cyrilzakka/clinical-trials huggingface dataset:
Osimertinib With Stereotactic Radiosurgery (SRS) in Brain Metastases From EGFR Positive NSCLC

Investigating potential of controlling brain metastases in patients with EGFR positive NSCLC.

In patients with EGFR positive NSCLC with 1-10 brain metastases, we are investigating whether we can control the macro brain metastases with Stereotactic Radiosurgery (SRS) and control the micro metastases with targeted agent Osimertinib and avoid whole brain radiation that could potentially lead to significant cognitive decline.

Eligibility Criteria:
Inclusion Criteria:

* Confirmed pathology of EGFR mutation positive NSCLC with new brain metastases.
* Ability to care for self and ability to walk 50% of waking hours (ECOG Performance Status of 0-2)
* 1-10 brain metastases with intra-cranial brain metastasis must measure 3cm or less in the greatest dimension.
* Hemoglobin ≥9 g/dL, White Blood Count Absolute ≥3.0 x 10\^9/L, Granulocyte count ≥1.5 x 10\^9/L, and platelet count ≥100 x 10\^9/L
* Serum Bilirubin ≤ 1.5 x upper limit of normal (ULN)
* AST and/or ALT ≤ 2 ULN (≤ 5 x ULN when clearly attributable to liver metastases)
* Serum creatinine ≤ 1.5 ULN or calculated creatinine clearance \> 60ml/min
* For women of childbearing potential-Negative pregnancy test within one week prior to start of therapy.
* For all sexually active male and female patients of reproductive potential, employ two methods of highly effective and acceptable forms of contraception throughout the study and for 120 days following the final dose of osimertinib.

Exclusion Criteria:

* Patients with leptomeningeal metastases documented by MRI or cerebrospinal fluid (CSF).
* Significant intratumoral or peritumoral hemorrhage
* Brain metastases within 5 mm of the optic chiasm or optic nerve
* Brainstem metastases
* Gastrointestinal disorders with diarrhea as a major symptom
* Clinically significant or uncontrolled cardiac disease (NYHA functional classification of 3 or 4)
* Pre-existing interstitial lung disease or pneumonitis
* Unable to undergo brain MRI
* HIV or Hepatitis B or C
* Prior treatments must be resolved to an asymptomatic state at time of enrollment
* Medical conditions that could cause safety risks
* Currently receiving investigational cancer therapy.
* Mean QT interval corrected heart rate (QTc)≥470ms calculated from 3 EKGs
* Left Ventricular Ejection Fraction (LVEF) ≤ 50%
* Use of strong CYP3A inhibitors
* Use of strong CYP3A4 inducers
* Use of potent CYP2C8 inhibitors
* Hypersensitivity to osimertinib or any of its ingredients
* corneal ulceration
* pregnant or breast-feeding
Intermediate Age-related Macular Degeneration - Multimodal Analysis and Longitudinal Study

Study: observational prospective clinical study. Study population: Subjects over 55 years old with drusen secondary to intermediate AMD.

Recruitment: at the Medical Retinal Consultation from the Ophthalmology Department of CHULC.

Primary outcome: Identifying imaging predictors of iAMD progression.

Individuals will be included consecutively and undergo retinal imaging including Color Fundus photography (CFP), Spectral Domain Optical Coherence Tomography (SD-OCT), OCT-Angiography (OCT-A) using Spectralis OCT, with OCT Angiography Module (Heidelberg Eng. GmbH, Germany), in order to characterize:

A. FUNDUS AUTOFLUORESCENCE

1. Analyse the correlation between drusen morphology and autofluorescent findings
2. Analyse the correlation between outer retinal layers morphology and autofluorescent findings
3. Assess anatomic biomarkers of disease progression

B. VASCULAR FINDINGS

1. Test if choriocapillaris perfusion is disturbed in Intermediate AMD patients;
2. Test if retinal capillary plexus perfusion is disturbed in Intermediate AMD patients:

   2.1. Analyze superficial retinal capillary plexus (SCP), 2.2. Analyze deep retinal capillary plexus (DCP);
3. Assess if choroidal and retinal vascular changes are related to disease progression.

Eligibility Criteria:
Inclusion Criteria:

* To verify the existence of drusen secondary to intermediate AMD; Soft, cuticular and reticular pseudo-drusen will be considered.
* Accept and sign the consent.

