cyrilzakka/clinical-trials huggingface dataset:
APR-548 in Combination With Azacitidine for the Treatment of TP53 Myelodysplastic Syndromes (MDS)

Phase 1 study evaluating the safety and efficacy of APR-548 in combination with Azacitidine for the treatment of TP53-Mutant Myelodysplastic Syndromes.

Open-label first-in-human (FIH) phase 1 clinical trial assessing the safety, pharmacokinetics (PK), and clinical activity of orally (p.o.) administered APR-548 alone and in combination with azacitidine for the treatment of TP53-mutant myelodysplastic syndromes (MDS).

Eligibility Criteria:
Inclusion Criteria:

1. Provision of signed and dated, written informed consent prior to any study specific procedures.
2. Documented diagnosis of TP53-mutant MDS, according to WHO criteria that is relapsed/refractory or previously untreated MDS.
3. Adequate organ function as defined by the following laboratory values:

   1. Creatinine clearance ≥60 mL/min (by Cockcroft-Gault method, Appendix I),
   2. Total serum bilirubin ≤1.5 × upper limit of normal (ULN) unless due to Gilbert's syndrome or MDS organ involvement,
   3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN, unless due to MDS organ involvement.
4. Age ≥18 years at the time of signing the informed consent form.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Appendix II).
6. Projected life expectancy of ≥12 weeks.
7. Clear ocular media and adequate pupil dilation to permit fundus examination and retinal imaging.

Exclusion Criteria:

1. Cardiac abnormalities, which includes, but not limited to:

   1. Myocardial infarction within six months prior to enrollment
   2. New York Heart Association Class III or IV heart failure or known LVEF \<40%
2. Concomitant malignancies or previous malignancies with less than a 1 year disease-free interval at the time of signing informed consent.
3. Use of cytotoxic chemotherapeutic agents, or experimental agents for the treatment of MDS within 14 days or 5 half-lives of the product (whichever is shorter) of the first day of study drug treatment.
4. Prior exposure to eprenetapopt (APR-246).
5. A female subject who is pregnant or breast-feeding.
6. Known history of human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection.
7. Malabsorption syndrome or other condition likely to affect gastrointestinal absorption of APR-548.
8. Known history or current evidence of ocular disease in either eye
Cervical Preparation of Abortions Under Paracervical Block in the First Trimester:

Surgical abortion is one of the most frequently surgery of women in the world. 43 millions are annually performed in the world.

90% of the abortions are performed during the first trimester of pregnancy before 13 weeks. Legal surgical abortion during the first trimester of pregnancy is a low risk intervention with a mortality rate lower than 1/100 000 abortions, with a risk of complications from 0.3 % to 3.4 %.

Surgical abortion is one of the most frequently surgery of women in the world. 43 millions are annually performed in the world.

Legal surgical abortion during the first trimester of pregnancy is a low risk intervention with a mortality rate lower than 1/100 000 abortions, with a risk of complications from 0.3 % to 3.4 %. In France, about 75 % of the surgical abortions are performed under general anesthesia (GA). Nevertheless, the risk of complications is higher under GA. The risk of death is more important (0,58 for 100 000) with GA. GA increases by a factor 1,7 the risk of bleeding, 2,2 the risk of uterine perforation, 8,2 the risk of intra-abdominal bleeding, 2,9 the risk of cervical tearing, and 5 the risk of transfusion. The difficulty of pain control under local anesthetia (LA) explains this method is less choosen by the women. Indeed, a lot of women consider the surgical abortion under LA extremely uncomfortable. The paracervical block for the abortion under LA in the first trimester demonstrated its efficiency in the reduction of the per-operating pain whatever the term of the pregnancy compared with the absence of anesthesia. The cervical preparation demonstrated benefits in term of cervical dilation, per-operating bleeding, and complications incidence. The misoprostol and the mifepristone are 2 molecules recommended for the cervical preparation on the first trimester

Eligibility Criteria:
Inclusion Criteria:

aged 18 or over with a single intra uterine pregnancy whose term is between 6 and 14 weeks the day of the abortion estimated by ultrasound by a measurement of the cranio-caudal length between 5 and 84 millimeters surgical abortion under local anesthesia informed written consent

