Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy

• Status: Completed
• Trial end date: 2016-07-13
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Michigan
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Criteria

Inclusion Criteria:

• Is male or female ≥ 5 years old at baseline.

• Is male, female not of childbearing potential, or meets all the following criteria if female of childbearing potential (including perimenopausal women who have had a menstrual period within one year):

• Not breastfeeding

• Negative pregnancy test result (human chorionic gonadotropin, beta subunit [βhCG]) at baseline (not applicable to hysterectomized females).

• Must practice and be willing to continue to practice appropriate birth control (defined as a method which results in a low failure rate when use consistently and correctly, such as implants, injectables, oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, tubal ligation, or a vasectomized partner) during the entire duration of metreleptin treatment.

• Has physician-confirmed lipodystrophy as defined by evidence of generalized (whole body) or partial (limbs) loss of body fat outside the range of normal variation.

• Alcohol consumption of less than 40 grams/week.

• A liver ultrasound confirming non-alcoholic fatty liver disease, or previous liver biopsy confirming NASH status.

• If ≥ 18 years of age, is able to read, understand and sign the U of M IRBMED approved informed consent form (ICF), communicate with study physician and study team, understand and comply with protocol requirements.

• If < 18 and ≥ 7 years of age, is able to read, understand and sign the appropriate U of M IRBMED approved assent form and has a parent or legal guardian that is able to read, understand and sign the ICF.

• If < 7 and ≥ 5 years of age or unable to read, the appropriate assent form must be explained to the child.

• If previously treated with thiazolidinediones or Vitamin E, stable dose of these medications for at least 3 months.

Exclusion Criteria:

• Presence of advanced liver disease (as evidenced by abnormal synthetic function, abnormal PT or albumin).

• Evidence of other etiologies of viral hepatitis.

• Presence of clinically significant hematologic abnormalities (such as neutropenia and/or lymphadenopathy).

• Presence of HIV infection.

• Very poorly controlled diabetes; HbA1c >10%

• Inability to give informed consent.

• Presence of ESRD, any type of active cancer, or >class 2 congestive heart failure ((New York Heart Association Functional Classification System), based on medical history and physical examination.

• Active infection (may be transient).

• Has known allergies to E. coli-derived proteins or hypersensitivity to any component of metreleptin treatment.

• Any other condition in the opinion of the investigators that may impede successful data collection.