Clinical trial NCT00140244: Randomized, Placebo-Controlled Study of Leptin for the Treatment of HIV Lipodystrophy and Metabolic Syndrome
Official title: Role of Leptin in Highly Active Antiretroviral Therapy (HAART)-Induced Lipodystrophy and Metabolic Syndrome in HAART-Treated HIV Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HAART-induced Lipodystrophy and Metabolic Syndrome
Keywords: leptin
lipodystrophy
insulin resistance
hyperlipidemia
metabolic syndrome
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Amgen
First posted: 2005-09-01
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Serum Lipid Levels
timeFrame: At the end of each two month intervention
Secondary outcomes:
measure: Insulin Resistance (as Assessed by HOMA-IR)
timeFrame: At the end of each two month intervention
measure: Glycemia (as Assessed by Fasting Glucose)
timeFrame: At the end of each two month intervention
measure: Low Density Lipoprotein (LDL) Cholesterol Levels
timeFrame: At the end of each two month intervention
measure: Free Fatty Acid (FFA) Levels
timeFrame: At the end of each two month intervention
measure: Blood Pressure
timeFrame: At the end of each two month intervention
measure: Fibrinogen
timeFrame: At the end of each two month intervention
measure: Insulin Levels
timeFrame: At the end of each two month intervention
measure: Lean Body Mass
timeFrame: At the end of each two month intervention
measure: Viral Load
timeFrame: At the end of each two month intervention
measure: CD4+ Lymphocytes
timeFrame: At the end of each two month intervention
measure: Interleukin-6 (IL-6) Levels
timeFrame: At the end of each two month intervention
measure: Hepatic Fat Content
timeFrame: At the end of each two month intervention
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
References:
citation: Bouzoni E, Perakakis N, Connelly MA, Angelidi AM, Pilitsi E, Farr O, Stefanakis K, Mantzoros CS. PCSK9 and ANGPTL3 levels correlate with hyperlipidemia in HIV-lipoatrophy, are regulated by fasting and are not affected by leptin administered in physiologic or pharmacologic doses. Metabolism. 2022 Sep;134:155265. doi: 10.1016/j.metabol.2022.155265. Epub 2022 Jul 9.
citation: Magkos F, Brennan A, Sweeney L, Kang ES, Doweiko J, Karchmer AW, Mantzoros CS. Leptin replacement improves postprandial glycemia and insulin sensitivity in human immunodeficiency virus-infected lipoatrophic men treated with pioglitazone: a pilot study. Metabolism. 2011 Jul;60(7):1045-9. doi: 10.1016/j.metabol.2010.10.002. Epub 2010 Nov 16.