At a glance
ClinicalIndex Comparison Record- ✓Age at least 18 years
- ✓Elevated serum ALT or AST above upper limits of normal
- ✓Biopsy-proven steatohepatitis within 12 months with NASH activity score ≥4 including minimum score of 1 each for steatosis, hepatocellular injury and parenchymal inflammation
- ✓Written informed consent
- ✕Evidence of another form of liver disease including hepatitis B (HBsAg+), hepatitis C (HCV RNA+), autoimmune hepatitis, autoimmune cholestatic disorders, Wilson disease, alpha-1-antitrypsin deficiency, hemochromatosis, or drug-induced liver disease
- ✕History of excess alcohol ingestion (>30 g/day average in previous 10 years or >10 g/day in previous 1 year)
- ✕Contraindications to liver biopsy: platelet count <75,000/mm³ or prothrombin time >16 seconds
- ✕Decompensated liver disease with Child-Pugh score ≥7
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
Treatment of Nonalcoholic Steatohepatitis With Metformin
In Brief
A Phase 2 clinical trial evaluating Metformin for Hepatitis. Completed, enrolled 28 participants across 1 site.
Detailed Summary
Nonalcoholic Steatohepatitis (NASH) is associated with progressive liver disease, fibrosis, and cirrhosis. Although the cause of NASH is unknown, it is often associated with obesity, type 2 diabetes, and insulin resistance. At present, there are no approved treatments for NASH patients, but an experimental approach has focused on improving their insulin sensitivity. Metformin is one of the most commonly used medications for the treatment of diabetes. The purpose of this study is to determine whether the medical problems of NASH patients, specifically liver damage, improves when their insulin sensitivity is enhanced with metformin. The study will last 3 to 5 years and will enroll up to 30 patients. Participants will undergo a complete medical examination, a series of lab tests, and a liver biopsy. They will then start taking a single 500-mg tablet of metformin once a day for 2 weeks, then the same dosage twice a day for 2 more weeks, if they tolerate the first dosage. The dosage will increase to 1,000 mg twice a day for the remaining 44 weeks of the study. After 1 year, participants will undergo a repeat medical examination and liver biopsy.
Study Details
Timeline
Interventions
After complete medical evaluation and liver biopsy, patients who qualified for therapy were started on metformin in an initial dose of 500 mg once daily. After 2 weeks, the dose was increased to 500 mg twice daily and after 4 weeks to the full dose of 1000 mg twice daily. Subsequent dose reductions were carried out based on tolerance, with particular attention to gastrointestinal upset and abdominal bloating. Patients were seen in the out-patient clinic, had a brief medical history and examination and routine blood tests at 2 and 4 weeks after enrolment and every 4 weeks thereafter. The oral and intravenous glucose tolerance tests were repeated after 40 and 44 weeks respectively and liver biopsy and imaging tests at 48 weeks. Metformin was discontinued after 48 weeks in patients without diabetes on the pre-treatment evaluation.