Exclusion Criteria:

minor multiple pregnancy Uterine malformation coagulation disorder defined by biological parameters (TP\<70%, TCA patient / control ratio \< 1.20) Allergy or hypersensitivity to any of the active substance or to any of the excipients Contraindication to mifepristone chronic renal insufficiency severe asthma uncontrolled by treatment hereditary porphyria allergy to the active substance or to any of the excipients; not affiliated to the social security system; no informed consent. Suspicion of ectopic pregnancy
Regional Registry-based Biobank Development and Pharmacogenetic Analysis in Rheumatoid Arthritis

Aim of this project is the building-up of an integrated model of multidisciplinary research tools to support large-scale and high-quality disease-based studies.

Biologics have revolutionized rheumatoid arthritis (RA) management, with a great impact on patient that justifies treatment with these high-cost drugs. Nevertheless, timing and proper therapeutic decision making remain the main challenge in clinical practice.

Pharmacogenetics approach might open promising perspectives, increasing our understanding on genetic-related drug efficacy. Nevertheless, to ensure feasibility and reliability of translational applications of this strategy in clinical practice, large population-based research studies represent a crucial key step.

Objectives

Major aim of this project is the building-up of an integrated model of multidisciplinary research tools to support large-scale and high-quality disease-based studies. The main targets of this proposal will be:

* to develop a disease-based biobank, integrated with already established Emilia-Romagna regional RA Registry, providing a large-scale prospective collection and storing of multiple biological samples
* to perform a pharmacogenetic study analyzing a panel of gene variants potentially influencing the response to Tumor Necrosis Factor (TNF) blockers. Methods
* Biobank development. A step-wise plan will be considered for: designing biobank governance frame-work, defining Standard Operating Procedures, implementing information system resources. All these procedures will be applied for collecting, processing and storing biological samples of patients included in regional RA registry.
* Pharmacogenetic study. A panel of candidate gene variants will be studied in genomic DNA from 300 patients enrolled in the regional RA registry. The association between genotypes and response to biological drugs will be assessed by data-mining approach, and a predictive model will be defined. Expected Results This proposal will create a disease-based biobank, tightly integrated with the already established Emilia-Romagna regional RA Registry, and pave the way towards personalized therapy applications in Rheumatology.

Eligibility Criteria:
Inclusion Criteria:

1. Diagnosis of Arthritis Rheumatoid according American College of Rheumatology (ACR)1987 or according ACR/European League Against Rheumatism (EULAR) 2010 criteria
2. Patients with new diagnosis or patients already diagnosed with active disease \[with Disease Activity Score (DAS) 28 \> o = 4,2\] or patients switching therapy
3. Male and female patients of minimum 18 years old
4. Provision of informed consent

Exclusion Criteria:

1) Patients living outside Emilia Romagna region
Effect of Ketamine Infusion on BIS Values

Aim of this trial is to define if Concentration at the effector site (Ce) of Ketamine, during a continuous infusion and calculated with DOMINO model infusion pump are correlated with Bispectral Index BIS values during general anaesthesia for breast surgery.

Correlation between Concentration at the effector site (Ce) of Ketamine and Bispectral Index (BIS) values during general anaesthesia for breast surgery has not been defined yet during a continuous infusion.

Authors want to analyze this correlation during general anaesthesia conducted using Propofol, ketamine and remifentanil. All of these drugs will be delivered with Target-Controlled Infusion pumps (in particular Eleveld for Propofol, Minto for Remifentanil and Domino for Ketamine).

Ketamine will be observationally set at anaesthesiologist's discretion, but only CeK 0.1, 0.2, 0.4 and 0.6 for at least 30 minutes will be considered for analysis.

Eligibility Criteria:
Inclusion Criteria:

* Undergo general anaesthesia with Targeted Controlled Infusion of Ketamine (Domino model), Propofol (Schnider model) and Remifentanil (Minto model)

Exclusion Criteria:

* Neurological disease
* Psychiatric disease
* Benzodiazepines intake
* Obesity
Sacral Erector Spinae Plane Block in Normal Birth

Pregnant women feel severe pain during normal birth and in the postpartum period. Preventing pain during and after birth is very important for both the mother and the baby. Rapid recovery in the postoperative period in pregnant women is very important for both mother and baby. To evaluate this recovery, the quality of recovery-10 scores developed by Shalev et al. are used in pregnant women. Our study will be the first in the literature to use sacral erectör spinae plane block (S-ESPB) in normal birth. Our primary aim in this study is to evaluate the effects of S-ESPB on the quality of recovery and recovery at the 24th hour in pregnant women who will undergo vaginal birth with epidural analgesia, using the Quality of Recovery-10T scores.

