title: Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C.
abstract: BACKGROUND
  Chronic hepatitis C is associated with significant morbidity and mortality as a consequence of progression to cirrhosis, hepatocellular carcinoma, and liver failure. Current treatment for chronic hepatitis C with pegylated interferon (IFN) and ribavirin is associated with suboptimal responses and numerous adverse effects. A number of botanical products have been used to treat hepatic disorders. Silymarin, extracted from the milk thistle plant, Silybum marianum (L) Gaertn. (Asteraceae), has been most widely used for various liver disorders, including chronic hepatitis C, B, and alcoholic liver disease. However, the safety and efficacy of silymarin have not been studied systematically in chronic hepatitis C.
  
  
  OBJECTIVE
  We describe our strategy for a phased approach for studying the impact of silymarin in hepatitis C, in the context of the unique challenges of botanical product clinical trials and the development of specific and curative antiviral therapy.
  
  
  METHODS
  This multicenter, randomized, double-masked, placebo-controlled trial was conducted with four clinical centers and a data-coordinating center in the United States, to assess the impact of silymarin therapy in patients with chronic hepatitis C who failed conventional antiviral therapy.
  
  
  RESULTS
  Key aspects relevant to performing clinical trials of botanical products include early identification of an appropriate product with standard product chemistry, acquisition of pharmacokinetic and dosing information, selection of the appropriate study group, and choosing rigorous outcome variables. POTENTIAL LIMITATIONS: Trial participants were chronic hepatitis C patients who were nonsustained virologic responders to IFN-based therapy; therefore, the findings are not generalizable to all hepatitis C populations. Further, alanine aminotransferase, a biochemical liver test, rather than hepatitis viral RNA or liver histology was the primary end point.
  
  
  CONCLUSIONS
  The challenges identified and addressed during development of this United States multicenter Phase II trial to evaluate silymarin for treatment of patients with chronic hepatitis C infection who had failed to respond successfully to previous IFN-based therapy are common and must be addressed to conduct rigorous trials of botanical products.
authors: University of Pennsylvania, Philadelphia, PA, USA. rajender.reddy@uphs.upenn.edu
authors: K Rajender
authors: KR
authors: Reddy
authors: Steven H
authors: SH
authors: Belle
authors: Michael W
authors: MW
authors: Fried
authors: Nezam
authors: N
authors: Afdhal
authors: Victor J
authors: VJ
authors: Navarro
authors: Roy L
authors: RL
authors: Hawke
authors: Abdus S
authors: AS
authors: Wahed
authors: Edward
authors: E
authors: Doo
authors: Catherine M
authors: CM
authors: Meyers
mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008517:Phytotherapy; D012107:Research Design; D012838:Silymarin / Q000627:therapeutic use*
chemical_list: D012838:Silymarin