A phase I/II randomized, placebo controlled trial of silymarin for hepatitis C

水飞蓟素治疗丙型肝炎的 I/II 期随机、安慰剂对照试验

• 批准号: 7123141
• 负责人: MICHAEL W FRIED
• 金额: $ 14.94万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7123141
• 关键词: biomarker; clinical research; clinical trials; hepatitis C; isomer; liver; pharmacokinetics; placebos

DESCRIPTION (provided by applicant): Major advances have been made over the last decade in the field of antiviral therapy for chronic hepatitis C. Approximately 50% of patients treated with the combination of peginterferon and ribavirin achieve a sustained virological response. Unfortunately, the remainder either fails to respond or must discontinue treatment prematurely due to adverse events. In addition, a significant number of patients with chronic hepatitis C are never offered therapy because they have contraindications to the rigors of treatment with currently available medications. Additional therapeutic options are needed. Herbal products have been used empirically for centuries as alternative medicines to treat a variety of human disorders. Silybum marianum, or silymarin, is primarily used for its purported beneficial effects in disorders of the liver, which include anti-inflammatory, anti-oxidant, and anti-fibrogenic activities. However, there is little evidence from clinical trials to support the use of silymarin as a treatment for diseases of the liver. Several major limitations of prior clinical investigations on the hepatoprotective effects of silymarin include: 1) the use of non- standardized silymarin extracts 2) the incomplete understanding of the relationship between silymarin dose and steady-state exposures to the potentially active isomers of silymarin, confounding the evaluation of safety and efficacy; and 3) the use of heterogeneous patient populations and variable endpoints to assess therapeutic response. In this application we will focus on the design of a phase I pharmacokinetic study that will characterize relationships between high silymarin doses and subject exposure to the four isomers of silymarin. The information obtained from the phase I study will allow a rational decision regarding dosages to be used for a phase II study that will then be performed to evaluate the safety and efficacy of silymarin for the treatment on subjects with chronic hepatitis C who were previously treated with conventional therapies. Our application to participate as a Clinical Center for this cooperative study will emphasize the unique attributes and expertise in drug development of the Liver Program and the faculty at the School of Pharmacy at the University of North Carolina at Chapel Hill that will ensure successful completion of this collaborative project.

描述（由申请人提供）：过去十年，慢性丙型肝炎的抗病毒治疗领域取得了重大进展。接受聚乙二醇干扰素和利巴韦林联合治疗的患者中，约 50% 实现了持续的病毒学应答。不幸的是，其余的人要么没有反应，要么由于不良事件而必须提前停止治疗。此外，大量慢性丙型肝炎患者从未接受过治疗，因为他们对现有药物的严格治疗有禁忌。需要额外的治疗选择。几个世纪以来，草药产品一直被经验地用作治疗各种人类疾病的替代药物。水飞蓟或水飞蓟素主要用于治疗肝脏疾病，包括抗炎、抗氧化和抗纤维形成活性。然而，几乎没有临床试验证据支持使用水飞蓟素治疗肝脏疾病。先前关于水飞蓟素保肝作用的临床研究的几个主要局限性包括：1）使用非标准化水飞蓟素提取物2）对水飞蓟素剂量与水飞蓟素潜在活性异构体稳态暴露之间关系的不完全了解，混淆了安全性和有效性的评估； 3) 使用异质患者群体和可变终点来评估治疗反应。在本申请中，我们将重点关注 I 期药代动力学研究的设计，该研究将表征高水飞蓟素剂量与受试者接触水飞蓟素四种异构体之间的关系。从第一阶段研究中获得的信息将有助于合理决定第二阶段研究的剂量，然后进行第二阶段研究，以评估水飞蓟素治疗先前接受过常规疗法的慢性丙型肝炎受试者的安全性和有效性。我们作为临床中心参与这项合作研究的申请将强调肝脏项目和北卡罗来纳大学教堂山分校药学院在药物开发方面的独特属性和专业知识，这将确保该合作项目的成功完成。