Effects of SAMe in Patients With Alcoholic Liver Disease

NCT ID: NCT00573313

Last Updated: 2017-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2009-09-30

Brief Summary

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.

Detailed 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.

Conditions

Liver Disease, Alcoholic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

S-adenosylmethionine (SAMe)

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

Group Type: EXPERIMENTAL

S-adenosylmethionine

Intervention Type: DRUG

Alcoholic liver disease patients received drug at dose of 400 mg three times daily for 24 weeks.

Sugar pill

ALD subjects receiving Placebo three times daily for 24 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Alcoholic liver disease patients received identical size and shape sugar pill placebo three times daily for 24 weeks.

Interventions

S-adenosylmethionine

Alcoholic liver disease patients received drug at dose of 400 mg three times daily for 24 weeks.

Intervention Type: DRUG

Placebo

Alcoholic liver disease patients received identical size and shape sugar pill placebo three times daily for 24 weeks.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Abbott

INDUSTRY

Sponsor Role: collaborator

Joint Clinical Research Center

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles H Halsted, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

University of California, Davis Medical Center

Sacramento, California, United States

Countries

United States

References

Medici V, Peerson JM, Stabler SP, French SW, Gregory JF 3rd, Virata MC, Albanese A, Bowlus CL, Devaraj S, Panacek EA, Rahim N, Richards JR, Rossaro L, Halsted CH. Impaired homocysteine transsulfuration is an indicator of alcoholic liver disease. J Hepatol. 2010 Sep;53(3):551-7. doi: 10.1016/j.jhep.2010.03.029. Epub 2010 May 31.

Reference Type: RESULT

PMID: 20561703 (View on PubMed)

Medici V, Virata MC, Peerson JM, Stabler SP, French SW, Gregory JF 3rd, Albanese A, Bowlus CL, Devaraj S, Panacek EA, Richards JR, Halsted CH. S-adenosyl-L-methionine treatment for alcoholic liver disease: a double-blinded, randomized, placebo-controlled trial. Alcohol Clin Exp Res. 2011 Nov;35(11):1960-5. doi: 10.1111/j.1530-0277.2011.01547.x.

Reference Type: RESULT

PMID: 22044287 (View on PubMed)

Other Identifiers

R01AA014562

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIAAA_HAL-014562

Identifier Type: OTHER

Identifier Source: secondary_id

200311168

Identifier Type: -

Identifier Source: org_study_id