Rosiglitazone Versus Rosiglitazone and Metformin Versus Rosiglitazone and Avandia in the Treatment of Nonalcoholic Steatohepatitis (NASH)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of rosiglitazone alone compared with rosiglitazone plus metformin or rosiglitazone plus losartan in the treatment of biopsy proven nonalcoholic steatohepatitis (NASH). This study was designed to answer the question: are there differences in the efficacy (as measured by histopathology and insulin resistance) of three different therapeutic modalities used to treat NASH?

Official Title
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Rosiglitazone Versus Rosiglitazone and Metformin (Avandamet) Versus Combination Rosiglitazone and Losartan in the Treatment of Nonalcoholic Steatohepatitis (NASH). A Prospective, Open-Label, Randomized Trial

Conditions
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Nonalcoholic Steatohepatitis, Nonalcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: avandia
* Drug: metformin
* Drug: losartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between 18-70 years old Negative urine pregnancy test in females History of elevated liver associated enzymes (ALT > 40) Liver biopsy within 1 year of screening in this study that shows histopathologic findings consistent with NASH Exclusion Criteria: ALT greater than three times normal NYHA class 3 or 4 heart failure Any congestive heart failure patient on insulin Patients on one of the 3 study drugs within the past 3 months prior to enrollment Alcohol consumption >20 gm/day in a female and > 30 gm/day in a male Evidence of co-existent chronic liver disease to include viral hepatitis, Wilson's disease, autoimmune hepatitis, hemochromatosis, primary biliary cirrhosis, or primary sclerosing cholangitis Serum creatinine on initial screening of greater than 1.4 Known hypersensitivity to rosiglitazone, metformin, or losartan Known history of diabetic ketoacidosis Female that is breastfeeding Insulin dependent diabetic

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>avandia | Drug: avandia<br>* 4 mg twice daily<br>|
| Experimental: 2<br>avandia plus metformin | Drug: avandia<br>* 4 mg twice daily<br>Drug: metformin<br>* 500 mg twice daily for 48 weeks<br>|
| Experimental: 3<br>avandia plus losartan | Drug: avandia<br>* 4 mg twice daily<br>Drug: losartan<br>* losartan 50 mg once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| liver biopsy histologic improvement |  | end of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum transaminases |  | throughout study (ongoing) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nonalcoholic steatohepatitis (NASH), fatty liver, insulin resistance