Metformin for the Treatment of Nonalcoholic Fatty Liver Disease (NAFLD)

Study Overview
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Brief Summary
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The purpose of this study is to find out if Metformin is safe and useful in the treatment of NAFLD.

Detailed Description
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NAFLD is a poorly understood disease which may cause an enlarged liver, abnormal liver test results, and scarring of the liver. It may occur more often in people with obesity, high levels of cholesterol (blood fats), diabetes (high blood sugar), or the insulin resistance syndrome (where a person's body does not respond to the hormone insulin which helps keep blood sugar levels normal). Currently, no effective drug treatment for NAFLD exists. There is increasing evidence that NAFLD may be a condition due to a problem with metabolism (the way your body uses energy). Previous studies have shown that high glucose (sugar) levels may play an important role in the development of fatty liver disease. Medications that decrease your natural glucose level may reduce the amount of fat in the liver and, therefore, might be useful in the treatment of NAFLD. Metformin, a drug approved by the U.S. Food and Drug Administration (FDA) for use in patients with diabetes, has been shown to improve fatty liver in animals and in a small number of human beings.

Official Title
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Hyperinsulinemia and Insulin Resistance in Nonalcoholic Fatty Liver Disease. Metformin for the Treatment of Nonalcoholic Fatty Liver Disease: A Randomized, Double-Blinded, Placebo-Controlled Trial

Conditions
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Fatty Liver

Intervention / Treatment
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* Drug: Glucophage (Metformin)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: biopsy-proven NAFLD, determined within 12 months of study initiation Exclusion Criteria: > 20 grams of alcohol/day impaired oral glucose tolerance test known diagnosis of diabetes mellitus hepatitis C infection cirrhosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metformin<br>Metformin XR (extended-release) 2000 mg daily | Drug: Glucophage (Metformin)<br>* metformin XR 2000 mg daily for 12 months<br>* Other names: Riomet;|
| Placebo Comparator: Placebo<br>Placebo capsule | Drug: Placebo<br>* placebo 2000 mg daily for 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study Endpoints Will Include Measurements of Insulin Sensitivity, Hepatic Insulin Clearance, and Altered Parameters of Lipid Metabolism, Changes in the Histological Features That Define NAFLD, and Quantitative Measurements of Visceral and Peripheral Fat. |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tests the Postulate That Metformin Will Improve Insulin Sensitivity in NAFLD. Also Test the Postulate That Improving IR (Insulin Resistance) With an Insulin Sensitizing Agent Will Improve Biochemical and Histological Features of NAFLD. |  | 24 months | 
| Determine if Metformin Improves the Altered Parameters of Lipid Metabolism as Compared to Placebo. |  | 24 months | 
| Measure the Differential Effects of IR and Lipid Metabolism on Peripheral Mononuclear Cell (PBMC) Inflammatory Response and the Associated Hepatocyte Mitochondrial Ultrastructure and Measures of Oxidative Stress |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nonalcoholic fatty liver disease