Effects of SAMe in Patients With Alcoholic Liver Disease

This study has been completed.
Sponsor:
Collaborators:
Abbott
Joint Clinical Research Center
University of Colorado, Denver
University of California, Los Angeles
Information provided by (Responsible Party):
Charles Halsted, MD, University of California, Davis
ClinicalTrials.gov Identifier:
NCT00573313
First received: December 12, 2007
Last updated: June 7, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Liver Disease, Alcoholic
Drug: S-adenosylmethionine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effects of SAMe in Patients With Alcoholic Liver Disease

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Changes in Serum AST Levels [ Time Frame: Week 0 to week 24 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Changes in Serum SAM [ Time Frame: September 2005- June 2009 ] [ Designated as safety issue: No ]
    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.


Enrollment: 94
Study Start Date: September 2005
Study Completion Date: September 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00573313

Locations
United States, California
University of California, Davis Medical Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
Abbott
Joint Clinical Research Center
University of Colorado, Denver
University of California, Los Angeles
Investigators
Principal Investigator: Charles H Halsted, MD University of California, Davis
  More Information

Publications:
Responsible Party: Charles Halsted, MD, Principal Investigator, University of California, Davis
ClinicalTrials.gov Identifier: NCT00573313     History of Changes
Other Study ID Numbers: NIAAA_HAL-014562, R01AA014562
Study First Received: December 12, 2007
Results First Received: February 6, 2013
Last Updated: June 7, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Davis:
Alcoholic Liver Disease (ALD)
S-adenosylmethionine
SAMe

Additional relevant MeSH terms:
Liver Diseases
Liver Diseases, Alcoholic
Digestive System Diseases
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders

ClinicalTrials.gov processed this record on September 22, 2014