Pregnant women feel severe pain during normal birth and in the postpartum period. Preventing pain during and after birth is very important for both the mother and the baby. Rapid recovery in the postoperative period in pregnant women is very important for both mother and baby. To evaluate this recovery, the quality of recovery-10 scores developed by Shalev et al. are used in pregnant women. Our study will be the first in the literature to use sacral erectör spinae plane block in normal birth. Our primary aim in this study is to evaluate the effects of sacral erectör spinae plane block on the quality of recovery and recovery at the 24th hour in pregnant women who will undergo vaginal birth with epidural analgesia, using the Quality of recovery-10T score. the numeric rating scale at the 0-15th minute-30th minute-45th minute-1-2-4-8-12-24th hour after the S-ESPB application, and to evaluate the patient satisfaction at the 24th hour with a Likert scale. , the total amount of rescue analgesic ( bupivacaine ) consumed since the application of sacral erectör spinae plane block, the number of pregnant women given oxytocin, the time of the first breastfeeding, complications in the mother (fever, nausea, vomiting, motor block, hip pain), the need for antiemetics, the baby's 1st and 5th minutes. Apgar score at the 1st-2nd-3rd week of birth. is to evaluate the duration of the phases .

Eligibility Criteria:
Inclusion Criteria:

* 36-42. Pregnant women who are their gestational age and request epidural anesthesia
* Pregnant women aged 18-42 with ASA II
* Pregnant women who will stay in the hospital for at least 24 hours
* Primiparous pregnant women who will have a planned normal birth
* Singleton births with vertex presentation

Exclusion Criteria:

* Pregnant women who do not want to give consent
* Regional anesthesia is contraindicated
* Pregnant women who use anticoagulants and have an abnormal bleeding profile
* Pregnant women with infection in the area to be treated
* Emergency cases and pregnant women who had a birth with instruments (forceps and vacuum)
Advanced Multi-Modal Wearable Sensing for the Prediction of Pre-Term Labor

Percent agreement of vital signs monitoring between the experimental sensor and standard of care monitoring

The primary objective of the Prentice study is to assess and validate EMG performance of the new home-use sensor with extended battery life in detecting continuous EHG in a range of uterine contraction intensities, frequencies, and durations compared to gold-standard FDA-cleared tocodynamometer (GE Corometrics 250cx) in non-stress testing for antepartum surveillance.

An "at-home" study will validate the developed modifications to the wearable sensors system that provides a continuous electrohysterography (EHG) along with other additional physiological parameters (e.g. heart rate, heart rate variability, sleep quality, physical activity, and continuous blood pressure) for longitudinal monitoring in the home setting.

Eligibility Criteria:
* Maternal age \>18 years old
* Pregnant mothers \>13 weeks (home study only)
* Pregnant mothers \>26 weeks undergoing nonstress testing or delivering
* Singleton pregnancy (inpatient or clinic visit patients only)
* History of preterm labor or premature birth, active smoker, chronic condition (ex: HTN or DM), or an interval of less than 6 months between the prior pregnancy
* Singleton pregnancy (home study only)
* No fetal abnormality or chromosomal abnormality
* Subjects willing and able to comply with requirements of the protocol

Exclusion Criteria

* Women who refuse to signed the informed consent form
* Maternal age under 18 years old
* Multiple pregnancy
* Known major fetal malformation or chromosomal abnormality
* Medical or obstetric problem that would preclude the use of abdominal electrodes
* Inability to consent to this study due to medical illness, diminished intellectual capacity, or language barrier
* Women using pacemakers
A Pilot Study to Evaluate the Pharmacokinetics of Omega-3 Between Rosuvastatin and Omega-3 Coadministration and HCP1007

The purpose of this study is to evaluate the pharmacokinetics of omega-3 between rosuvastatin and omega-3 coadministration and HCP1007 in healthy male volunteers.


