SAMe to Treat Biliary Cirrhosis Symptoms
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.
|Liver Cirrhosis, Biliary||Drug: S-adenosyl-methionine (SAMe) capsules||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (masked roles unspecified)
Primary Purpose: Treatment
|Official Title:||S-Adenosyl Methionine for Symptomatic Treatment of Primary Biliary Cirrhosis|
- Improvement in symptoms as assessed by validated questionnaires and visual analogue scales administered at 2 to 4 week intervals during therapy. [ Time Frame: 12 weeks of therapy ]
- Improvement in serum alanine aminotransferase and alkaline phosphatase. [ Time Frame: 12 weeks ]
|Study Start Date:||July 25, 2005|
|Study Completion Date:||July 2, 2008|
|Primary Completion Date:||July 31, 2007 (Final data collection date for primary outcome measure)|
To assess the efficacy of S-adenosyl methionine (SAMe) in symptomatic relief of primary biliary cirrhosis (PBC), we will treat up to 50 patients with either SAM-e (800 mg BID) or placebo for 12 weeks in a cross-over, double-blind placebo-controlled study.
S-adenosyl methionine is a nutritional supplement which is available as an over-the-counter formula and is used for treatment of depression and arthritic pain. SAMe is produced in virtually all cells and participates in many biochemical pathways as a major methyl contributor. Intracellular levels of SAMe are often decreased in advanced liver disease. At present SAMe is undergoing extensive evaluation in a large multicenter, randomized controlled trial as an adjunctive therapy of alcoholic liver disease. SAMe has also been evaluated in patients with intrahepatic cholestasis and cholestasis of pregnancy with promising effects of relieving pruritus and fatigue and improving serum liver associated enzymes.
In this study, we will recruit patients with PBC who have pruritus or fatigue despite therapy with ursodiol (the currently recommended therapy of PBC which is partially effective in relieving pruritus and fatigue). After medical evaluation and a brief period of monitoring, patients will be randomized to receive either SAMe or placebo given in oral form in similar appearing capsules twice daily. Patients will be followed at regular intervals for symptoms as monitored by validated questionnaires as well as for side effects and serum biochemical and hematological tests. After 12 weeks, therapy will be withdrawn for 2 weeks and patients will then be switched to the alternative capsules, either SAMe or placebo, for another 12 weeks. The primary endpoints of therapy will be improvements in symptoms of pruritus or fatigue or both. Secondary endpoints will be improvements in serum biochemical liver related enzymes.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00125281
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|