Effects of SAMe in Patients With Alcoholic Liver Disease

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.

Study Overview

• Status: Completed
• Conditions: Liver Disease, Alcoholic
• Intervention / Treatment: Drug: S-adenosylmethionine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S-adenosylmethionine (SAMe); Alcoholic liver disease patients receiving S-adenosylmethionine (SAMe)at 400 mg capsule three times daily for 24 weeks	Drug: S-adenosylmethionine; Alcoholic liver disease patients received drug at dose of 400 mg three times daily for 24 weeks.
Placebo Comparator: Sugar pill; ALD subjects receiving Placebo three times daily for 24 weeks.	Drug: Placebo; Alcoholic liver disease patients received identical size and shape sugar pill placebo three times daily for 24 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Serum AST Levels	Biochemical values for liver function tests and histopathology scores were obtained at week 0 and 24 of the treatment trial, and changes in each were recorded. Here are reported changes in aspartate transaminase (AST) as representative of all changes. Since only baseline values were obtained in the Healthy and Lifestyle counseling groups, there are no recorded changes in these two groups.	Week 0 to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Serum SAM	We compared serum levels of SAM at time 0 and week 24 of the study in the alcoholic liver disease groups only, since these parameters were measured in the healthy and lifestyle coaching groups only at baseline.	September 2005- June 2009

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); University of Colorado, Denver; University of California, Los Angeles; Abbott; Joint Clinical Research Center
• Investigators: Principal Investigator: Charles H Halsted, MD, University of California, Davis

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: December 12, 2007
• First Submitted That Met QC Criteria: December 12, 2007
• First Posted (Estimate): December 14, 2007

Study Record Updates

• Last Update Posted (Actual): May 30, 2017
• Last Update Submitted That Met QC Criteria: May 24, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: SAMe; S-adenosylmethionine; Alcoholic Liver Disease (ALD)
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol-Induced Disorders; Liver Diseases; Liver Diseases, Alcoholic
• Other Study ID Numbers: 200311168; R01AA014562 (U.S. NIH Grant/Contract); NIAAA_HAL-014562 (Other Identifier: UC Davis)