Effects of SAMe in Patients With Alcoholic Liver Disease
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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: Single Group Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | Effects of SAMe in Patients With Alcoholic Liver Disease |
- Liver Histopathology [ Time Frame: September 2005- June 2009 ] [ Designated as safety issue: No ]
- Liver biochemistry [ Time Frame: September 2005- June 2009 ] [ Designated as safety issue: No ]
| 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.
|
|
No Intervention: Healthy
Healthy subjects no treatment
|
|
|
No Intervention: Lifestyle counseling
Active Drinkers Non Liver Disease subjects
|
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). Comparing the initial groups, serum homocysteine was elevated in both ALD and AD groups. Both folate and vitamin B6 levels were decreased in ALD compared to HS, with intermediate levels in AD. Serum cystathionine was elevated and vitamin B6 was decreased in ALD and correlated negatively with levels of cystathionine in ALD patients. Cystathionine also correlated with severity of fibrosis in liver biopsies. Thirty seven (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. Whereas serum biochemical features improved similarly in both groups, there were no significant treatment effects within either group or between the groups on serum levels of methionine metabolites or on liver histopathology scores, including those for steatosis, inflammation, or fibrosis. Summarizing, while the presence of ALD is associated with abnormal patterns of serum methionine metabolites that may be predictive of fibrosis, 24 weeks of SAM treatment was no more effective than placebo in improving clinical and histopathological features of ALD.
Eligibility| Ages Eligible for Study: | 21 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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| United States, California | |
| University of California, Davis Medical Center | |
| Sacramento, California, United States, 95817 | |
| 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 |
| Last Updated: | December 21, 2012 |
| 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 |
ClinicalTrials.gov processed this record on May 22, 2013