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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 抽象的 这项纵向观察性研究将研究儿童肝内胆汁淤积的四个遗传原因的自然历史和进展，包括alpha-1抗胰蛋白酶缺乏症（A1-AT），阿拉吉尔综合征（AGS），进行性家族性肝内胆汁淤积性胆汁淤积（PFIC）和比氏酸合成（BAD）。这项研究将作为NIH资助的多中心稀有疾病临床研究联盟的胆固性肝病联盟（CLIC）的一部分进行。在这项研究中，我们将在相对较大的患有这些罕见疾病的患者中以固定的时间间隔以固定的时间间隔以固定的方式收集定义的数据元素。 此外，除本研究外，还将建立一组患者标本和DNA样品的生物库，以用于辅助研究。 通过比较四种肝病（即使用每种疾病作为其他疾病的疾病对照）之间的结果测量方法，可以最好地确定每种疾病的全部影响与其他肝脏疾病相比。 该研究使用纵向数据库，将对儿童期胆汁淤积性肝脏的影响有所改善，无论对潜在的病因以及每种疾病的病理生理学，结果和并发症的影响如何。 此初始表征将允许计算样本量以进行将来的治疗干预临床试验，并提供了应比较干预措施的基线。