Randomized, Controlled Trial of S-adenosylmethionine in Alcoholic Liver Disease

NCT00851981 | Completed Phase 2

• 2 other identifiers: 553021R21AA014269-01A1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Alcoholic liver disease is one of the most important causes of chronic liver disease in this country. There is currently no treatment for chronic alcoholic liver disease other than abstinence. Hepatic methionine metabolism is abnormal in these patients and one of the consequences is depletion of S-adenosylmethionine (SAMe) levels, which can affect numerous important cellular processes. SAMe has been increasingly utilized for the treatment of liver diseases although the protective mechanisms remain unclear. A recent randomized double-blind trial using SAMe in patients with alcoholic liver disease and found improvement in 2-year survival in those with less advanced liver disease. However, important changes in methionine metabolism and histological changes were not included in the study. Aim: The goal of this study is to determine the effect of SAMe administration on key metabolic abnormalities of the methionine cycle and on the recovery from alcoholic liver disease.

Conditions

Alcoholic Hepatitis

Keywords

Alcohol Liver Disease

Outcome Measures

Primary Outcomes (1)

• Change in plasma homocysteine, hepatic GSH and SAMe levels and hepatic expression of TNF,MAT1A,MAT2A,MS,CBS and BHMT.

  1 year

Secondary Outcomes (1)

• Changes in routine liver pathology,c-myc expression and markers of apoptosis, stellate cell activation and hepatocyte proliferation.

  1 year

Study Arms (2)

1

PLACEBO COMPARATOR

Other: Placebo

SAMe

ACTIVE COMPARATOR

Dietary Supplement: SAMe

Interventions

Placebo OTHER

TID

1

SAMe DIETARY_SUPPLEMENT

300 mg TID

SAMe

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The presumptive diagnosis for alcoholic hepatitis will be: recent binge drinking; compatible physical findings (one or more: jaundice, enlarged liver, hepatic bruit, abdominal pain, loss of appetite, nausea); and a compatible biochemical profile (moderate elevation of AST over ALT, elevated total serum bilirubin); or a liver-spleen colloid scan suggestive of reticulo-endothelial redistribution and hepatic arterialization.
• The diagnosis of alcoholic hepatitis must be confirmed on liver biopsy, showing typical features of acute sclerosing hyaline necrosis 70.
• The degree of portal fibrosis as determined on liver biopsy, graded according to the Knodell score-modified by Ishak 71 must be less than or equal to 5 out of a possible score of 6, 6 indicating cirrhosis.
• The alcoholic hepatitis must be "stable", i.e. not requiring treatment by either pentoxifylline 72 or prednisone, with a Maddrey Score 73 {(PTpatient - PTcontrol) x 4.6 + TBmg/dL} \< 32.
• Patients must be willing to participate in the trial, remain abstinent to alcohol, and compliant to the treatment regimen, and undergo a post-treatment liver biopsy.

You may not qualify if:

• Patients who have either compensated cirrhosis (biopsy proven) or a clinical picture of severe cirrhosis defined as Child's class C and/or with a recent history (within one month) of decompensated liver disease (history of ascites, encephalopathy or variceal bleeding within one month of trial entry). These patients have reduced life expectancy below one year and are most often severely coagulopathic and cannot be biopsied.
• Patients who have severe acute alcoholic hepatitis of poor prognosis defined as a Maddrey Score \> 32. These patients have a mortality rate of 50% during their hospitalization period when untreated by either prednisone or pentoxifylline.
• Patients who are receiving hepatotropic treatments such as colchicine, penicillamine, corticosteroids, ursodeoxycholic acid, and pentoxifylline.
• Patients who are receiving known hepatotoxic long-term treatments such as NSAIDs, statins, neuroleptics, certain anti-convulsive medications, or high-dose acetaminophen.
• Patients suspected of having hepatocellular carcinoma.
• Patients who have contra-indications to liver biopsy.
• Patients who have a liver biopsy that does not yield sufficient specimen for analyses.
• Patients who have untreated deficiencies of folic acid, vitamin B6 or B12.
• Patients who have chronic active Hepatitis B or C, hemochromatosis, autoimmune hepatitis, or a cholangiopathy.
• Patients with psychotic disorders, and in particular manic depression (contra indication to SAMe treatment).

Sponsors & Collaborators

• Loma Linda University: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Loma Linda University

Loma Linda, California, 92354, United States

Location

MeSH Terms

Conditions

Hepatitis, Alcoholic

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Study Officials

• Michel H Mendler, M.D.

  Loma Linda Univeristy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 24, 2009
• First Posted: February 26, 2009
• Study Start: October 1, 2008
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: September 13, 2010

Record last verified: 2010-09

Locations

US (1)