>50% narrowing of one or more coronary arteries)
* Volunteers must be asymptomatic with no cardiac risk factors and no previous cardiac history

Exclusion Criteria:

* Patients suspected to have HFpEF but echocardiography and/or invasive pressure measurements do not confirm diagnosis of HFpEF.
* Significant underlying ischaemia based on clinical history and non-invasive imaging or catheter coronary angiography if indicated.
* Contraindication to CMR study
* Estimated glomerular filtration rate \<30 ml/min/1.73 m2
* More than moderate valvular disease
* Severe pulmonary disease (ie. FEV1 \<- 50% predicted)
* Cardiomyopathy
* Constrictive pericarditis
A Multiple Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of ACHN-975 in Healthy Volunteers

This is a randomized, double-blind, placebo-controlled, multiple-dose study, designed to assess the safety, tolerability, and pharmacokinetics (PK) of ACHN-975. This study will take place in the US at one clinical site.


Eligibility Criteria:
Key Inclusion Criteria:

* Body weight between 40 and 100 kilograms (between \~88 pounds and \~220 pounds)
* Use of contraception
* Stable health
* Negative tests for alcohol, tobacco, and drugs of abuse

Key Exclusion Criteria:

* History of clinically significant disease
* Pregnancy
Efficacy of Buffered Hypertonic Saline(BHS)Nasal Irrigation in Allergic Rhinitis (AR) Children

The purpose of this study is to investigate whether buffered hypertonic saline (BHS) is superior to normal saline (NSS) for improving mucociliary function and relief nasal symptoms in children with allergic rhinitis.

1. BHS is superior to NSS for improving mucociliary function that by measure saccharine clearance time(SCT)at 10 minute after nasal irrigation compare to baseline.
2. BHS is superior to NSS for clinical effectiveness at short period and 1 month follow up

   * at short period: compare the following results at baseline and 10 minute after nasal irrigation

     1. total nasal symptom score(TNSS)
     2. satisfaction to nasal irrigation
     3. side effect
   * at 2 and 4 weeks follow up : compare the following results at baseline and 10 minute after nasal irrigation

     1. quality of life(by specific questionnaire for Thai allergic rhinoconjunctivitis patient)
     2. medication use to relieve AR symptom(from diary record)
     3. compliance for nasal irrigation (from diary record)
     4. side effect (from diary record)
     5. overall satisfaction to nasal irrigation

Eligibility Criteria:
Inclusion Criteria:

1. age 6-15 years
2. diagnosed AR obtained by history, physical examination and positive skin prick test or nasal cytology
3. TNSS ≥ 4 at the first visit of this study

Exclusion Criteria:

1. Patients with a history of nasal anatomical defects
2. Abnormal nasal ciliary function or an upper respiratory tract infection in the preceding 2 weeks
Quaternium-15, Use Test

The study is required by the FDA as part of a post-marketing commitment. The purpose of the study is to compare the reactivity of the TRUE Test quaternium-15 patch and a real use exposure.The subjects will wear the patch test for 48 hours and reading will be performed day 3 or 4. The use test will be applied from day 3 or 4 and untill reaction appears. Reactions from respectively TRUE Test and use test will be compared using the McNemar Change Test.


Eligibility Criteria:
Inclusion Criteria:

* Sensitivity to quaternium-15
* Age more than 18 years

Exclusion Criteria:

* Topical or systemic treatment with corticosteroids or immunosuppresives.
* Treatment with UV-light
* Widespread active dermatitis or dermatitis on test area
Efficacy and Safety Study of GB-0998 for Treatment of Generalized Myasthenia Gravis

This randomized controlled, multi-center study will carry out to assess the efficacy of GB-0998 compared to plasmapheresis in the treatment of the generalized Myasthenia Gravis based on the changes in Quantitative Myasthenia Gravis score (QMG score) as primary endpoint, and in addition, to assess the safety of GB-0998


Eligibility Criteria:
Inclusion Criteria:

* Patients diagnosed as generalized myasthenia gravis
* Patients who are not controlled by current therapy and need plasmapheresis therapy
* Patients who have the high-dose steroid therapy for over a month in past years, and also who take steroid or immunosuppressant on the day of consent
* Patients who had not any dose increase or new dosing of steroid or immunosuppressant within 4 weeks prior to enrollment

Exclusion Criteria:

* Patients who received steroid pulse therapy, globulin therapy or plasmapheresis therapy within 12 weeks prior to enrollment
* Patients who had undergone thymectomy within 24 weeks prior to enrollment
* Patients with 3 points item in bulbar symptom of MG-ADL scale
* Patients with severe hepatic disorder, severe renal disorder or severe heat disorder
* Patients who have received treatment of malignant tumors
* Patients who have the anamnesis of shock or hypersensitivity to this drug
* Patients who have been diagnosed as hereditary fructose intolerance
* Patients who have the anamnesis of cerebral infarction or symptom of these diseases
* Patients who have been diagnosed as IgA deficiency in their past history
* Pregnant, lactating, and probably pregnant patients, and patients who want to become pregnant
* Patients who were administered other investigational drug within 12 weeks before consent
Validation of Pulse Wave Doppler Demodulation Algorithm for the Continuous, Non-invasive Measurement of Blood Flow Velocity

