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Tracking Information | |
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First Received Date † | June 23, 2003 |
Last Updated Date | March 28, 2008 |
Start Date † | June 2003 |
Current Primary Outcome Measures † | |
Original Primary Outcome Measures † | |
Change History | Complete list of historical versions of study NCT00063232 on ClinicalTrials.gov Archive Site |
Current Secondary Outcome Measures † | |
Original Secondary Outcome Measures † | |
Descriptive Information | |
Brief Title † | Treating Nonalcoholic Steatohepatitis (NASH) With Metformin |
Official Title † | Treatment of Nonalcoholic Steatohepatitis With Metformin |
Brief 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. |
Detailed Description | Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple fatty liver (steatosis) to steatosis with inflammation and necrosis to cirrhosis, that occurs in persons who drink little or no alcohol. Nonalcoholic steatohepatitis (NASH) represents the more severe end of this spectrum and is associated with progressive liver disease, fibrosis and cirrhosis. The etiology of NASH is unclear, but it is often associated with obesity, type 2 diabetes, hyperlipidemia and insulin resistance. We have recently conducted a study of a 48-week course of pioglitazone in 21 non-diabetic patients with NASH. Serum aminotransferase levels and liver histology improved in most patients and the improvements correlated with changes in insulin sensitivity. These results are promising, but pioglitazone is associated with significant weight gain, is quite expensive, and its long-term safety is yet to be proven. In contrast, metformin is inexpensive, extremely well tolerated, and of proven long-term safety in patients with diabetes and pre-diabetes. In this study, we propose to treat 20 non-diabetic patients with NASH with metformin for 48-weeks. After an initial evaluation for insulin sensitivity, fat distribution and liver biopsy, patients will receive gradually increasing doses of metformin orally to a maximum of 2000 mg daily. Patients will be monitored at regular intervals for symptoms of liver disease, side effects of metformin and serum biochemical and metabolic indices. At the end of 48-weeks, patients will have a repeat medical evaluation and liver biopsy. Pre and post treatment liver histology, fat distribution and insulin sensitivity will be compared. The primary end point of successful therapy will be improvement in hepatic histology as determined by reduction of at least three points in NASH activity score. Secondary end points will be improvement in insulin sensitivity, body fat distribution, and liver biochemistry. |
Study Phase | Phase II |
Study Type † | Interventional |
Study Design † | Treatment |
Condition † | Hepatitis |
Intervention † | Drug: Metformin |
Study Arms / Comparison Groups | |
Publications * | Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology. 1999 Mar;29(3):664-9. |
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline. |
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Recruitment Information | |
Recruitment Status † | Completed |
Enrollment † | 30 |
Completion Date | March 2008 |
Primary Completion Date | |
Eligibility Criteria † |
EXCLUSION CRITERIA:
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Gender | Both |
Ages | 18 Years and older |
Accepts Healthy Volunteers | No |
Contacts †† | |
Location Countries † | United States |
Expanded Access Status | |
Administrative Information | |
NCT ID † | NCT00063232 |
Responsible Party | |
Secondary IDs †† | 03-DK-0233 |
Study Sponsor † | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
Collaborators †† | |
Investigators † | |
Information Provided By | National Institutes of Health Clinical Center (CC) |
Verification Date | March 2008 |
† Required WHO trial registration data element. †† WHO trial registration data element that is required only if it exists. |