Effects of SAMe in Patients With Alcoholic Liver Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of SAMe in Patients With Alcoholic Liver Disease

Conditions
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Liver Disease, Alcoholic

Intervention / Treatment
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* Drug: S-adenosylmethionine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcoholic Liver Disease (ALD), S-adenosylmethionine, SAMe