Exclusion Criteria:

* Patients are excluded if it is not possible to obtain good quality CFP, SD-OCT, OCT-A images, if refractive error is ≥±6D or if there is any evidence of accumulation of extracellular fluid, haemorrhage, exudates or fibrosis.
* Additional exclusion criteria included any history of retinal surgery including laser treatment, signs of diabetic retinopathy, history of retinal vascular occlusion, history of anti-VEGF treatment in the study eye or any signs or history of hereditary retinal or macular dystrophy.
Open-Label, Long-Term Treatment Study, to Assess the Long-Term Safety and Tolerability and Efficacy of Neramexane in Patients With Subjective Tinnitus

The purpose of this study is to investigate the long-term safety and tolerability and efficacy of neramexane mesylate in the long-term treatment of subjective tinnitus after a completed double-blind randomized placebo controlled study


Eligibility Criteria:
Main Inclusion Criteria:

* Male or female patients who have successfully completed one of the double-blind Phase 3 tinnitus studies of Merz with Neramexane mesylate
* patients aged equal or older 18 but not older than 75 years with clinical diagnosis of first onset, persistent (i.e. tinnitus should never be absent for more than 24 hours in a row), subjective, uni-or bilateral subacute tinnitus at the timepoint of the lead-in study

Main Exclusion Criteria:

* clinical diagnosis of intermittent or pulsatile tinnitus
* Patients who have tinnitus as a concomitant symptom of an otological/neurological disease (such as otitis media, Meniére´s disease, otosclerosis etc.)
Feasibility, Tolerability and Efficacy of the Ketogenic Diet in Children With Drug-resistant Epilepsy in South Vietnam

According to the World Health Organization, more than 50 million people have epilepsy. Among them, nearly 80% of epileptic patients live in developing countries and 75% of them do not have access to treatment. The ketogenic diet (KD) has been shown as an effective alternative for patients with drug-resistant epilepsy. Although it has been studied by few studies in Asia, no such studies have been conducted in Vietnam. The purpose of this study was to verify the feasibility, tolerability, and efficacy of the KD in children with refractory epilepsies followed at a pediatric center in South Vietnam.

Children with drug-resistant epilepsy followed at Children's Hospital No.2, Viet Nam treated by KD were included in a prospective study from June 2019 to October 2021. Side-effects, retention rate, number, and duration of seizures were recorded after 1, 3, 6, 9, and 12 months of KD. Patients were considered as responders when a 50% seizure frequency was reached. Tolerance and acceptability of the KD were closely monitored.

Eligibility Criteria:
Inclusion Criteria:

* age from 1 to 10 years at the time of enrolment,
* drug-resistant epilepsy according to the 2010 ILAE criteria,
* an indication for a ketogenic diet trial according to the 2018 ILAE recommendations

Exclusion Criteria:

- clinical or laboratory features suggesting an underlying disease contra-indication the use of a ketogenic diet
Early Life Cohort in Papua Indonesia (ELIPI Study)

Malaria remains an important cause of illness in young infants. Our clinical and epidemiological studies in Papua (Indonesia) have shown the magnitude of malaria morbidity in infants in the first 5 years of life, including recurrent episodes of malaria, anaemia, malnutrition and coinfection. Together these contribute significantly morbidity in early life, and almost certainly to the very high infant mortality rates in this region. However the body of knowledge around infant malaria outside of Africa, where both species P. vivax and P. falciparum are prevalent is considerable smaller. The impact of recurrent vivax malaria and severe anaemia on neurodevelopment and growth in young children is unknown in Papua.

This study therefore aims to provide longitudinal data on the incidence of symptomatic and asymptomatic malaria (P. falciparum and P. vivax) and the associated risk of anaemia. It also provides an opportunity to assess incidence risk of non-malaria febrile illnesses and bacterial co-infections and the long term outcomes in terms of neurodevelopment and growth in a vulnerable age group. The study is a continuation from two already established cohort studies: "STOP MIP", which enrolled pregnant women and followed them until delivery and a "baby-cohort", which enrolled babies from mothers included in the cohort and followed them through their first year of life. Continuous follow up of those babies until they are 4 years old will increase our understanding of long term impact especially of vivax malaria. The cohort will be linked to a randomized controlled trial (RCT) and will offer cohort patients to be enrolled into the RCT when they are diagnosed with malaria (symptomatic), allowing to estimate treatment effectiveness.


