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: 8166708
• 负责人: SAUL J. KARPEN
• 金额: $ 0.85万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166708
• 关键词: Address; Adrenal Cortex Hormones; Affect; Bile fluid; Biliary; Biliary Atresia; Child; Childhood; Cholestasis; Clinical; Clinical Research; Clinical Trials; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Diagnosis; Disease; Drainage procedure; Environmental Risk Factor; Epidemiology; Epithelium; Etiology; Extrahepatic Bile Ducts; Fibrosis; Funding; Genetic; Grant; Infant; Inflammatory; Institution; Medical; Modeling; Outcome; Pathogenesis; Patients; Phase; Process; Randomized; Research; Research Infrastructure; Research Personnel; Resources; Sampling; Source; Testing; United States National Institutes of Health; base; biliary tract; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. Our overall hypothesis is that therapy with corticosteroids following portoenterostomy will improve bile drainage and long-term outcome in infants with biliary atresia. This hypothesis will be tested through the following hypotheses:

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 胆道闭锁是婴儿中胆汁淤积的最常见原因，也是小儿肝移植的最常见指示。该疾病是由影响肝外胆管和外部胆管导致纤维化和胆道闭塞的破坏性炎症过程引起的。尽管对胆道闭锁的病因学或发病机理知之甚少，但流行病学和病毒学研究表明了一种复杂的性状疾病，在这种特定的特定阶段，环境因素会触发炎症过程，该过程识别并异常针对胆汁系统。基于这些数据，可以先提出以下统一的发病机理模型： 不管疾病发育的起始（环境）和修饰（遗传）因素如何，胆道上皮的炎症和纤维化破坏都是胆道闭锁的所有临床形式共同的。在这种情况下，通过皮质类固醇治疗的这种炎症成分的潜在减少可能会导致胆汁流量的改善和portoteenterostomy后的更好结果。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。该试验的意义在于，它将确定皮质类固醇是否是改善胆汁排水和长期结局的有效医疗，以及其使用是否减少了胆道闭锁婴儿肝移植的需求。 该试验将由NIH支持的胆道闭锁研究联盟（BARC）进行。 BARC具有前瞻性遵循大量患者的基础设施，并收集针对临床研究所需的样本，以解决胆道闭锁儿童的病因，发病机理，诊断和治疗。 我们的总体假设是，术后治疗皮质类固醇的治疗将改善胆汁性闭锁婴儿的胆汁引流和长期结局。该假设将通过以下假设进行检验：