Clinical trial NCT00475176
Conditions: Chronic Hepatitis C
Keywords: Hepatitis C Virus Genotype 1 Non-Responders SAMe Natural Killer Cells Interferon Signaling Ribavirin Peginterferon Hemolysis STAT Hepatitis C
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Start date: 2007-05-01; Completion date: 2011-05-01
Enrollment: 24 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study will examine the effectiveness of S-adenosyl methionine (SAMe) in combination with peginterferon and ribavirin for treating hepatitis C virus. One out of three patients with hepatitis C develops cirrhosis of the liver, which can lead to liver failure or liver cancer. SAMe is a nutritional supplement that is made naturally in all cells of the body and acts to improve how the body handles stress. In laboratory experiments with liver cells, SAMe decreases the injury caused by liver toxins and improves the ability of interferon to block hepatitis C virus.

Patients 18 years of age and older with hepatitis C infection who did not respond successfully to prior treatment with interferon and ribavirin or peginterferon and ribavirin may be eligible for this study.

Participants receive the following treatment:

* Peginterferon (given by injection) and ribavirin (taken by mouth) for 2 weeks
* Washout period (no medications) for 4 weeks
* SAMe (taken by mouth) for 2 weeks
* Peginterferon, ribavirin and SAMe for 12-48 weeks, depending on patient response to treatment.

Participants have a thorough physical evaluation before beginning treatment and again at the study's end. After starting treatment, patients return for clinic visits and blood tests weekly for the first several weeks, then less frequently (at 2-week, then 4-week and 8-week intervals until up to 72 weeks) to monitor symptoms, drug side effects, hepatitis C virus levels, liver enzyme levels and immune responses to hepatitis C.

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Detailed description:
S-adenosyl methionine (SAMe) is a nutritional supplement which is available as an over-the-counter formula. It is a naturally occurring, modified amino acid that is produced in virtually all cells and participates in many biochemical pathways as a major methyl donor and may play a role in intracellular interferon signaling.

This study will assess the effects of SAMe on antiviral responses to peginterferon and ribavirin in patients with chronic hepatitis C, genotype 1, who have failed to respond to a previous course of therapy. After screening evaluation, patients will receive a first course of 2 weeks of peginterferon alfa-2a (180 micrograms weekly) and ribavirin (1000-1200 mg daily) during which symptoms, routine laboratory tests, HCV RNA levels, natural killer (NK) cell activity, and lymphocyte interferon-signaling responses will be monitored. After a 4-week washout period, patients will start SAMe (800 mg twice daily) for 2 weeks and then begin a second course of peginterferon and ribavirin in the same doses with similar monitoring. Therapy will be continued for at least 12 weeks, and patients with an early viral response will continue for a full 48 weeks. The primary criterion for efficacy of SAMe will be improved HCV kinetic responses comparing the first and second courses of peginterferon and ribavirin. Secondary endpoints will be improvement in NK cell activity and intracellular interferon signaling.

This is a pilot study to determine whether SAMe improves responses to peginterferon therapy in terms of intracellular interferon signaling, innate immune responses, and decline in viral levels.

Arms: arm 1: None
Interventions: intervention 1: Peginterferon alfa-2a intervention 2: Ribavirin intervention 3: S-adenosyl methionine for Chronic Liver Disease
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents: