Trial of Leptin Replacement Therapy in Patients With Lipodystrophy

Study Overview
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Brief Summary
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Lipodystrophies represent a therapeutic challenge with regards to insulin resistance, hypertriglyceridemia and fatty liver which often is coupled with significant adipose tissue loss. The purpose of the study is to examine the safety and efficacy of Leptin on subjects with lipodystrophy.

Detailed Description
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The mechanism by which leptin improves glucose and lipid control is not clear. We will examine the possible mechanisms of leptin action by studying the effects of leptin administration on food intake, insulin resistance, insulin secretory response, hepatic and intramuscular triglyceride stores in a large sample of patients with lipodystrophy. Hypothesis: Leptin replacement in patients with generalized and partial lipodystrophy and hypoleptinemia will be safe and efficacious in improving the metabolic abnormalities associated with insulin resistance.

Official Title
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Double-Blind, Placebo-Controlled Trial of Leptin Replacement Therapy in Patients With Lipodystrophy

Conditions
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Hypoleptinemia, Generalized Lipodystrophy, Partial Lipodystrophy, Insulin Resistance

Intervention / Treatment
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* Drug: Leptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 6 years Partial and generalized lipodystrophy Serum leptin levels less than the 7th percentile of normal values reported by the 3rd National Health and Nutrition Examination survey (less than 7.0 ng/mL in females and less than 3/0 ng/mL in males) Presence of at least one of the following metabolic abnormalities: Type 2 Diabetes Mellitus Fasting serum insulin >20 uU/mL Fasting serum triglycerides > 300 mg/dL Previous participation in leptin trial (Amgen 991265, GCRC 660) - for Part B of the Study. Exclusion Criteria: Known liver disease due to causes other than non-alcoholic steatohepatitis. Hematocrit of less than 30%. Current alcohol or substance abuse. Use of anorexigenic drugs, anabolic steroids, GH and thiazolidinediones Active tuberculosis Psychiatric disorder impeding competence or compliance Malignancies HIV infection Subjects who have a known hypersensitivity to E. Coli derived proteins Other condition, which in the opinion of the clinical investigators would impede completion of the study.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1 Leptin<br>Active Comparator for 4 months, then for 8 months. | Drug: Leptin<br>* Leptin injected subcutaneously twice a day, to be administered at 100% of the estimated replacement dose during the first month, which is a dosage of 0.03mg/kg for female children, 0.04mg/kg for adult females, and0.02 mg/kg for all males, and then at 200% subsequently, or placebo.<br>* Other names: r-metHuLeptin;|
| Placebo Comparator: 2 Sugar pill<br>Placebo for 4 months, then active comparator for 8 months. | Drug: Placebo<br>* Sugar pill<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Serum Triglycerides |  | 4 months | 
| HbA1c |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Serum Glucose |  | 4 months | 
| Body Weight |  | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lipodystrophy, Insulin secretory response