Eligibility Criteria:
Inclusion Criteria:

* Patient enrolled in the Baby-Cohort study

Exclusion Criteria:

* Patients not enrolled in the Baby-Cohort study
Preliminary Study of Pediatric Diaphragmatic Elastography

This diaphragmatic elastography study is a preliminary pilot study to have first values of diaphragmatic stiffness in patients with a history of diaphragmatic hernia and to estimate the difference in stiffness compared to a group of patients without a history of hernia.

The hypothesis is to be able to correlate the values found with the patients' symptomatology and thus to better monitor patients by a simple, accessible, painless and reproducible diagnostic tool, to better understand their evolution and even to be able to anticipate possible difficulties (reflux, respiratory disorders, scoliosis, etc.).

Ultrasound elastography is a recent and clinically recognized method that uses an ultrasound approach to determine tissue stiffness in a non-invasive way.


Eligibility Criteria:
Inclusion Criteria:

* Group HDC:
* Patient followed at the CCMR (centres de compétence maladies rares) HDC of the Strasbourg University Hospital
* Aged between 3 and 17 years old inclusive
* Indifferent Sex
* Subject affiliated to a social protection health insurance scheme or beneficiary of such a scheme
* Subject able to understand the objectives and risks of the research and to provide dated and signed informed consent
* Subject who has been informed of the results of the preliminary medical examination

Control group:

* Subject followed in pediatric surgery
* Aged between 3 and 17 years old inclusive
* Indifferent Sex
* Subject affiliated to a social protection health insurance scheme or beneficiary of such a scheme
* Subject able to understand the objectives and risks of the research and to provide dated and signed informed consent
* Subject who has been informed of the results of the preliminary medical examination

Exclusion Criteria:

* Group HDC:

  * Refusal
  * Language barrier
  * Diaphragmatic surgery within the last 3 months
  * Patient with a viral picture in progress at the time of examination (assessment by the investigator)
  * Patient treated with muscle relaxant
  * Inability to give the subject informed information (subject in an emergency situation, difficulties in understanding the subject, etc.)
  * Subject under safeguard of justice
  * Subject under guardianship or curatorship
  * Pregnant or breastfeeding woman

Control group:

* Patient without thoracic pathology
* Refusal
* Language barrier
* Diaphragmatic pathology
* Any myopathy
* History of surgery of the upper digestive tract (esophagus and/or gastric and/or duodenal)
* Patient on muscle relaxant
* Patient with a viral picture in progress at the time of examination (assessment by the investigator)
* Patient treated with muscle relaxant
* Inability to give the subject informed information (subject in an emergency situation, difficulties in understanding the subject, etc.)
* Subject under safeguard of justice
* Subject under guardianship or curatorship
* Pregnant or breastfeeding woman
Oncolytic Virus Ad-TD-nsIL12 for Primary Pediatric Diffuse Intrinsic Pontine Glioma

This is a drug safety assessment clinical trial with a 3+3 dose escalation design, to observe the safety, tolerability and toxicity of a novel oncolytic virus Ad-TD-nsIL12 intratumoral injection in primary DIPG patients (NCI-CTCAE V5.0).


Eligibility Criteria:
Inclusion Criteria:

1. Informed consent of the parents or patient.
2. Patient must be, in the investigator opinion, able to comply with all the protocol procedures.
3. Age 1-18 years.
4. A negative pregnancy test in fertile women (women are considered of childbearing potential (WOCBP) after menarche, unless permanently infertile, including hysterectomy, bilateral salpingectomy, and bilateral oophorectomy).
5. Patient newly diagnosed of DIPG in MRI.
6. Pre-enrollment patients LPS (patients aged ≥1 and \<16 years) and KPS (patients aged ≥16 years) ≥ 50.
7. Lesion considered by the investigator to be accessible for stereotactic biopsy. The location of the lesion allows injection without virus entering the ventricular system.
8. No previous treatment for DIPG.

Exclusion Criteria:

1. Serious infections or intercurrent conditions, including but not limited to severe renal failure, liver failure, heart failure, or bone marrow failure, which are not permitted for inclusion according to the investigator's criteria. Patients must be afebrile at baseline (\<38℃).
2. Other investigational medications within 30 days prior to viral treatment.
3. Participants with immunodeficiency, autoimmune disease, or active hepatitis.
4. Any medical or psychological condition that might interfere with the patient's ability to participate if older than 16 years or parents ability when younger than 16, or give informed consent or would compromise the patient's ability to tolerate therapy or any disease that will obscure toxicity or dangerously alter drug metabolism.
5. Tumor with multiple location.
6. Pregnant or breast-feeding females.
7. Severe bone marrow hypoplasia.
8. Transaminases (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)) or total bilirubin \> 3 times the upper limit of normal.
9. Neutrophils \< 1x10\^9/L.
10. Platelets ≤ 100x10\^9/L.
11. Hemoglobin \< 9 g/dl.
12. Patients with Li-Fraumini syndrome or a known germline defect in the retinoblastoma gene or its associated pathways.
13. Administer any type of vaccine within 30 days prior to Ad-TD-nsIL12 administration.
14. Blood transfusions or drugs (such as G-CSF) within 28 days before baseline to treat pancytopenia or other blood disorders.
Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy.

