Randomized, Placebo-Controlled Study of Leptin for the Treatment of HIV Lipodystrophy and Metabolic Syndrome
April 6, 2017 updated by: Christos Mantzoros, Beth Israel Deaconess Medical Center
Role of Leptin in Highly Active Antiretroviral Therapy (HAART)-Induced Lipodystrophy and Metabolic Syndrome in HAART-Treated HIV Patients
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.
Study Overview
Status
Completed
Intervention / Treatment
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
Study Type
Interventional
Enrollment (Actual)
7
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: r-MetHuLeptin
r-MetHuLeptin SubQ once daily
|
|
|
Placebo Comparator: Placebo
SubQ once daily
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Serum Lipid Levels
Time Frame: At the end of each two month intervention
|
At the end of each two month intervention
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Insulin Resistance (as Assessed by HOMA-IR)
Time Frame: At the end of each two month intervention
|
At the end of each two month intervention
|
|
|
Glycemia (as Assessed by Fasting Glucose)
Time Frame: At the end of each two month intervention
|
At the end of each two month intervention
|
|
|
Low Density Lipoprotein (LDL) Cholesterol Levels
Time Frame: At the end of each two month intervention
|
At the end of each two month intervention
|
|
|
Free Fatty Acid (FFA) Levels
Time Frame: At the end of each two month intervention
|
At the end of each two month intervention
|
|
|
Blood Pressure
Time Frame: At the end of each two month intervention
|
percent change in mean blood pressure
|
At the end of each two month intervention
|
|
Fibrinogen
Time Frame: At the end of each two month intervention
|
Fibrinogen
|
At the end of each two month intervention
|
|
Insulin Levels
Time Frame: At the end of each two month intervention
|
At the end of each two month intervention
|
|
|
Lean Body Mass
Time Frame: At the end of each two month intervention
|
lean body mass
|
At the end of each two month intervention
|
|
Viral Load
Time Frame: At the end of each two month intervention
|
At the end of each two month intervention
|
|
|
CD4+ Lymphocytes
Time Frame: At the end of each two month intervention
|
At the end of each two month intervention
|
|
|
Interleukin-6 (IL-6) Levels
Time Frame: At the end of each two month intervention
|
At the end of each two month intervention
|
|
|
Hepatic Fat Content
Time Frame: At the end of each two month intervention
|
At the end of each two month intervention
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2001
Primary Completion (Actual)
June 1, 2011
Study Completion (Actual)
June 1, 2011
Study Registration Dates
First Submitted
August 30, 2005
First Submitted That Met QC Criteria
August 30, 2005
First Posted (Estimate)
September 1, 2005
Study Record Updates
Last Update Posted (Actual)
May 11, 2017
Last Update Submitted That Met QC Criteria
April 6, 2017
Last Verified
April 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2001P000484
- R01DK058785 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.