Official Title: “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”

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

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: July 2011

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.

Intervention(s) in this Clinical Trial

• Drug: Glucophage (Metformin)
  • metformin XR 2000 mg daily for 12 months
• Drug: Placebo
  • placebo 2000 mg daily for 12 months

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Metformin
• Placebo Comparator: 2
  • Placebo

Primary Measures

• 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.
  • Time Frame: 24 months
    Safety Issue?: No

Secondary Measures

• Tests the postulate that metformin will improve insulin sensitivity in NAFLD. Also test the postulate that improving IR with an insulin sensitizing agent will improve biochemical and histological features of NAFLD.
  • Time Frame: 24 months
    Safety Issue?: No
• Determine if metformin improves the altered parameters of lipid metabolism as compared to placebo.
  • Time Frame: 24 months
    Safety Issue?: No
• 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
  • Time Frame: 24 months
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Duke University

Overall Clinical Trial Officials and Contacts

Manal F Abdelmalek, MD, MPH Principal Investigator Duke University Medical Center, Department of Medicine, Division of Gastroenterology  

Overall Contact: Dawn Piercy, MS, NP 866-704-4673 dawn.piercy@duke.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00736385

Study ID Number: Pro00006196

ClinicalTrials.gov Identifier: NCT00736385

Health Authority: United States: Food and Drug Administration