Randomized, Placebo-Controlled Study of Leptin for the Treatment of HIV Lipodystrophy and Metabolic Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to examine whether replacing leptin to normal levels can reverse the changes in fat distribution, lipid profile, and other metabolic problems associated with highly active antiretroviral therapy (HAART)-induced lipodystrophy and metabolic syndrome in HIV patients.

Detailed Description
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Exposure to HIV medications has been associated with metabolic changes including generalized fat depletion (lipoatrophy), high triglyceride levels, and in some patients, high sugar levels or diabetes. This syndrome is associated with a deficiency of leptin, a hormone produced by fat cells. Recent studies involving leptin administration to patients with congenital lipoatrophy have shown dramatic improvements in metabolic parameters such as insulin resistance and hyperlipidemia. Leptin administration to patients with HAART-induced lipoatrophy may also lead to significant improvements in the metabolic abnormalities found in these HIV+ patients. The aims of this study are to examine the effect of leptin administration on insulin resistance and other parameters of the metabolic syndrome in HIV patients with HAART-induced lipoatrophy. Comparison: Leptin-treated group to placebo-treated group

Official Title
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Role of Leptin in Highly Active Antiretroviral Therapy (HAART)-Induced Lipodystrophy and Metabolic Syndrome in HAART-Treated HIV Patients

Conditions
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HAART-induced Lipodystrophy and Metabolic Syndrome

Intervention / Treatment
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* Drug: r-metHuLeptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years old Documented HIV infection Exposed to at least 6 months of cumulative highly active antiretroviral medications for HIV Developed fat depletion after starting HIV medications Low leptin level in the blood Fasting triglyceride level > 300 mg/dl Exclusion Criteria: Active infectious diseases, except HIV Diabetes prior to starting HIV medications Alcohol or drug abuse Triglyceride level > 1000 mg/dl Significant kidney, liver, or thyroid dysfunction Cancer or lymphoma Pregnancy or planning to become pregnant during the study

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: r-MetHuLeptin<br>r-MetHuLeptin SubQ once daily | Drug: r-metHuLeptin<br> <br> |
| Placebo Comparator: Placebo<br>SubQ once daily | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Lipid Levels |  | At the end of each two month intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Resistance (as Assessed by HOMA-IR) |  | At the end of each two month intervention | 
| Glycemia (as Assessed by Fasting Glucose) |  | At the end of each two month intervention | 
| Low Density Lipoprotein (LDL) Cholesterol Levels |  | At the end of each two month intervention | 
| Free Fatty Acid (FFA) Levels |  | At the end of each two month intervention | 
| Blood Pressure | percent change in mean blood pressure | At the end of each two month intervention | 
| Fibrinogen | Fibrinogen | At the end of each two month intervention | 
| Insulin Levels |  | At the end of each two month intervention | 
| Lean Body Mass | lean body mass | At the end of each two month intervention | 
| Viral Load |  | At the end of each two month intervention | 
| CD4+ Lymphocytes |  | At the end of each two month intervention | 
| Interleukin-6 (IL-6) Levels |  | At the end of each two month intervention | 
| Hepatic Fat Content |  | At the end of each two month intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leptin, lipodystrophy, insulin resistance, hyperlipidemia, metabolic syndrome