The investigators hypothesize that performance of fast-Fourier transformation on the raw Doppler signals obtained from ascending aortic blood flow will recreate the pulse wave Doppler trace visualized on modern echocardiography machines, and that this will allow for the measurement and recording of vascular flow waveforms

Currently there is no commercially available mechanism for the measurement of blood flow velocity waveforms non-invasively. Blood flow velocity waveforms require the use of invasive catheters, thus precluding clinical use. Such information would allow the researcher / practitioner the ability to continuously measure blood flow, pulse pressure, and the pulsatility index of any vascular structure accessible by ultrasound with minimal additional risk to the subject / patient. This data, when combined with arterial blood pressure data, could also be used to measure peripheral pressure volume loops as well as aortic vascular impedance, both of which cannot be currently measured in vivo.

The ability to measure blood flow velocity waveforms at high temporal resolution would provide clinicians with new tools for hemodynamic optimization (both a novel means of estimating myocardial oxygen consumption \[pressure volume area\] as well as afterload \[aortic vascular impedance\]) and researchers with the ability to conduct hemodynamic experiments that were not previously possible. This work will serve as the foundation for several other related projects which depend on the ability to continuously record blood flow velocity waveforms.

Eligibility Criteria:
Inclusion Criteria:

* 18-65
* Healthy

Exclusion Criteria:

* Cannot visualize ascending aorta with ultrasound
Pilot Study for the Development of a Diagnostic Score to Differentiate Myeloproliferative Neoplasms.

Prospective study for the development of a non-invasive score for differentiating prefibrotic myelofibrosis from essential thrombocytosis and overt myelofibrosis.

The diagnostic criteria for myeloproliferative neoplasia have recently been revised in the WHO 2016 classification, which now recognizes a new entity between essential thrombocythemia (TE) and overt myelofibrosis (or primary myelofibrosis): prefibrotic myelofibrosis. Prefibrotic myelofibrosis patients seem to have a poorer prognosis compared to essential thrombocythemia in term of overall survival and myelofibrotic evolution. The dichotomy between these diseases is based on the bone marrow biopsy evaluation and is challenging with a lack of reproducibility showed in the literature.

This study aims to develop a diagnostic non-invasive score for differentiating prefibrotic myelofibrosis from essential thrombocytosis and overt myelofibrosis.

The parameters studied are :

* spleen fibrosis by elastography
* plasma cytokines levels
* mutationnal landscape by NGS
* CD34 circulating cells

Bone marrow biopsy were reviewed by 2 anatomopathologists. Number of patients to be enrolled : 130

Eligibility Criteria:
Inclusion Criteria:

* Adult (18 years of age or older) with the diagnosis of essential thrombocytosis, prefibrotic myelofibrosis or overt myelofibrosis according to WHO 2016 criteria;
* Patient who has not received specific treatment for neoplasms;
* Patient who has signed the consent to participate in the study;
* Patient who has consented to be included in the "Malignant Haemopathies" collection at the University Hospital of Angers or Brest and for whom the samples necessary for the study are available in the biocollection.

Exclusion Criteria:

* Patient with another hematologic neoplasm or progressive cancer at the time of diagnosis;
* Patient with a diagnosis of secondary myelofibrosis;
* Pregnant or breastfeeding woman;
* Person prived of liberty by judicial or administrative decision;
* Person subject to a legal protection measure;
Combined Gut-brain Therapy for Children With Autism

CLINICAL ISSUE: Children with Autism Spectrum Disorder (ASD) are four times more likely to suffer with functional gastrointestinal disorders (FGIDs) than their neurotypical peers. The presence of FGIDs are linked to increased undesirable behaviour and ASD severity. Current behavioural approaches for ASD therapy do not alleviate the high comorbidity of FGIDs within this population.

BACKGROUND: Dysfunction of the microbiome-gut-brain (MGB) axis has been implicated in pathogenesis of both ASD and FGIDs. Probiotics and prebiotics can modulate the gut microbiome and research has shown efficacy at improving gastrointestinal (GI) symptoms in children with ASD and neurotypical (NT) children with FGIDs. Gut-directed hypnotherapy (GDH) has shown utility in treating FGIDs in NT children and adults but has not yet been trialed in children with ASD. Targeting therapies to address the dysfunction of the bidirectional MGB axis will likely be more effective than either brain/behavioural or gut-based therapy alone.

