SAMe to Treat Biliary Cirrhosis Symptoms

• Status: Terminated
• Trial end date: 2008-07-02
• Target enrollment: 0
• Participant gender: All

Summary

This study will examine the effect of S-adenosyl methionine (SAMe) on itching and fatigue in patients with primary biliary cirrhosis, a disease of the small bile ducts in the liver. Ursodiol, the only currently available treatment for biliary cirrhosis, does not cure the disease, and many people continue to have symptoms or liver test abnormalities despite treatment. SAMe is a naturally occurring substance found in most cells of the body. The highest levels of the substance are produced by the liver, where it helps to rid the body of toxins and breakdown products of metabolism. Studies in Europe suggest that SAMe may help to: 1) decrease the fatigue and itching that are common in persons with liver problems, and 2) decrease levels of liver enzymes in the blood, suggesting that it may decrease the amount of liver injury.

Patients 21 years of age or older with primary biliary cirrhosis who are taking ursodiol and have symptoms of itching or fatigue may be eligible for this study. Candidates are screened with a medical history, physical examination, review of medical records, routine blood tests, and a symptoms rating scale.

Participants stop all medications for itching 4 weeks before starting the study, but continue to take ursodiol during the 42-week trial. On entering the study, patients are assigned to take either SAMe or placebo tablets twice a day for 12 weeks. While taking the medications, they are followed in the clinic every 2 weeks for the first month and then every 4 weeks to fill out symptoms questionnaires and have a short medical evaluation and blood tests. At the end of 12 weeks, treatment is interrupted for a 2-week "wash-out" period, after which patients begin a 12-week crossover treatment; that is, patients who were taking SAMe are switched to placebo, and those who were taking placebo are switched to SAMe.

After completing the second 12-week treatment course, patients come to the clinic at 4, 8, and 12 weeks to fill out symptoms questionnaires and have a medical evaluation and blood tests. At the last visit, patients are told which type of tablet they received during the two courses of treatment. SAMe is available without prescription in many forms as an over-the-counter medication.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Criteria

• INCLUSION CRITERIA:

Age at entry at least 21 years old.

Pathologically diagnosed primary biliary cirrhosis (made by a liver biopsy performed within 10 years of enrollment) with receipt of stable doses of ursodiol for at least 6 months before enrollment. The dose of urosodiol will be adjusted to achieve stable serum liver enzymes levels.

Symptoms of itching or fatigue or both. The presence of symptoms will be verified by medical history, symptom questionnaire and visual analogue scales (results greater than 20 mm) on at least two screening visits.

Written informed consent.

EXCLUSION CRITERIA:

Evidence of another form of liver disease.

Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg) in serum.

Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA 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 or equal to 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 defined by a Child-Pugh score of 7 or greater.

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. Patients who are suffering from severe depression defined by a score of greater than or equal to 25 in CES-D screening test will not be eligible for enrollment.

Known HIV infection.

Active substance abuse, such as alcohol, inhaled or injection drugs within the previous one year.

Pregnancy, lactation or inability to practice adequate contraception in women in child bearing age.

Evidence of hepatocellular carcinoma as shown by a liver mass on imaging studies or alphafetoprotein levels greater than 200 ng/ml.

Any other condition, which in the opinion of the investigators would impede competence or compliance or possibly hinder completion of the study.

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.