Eligibility Criteria:
Inclusion Criteria:

* Adult male aged 20 to 55 years
* A body mass index between 19 and 27 kg/m2

Exclusion Criteria:

* History of hepatobiliary, renal, gastrointestinal, respiratory, musculoskeletal, endocrinal, hemato-oncologic or cardiovascular disease
* SBP \< 90 or ≥ 150 mmHg, DBP \< 60 or ≥90 mmHg
* Use of herbal medicine within 30 days, prescriptive medicine within 14 days, or over-the-counter drug within 7 days
* Heavy alcohol consumption (140 g/day)
A Study of SC10914 in Patients With Advanced Solid Tumors

SC10914 is a potent selective PARP-1 and PARP-2 inhibitor. This study aims to determine the safety , tolerability , pharmacokinetic/pharmacodynamics profile of increasing doses of SC10914 when administered orally to patients with advanced solid tumors. Furthermore, the safety and efficacy of SC10914 in patients with advanced solid tumors and negative expression of ATM or BRCA1 or BRCA2 mutation will be evaluated in expanded cohorts to establish the Recommended Phase 2 Dose(RP2D).


Eligibility Criteria:
Inclusion Criteria:

* Signed written informed consent
* Aged 18-70 years
* Dose escalation study: Subjects diagnosed with advanced solid malignancies who are refractory to standard therapies or for which no standard therapy exists/Dose Expansion study: Subjects diagnosed with advanced solid malignancies who are refractory to standard therapies or for which no standard therapy exists and negative expression of ATM or BRCA1 or BRCA2 mutation
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* Have measurable lesion exists(RECIST 1.1)
* Life expectancy≥3 months
* Have adequate bone marrow, hepatic and renal functions

Exclusion Criteria:

* Allergic constitution or hypersensitivity to investigational drugs or relevant drug
* Patients who received any previous treatment with a PARP inhibitor
* Patients accepted anti-cancer therapy including chemotherapy, radiotherapy, endocrinotherapy, immunotherapy, Chinese herbal treatment or other investigational drugs within 4 weeks prior to trial entry (or a longer period depending on the defined characteristics of the drugs used eg,. 6 weeks for mitomycin C or nitrosourea)
* With serious pre-existing medical conditions, such as significant cardiovascular disease and psychogenic disorders
* With family history of long QT syndrome or QTc ≥ 450 ms
* With persistent CTCAE ≧grade 2 toxicities (excluding alopecia) caused by prior medication
* With symptomatic brain metastases
* Pregnancy or lactation
* With Hepatitis B or C or human immunodeficiency virus infections
Head-Cancelled Virtual Reality for Ocular Cranial Nerve Palsies

This study is investigating whether eye exercises for abducens palsy and internuclear ophthalmoplegia increase ocular range of motion in the paretic direction when performed in virtual reality under head-cancelled compared to head-active conditions.

Participants with abducens palsy or internuclear ophthalmoplegia, two common types of ocular cranial nerve palsies, will perform 3 different tasks in virtual reality under head-cancelled and head-active conditions. Head active is the normal state, where gaze can be shifted by moving the head, the eyes, or a combination of the two. Head-cancelled refers to the condition where the scene moves with the head, rendering head movement ineffective to shift gaze. In this condition, the eyes must move in order to shift gaze. The hypothesis is that this requirement for eye movement will result in larger eye movements, which could be therapeutic. The tasks performed under the two conditions will include horizontal transposition of coins, repetitive horizontal saccades, and game play. The primary analysis will be a within subject's comparison of eye movement amplitude in head-cancelled (experimental) versus head-active (control) conditions. Additionally, as a control comparison for secondary analysis, a group with normal vision will also perform the tasks under both conditions.

Eligibility Criteria:
OCNP Group Inclusion Criteria:

* Presence of OCNP in one eye with 50% range-of-motion limitation or worse
* Able to provide informed consent and will be able to fluently read and understand spoken English

OCNP Group Exclusion Criteria:

* Presence of bilateral OCNP
* Range of motion better than 50%
* Visual acuity worse than 20/100 in either eye
* Greater than 4-line difference in visual acuity between the eyes,
* Structural anomalies or sensory sensitivities (e.g. visual motion sensitivity) that would prevent them from wearing or tolerating a VR headset

Participants will be excluded if they are unable to participate if inclusion criteria are not met.

