Track topics on Twitter Track topics that are important to you
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.
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.
Primary Purpose: Treatment
National Institutes of Health Clinical Center, 9000 Rockville Pike
National Institutes of Health Clinical Center (CC)
Published on BioPortfolio: 2014-08-26T22:55:07-0400
This study aims to provide clinical information on a potential drug-drug interaction between daclatasvir and metformin.
Chronic hepatitis C virus (HCV) infection is associated with an increased risk for the development of type 2 diabetes and HCV infection itself may promote insulin resistance, irrespective ...
The purpose of this clinical research study is to learn whether Saxagliptin added to Metformin therapy is more effective than Metformin alone as a treatment for type 2 diabetic subjects wh...
The purpose of this study was to study the effect of different combinations of fenofibrate and metformin on the cluster of metabolic syndrome (MetS) biochemical abnormalities, and to deter...
Single-dose, randomized, open-label, cross over study. The study will have an open-label, 3 period, 3 treatments, and randomized design. Each volunteer will receive a Metformin gum 2x250m...
Metformin, a biguanide derivative, is the most commonly prescribed medication in the treatment of type 2 diabetes mellitus. More recently, the use of metformin has shown potential as a preventive and ...
Metformin has been used for nearly a century and is now the most widely prescribed oral anti-diabetic agent worldwide. Yet how metformin acts remains only partially understood and controversial. One k...
Metformin is a commonly used antidiabetic drug. It has been shown that this drug activates the AMP-activated protein kinase, which inhibits downstream the mammalian target of rapamycin. In addition, s...
Chronic infection with hepatitis B virus (HBV) often causes chronic inflammation of the liver with an increased incidence of hepatocellular carcinoma (HCC). HBV-infected individuals may also have an i...
Consensus on combination options for patients with type 2 diabetes mellitus (T2DM) unable to use metformin is lacking. This review summarizes data describing-non-metformin based combination therapy.
INFLAMMATION of the LIVER in humans due to infection by VIRUSES. There are several significant types of human viral hepatitis with infection caused by enteric-transmission (HEPATITIS A; HEPATITIS E) or blood transfusion (HEPATITIS B; HEPATITIS C; and HEPATITIS D).
A family of hepatotropic DNA viruses which contains double-stranded DNA genomes and causes hepatitis in humans and animals. There are two genera: AVIHEPADNAVIRUS and ORTHOHEPADNAVIRUS. Hepadnaviruses include HEPATITIS B VIRUS, duck hepatitis B virus (HEPATITIS B VIRUS, DUCK), heron hepatitis B virus, ground squirrel hepatitis virus, and woodchuck hepatitis B virus (HEPATITIS B VIRUS, WOODCHUCK).
A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)
A species in the genus HEPATOVIRUS containing one serotype and two strains: HUMAN HEPATITIS A VIRUS and Simian hepatitis A virus causing hepatitis in humans (HEPATITIS A) and primates, respectively.
INFLAMMATION of the LIVER in humans caused by HEPATITIS DELTA VIRUS, a defective RNA virus that can only infect HEPATITIS B patients. For its viral coating, hepatitis delta virus requires the HEPATITIS B SURFACE ANTIGENS produced by these patients. Hepatitis D can occur either concomitantly with (coinfection) or subsequent to (superinfection) hepatitis B infection. Similar to hepatitis B, it is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.
Latest News Clinical Trials Research Drugs Reports Corporate
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...
metformin and fatty liver nashdoes metformin help NASHmetformin nafldmetformin and fatty liver nashmetformin and fatty liver nashmetformin and nashhow does metformin help with nashmetformin for nashmetformin and nashmetformin for NASHtreatment of fatty liver with metformin oes metforman help with fatty livermetformin for nashmetformin nash cirrhosismetformin use in NASH