Recombinant Leptin Therapy for Treatment of Nonalcoholic Steatohepatitis (NASH)
Summary
Nonalcoholic steatohepatitis (or NASH) is known to be caused by deposition of fat in the liver and development of scarring. This condition occurs more frequently in overweight and obese persons. It is often associated with resistance to the actions of insulin hormone. Fat cells secrete a hormone called leptin. Recently, we have learned that obese or overweight persons make too much leptin, which may contribute to insulin resistance. Paradoxically, patients who do not have any fat cells, also have insulin resistance. In these patients, insulin resistance is caused by the absence of leptin and leptin replacement significantly improves insulin resistance and fat deposition in the liver. In an earlier study, we determined the leptin levels in patients with NASH and how these levels are related to body fat levels as well as responsiveness to insulin. We saw that a subgroup of patients with NASH have relatively low levels of leptin in contrast to the amount of body fat they had. We now would like to see if restoring leptin levels to normal will improve the disease process in these patients. Our study patients will be male patients, aged between 18 and 65 (inclusive), who do not have any other cause for their liver disease. We have put some restrictions in body size such that a spectrum of patients from normal weight to obese range would be included. They will also demonstrate low leptin levels (levels similar to only 25% of normal population). We will use a genetically engineered form of leptin manufactured by Amylin Inc. given via injections under the skin. We plan to continue therapy for a period of one year and evaluate the change in liver disease by a liver biopsy. We will also follow the metabolic parameters and body composition characteristics that we examined in our earlier study. We expect that patients with low blood leptin levels will show improvement in their liver disease and insulin resistance when their blood leptin levels are restored to normal.
Study Design
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Fatty Liver Disease, Nonalcoholic
Intervention
metreleptin
Location
University of Michigan
Ann Arbor
Michigan
United States
48109
Status
Completed
Source
University of Michigan
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00596934
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Fatty Liver
Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.
Fatty Liver, Alcoholic
Lipid infiltration of the hepatic parenchymal cells that is due to ALCOHOL ABUSE. The fatty changes in the alcoholic fatty liver may be reversible, depending on the amounts of TRIGLYCERIDES accumulated.
End Stage Liver Disease
Final stage of a liver disease when the liver failure is irreversible and LIVER TRANSPLANTATION is needed.
Liver Diseases, Alcoholic
Liver diseases associated with ALCOHOLISM. It usually refers to the coexistence of two or more subentities, i.e., ALCOHOLIC FATTY LIVER; ALCOHOLIC HEPATITIS; and ALCOHOLIC CIRRHOSIS.
Reye Syndrome
A form of encephalopathy with fatty infiltration of the LIVER, characterized by brain EDEMA and VOMITING that may rapidly progress to SEIZURES; COMA; and DEATH. It is caused by a generalized loss of mitochondrial function leading to disturbances in fatty acid and CARNITINE metabolism.
Clinical Trials
Abundance and Distribution of Lipids and Proteins in Nonalcoholic Fatty Liver Disease (NAFLD)
Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease in the United States. The incidence of NAFLD is very similar to that of obesity, type 2 diabetes, and the...
Treatment of Nonalcoholic Fatty Liver Disease With Probiotics and Prebiotics
The investigators' aim is to determine whether probiotic and prebiotic treatment plus lifestyle advice is more effective in reducing hepatic fat content than lifestyle advice alone in pati...
Effects of Docosahexaenoic Acid (DHA) on Children With Nonalcoholic Fatty Liver Disease (NAFLD)
The purpose of this interventional study is to evaluate the efficacy and tolerability of docosahexaenoic acid (DHA) in children or adolescents with well-characterized and liver biopsy conf...
The most common cause of death in patients with NAFLD(Nonalcoholic Fatty Liver Disease) is CAD(Coronary Artery Disease). NAFLD patients have 65% more mortality than general population. The...
Low Glycemic Index Dietary Intervention Program in Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in affluent countries. It may progress to cirrhosis and liver cancer. At present, there is no approved dru...
PubMed Articles
Endoplasmic reticulum stress in nonalcoholic Fatty liver disease.
The underlying causes of nonalcoholic fatty liver disease are unclear, although recent evidence has implicated the endoplasmic reticulum in both the development of steatosis and progression to nonalco...
Hyperinsulinemia and the development of nonalcoholic Fatty liver disease in nondiabetic adults.
Insulin resistance is known to be the most important pathogenic factor in the development of nonalcoholic fatty liver disease. We performed a prospective study to analyze the associations of baseline...
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in US children and adolescents and can present with advanced fibrosis or nonalcoholic steatohepatitis (NASH). No treat...
Nonalcoholic Fatty liver disease.
As the hepatic manifestation of the metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of asymptomatic liver enzyme elevations in Western nations. Although i...