Normal Group Inclusion Criteria:

* Absence of OCNP or other neurological or neuro-ophthalmic diseases
* No strabismus
* Have normal or near-normal vision with glasses or contact lenses.
* Be able to provide informed consent and will be able to fluently read and understand spoken English

Normal Group Exclusion Criteria:

* Visual acuity worse than 20/100 in either eye
* Greater than 4-line difference in visual acuity between the eyes
* Structural anomalies or sensory sensitivities (e.g. visual motion sensitivity) that would prevent them from wearing or tolerating a VR headset
* Known inability to tolerate visual testing of at least 20 minutes continuously.
Directly Observed Therapy for Community-Released HIV+ Prisoners

The aim of this study is to develop effective interventions for HIV-infected prisoners who are released to the community. The intervention that we will study will be directly observed therapy (DAART/DOT) and we will compare this to the current standard of care that involves self-administered therapy (SAT). All subjects will get transitional case management and all subjects with a prior history of opiate dependence will be offered opiate substitution therapy (buprenorphine or methadone).

Hypotheses:

* At the end of six months those receiving DAART will have a higher level of adherence to HAART as compared to the SAT group.
* The DAART Intervention will result in subjects having lower viral loads and higher CD4 counts as compared to the SAT group.
* At the end of six months, the DAART group will have a lower rate of recidivism to jail/prison as compared to the SAT group.
* Over the year, the DAART group will be more likely to make repeated primary HIV care visits than the SAT group.

Any individual that is HIV positive and incarcerated for at least a period of 90 days and on antiretroviral medications would be referred to the study by the medical staff of the incarceration facilities prior to release or within 30 days of release an individual would be able to self refer.

Subjects would be screened and consented and interviewed prior to their release from incarceration, on their day of release, and monthly for a period of one year. At the time of their day of release interview, subjects are randomized to either the intervention DAART group or the standard of care SAT group. All subjects would be assessed and offered opiate substitution therapy if there was a prior history of opiate dependency as a means of relapse prevention.

Subjects in DAART would be seen everyday for a period of six months by a team of research assistants who observe the subjects taking their medications, and their last six months would be done as standard of care. Standard of care SAT subjects would continue to take their medications on their own as prescribed. All subjects would be interviewed monthly and quarterly would have laboratory blood tests completed.

Eligibility Criteria:
Inclusion Criteria:

* HIV seropositive
* 18 years of age or older
* incarcerated for a minimum of 90days
* living in New Haven or Hartford
* currently on HAART or willing to begin HAART medications

Exclusion Criteria:

* Not meeting inclusion criteria
Effectiveness of Bracing in Preventing Scoliosis in Children With Spinal Cord Injury

The purpose of this study is to determine whether full-time high dose prophylactic bracing (23 hours or more per day) is more effective than low dose bracing (12 hours or less per day) in preventing or delaying spinal curve progression in children with scoliosis after spinal cord injury.

This is a randomized control trial to determine the effectiveness of high dose bracing (≥ 23 hours per day) and low dose bracing (≤ 12 hours per day) in skeletally immature children with Spinal Cord Injury. Subjects will be randomized into either a prophylactic high dose-bracing group (≥ 23 hours per day) or low dose-bracing group (≤ 12 hours per day). Subjects will be stratified by age (younger than age 10 and older than age 10), and curve severity (\< 20 degrees and 20-40 degrees) using a matching random blocks design.

Eligibility Criteria:
Inclusion Criteria:

1. Children with C5 to L2 SCI.
2. ASIA impairment levels A, B, or C.
3. Age greater than 5 up to one year before end of growth (14 in girls, 16 in boys)
4. A single structural curve \<40 degrees or a double curve \<40 degrees where the largest compensatory curve is \<25 degrees on bending film.
5. Children at risk for Paralytic Scoliosis
6. Ability to follow simple instructions.

Exclusion Criteria:

1. Curve magnitude \>40 degrees, pressure sores over the trunk.
2. Inability to tolerate TLSO wears.
3. Structural compensatory curves of 25 degrees or greater (double structural curves).
4. Severe Traumatic Brain Injury, TBI (8 and below on Glasgow Coma Scale).
5. Cognitive Impairment
6. Less than 6 months from date of injury