Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy
|ClinicalTrials.gov Identifier: NCT01679197|
Recruitment Status : Completed
First Posted : September 5, 2012
Results First Posted : June 14, 2017
Last Update Posted : June 14, 2017
|Condition or disease||Intervention/treatment||Phase|
|Fatty Liver Disease, Nonalcoholic Nonalcoholic Steatohepatitis Lipodystrophy||Drug: Metreleptin||Phase 2|
The goal is to test the efficacy of restorative leptin therapy on the degree of hepatic steatosis and on amelioration of pathological features of NASH/NAFLD. In addition, the study will evaluate the impact of leptin therapy on total body insulin sensitivity and lipid levels as well as energy expenditure. In order to accomplish this aim, we now propose an efficacy study with recombinant human leptin therapy in patients with all forms of lipodystrophy who also have NASH/NAFLD.
- AIM 1: To determine the efficacy of leptin in promoting amelioration of body composition, hepatic steatosis and histopathological scores in patients with all forms of lipodystrophy and NAFLD/NASH. We will conduct a 1 year, open-label study, to assess the metabolic effects of recombinant human leptin (METRELEPTIN, AztraZeneca, Wilmington, DE). The primary outcome measure will be NASH scores. We will also explore body weight, insulin sensitivity, glucose and lipid control, body composition, and free fatty acid levels.
- AIM 2: To Investigate molecular effects of leptin therapy. In parallel to our preliminary studies, gene expression will be performed on individuals participating in Aim 1 at baseline and following 1 year of leptin. We will combine this with measures of liver metabolite levels to provide novel insights into alterations in metabolism that occur secondary to leptin therapy. We will also measure plasma metabolites at baseline and after 2 (optional), 24 and 48 weeks of therapy to assess the dynamic changes induced by leptin and correlate these changes with phenotypic measures.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||23 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy|
|Actual Study Start Date :||October 8, 2012|
|Actual Primary Completion Date :||July 13, 2016|
|Actual Study Completion Date :||July 13, 2016|
U.S. FDA Resources
Other Name: (originally A100, recombinant-human-methionyl-leptin
- Liver Histopathology [ Time Frame: 1 year ]Primary outcome will be the total non-alcoholic steatohepatitis (NASH) score read histopathologically from the liver biopsy samples. This outcome measure quantifies the severity of fatty liver disease. At baseline and at the end of the year, patients have undergone a transcutaneous liver biopsy and the specimens were graded for the severity of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) pathology. Histological features of NAFLD/NASH were scored using the validated NASH-CRN (NASH Clinical Research Network) scoring system. This scoring system is the total of 4 subscales: steatosis (0-3), lobular inflammation (0-3), hepatocellular ballooning (0-2) and fibrosis (0-4), which are evaluated semi-quantitatively. The total scale range for this scoring system is 0-12, with 0 representing no features of fatty liver disease, and 12 representing the highest degree of fatty liver disease.
- Liver Fat by MRI and MR Spectroscopy [ Time Frame: 1 year ]All enrolled patients will have a baseline MRI of the liver to evaluate liver volume and liver fat. For determination of hepatic fat content by MRI and MR spectroscopy in patients, a series of out-phase and in-phase MRI at multiple flip angles are used. By combination of out-phase and in-phase MRI at multiple flip-angles and TE times, relaxation-time effects can be removed to yield quantitative intra-hepatic (and other organs') fractional fat content throughout the liver in a few breath-hold intervals.
- Liver Function Tests [ Time Frame: 1 year ]AST and ALT are the liver function tests. We are reporting the liver function tests where the treatment group arm would normally be listed, though, we are looking at the same single arm population of 23 participants who received treatment in this study.
- Fasting Lipids [ Time Frame: 1 year ]Cholesterol, triglycerides, HDL cholesterol, and LDL together make up the lipid profile and must be reported together. We are reporting the lipid profile where the treatment group arm would normally be listed, though, we are looking at the same single arm population of 23 participants who received treatment in this study.
- Fasting Glucose [ Time Frame: 1 year ]
- Body Weight [ Time Frame: 1 year ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01679197
|United States, Michigan|
|University of Michigan|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Elif A Oral, MD, MS||University of Michigan|