Clinical Trials

The objective of the study is to investigate the efficacy of fresh, frozen or lyophilized fecal microbiota transplantation (FMT) via colonoscopy in patients with recurrent C. difficile associated diarrhea (RCDAD). Frozen, lyophilized or fresh fecal microbiota transplantation (FMT) inoculum will be generated from well-screened healthy volunteer donors of ≥150 gram/sample. Delivery of FMT will be performed colonoscopically. Fecal samples from donors and recipients will be saved for later metagenomic studies to characterize the microbiome of the gut in patients before and after FMT.

The purpose of this study is to analyze associations between symptoms and specific markers in the blood in patients suffering from neuropathic pain linked to diseases of different origin. Such markers could be utilized in the future for precise diagnosis of neuropathic pain and might lead to targeted pain treatment.

Periodontal wound healing is a complex multifactorial process that involves interactions among various cells, growth factors, hormones and extracellular matrices. Although still poorly understood, these interactions trigger a series of events that lead to new tissue formation. One growth factor that plays an important role in wound healing is fibroblast growth factor 2 (FGF2). Many animal and human studies have shown this protein is effective in periodontal regeneration. Recently, epigenetic modifications, such as DNA methylation, have been associated with changes in patterns of gene expression. Preliminary data suggests that FGF2 gene may be differentially methylated in periodontal tissues. Aberrant gene promoter methylation in smokers and diabetics has also been reported in many studies. However, the role of DNA methylation in wound healing has not yet been investigated. The investigators hypothesize that the methylation status of FGF2 gene can affect the levels of FGF2 secreted during wound healing phase after dental implant surgery. The investigators also hypothesize there exists a difference in methylation levels of FGF2 gene in healthy, smoking and diabetic patients that can interfere with wound healing. The investigators seek to determine whether DNA methylation plays a role in wound healing and whether the methylation level of FGF2 gene varies among healthy, smoking and diabetic patients.

This study will test the theory that therapy designed for each individual's tumor will improve outcomes over standard of care in a population that needs a better standard.

This study aims to evaluate whether a short-term intervention strategy using air cleaner reduces indoor exposure to airborne particles (particulate matter with an aerodynamic diameter ≤2.5μm, PM2.5) and phthalates and improves cardiopulmonary health among Chinese healthy adults based on a randomized double-blinded crossover trial.

To explore the epigenetic mechanism of postoperative analgesia and side effect induced by μ-opioid Receptor Agonists presented with sufentanil among general population.

Identification of biomarkers that can predict the outcome of the surgical treatment (i.e. the rate of re-rupture) of tears in the rotator cuff tendon.

Background The main risk factor for cervical cancer is the infection by human papillomavirus (HPV), with several intermediate steps between HPV infection and cervical cancer. Cervical screening with pap smear test and HPV vaccination are effective preventions. A high frequency of HPV carriage and of cervical dysplasia have been described in transplanted women. The majority of women with cystic fibrosis reach adulthood and some will face transplantation. Particular attention should therefore be paid to cervical screening. However, low adherence to screening recommendations was noted. In addition, preliminary data has found a high frequency of abnormal smears and of inflammatory aspect of the cervix in women with cystic fibrosis. Objectives of the study The main objective of the study is to determine the prevalence of HPV carriage in a cohort of women with cystic fibrosis The secondary objectives are: - To study the factors associated with the prevalence of HPV (transplantation, smoking, age at first intercourse, number of sexual partners in the year, contraception, gravidity and parity, HPV vaccination) - To describe and to compare with data in the general population, in hospital-based population, (and with data in transplanted population for transplanted women) 1. the prevalence of HPV (and of different genotypes) infection, of cervical dysplasia, of vulvar/vaginal/cervical condylomatosis 2. the rate of HPV persistence (> 12 months), the mean time of HPV clearance; rates of spontaneous regression / persistence / worsening of cervical dysplasia Study design: The study will last 24 months. Includable patients are adult women, transplanted or not, followed at Lyon CRCM. Included women will attend a consultation with a gynaecologist. Pap smear test (liquid phase cytology) and genomic DNA microarray assay enabling the detection of 35 different HPV genotypes will be performed. Patients with an initial abnormal pap smear or a positive HPV test will be monitored: - In case of an abnormal smear and / or positive HPV test, pap smear and HPV testing will be renewed every 6 months during the study period - In case of an abnormal smear: Atypical squamous cells of undetermined significance (ASC-US) : the attitude will depend on the result of the HPV test Atypical squamous cells - cannot exclude HSI L (ASC-H), Low-grade squamous intraepithelial lesion (LSIL), High-grade squamous intraepithelial lesion (HSIL), Atypical glandular cell of undetermined significance (AGUS) , Atypical glandular cells (AGC) , Adenoma carcinoma in situ (AIS), carcinoma: a colposcopy will be systematically performed Expected results This study will help to determine the frequency of HPV infection and the pathogenic power of HPV in non-transplanted and in transplanted women with cystic fibrosis This data will help to sensitize health professionals on the importance of gynecological care and regular cervical screening, and on the importance of HPV vaccination. In case of a high frequency of genital diseases linked to HPV, recommendations on gynecological monitoring procedures for women with cystic fibrosis could evolve.

