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）：在过去十年中，慢性丙型肝炎抗病毒治疗领域取得了重大进展。大约50%的患者使用聚乙二醇干扰素和利巴韦林联合治疗获得了持续的病毒学应答。不幸的是，其余患者要么没有反应，要么由于不良事件而必须过早停止治疗。此外，大量慢性丙型肝炎患者从未接受治疗，因为他们有目前可用药物治疗的禁忌症。需要额外的治疗方案。几个世纪以来，草药产品一直被用作治疗各种人类疾病的替代药物。水飞蓟，或水飞蓟素，主要用于其对肝脏疾病的有益作用，包括抗炎，抗氧化和抗纤维化活性。然而，临床试验几乎没有证据支持水飞蓟素用于治疗肝脏疾病。先前水飞蓟素肝保护作用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)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理解，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。在本应用程序中，我们将重点设计I期药代动力学研究，该研究将描述高水飞蓟素剂量与受试者暴露于水飞蓟素的四种异构体之间的关系。从I期研究中获得的信息将允许合理决定用于II期研究的剂量，II期研究将评估水飞蓟素治疗慢性丙型肝炎患者的安全性和有效性，这些患者之前接受过传统疗法的治疗。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在药物开发方面的独特属性和专业知识，以及北卡罗来纳大学教堂山分校药学院的教师，这将确保这项合作项目的成功完成。