A RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED TRIAL OF CORTICOSTEROID THERAPY

皮质类固醇治疗的随机、双盲、安慰剂对照试验

• 批准号: 8356692
• 负责人: SAUL J. KARPEN
• 金额: $ 0.67万
• 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/8356692
• 关键词: Address; Adrenal Cortex Hormones; Affect; Bile fluid; Biliary; Biliary Atresia; Child; Childhood; Cholestasis; Clinical; Clinical Research; Clinical Trials; Complex; Data; Development; Diagnosis; Disease; Drainage procedure; Environmental Risk Factor; Epidemiology; Epithelium; Etiology; Extrahepatic Bile Ducts; Fibrosis; Funding; Genetic; Grant; Infant; Inflammatory; Medical; Modeling; National Center for Research Resources; Outcome; Pathogenesis; Patients; Phase; Principal Investigator; Process; Randomized; Research; Research Infrastructure; Resources; Sampling; Source; United States National Institutes of Health; base; biliary tract; cost; double-blind placebo controlled trial; improved; intrahepatic; liver transplantation; postnatal; research study; trait

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 Biliary atresia is the most common cause of cholestasis in infants and the most frequent indication for pediatric liver transplantation. The disease results from a destructive inflammatory process that affects intra- and extrahepatic bile ducts, leading to fibrosis and obliteration of the biliary tract. Although little is known about the etiology or pathogenesis of biliary atresia, epidemiologic and virologic studies point to a complex trait disorder, in which environmental factors trigger an inflammatory process that recognizes and abnormally targets the biliary system during a specific phase of postnatal development. Based on these data, the following unifying pathogenesis model can be preliminarily proposed: Regardless of initiating (environmental) and modifying (genetic) factors for disease development, the inflammatory and fibrosing destruction of the biliary epithelium is common to all clinical forms of biliary atresia. In this setting, the potential decrease of this inflammatory component by corticosteroid treatment may result in improved bile flow and better outcome after portoenterostomy. Therefore, in this clinical trial we propose to objectively determine whether corticosteroid treatment improves bile flow in infants with biliary atresia. The significance of the proposed trial is that it will determine whether corticosteroids are an effective medical treatment to improve bile drainage and long-term outcome, and whether its use reduces the need for liver transplantation in infants with biliary atresia. The trial will be performed by the NIH-supported Biliary Atresia Research Consortium (BARC). BARC has the infrastructure to prospectively follow a sufficiently large number of patients and to collect samples necessary for clinical research studies addressing etiology, pathogenesis, diagnosis, and treatment of children with biliary atresia.

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 胆道闭锁是婴儿胆汁淤积的最常见原因，也是小儿肝移植最常见的适应症。该疾病是由影响肝内和肝外胆管的破坏性炎症过程引起的，导致胆道纤维化和闭塞。尽管对胆道闭锁的病因或发病机制知之甚少，但流行病学和病毒学研究指出这是一种复杂的特征性疾病，其中环境因素触发炎症过程，在出生后发育的特定阶段识别并异常靶向胆道系统。根据这些数据，可以初步提出以下统一发病机制模型： 无论疾病发展的起始（环境）和修饰（遗传）因素如何，胆道上皮的炎症和纤维化破坏对于所有临床形式的胆道闭锁来说都是常见的。在这种情况下，通过皮质类固醇治疗可能减少这种炎症成分，可能会导致胆汁流量改善和门肠造口术后更好的结果。因此，在这项临床试验中，我们建议客观地确定皮质类固醇治疗是否可以改善胆道闭锁婴儿的胆汁流量。拟议试验的意义在于，它将确定皮质类固醇是否是改善胆汁引流和长期结果的有效药物治疗方法，以及其使用是否会减少胆道闭锁婴儿的肝移植需求。 该试验将由 NIH 支持的胆道闭锁研究联盟 (BARC) 进行。 BARC 拥有基础设施，可以前瞻性地跟踪足够多的患者，并收集临床研究所需的样本，以解决胆道闭锁儿童的病因、发病机制、诊断和治疗。