This study compared the efficacy and safety of ruxolitinib to Best Available Therapy (BAT) in patients with polycythemia vera (PV) who were hydroxyurea (HU) resistant or intolerant and did not have a palpable spleen.

This was a prospective, multi-center, open-label, randomized, Phase IIIb study evaluating efficacy and safety of ruxolitinib versus BAT as selected by the Investigator in patients with PV who are resistant to, or intolerant of HU.

The study comprised of the following periods:

Screening Period (up to 5 weeks: Day -35 to Day -1): Screening evaluations were performed at one or more clinic visits, and reviewed to determine eligibility before the patient was randomized in the study.

Core Treatment Period (Day 1 to Week 80):

Patients were randomized in 1:1 ratio to either treatment group (ruxolitinib or BAT) and were to be treated with their randomized treatment.

Crossover Treatment Period (Week 28 or after) for BAT patients only:

Patients randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib. Patients crossing over on or after Week 28 had to complete all assessments for the End of Treatment (EoT) visit of the Core Treatment Period followed by the assessments in Cross-over visit evaluation schedule.

Extended Treatment Period (Week 80 to Week 260):

Patients receiving ruxolitinib at Week 80 (including patients who have crossed over from BAT) were eligible to continue up to Week 260 in the Extended Treatment Period. Patients continued the ruxolitinib dose that they received at Week 80. Patients who received BAT at Week 80 were not eligible to enter the Extended Treatment Period and had to have the EoT visit at Week 80 and an End of study (EoS) visit 30 days after the EoT visit.

Follow-up Period:

Patients were followed for safety during 30 days after the last dose of study drug and EoS visit assessments were performed post 30 days after the last dose of study drug. Patients who completed EoT (Week 80 for patients who received BAT, Week 260 for patients who received ruxolitinib or from the time of premature discontinuation) were to be followed-up for every 3 months for survival till the end of the study.

Eligibility Criteria:
Inclusion Criteria:

Confirmed diagnosis of PV according to the 2008 World Health Organization criteria, Non-palpable spleen, Phlebotomy dependent, Resistant to or intolerant of hydroxyurea, ECOG performance status of 0, 1 or 2.

Exclusion Criteria:

Inadequate liver or renal function, Significant bacterial, fungal, parasitic, or viral infection requiring treatment, Active malignancy within the past 5 years, excluding specific skin cancers, Previously received treatment with a JAK inhibitor, Being treated with any investigational agent, Women who are pregnant or nursing.

Other inclusion/exclusion criteria apply.
Effect of Interscalene Block on Ventilatory Function

Interscalene block with local anesthetic impairs ventilation (unilateral diaphragmatic dysfunction). Single injection of local anesthetic induced transitory dysfunction (\< 24h). The investigators hypothesized that continuous interscalene block would prolonged ventilatory impairment

Unilateral pulmonary dysfunction occured after interscalene block due to phrenic nerve paralysis. This reduction induced vital capacity alteration and peek flow reduction.Several studies analysed dysfunction recovery duration after single injection using short (lidocaine)or intermediate (ropivacaine, bupivacaine)local anesthetic drug. Because continuous infusion prolonged block duration, phenic nerve may be also prolonged. However no study with continuous interscalene infusion have been performed for this dysfunction.

Eligibility Criteria:
Inclusion Criteria:

* surgery : scheduled for elective shoulder surgery
* available for 1 month of follow up
* physical status : 1, 2, 3

Exclusion Criteria:

* body mass index \> 35
* contraindication for interscalene block (local sepsis, bleeding, allergy, peripheral neuropathy)
* vital capacity less than 1.5 liters
* cardiac or renal insufficiency
* physical status \>3, pregnant, weigh less than 50 kg
Internet-based Intervention Culturally Adapted for Treatment of Depression in the Ecuadorian Population

Internet-Based Interventions are increasingly relevant as an alternative for reducing the gap in treatment of metal disorders such as depression, especially in resource-limited regions.

