Pediatric Trials in Non-Alcoholic Steatohepatitis (NASH)

描述（由申请人提供） 儿科胃肠病学联合项目中的儿科肝病学家， 加州大学圣地亚哥分校的肝病学和营养学提出， 他们作为一个临床中心列入“临床研究网络， 非酒精性脂肪性肝炎”。虽然NASH通常被认为是常见的 最近的研究表明，NASH是成人中最常见的疾病之一。 10-18奥尔兹肝病的常见原因。本申请提出 根据校长以往的经验，以UCSD为中心参与 儿童NASH的研究者，我们可以使用的儿童数量 研究中心，以及我们人口的种族多样性，基于我们的 独特的地理位置。UCSD成人肝病学家和Scripps的合作 转诊NASH成人患者的临床肝病学家将允许 参与临床研究中其他中心发起的提案 专注于成年人的网络。我们的NIH资助的一般临床研究中心 将促进拟议研究的各个方面。我们的应用程序提供了 用于制备多中心数据库和组织/血清库模板， 研究儿童NASH，基于知识和经验的介绍， 提出了这种情况的病理生理学。本文件详细介绍了两项建议 应用程序.一是前瞻性、多中心、流行病学分析 与肥胖儿童NASH发展相关的因素， 评估年龄、种族和性别的作用。潜在的影响因素 发病机制将根据青春期发育、胰岛素 抵抗，增加炎症介质的暴露， 氧化应激的指标。第二项研究是前瞻性的， 一项多中心、随机、双盲试验，评估儿童期 NASH与维生素E对比。随机分配至安慰剂组的儿童 作为一个长期的队列，以了解这种未经治疗的自然史， 早期发病的情况。在先前的开放标签研究中， 初步研究显示，肝损伤的血清标志物正常化， 进行严格的研究，以确定抗氧化剂治疗是否能改善结果， 通过肝脏组织学和NASH相关标志物的变化进行评估 发病机制

DESCRIPTION (provided by the applicant) Pediatric hepatologists in the Joint Program in Pediatric Gastroenterology, Hepatology and Nutrition at the University of California, San Diego propose their inclusion as a Clinical Center in the "Clinical Research Network in Non-Alcoholic Steatohepatitis". Although NASH generally is regarded as a common condition in adults, recent research reveals that NASH is one of the most common causes of liver disease in 10-18 year olds. This application proposes UCSD participation as a center on the basis of past experience of the Principal Investigator with pediatric NASH, the number of children available to our center for studies, and the ethnic diversity of our population based on our unique geographic location. Cooperation of UCSD adult hepatologists and Scripps Clinic hepatologists for referral of adult patients with NASH will allow participation in proposals initiated by other centers in the clinical research network which focus on adults. Our NIH-funded General Clinical Research Center will facilitate all facets of proposed studies. Our application provides a template for preparation of a multicenter database and tissue/serum bank to study pediatric NASH, based on knowledge and experience of the presentation and proposed pathophysiology of the condition. Two proposals are detailed in this application. The first is a prospective, multi-center, epidemiologic analysis of factors associated with the development of NASH in obese children, evaluating the role of age, race and gender. Potential factors involved in pathogenesis will be assessed with respect to pubertal development, insulin resistance, increased exposure to mediators of inflammation, and increased indicators of oxidative stress. The second study is a prospective, multi-center, randomized, double-blind trial evaluating treatment of childhood NASH with Vitamin E versus placebo. Children randomized to placebo will serve as a long-term cohort to understand the natural history of this untreated condition with early onset. The treated children, who in previous open-label pilot studies have been shown to normalize serum markers of liver damage, will be rigorously studied to determine if antioxidant therapy improves outcome as assessed by changes in liver histology and markers found associated with NASH pathogenesis.