CHOLESTATIC LIVER DISEASE CONSORTIUM (CLIC): LONGITUDINAL STUDY OF GENETIC CAUSE

胆汁淤积性肝病联盟 (CLIC)：遗传原因的纵向研究

• 批准号: 8356694
• 负责人: SAUL J. KARPEN
• 金额: $ 0.79万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8356694
• 关键词: Alagille Syndrome; Ancillary Study; Bile Acid Biosynthesis Pathway; Childhood; Clinical Research; Clinical Trials; DNA; Data Element; Defect; Disease; Etiology; Functional disorder; Funding; Future; Genetic; Grant; Intervention; Intrahepatic Cholestasis; Liver; Liver diseases; Longitudinal Studies; National Center for Research Resources; Natural History; Observational Study; Outcome; Outcome Measure; Patients; Principal Investigator; Progressive intrahepatic cholestasis; Rare Diseases; Research; Research Infrastructure; Resources; Sample Size; Sampling; Source; Specimen; Therapeutic Intervention; United States National Institutes of Health; alpha 1-Antitrypsin Deficiency; biobank; cost; disorder control; improved; longitudinal database

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT This longitudinal observational study will investigate the natural history and progression of four genetic causes of intrahepatic cholestasis of childhood, including alpha-1 antitrypsin deficiency (a1-AT), Alagille syndrome (AGS), progressive familial intrahepatic cholestasis (PFIC), and bile acid synthesis defects (BAD). This study will be conducted as part of the Cholestatic Liver Disease Consortium (CLiC), an NIH-funded multi-centered Rare Disease Clinical Research Consortium. In this study, we will collect defined data elements in a uniform fashion at fixed intervals for five years over a relatively large number of patients with these rare disorders. In addition, a biobank of patient specimens and DNA samples will be established for use in ancillary studies to be performed in addition to this study. By comparing outcome measures between the four liver diseases (i.e., using each disorder as a disease-control for the other disorders), the full impact of each disorder can best be determined in comparison to the other liver diseases. Using the longitudinal database in this fashion, this study will provide an improved understanding of the effects of the cholestatic liver during childhood irrespective of the underlying etiology as well as to the pathophysiology, outcome, and complications of each of the disorders. This initial characterization will allow calculation of sample sizes for future therapeutic intervention clinical trials and provide the baseline to which interventions should be compared.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 抽象的 这项纵向观察性研究将调查儿童期肝内胆汁淤积的四种遗传原因的自然史和进展，包括 α-1 抗胰蛋白酶缺乏症 (a1-AT)、Alagille 综合征 (AGS)、进行性家族性肝内胆汁淤积 (PFIC) 和胆汁酸合成缺陷（BAD）。这项研究将作为胆汁淤积性肝病联盟 (CLiC) 的一部分进行，该联盟是一个由 NIH 资助的多中心罕见病临床研究联盟。在这项研究中，我们将以统一的方式在五年内以固定的时间间隔收集相对大量患有这些罕见疾病的患者的定义数据元素。 此外，还将建立患者标本和 DNA 样本的生物库，用于除本研究之外的辅助研究。 通过比较四种肝脏疾病之间的结果测量（即，使用每种疾病作为其他疾病的疾病控制），可以通过与其他肝脏疾病的比较来最好地确定每种疾病的全面影响。 通过以这种方式使用纵向数据库，本研究将更好地了解儿童期胆汁淤积性肝的影响，无论其潜在病因以及每种疾病的病理生理学、结果和并发症如何。 这一初步特征将允许计算未来治疗干预临床试验的样本量，并提供干预措施比较的基线。