Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy
This study involves research about an investigational medicine called metreleptin. The reason for this study is to find out how metreleptin can improve non-alcoholic steatohepatitis or nonalcoholic fatty liver disease associated with lipodystrophy, a rare disorder associated with abnormal loss of the body's fat tissue. In this study, metreleptin is considered to be investigational for the treatment of lipodystrophy. Metreleptin will be 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 (e.g. blood cholesterol, liver function, insulin resistance) and body composition characteristics (e.g. the pattern of fat distribution in the body).
Fatty Liver Disease, Nonalcoholic
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Liver histopathology [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]Primary outcome will be the Total NASH score read histopathologically from the liver biopsy samples, as determined by the NIH NASH Clinical Network criteria. At baseline and at the end of the year, patients will undergo a transcutaneous liver biopsy and the specimen will be graded for the severity of NAFLD/NASH pathology.
- Liver fat by MRI and MR spectroscopy [ Time Frame: 1 year ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]
- Fasting lipids [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Fasting glucose [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Body weight [ Time Frame: 1 year ] [ Designated as safety issue: No ]
|Study Start Date:||October 2012|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
Other Name: (originally A100, recombinant-human-methionyl-leptin
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, Amylin Pharmaceuticals, San Diego, CA). 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.
|Contact: Adam Neidert, MSemail@example.com|
|Contact: Elif A Oral, MD, MSfirstname.lastname@example.org|
|United States, Michigan|
|University of Michigan||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Adam Neidert, MS 734-615-0539 email@example.com|
|Principal Investigator: Elif A Oral, MD, MS|
|Sub-Investigator: Charles Burant, MD, PhD|
|Sub-Investigator: Barbara McKenna, MD|
|Sub-Investigator: Hari Conjeevaram, MPH|
|Sub-Investigator: Thomas Chenevert, PhD|
|Sub-Investigator: Hero Hussain, MD|
|Sub-Investigator: Nevin Ajluni, MD|
|Principal Investigator:||Elif A Oral, MD, MS||University of Michigan|