Genetic and environmental factors are believed to play a major role in intrauterine growth and intrauterine programming. We intend to study genetic factors such as Telomere homeostasis, senescence, genomic instability and the presence of Genomic copy number variations in placental tissue from pregnancies complicated with Intrauterine growth restriction(IUGR), Gestational and pre gestational Diabetes, placentas from IVF pregnancies and from normal pregnancies. We also intend to assess these factors in cord blood and maternal blood.

The main goal of this study is to identify mitochondrial mutations associated with presbycusis. Patients affected by severe presbycusis and normal hearing controls (according to ISO7029 norm) will be enrolled if satisfying inclusion criteria (aged from 40 to 80 years old) in existing biocollections in the University Hospital of Angers. After DNA extraction, the mitochondrial genome will be sequenced and data in silico analysed.

Telomeres are protein-bound DNA repeat structures at the end of eukaryotic chromosomes that are made up of a simple repetitive sequence (in humans, TTAGGG) and regulate cellular replicative capacity and cellular proliferation, protect chromosomes from fusing together during mitosis and maintain genomic stability, and prevent the loss of genetic data. Telomeres are specialized repetitive DNA sequences, typically ranging from 5,000 to 15,000 bp in humans, which are the critical chromosome capping DNA sequences. The loss of telomere repeats diminishes telomeric functional capacity.Telomere length(TL) is important in determining telomere function.This is known as the end replication problem and results in a gradual decline in TL over time. Consequently,leukocyte TL shortens in a predictable way with age by roughly 20-40 base pairs per year. Cellular senescence and subsequent cell death often occur when the mean telomere length reaches a critical value.Shortened telomeres and lower telomerase are linked to age-related risk factors and disease.Peripheral blood leukocyte express telomerase at low levels, which can be measured over a short duration (hours) to demonstrate immediate, short-term changes. Shorter mean leukocyte telomere length has been shown to be associated with risk of several age-related diseases.The dosage of propofol gradually reduced with the aging process. However,it is not known whether the telomere length and variation of telomerase in PBL relate to the dosage of propofol and time of consciousness disappearance in anesthesia induction. In this exploratory study, the investigators examined that the changes of peripheral blood leukocyte telomere length was associated with the dosage of propofol and time of consciousness disappearance in anesthesia induction. Given the importance of telomeres in nuclear and cellular function, the central role of telomere length in determining telomere function,the investigator study that the changes of telomere length in peripheral blood leukocyte of patients are associated with the dosage of propofol in anesthesia induction.

Coronary heart disease (CHD) poses a major health burden in the Gulf countries. It is the leading cause of mortality and morbidity in the world and poses an enormous societal burden in the Gulf countries. Early detection of disease is imperative to reduce the health care burden and financial costs associated with CHD. Knowledge of novel genetic and proteomic markers of CHD will provide more precise estimates of risk while defining the pathways important in individual patients, revealing new targets for intervention, and ultimately enabling an individualized approach to care. To translate recent advances in genomics and proteomics into clinical practice, these newly discovered biomarkers will need to be evaluated in patients of diverse ethnic groups with varying characteristics, environmental factors, and medication use. The investigators propose to establish a biorepository of plasma and Deoxyribonucleic acid (DNA) linked to demographic and clinical variables to facilitate biomarker studies of CHD risk, progression, and outcome. The overarching goal in developing the Qatar Cardiovascular Biorepository (QCBio) is to create a resource that fosters research aimed at identifying novel biochemical and genetic markers of CHD. A biorepository with linkage to clinical data will also provide an invaluable resource for cardiovascular research, including genomic and proteomic studies of CHD and development of biomarkers for early detection of disease and personalized drug therapy (pharmacogenetics and pharmacoproteomics).

To explore the genetic background of patients with HER2 positive breast cancer that benefit from trastuzumab combined with neoadjuvant chemotherapy, identify clinically actionable mutations that associated with trastuzumab resistance or drug efficacy, we designed this Observational phase II trial. The primary endpoint is genetic profile of HER2+ breast cancer patients treated with trastuzumab combined neoadjuvant chemotherapy. Secondary endpoints included pathological complete response (pCR) rate and safety.

To assess the indications and diagnostic efficiency of whole genome sequencing (WGS) in pediatric patients with unexplained intellectual disability/developmental delay, multiple congenital abnormalities and other rare and undiagnosed diseases

The purpose of this study is to use genomic information from individual patients to create simulation avatars that will be used to predict novel drug combinations with therapeutic potential.

