BCM/TCH CHOLESTATIC LIVER DISEASE CONSORTIUM

BCM/TCH 胆汁淤积性肝病联盟

基本信息

批准号：
10414980
负责人：
BENJAMIN L SHNEIDER
金额：
$ 43.19万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-10 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10414980
关键词：
Acetylcysteine Address Adjuvant Therapy Alagille Syndrome American Bacterial Genes Bile Acid Biosynthesis Pathway Bile Acids Bile fluid Biliary Atresia Biological Markers Child Child Health Childhood Cholestasis Clinical Clinical Data Clinical Research Clinical Trials Cystic Fibrosis Defect Development Diagnosis Disease Duct (organ) structure Enrollment Etiology Evidence based treatment Feces Fibrosis Funding Gene Expression Profile Genomics Hepatology Hour Impairment Individual Infant Inflammatory Bowel Diseases Intervention Intravenous Investigation Lead Leadership Life Liver Liver diseases Longitudinal Studies Medicine Metagenomics Methods Mitochondria Morbidity - disease rate Observational Study Outcome Outcome Measure Pathogenesis Patients Pattern Pediatric Hospitals Performance Phase Pilot Projects Progressive intrahepatic cholestasis Protocols documentation Research Research Activity Research Personnel Role Safety Sampling Sclerosing Cholangitis Serum Severity of illness Testing Texas Translational Research Treatment Factor United States Validation Whole-Genome Shotgun Sequencing alpha 1-Antitrypsin Deficiency base clinical center clinical investigation clinical phenotype college data repository disease phenotype disease prognosis feasibility trial fecal microbiome follow-up genome sequencing gut microbiome improved improved outcome liver transplantation longitudinal analysis metropolitan microbial signature microbiome analysis microbiome research microbiome signature mortality novel open label pilot trial population based primary outcome primary sclerosing cholangitis prospective research study secondary outcome stool sample trial design whole genome

项目摘要

Project Summary Cholestatic liver diseases including Alagille syndrome, alpha-1 antitrypsin deficiency, bile acid synthesis defects, biliary atresia, cystic fibrosis, mitochondrial hepatopathies, progressive familial intrahepatic cholestasis and primary sclerosing cholangitis, lead to significant morbidity and mortality in childhood, frequently necessitating liver transplantation. No single North American clinical center sees a large enough number of patients with these disorders to permit a rigorous approach to addressing unresolved questions including etiology and pathogenesis, optimal methods of diagnosis and treatment, and factors that influence disease severity and prognosis. This competitive renewal proposal from the Baylor College of Medicine and Texas Children's Hospital (BCM/TCH) seeks to continue ongoing research activities in the Childhood Liver Disease Research Network (ChiLDReN). This application for renewal funding includes a strong commitment to continuing the on-going research efforts and two new proposals, a novel pilot and feasibility clinical trial applied to biliary atresia and a translational protocol focused on the pathogenesis of sclerosing cholangitis. The clinical center at BCM/TCH includes an outstanding group of clinician investigators with an extensive track record in synergistic translational and clinical research relevant to pediatric liver diseases. Performance to date in the on-going studies of ChiLDReN has been exemplary and has taken full advantage of a predominant market share of the population base of the Houston metropolitan region (5th largest in the United States) and the large referral patterns to TCH as a quaternary center for Pediatric Hepatology and Liver Transplantation. A pilot and feasibility trial of intravenous NAC will be conducted as an open label investigation in infants undergoing hepatoportoenterstomy for biliary atresia (IND 135796 and NCT03499249). The primary outcome measure will focus on biomarkers of bile flow. Promising findings in this pilot study could be expanded to a larger scale multi-center investigation as part of ChiLDReN. The proposed translational protocol will use metagenomic whole genome sequencing to assess the bacterial fecal microbiome in children with sclerosing cholangitis and correlate microbial signatures and bacterial gene expression patterns with clinical phenotypes characterized in the newly developed prospective observational study of primary sclerosing cholangitis in children.

项目摘要包括阿拉吉尔综合征，α-1抗胰蛋白酶缺乏，胆汁酸合成在内的胆汁淤积性肝疾病缺陷，胆道闭锁，囊性纤维化，线粒体肝病，进行性家族性肝内胆汁淤积和原发性硬化性胆管炎，导致童年的发病率和死亡率显着，经常需要肝移植。没有一个北美临床中心看到足够多的这些疾病的患者允许一种严格的方法来解决未解决的问题病因和发病机理，诊断和治疗的最佳方法以及影响疾病的因素严重性和预后。贝勒医学院和德克萨斯州的竞争性更新提案儿童医院（BCM/TCH）寻求继续在儿童期肝病中继续进行的研究活动研究网络（儿童）。此续签资金申请包括对继续进行正在进行的研究工作和两项新建议，新的飞行员和可行性临床试验应用了胆道闭锁和转化方案的重点是硬化性胆管炎的发病机理。临床 BCM/TCH的中心包括一群出色的临床研究人员，具有广泛的记录与儿科肝病有关的协同翻译和临床研究。迄今为止的性能对儿童进行的持续研究是模范的，并且已经充分利用了一个主要的市场休斯顿都会区（美国第五大）和大型人口基地的份额 TCH作为小儿肝病学和肝移植的第四纪中心的转介模式。飞行员和静脉NAC的可行性试验将作为接受婴儿的开放标签研究用于胆道闭锁的肝脏肠道术（IND 135796和NCT03499249）。主要结局措施将专注于胆汁流的生物标志物。在这项试验研究中有希望的发现可以扩展到更大的规模多中心调查是儿童的一部分。提出的翻译协议将使用元基因组整个基因组测序以评估硬化性胆管炎儿童的细菌粪便微生物组将微生物特征和细菌基因表达模式与临床表型相关新开发的对儿童原发性硬化性胆管炎的前瞻性观察性研究。