Clinical trial NCT00573313: Effects of SAMe in Patients With Alcoholic Liver Disease
Official title: Effects of SAMe in Patients With Alcoholic Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Liver Disease, Alcoholic
Keywords: Alcoholic Liver Disease (ALD)
S-adenosylmethionine
SAMe
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: Abbott
name: Joint Clinical Research Center
name: University of Colorado, Denver
name: University of California, Los Angeles
First posted: 2007-12-14
Enrollment: 94
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Changes in Serum AST Levels
timeFrame: Week 0 to week 24
Secondary outcomes:
measure: Changes in Serum SAM
timeFrame: September 2005- June 2009
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
Study officials:
affiliation: University of California, Davis
name: Charles H Halsted, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.