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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

基本信息

批准号：
7497799
负责人：
MICHAEL W FRIED
金额：
$ 4.25万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
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/7497799
关键词：
Adverse event Affect Alternative Medicine Anti-Inflammatory Agents Anti-inflammatory Antioxidants Antiviral Therapy Apoptosis Biochemical Biological Markers Chronic Chronic Hepatitis C Clinical Clinical Trials Collaborations Controlled Clinical Trials Development Disease Disease Progression Dose Drug Kinetics End Point Ensure Evaluation Exhibits Exposure to Faculty Future Hepatic Hepatitis C Hepatitis C virus Human Immune response Inflammation Isomerism Liver Liver diseases Measures Milk Thistle Monitor Multicenter Studies Multicenter Trials North Carolina Numbers Oral Oxidative Stress Pathogenesis Patients Peripheral Blood Mononuclear Cell Pharmaceutical Preparations Pharmacy Schools Phase Phase I Clinical Trials Phase II Clinical Trials Phase III Clinical Trials Placebo Control Placebos Population Preparation Property Randomized Range Ribavirin Risk Safety Serum Silymarin Study Subject Surrogate Markers Therapeutic Universities cooperative study day design dosage drug development fibrogenesis in vivo interest nonalcoholic steatohepatitis programs randomized placebo controlled trial response

项目摘要

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 proposal 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.

在过去十年中，慢性丙型肝炎的抗病毒治疗领域取得了重大进展。