Clinical Center for Phase I/II trials of Silymarin in Chronic Liver Disease

描述（由申请人提供）：补充和替代药物（CAM）是全球和美国最常用的慢性肝病治疗方法之一。水飞蓟素是水飞蓟的活性成分，是最常用的草药之一，但其对慢性肝病的疗效尚未得到证实。丙型肝炎（HCV）和非酒精性脂肪性肝炎（NASH）继发的肝脏疾病是美国最常见的两种肝脏疾病，有必要在对照临床试验中研究水飞蓟素在这些疾病中的作用。我们建议进行三项合作临床试验，以评估水飞蓟素与安慰剂在从未接受过治疗的HCV患者、治疗失败的HCV患者和NASH患者中的疗效。这些将是双盲、安慰剂对照的1 / 11期试验，重点是水飞蓟素的剂量、安全性和有效性。试验的终点将包括肝脏疾病的组织学改善和多个次要替代标记物，以了解水飞蓟素如何起作用，并初步了解将在更大规模的3期试验中使用的终点。我们还打算评估重要的次要因素，如患者对CAM的期望和水飞蓟素对生活质量的影响。这些研究的目的是确定是否有理由对慢性肝病患者进行更大规模的水飞蓟素3期研究。

DESCRIPTION (provided by applicant): Complimentary and alternative medicines (CAM) are amongst the most commonly used therapies worldwide and in the US for chronic liver diseases. Silymarin, the active ingredient of the milk thistle, Silybum marianum, is one of the commonest used herbal medications but its efficacy in chronic liver disease is unproven. Liver disease secondary to both hepatitis C (HCV) and non-alcoholic steatohepatitis (NASH) represent 2 of the commonest liver diseases in the US and there is a need for the study of silymarin in these diseases in a controlled clinical trial. We are proposing three collaborative clinical trials to evaluate silymarin versus placebo in HCV patients who have never received treatment, in HCV patients who have failed treatment and in patients with NASH. These will be double blind, placebo controlled phase l/ll trials focusing on dose finding, safety and efficacy of silymarin. The endpoints of the trials will include histological improvement in liver disease and multiple secondary surrogate markers to understand both how silymarin works and to get a preliminary idea of the endpoints to be utilized in larger Phase 3 trials. We also intend to evaluate important secondary factors such as expectations of patients on CAM and effect of silymarin on quality of life. The goal of these studies is to determine whether there is a rationale for larger Phase 3 studies of silymarin in patients with chronic liver disease.