In this study the investigators will try to evaluate the effectiveness of an Internet-Based Intervention culturally adapted to the Ecuadorian population for treatment of depression.

Our participants will be randomized to one of the following three conditions: 1) Internet-Based intervention (IBI) with automated support (e.g. e-mails or text messages), 2) IBI plus human support by phone calls (automated + human support), 3) Waiting list control group .

The corresponding evaluations of the outcomes will be carried out at different moments of the process: baseline, three, six and twelve months.

This study will use the Smile is Fun program for the treatment of depression previously adapted to the Ecuadorian context.

Eligibility Criteria:
Inclusion Criteria:

* Ability to understand and read Spanish and access to Internet and having an email address
* Access to a computer or smart phone with internet at home
* Criteria for diagnosis of depression disorder according to the MINI interview and score between 5 to 9 (mild) 10 to 14 (moderate) and 15 to 19 (Moderate/severe) on PHQ-9

Exclusion Criteria:

* Scores 20-27 (severe depression) on PHQ-9
* Suicidal risk
* Severe psychiatric disorders (schizophrenia, substance dependence, bipolar disorder, psychotic illness)
* Receiving psychological treatment for depression at the time of recruitment
Long-Term Treatment Effect of DiaPep277 in Type 1 Diabetes

The study is an open-label extension study, offering patients who participated and completed previous study 901 to continue treatment with DiaPep277 and clinical follow-up, for 2 additional years. The expectation is first to demonstrate that extended treatment with DiaPep277 is safe and second to evaluate the long-term effectiveness of treatment. Only patients who completed the previous 2-year study and still have beta-cell function above a threshold level will be eligible for this extension study.


Eligibility Criteria:
Inclusion Criteria:

* A patient that participated in previous 461/PO and 901 studies and received all doses of study medication, per protocol.
* Evidence of clinically significant residual beta-cell function demonstrated by MMTT stimulated C-peptide concentrations ≥ 0.20 nmol/L.

Exclusion Criteria:

* The patient is pregnant or intends to become pregnant or is unwilling to use effective contraceptive method throughout the study.
* The subject has clinical evidence of any diabetes-related complication, or severe allergy or immune deficiency.
Multiparametric Assessment of Maternal Vascular Function in the Prediction of Hypertensive Disorders of Pregnancy

The present study is a single-centre prospective study that will enrol pregnant women during their first trimester of pregnancy (11+0 - 13+6 weeks of gestation).

During pregnancy, women will undergo standard clinical evaluation and management. During the two study visits (enrollment and 24+0 - 27+6 weeks of gestation) the investigators will perform arterial tonometry (Pulsepen) and in vivo darkfield microscopy (Glycocheck) to evaluate endothelial and vascular function. A urine sample and a blood sample for specific study analyses on metabolic profile, endothelial and angiogenic markers will be collected. Pregnancy outcomes will be collected at delivery and five years after delivery all the participants will be interview to collect long-term cardiovascular outcomes. Serum endothelial and angiogenic markers will be evaluated only in participants who will develop hypertensive disorders of pregnancy and in an equal number of controls matched for age and body mass index at the time of conception.

Primary aim:

To determine the role of the combination of arterial tonometry and endothelial glycocalyx measurement in predicting the risk of developing hypertensive disorders in pregnancy.

Secondary aims:

* To determine the association between circulating markers of angiogenesis and endothelial dysfunction (ANG-1, ANG-2, ET-1, ICAM-1 and VCAM-1) and the development of hypertensive disorders of pregnancy.
* To define the trends of serum uric acid, lipids and xanthine oxidase activity in normotensive and hypertensive pregnancies.
* To determine the ability of the combination of arterial tonometry and endothelial glycocalyx measurement, performed in the two study visits during pregnancy, in predicting the risk of long-term maternal cardiovascular disease.

Eligibility Criteria:
Inclusion Criteria:

* Age greater than or equal to 18 years
* Single pregnancy
* No previous pregnancies lasting more than 12 weeks
* Participant willing and able to give informed consent for participation in the study

Exclusion Criteria:

* Intermediate-high risk of genetic abnormalities and/or need to perform invasive tests (amniocentesis, villocentesis)
* History of solid organ or hematopoietic stem cell transplantation
* Chronic renal failure (eGFR≤45ml/min/1.73m2)
* Chronic treatment with antihypertensive drugs and/or xanthine oxidase (XO) inhibitors