HYPOTHESIS: A synbiotic (prebiotic + probiotic mixture) with combined GDH will be more effective than a synbiotic alone at reducing GI symptoms in children with ASD aged 5.00 to 10.99 years over a 12-week period.


Eligibility Criteria:
Inclusion Criteria:

1. Aged 5.00 years to 10.99 years
2. A confirmed diagnosis of ASD or Pervasive Developmental Disorders (PDD) including autistic disorder, Asperger's disorder (AS); PDD not otherwise specified (PDD-NOS); and atypical autism.
3. A diagnosis of a functional gastrointestinal disorder (FGID) by a gastroenterologist or a score of three and above on the six-item gastrointestinal severity index (6-GSI). Accepted FGIDs include diarrhoea, constipation, bloating, abdominal pain or irritable bowel syndrome (IBS).

Exclusion Criteria:

1. Non-verbal children and/or those with severe cognitive impairment
2. Confirmed diagnosis of inflammatory bowel disease, coeliac disease, or current infection of the GI tract.

3) Any other medication, supplement or conditions which can impact the gut microbiome, including:

* antibiotics or antifungals in the last month
* probiotic or prebiotic supplements in the last two weeks
* immunocompromised or severely ill
* bipolar, schizophrenia, personality disorders
* diabetes mellitus or an eating disorder
Randomized, Controlled, Multicenter Study of Extracellular Vesicles From Human Adipose Tissue Promoting Wound Healing

By randomly assigning study subjects into groups, interventions with adipose tissue-derived extracellular vesicles (AT-EVs) and placebos are conducted to evaluate whether AT-EVs can promote effective healing of recalcitrant wounds.


Eligibility Criteria:
Inclusion Criteria:

* 1. Age 18 to 69 years old, regardless of gender 2. Full-layer skin ulcers on various parts of the body, lasting from 4 weeks to 1 year

  1. If the wound is post-amputation, the time from surgery must be \>30 days;
  2. If there is \>1 wound surface, the maximum wound surface is selected as the research target; 3. At the beginning of the induction period, the wound size after debridement was ≥1 and ≤20 cm2; 4.Texas classification 1A, 1B, 1C, 1D, 2A, 2B, 2C or 2D; 5. Ankle-brachial index ≥0.7, including percutaneous oxygen pressure (TcPO2) ≥30 mm Hg and cutaneous perfusion pressure ≥30 mm Hg; 6. Revascularization procedures or vascular surgery that are not scheduled in the past or the next 30 days; 7. The subject and family members are willing and able to comply with all prescribed care and medical requirements; 8. The subject has a reasonable expectation of completing the study; 9. The subject completed the 2-week induction period and the wound was reduced by 30%

Exclusion Criteria:

* 1. The subject has signs of gangrene in any part of the trunk and limbs; 2. A written diagnosis of osteomyelitis in any part of the affected limb; 3. Bone tissue at the wound site of the subject is exposed; 4. Poor blood glucose control in subjects: HbA1c\>12% (108 mmol/mol); 5. Subjects are receiving renal dialysis treatment or creatinine \>2.5mg/dl (221mmol/L); 6. The subject has obvious immune deficiency; 7. The subject has suspected tumor or is receiving tumor treatment; 8. Subject has used steroids or immunosuppressants in the past 3 months or is expected to use them during the study; 9. Subjects received growth factor therapy, autologous platelet-rich plasma gel, double-layer cell therapy, dermal substitute, extracellular matrix, etc., during the screening period; 10. The subject has participated in another research device, drug, or biological trial within the past 30 days; 11. The wound shows serious clinical symptoms of infection, requiring hospitalization or immediate surgical treatment; 12. The subject has developed deep vein thrombosis within the past 30 days; 13. The subject is pregnant or breastfeeding; 14. The subject has serious mental illness and psychological disorder; 15. The subject was judged unfit for the test by the attending physician.
Neurophysiological Intraoperative Monitoring During Aortic Surgery

The primary objective of this study is to evaluate if the motor-evoked potentials/motor action potential amplitude ratio and motor action potential amplitude measurement are useful in detecting spinal cord ischemia during thoracoabdominal aortic aneurysms surgery.

The secondary objective is to evaluate the presence of a correlation between neurophysiological changes and other factors (such as surgical maneuvers, anesthetic and physiologic changes) in order to find which factor is the most important in determining spinal cord ischemia.

This study is an observational, single-center, prospective study on patients with thoracoabdominal aortic aneurysms undergoing surgical repair with intraoperative motor-evoked potentials and somatosensory evoked potentials monitoring.


Eligibility Criteria:
Inclusion Criteria:

* satisfied criteria for Intraoperative neurophysiological monitoring;
* sign a written informed consent to participate in the study.

Exclusion Criteria:

* No exclusion criteria