Effects of SAMe in Patients With Alcoholic Liver Disease

University of California (UC) Davis

Status and phase: Completed; Phase 3

Conditions: Liver Disease, Alcoholic

Treatments: Drug: S-adenosylmethionine; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00573313

200311168

NIAAA_HAL-014562 (Other Identifier)

R01AA014562 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Prior studies in animal models have established that the pathogenesis of alcoholic liver disease (ALD) is regulated in part by the effects of chronic alcohol abuse on hepatic methionine metabolism. The hypothesis of the clinical study was that provision of the methionine metabolite S-adenosylmethionine (SAM) would correct abnormal hepatic methionine metabolism thereby effectively treating ALD. The two goals of the clinical research were a)to determine the clinical relationship of aberrant hepatic methionine metabolism to ALD by comparisons of patterns of serum methionine metabolites in groups of ALD patients, alcoholics without liver disease, and normal healthy subjects, and b) to determine the treatment effects of SAM on patterns of serum methionine metabolites and on the histopathology and biochemical features of liver injury in ALD patients.

Full description

We assessed a total of 297 potential ALD candidates, from whom 40 were enrolled in the study. In addition, we enrolled 26 gender matched active alcohol drinkers without liver disease (AD) and 28 age and gender matched healthy control subjects (HS). Of the original 40 ALD subjects who provided initial enrollment data, 3 declined to proceed with the trial. Therefore, 37 ALD patients were randomized to receive SAM at a dose of 400 mg or placebo three times daily for 24 weeks. However 11 of these dropped out after initial evaluation, leaving 26 ALD patients, 13 in each arm, who completed the 24 week trial.

Enrollment: 94 patients

Sex: All

Ages: 21 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• ALD) a history of chronic alcoholism according to established AUDIT and WHO criteria with the presence of clinical and laboratory features of established liver disease. Also, willingness to undergo liver biopsies at start and completion of the study, and to comply with study medication or placebo and required clinic visits and blood sampling.
• a history of chronic alcoholism without evidence of liver disease;
• healthy subjects without history of alcoholism or presence of liver disease.

Exclusion Criteria:

• viral Hepatitis B or C
• hemochromatosis
• Wilson Disease
• sclerosing cholangitis
• primary biliary cirrhosis
• other chronic disease
• renal insufficiency

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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94 participants in 2 patient groups, including a placebo group

S-adenosylmethionine (SAMe)

Experimental group

Description:

Alcoholic liver disease patients receiving S-adenosylmethionine (SAMe)at 400 mg capsule three times daily for 24 weeks

Treatment:

Drug: S-adenosylmethionine

Sugar pill

Placebo Comparator group

Description:

ALD subjects receiving Placebo three times daily for 24 weeks.

Treatment:

Drug: Placebo