BACKGROUND: - Wee1 is a tyrosine kinase involved in the phosphorylation and inactivation of cyclin-dependent kinase 1 (CDK1/CDC2)-bound cyclin B, resulting in G2 cell cycle arrest in response to deoxyribonucleic acid (DNA) damage to allow time for DNA repair. Recent preclinical data additionally implicates Wee1 in maintenance of genomic integrity during S phase. - Adavosertib (AZD1775) is a selective inhibitor of Wee1 kinase. Recent preclinical model data additionally show single agent anti-tumor activity in multiple cancer cell lines and tumor xenografts. - Preliminary data show AZD1775 is tolerable at lower doses in combination with chemotherapeutic agents. We propose to demonstrate single-agent activity for AZD1775. PRIMARY OBJECTIVE: - To establish the safety and tolerability of single-agent AZD1775 in patients with refractory solid tumors - To determine the pharmacokinetics of AZD1775 in patients with refractory solid tumors SECONDARY OBJECTIVES: - To determine the effect of AZD1775 on markers of DNA damage and apoptosis in tumor tissue and circulating tumor cells - To evaluate the antitumor activity of AZD1775 in patients with refractory solid tumors EXPLORATORY OBJECTIVES: -To identify tumor genomic alterations and gene expression patterns potentially associated with AZD1775 antitumor activity ELIGIBILITY: - Patients must have histologically confirmed solid tumors for which all standard therapy known to prolong survival have failed, or for which standard therapies do not exist. - No major surgery, radiation, or chemotherapy within 3 weeks or (5 half-lives, whichever is shorter) prior to entering the study. - Adequate organ function STUDY DESIGN: - This study will follow a traditional 3+3 design. - In Arm A starting at dose level 1, AZD1775 will be administered orally, twice a day (BID), for 5 doses (Day (D) 1-3) during each cycle. Starting at dose level 2 and onwards, AZD1775 will be administered orally, BID, for 5 doses for the first 2 weeks of each cycle (D1-3 and 8- 10). Each cycle is 21 days (+/- 1 day for scheduling). - Once maximum tolerated dose (MTD) is established, 6 additional patients will be enrolled at the MTD to further evaluate that dose for pharmacokinetics (PK) and pharmacodynamics (PD) endpoints. - A further expansion arm of 6 additional patients with documented tumors harboring breast cancer type 1 or 2 (BRCA)-1 or -2 mutations will also be enrolled at the MTD to further explore the safety of the agent and obtain preliminary evidence of activity in this patient population. - Based on preliminary evidence of drug activity in an alternative once-daily dosing schedule, patients without a documented BRCA mutation will be accrued to a once-daily dosing schedule Arm B, with mandatory paired tumor biopsies at the maximum tolerated single daily dose, to further evaluate PD endpoints. AZD1775 will be administered orally once daily for 5 days (D1-5 and 8-12) during weeks 1 and 2 of each 21-day cycle (+/- 1 day for scheduling). - During the escalation phase, tumor biopsies will be optional and will be evaluated for pharmacodynamic (PD) studies for evidence of Wee1 inhibition DNA damage and repair, and apoptosis (gamma H2A histone family member X (yH2AX), phosphorylated Nbs1 (pNbs1), Rad51, Rabbit polyclonal phospho-cyclin-dependent kinases (pTyr15-Cdk) and caspase 3). During the expansion phase, once MTD is reached, mandatory paired tumor biopsies will be pursued in up to 20 additional patients enrolled at the MTD to further evaluate PD endpoints.

Autism Spectrum Disorder is a neurodevelopmental disorder characterized by impaired social communication and repetitive or stereotyped behaviors. According to the World Health Organization , the prevalence of Autism Spectrum Disorder is one person in 160.

This study is designed to evaluate whether epigenetic markers in overweight men with type 1 diabetes (T1D) or type 2 diabetes (T2D) can be improved with a 3 month lifestyle intervention or program focused in glycemic intervention.

Microbial communities are key components of human environment. Consequently, human gut microbiome have been extensively studied providing a better understanding of the relations between bacterial populations and host physiology. However, a typical analysis tends to elude the complexity of the mixes in term of species, strains, as well as extra-chromosomal DNA molecules such as and phages. MetaKids project aims at bringing, at an unprecedented resolution, a new view of those populations and the internal relationships during human gut establishment, a crucial step with long-term impacts on host health. This project relies on the ability of Meta3C, a newly technique developed in the lab, to identify the bacterial host genomes of the different phages the investigators will detect thanks to the physical collision these molecules experience. Given the role that human gut phages may play in shaping the development of host microbiomes, their potential for application is of great interest.

SCANDARE is a prospective biobanking study on tumor (+/- nodes), plasma and blood samples at different time points in ovarian, triple negative breast, Head and Neck Cancer, advanced stage treatment-naïve cervical or vulva cancer and sarcoma (breast angiosarcoma and uterine sarcoma) cancers. This study will allowed to identify new molecular and/or immunological biomarkers associated with clinical and biological features of the tumors. All patients will receive standard treatment according to the stage of the diseases and usual procédures.