|
Treating Nonalcoholic Steatohepatitis (NASH) with Metformin Clinical Trials Resources presented on Clinical Trials Search isn't meant to be a substitute for qualified health advice, visits or professional assistance with a real medical. We aren't doctors. Always consult your mD about Treating Nonalcoholic Steatohepatitis (NASH) with Metformin conditions. Clinical Trials Search.org is a website dedicated to listing clinical research studies in human subjects. Treating Nonalcoholic Steatohepatitis (NASH) with Metformin Clinical research trials and Treating Nonalcoholic Steatohepatitis (NASH) with Metformin health trials occur in a lot of of places throughout the United States of America. A clinical trial or clinical study is a research project with human volunteer subjects. Clinical drug trials and pharmaceutical clinical trials typically assess the effectivity of new does drugs. The role of the studies / projects is to resolve certain human healthcare questions. Clinical trials are a popular way for doctors, government agencies, and private sector corporations to detect remedies for all varieties of circumstances, such as Treating Nonalcoholic Steatohepatitis (NASH) with Metformin. Treating Nonalcoholic Steatohepatitis (NASH) with Metformin Clinical Trials and other clinical trials allow volunteers to obtain health treatment choices before they are available to the general public. Most times the human subjects recieve professional assistance for free of charge, and every now and again they are paid for their time. Sometimes there is a cost for a Treating Nonalcoholic Steatohepatitis (NASH) with Metformin clinical trial. Human subjects frequently get the finest healthcare available for their Treating Nonalcoholic Steatohepatitis (NASH) with Metformin condition. Risks are a reality, however, and may include extra or frequent physician visits, medical dangers (possibly life-threatening), and/or the treatment being uneffective. Trials are federally governed with strict guidelines to protect clinical trials patients.
|
|
|
|
|
|
|
Home > "T" Clinical Trials Conditions > Treating Nonalcoholic Steatohepatitis (NASH) with Metformin  Treating Nonalcoholic Steatohepatitis (NASH) with Metformin
Treating Nonalcoholic Steatohepatitis (NASH) with Metformin
For Condition: Hepatitis
Status: Recruiting
Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ,
Synopsis: 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.
Details: 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.
Eligibility:
Study Type: Interventional, Treatment, Safety/Efficacy
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: INCLUSION CRITERIA: 1. Age at entry at least 18 years. 2. Serum alanine (ALT) or aspartate (AST) aminotransferase activities that are above the upper limits of normal. 3. Evidence of steatohepatitis on liver biopsy done within the previous 12 months with a NASH activity score of at least 4 (of a total possible score of 16) including a score of at least 1 each for steatosis, hepatocellular injury and parenchymal inflammation. Histological criteria of steatohepatitis include: (1) macrovesicular steatosis, (2) acinar zone 3 hepatocellular injury (ballooning degeneration), (3) parenchymal and (4) portal inflammation. Additionally helpful, but not required, features include the presence of (5) Mallory's hyaline and (6) pericellular and/or sinusoidal fibrosis that predominantly involves zone 3. 4. Written informed consent. EXCLUSION CRITERIA: 1. Evidence of another form of liver disease. a. Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg). b. Hepatitis C as dxefined by presence of hepatitis C virus (HCV) RNA in serum. c. Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppresive therapy. d. Autoimmune cholestatic liver disordersas defined by elevation of alkaline phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver histology consistent with primary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis. e. Wilson disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease. f. Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency. g. Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. h. Drug-induced liver disease as defined on the basis of typical exposure and history. i. Bile duct obstruction as shown by imaging studies. 2. History of excess alcohol ingestion, averaging more than 30 gm/day (3 drinks per day) in the previous 10 years, or history of alcohol intake averaging greater than 10 gm/day (1drink per day: 7 drinks per week) in the previous one year. 3. Contraindications to liver biopsy: platelet counts less than 75,000/mm(3) or prothrombin time greater than 16 seconds. 4. Decompensated liver disease, Child-Pugh score greater than or equal to 7 points. 5. History of gastrointestinal bypass surgery or ingestion of drugs known to produce hepatic steatosis including corticosteroids, high-dose estrogens, methotrexate, tetracycline or amiodarone in the previous 6 months. 6. Presence of diabetes mellitus as defined by: fasting plasma glucose of greater than or equal to 126 mg/dl on two separate occasion, or diabetic symptoms with a random plasma glucose of greater than or equal to 200 mg/dl (34). 7. Use of anti-diabetic drugs, including insulin, biguanides, sulfonylureas, or thiazolidinediones in the previous 6 months. 8. Significant systemic or major illnesses other than liver disease, including congestive heart failure, coronary artery disease, cerebrovascular disease, pulmonary disease with hypoxia, renal failure, organ transplantation, serious psychiatric disease, malignancy that, in the opinion of the investigator would preclude treatment with metformin and adequate follow up. 9. Positive test for anti-HIV. 10. Active substance abuse, such as alcohol, inhaled or injection drugs within the previous one year. 11. Pregnancy or inability to practice adequate contraception in women of childbearing potential. 12. Evidence of hepatocellular carcinoma: alpha-fetoprotein levels greater than 200 ng/ml and/or liver mass on imaging study that is suggestive of liver cancer. 13. Any other condition, which, in the opinion of the investigators would impede competence or compliance or possibly hinder completion of the study. 14. History of hypersensitivity reactions to metformin. 15. Serum creatinine greater than 1.5 mg/dl in men and greater than 1.4 mg/dl in women.
Total Enrollment: 30
Location and Contact Information:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) *Recruiting*
Bethesda, Maryland, 20892
United States
Recruiting Patient and Public Liaison Office 1-800-411-1222
Additional Information:
Study ID Numbers: 030233; 03-DK-0233
Study Start Date: June 20, 2003
Record last reviewed: June 18, 2003
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00063232
Other Hepatitis Studies:
1. Treating Nonalcoholic Steatohepatitis (NASH) with Metformin
2. Safety and Efficacy Study of a Caspase Inhibitor in Patients Undergoing Liver Transplantation
3. Lamivudine and Adefovir to Treat Chronic Hepatitis B
4. Telbivudine versus Lamivudine in Adults with Decompensated Chronic Hepatitis B and Evidence of Cirrhosis
5. A Controlled Prospective Study of Transfusion-Associated Hepatitis
Related Studies:
Other Hepatitis Clinical Trials
Other Maryland Clinical Trials
Other Bethesda Clinical Trials
Treating Nonalcoholic Steatohepatitis (NASH) with Metformin
|
|
|
|
|
|
|
|
