S-Adenosyl Methionine (SAMe) to Treat Patients With Chronic Hepatitis C
Condition: Chronic Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Peginterferon alfa-2a; Ribavirin; S-adenosyl methionine for Chronic Liver Disease
Intervention MeSH terms: Ribavirin; Peginterferon alfa-2a
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hepatitis C Virus Genotype 1; Non-Responders; SAMe; Natural Killer Cells; Interferon Signaling; Ribavirin; Peginterferon; Hemolysis; STAT; Hepatitis C

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.

      ...
    

Eligibility criteria:

        INCLUSION CRITERIA

          -  Age 18 years or above, male or female

          -  Serum alanine or aspartate aminotransferase (ALT & AST) activities that are above the
             upper limit of normal (ALT greater than 41 or AST greater than 31 IU/L).

          -  Presence of anti-HCV in serum.

          -  Presence of HCV RNA genotype 1 in serum at levels above 10,000 copies/ml.

          -  Previous adequate therapy with interferon and ribavirin or peginterferon and ribavirin
             without a sustained virological response. An adequate course of therapy is defined as
             at least 12 weeks of interferon in doses of 3 million units three times weekly or
             peginterferon in doses of 180 micrograms for peginterferon alfa-2a or 1.5
             micrograms/kg for peginterferon alfa 2b once weekly and ribavirin in starting doses of
             at least 1000 mg daily. Patients who initiated therapy at these doses, but required
             dose modification due to side effects will also be eligible.

          -  Written informed consent: Patients will be informed of the risk/benefits and
             side-effects of the medications used in this protocol and will be advised of the
             research blood drawn at each clinic visit. They will be given ample time to read the
             consent form and to ask any protocol related questions. Once this is done, the
             patient's signature will be obtained on the consent form to enroll them into the
             protocol.

        EXCLUSION CRITERIA

          -  Evidence of other forms of liver disease.

          -  Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg) in serum.

          -  Primary sclerosing cholangitis as defined by liver histology.

          -  Wilson disease as defined by ceruloplasmin below the limits of normal and liver
             histology consistent with Wilson disease.

          -  Autoimmune hepatitis as defined by antinuclear antibody (ANA) of 3 EU or greater
             (ELISA) and liver histology consistent with autoimmune hepatitis or previous response
             to immunosuppressive therapy for autoimmune hepatitis.

          -  Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than
             normal and liver histology consistent with alpha-1-antitrypsin deficiency.

          -  Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and
             homozygosity for C282Y or compound heterozygosity for C282Y/H63D. Patients with iron
             saturation indices of greater than 45% and serum ferritin levels of greater than 300
             ng/ml for men and greater than 250 ng/ml for women will undergo genetic testing for
             C282Y and H63D.

          -  Drug induced liver disease as defined on the basis of typical exposure and history.

          -  Bile duct obstruction as suggested by imaging studies done within the previous six
             months.

          -  Decompensated liver disease, as marked by bilirubin greater than 4 mg/dl, albumin less
             than 3.0 gm/l, prothrombin time greater than 2 sec prolonged, Child-Pugh score of 7 or
             greater or history of bleeding esophageal varices, ascites or hepatic encephalopathy.
             Patients with ALT levels greater than 1000 U/L (greater than 25 times the upper limit
             of the normal range) will not be enrolled but may be followed until three
             determinations are below this level.

          -  Significant systemic or major illnesses other than liver disease, including congestive
             heart failure, coronary artery disease, cerebrovascular disease, pulmonary disease
             with hypoxia, renal failure, organ transplantation, serious psychiatric disease
             including depression, malignancy and any other conditions that in the opinion of the
             investigator would preclude treatment.

          -  Pre existing, severe bone marrow compromise; anemia (hematocrit less than 34%),
             neutropenia (less than 1000 polymorphonuclear cells/mm(3)) or thrombocytopenia (less
             than 70,000 cells/mm(3)).

          -  Serious autoimmune disease that, in the opinion of the investigators, might be
             worsened by interferon therapy, such as lupus erythematous, rheumatoid arthritis or
             Crohn's disease

          -  Known HIV infection.

          -  Active substance abuse, such as alcohol, inhaled or injection drugs within the
             previous one year.

          -  Pregnancy, lactation or in women of child bearing potential or in spouses of such
             women, inability to practice adequate contraception, defined as vasectomy in men,
             tubal ligation in women, or use of condoms and spermicide, birth control pills/depot
             injection, or an intrauterine device.

          -  Evidence of hepatocellular carcinoma; either alpha-fetoprotein (AFP) levels greater
             than 50 ng/ml (normal less than 9 ng/ml) and/or ultrasound (or other imaging study)
             demonstrating a mass suggestive of liver cancer.

          -  Immunosuppressive therapy with either corticosteroids (more than 5 mg of prednisone
             daily) or major immunosuppressive agents (such as azathioprine or 6-mercaptopurine).

          -  Clinical gout at presentation.

          -  History of hypersensitivity reactions to S-adenosyl methionine.

          -  Serum creatinine greater than 1.5mg/dl in men and greater than 1.4 mg/dl for women.

          -  Any other condition, which in the opinion of the investigators would impede the
             patient's participation or compliance in the study.