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Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C
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 respo...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293174/ https://www.ncbi.nlm.nih.gov/pubmed/22058086 http://dx.doi.org/10.1177/1740774511427064 |
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author | Reddy, K Rajender Belle, Steven H Fried, Michael W Afdhal, Nezam Navarro, Victor J Hawke, Roy L Wahed, Abdus S Doo, Edward Meyers, Catherine M |
author_facet | Reddy, K Rajender Belle, Steven H Fried, Michael W Afdhal, Nezam Navarro, Victor J Hawke, Roy L Wahed, Abdus S Doo, Edward Meyers, Catherine M |
author_sort | Reddy, K Rajender |
collection | PubMed |
description | 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. Purpose 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. |
format | Online Article Text |
id | pubmed-3293174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-32931742012-03-07 Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C Reddy, K Rajender Belle, Steven H Fried, Michael W Afdhal, Nezam Navarro, Victor J Hawke, Roy L Wahed, Abdus S Doo, Edward Meyers, Catherine M Clin Trials Design 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. Purpose 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. SAGE Publications 2012-02 /pmc/articles/PMC3293174/ /pubmed/22058086 http://dx.doi.org/10.1177/1740774511427064 Text en © The Author(s) 2011 http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Design Reddy, K Rajender Belle, Steven H Fried, Michael W Afdhal, Nezam Navarro, Victor J Hawke, Roy L Wahed, Abdus S Doo, Edward Meyers, Catherine M Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C |
title | Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C |
title_full | Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C |
title_fullStr | Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C |
title_full_unstemmed | Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C |
title_short | Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C |
title_sort | rationale, challenges, and participants in a phase ii trial of a botanical product for chronic hepatitis c |
topic | Design |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293174/ https://www.ncbi.nlm.nih.gov/pubmed/22058086 http://dx.doi.org/10.1177/1740774511427064 |
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