Clinical Research on Nonalcoholic Fatty Liver Disease

描述(由申请人提供)： 加州大学圣地亚哥分校的研究人员建议继续将他们作为临床中心纳入“非酒精性脂肪性肝炎临床研究网络(NASH CRN)”。NASH是儿童中最常见的肝病，也是成人慢性肝病最常见的原因之一。NASH与心血管疾病风险因素有关，如2型糖尿病、高血压、血脂异常和肥胖。该网络的广泛和长期目标是促进对NASH的发病机制、自然病史、遗传学、组织病理学和治疗的了解。NASH CRN目前正在进行2项多中心、双盲、随机、安慰剂对照的临床试验，需要在更新期内完成，一项在8-17岁的儿童中完成，另一项在18岁及以上的成年人中进行。这项名为“奎宁”的儿科研究有173名受试者参加了为期两年的治疗，评估了二甲双胍或维生素E与安慰剂的安全性和有效性。这项名为“Pivens”的成人研究有247名受试者参加了为期两年的治疗，以评估吡格列酮或维生素E与安慰剂的对比。此外，还有一项名为“Goals”的遗传学研究，它需要更多的儿童及其父母参加，以确定与NASH相关的候选基因，以及正在进行的一项数据库研究，该研究涉及1262名当前受试者，旨在评估NASH的自然历史。该数据库还将对评估NASH的生活方式因素以及评估非侵入性生物标记物和诊断和进展的成像具有非常重要的价值。在这次更新中，我们的目标是扩大数据库，包括未被充分代表和重要的活检证实的亚群，如儿童(特别是女孩)、西班牙裔、黑人和肝硬化者，以更好地了解年龄、性别、民族、种族、遗传和生活方式在NASH及其并存疾病发展中的作用。我们的目标是确定没有NAFLD的适当匹配的对照人群，以便与那些有NAFLD的人群进行比较。我们建议进行另一项随机安慰剂对照临床试验，以评估NASH儿童的其他治疗选择，我们将完成、分析和报告自上一次拨款期间以来的治疗研究，目前正在取得成果。

DESCRIPTION (provided by applicant): Investigators at the University of California, San Diego propose their continued inclusion as a Clinical Center within the "Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)". NASH is the most prevalent liver disease in children and one of the most common causes of chronic liver disease in adults. NASH is associated with cardiovascular disease risk factors such as type 2 diabetes, hypertension, dyslipidemia and obesity. The Network's broad, long-term objectives are to advance understanding of the pathogenesis, natural history, genetics, histopathology and treatment for NASH. The NASH CRN currently is conducting 2 multi-center, double-blind, randomized, placebo-controlled clinical trials which require completion in the renewal period, one In children 8-17 years inclusive and the other in adults 18 years and over. The pediatric study called "TONIC", has 173 subjects enrolled for a 2-year treatment, assessing safety and efficacy of metformin or Vitamin E versus placebo. The adult study called "PIVENS", has 247 subjects enrolled for 2-years of treatment to assess pioglitazone or Vitamin E versus placebo. Additionally, there is a genetics study called "GOALS", which requires many more children and their parents to enroll in order to identify candidate genes associated with NASH, and an ongoing Database study with 1262 current subjects intended to assess the natural history of NASH. The Database also will be invaluable for evaluating life-style factors in NASH and evaluating noninvasive biomarkers and imaging for diagnosis and progression. In this renewal we aim to expand the database with under-represented and important biopsy-proven sub-populations such as children (particularly girls), Hispanics, blacks and those with cirrhosis to better understand the role of age, gender, ethnicity, race, genetics and lifestyle in the development of NASH and Its co-morbidities. We aim to Identify appropriately matched control populations without NAFLD to permit comparisons to those with NAFLD. We propose the conduct of another randomized placebo-controlled clinical trial to assess other treatment options for children with NASH, and we will complete, analyze and report on the treatment studies from the last grant period now coming to fruition.