Combination of Insulin Sensitizer and Leptin as Treatment for the HAART -Induced Metabolic Syndrome

February 2, 2017 updated by: Christos Mantzoros, Beth Israel Deaconess Medical Center

A Combination of Insulin Sensitizer and Leptin as Treatment for the HAART -Induced Metabolic Syndrome: A Randomized, Double-blind, Placebo-controlled Clinical Trial

The purpose of this study is to determine whether patients with HIV lipodystrophy (fat wasting) benefit from taking the combination of two drugs, one insulin sensitizer (either metformin or pioglitazone, both diabetes drugs) and leptin (a natural hormone produced by your fat cells). Our hope is that they will improve sugar and fat metabolism and positively affect the body fat changes you have noticed while taking HAART.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Highly active antiretroviral therapy (HAART) induces profound and sustained suppression of human immunodeficiency virus (HIV) replication, and is thus very effective in reducing disease-associated morbidity and mortality in this patient population. However, HAART also results in the development of a lipodystrophic syndrome which is characterized by fat accumulation, fat wasting, or a combination of both, and similar to congenital forms of lipodystrophy, is associated with components of the metabolic syndrome, including insulin resistance (IR), fasting hypertriglyceridemia, and hypercholesterolemia.

Our study is a "proof of concept" study on the treatment of the HAART-induced metabolic syndrome, which builds upon and represents a direct extension of a study previously funded by the American Diabetes Association (ADA). If our clinical trial proves that a combination treatment of leptin and an insulin sensitizer has additive or synergistic effects in reversing the metabolic abnormalities of HIV positive patients with lipoatrophy, it could lead to the design of larger multi-center, randomized, placebo-controlled trial(s) aiming at establishing safety and efficacy of this treatment for the HAART-induced metabolic syndrome.

Study Type

Interventional

Enrollment (Actual)

9

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

  • United States
    • 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:

  • Age18 years and above and ability and willingness to give written informed consent
  • Documented HIV-1 infection
  • At least 6 months of stable cumulative antiretroviral therapy with any available or investigational anti- retroviral medication (protease inhibitor, nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, nucleotide reverse transcriptase inhibitor)
  • Lipoatrophy developed after initiating HAART treatment (see criteria below). Leptin levels should be less than 4 ng/ml.
  • Insulin resistance, impaired fasting glucose, impaired glucose tolerance or type 2 diabetes developed after starting the antiretroviral medications. These categories are defined, respectively, as fasting insulin level above 15 µIU/ml; fasting serum glucose value above 100 mg/dl; 2-hour serum glucose level during a 75 gram oral glucose tolerance test (OGTT) between 140 and 200 mg/dl; and fasting glucose above 126 mg/dl or random glucose level above 200 mg/dl with presence of the classic symptoms of diabetes, such as polyuria, polydipsia, ketonuria, and rapid weight loss
  • Hypertriglyceridemia and/or hypercholesterolemia developed after starting the antiretroviral therapy. These categories are defined as fasting triglycerides greater than 150 mg/dl and LDL cholesterol greater than 130 mg/dl, respectively
  • Female subjects must have a negative urine pregnancy test before enrollment and must agree to use a barrier contraception i.e. condoms, diaphragm or IUD, with or without a hormonal-based method for the duration of the study. Women who are pregnant or become pregnant during the study and who do not accept some form of contraception will be excluded from the study.
  • Patients should have history of peripheral fat wasting of the face (e.g. sunken cheeks), limbs (including prominent veins), and/or buttocks, which developed after the initiation of HAART therapy
  • Patients should have physical exam findings of a) facial atrophy - sunken cheeks, sunken temporal regions, and/or prominent temporal veins and b) wasting of fat in periphery, limbs and/or buttocks (including prominent veins)
  • Patients should have anthropometric measurements suggestive of decreased subcutaneous fat content: Decreased triceps skinfold thickness (< 4 mm in men and < 8 mm in women) or Decreased upper arm circumference (< 27.1 cm in men and < 23.3 cm in women) or Decreased subscapular skinfold thickness (< 7 mm in men and < 7 mm in women) or dual energy X-ray absorptiometry (DEXA) scanning suggestive of fat depletion: total body fat < 14% in men and < 22% in women.

Exclusion Criteria:

  • History of impaired glucose metabolism or hyperlipidemia prior to antiretroviral use
  • Triglyceride levels higher than 1500 mg/dl after the 1 month run-in phase or anytime during the study
  • Abnormal hepatic function: liver function tests higher than twice the upper normal range
  • Abnormal renal function: creatinine higher than 1.3 mg/dl
  • Any condition/illness that may affect study outcomes such as pregnancy, active infection except HIV, clinically significant malabsorption/malnutrition, malignancy
  • Any active hormonal disease and/or hormonal treatment that may affect the outcomes of interest such as clinically overt hypo/hyperthyroidism, hypogonadism, hypercortisolism, or treatment with steroids or growth hormone (exception: patients taking testosterone can be included in the trial if they agree to continue the same dosage for the duration of the trial)
  • Present alcoholism or drug abuse. These conditions will be screened for by a detailed history and systems review and baseline laboratory analysis with chemistries, CBC, and hormone levels, and EKG.

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: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Leptin
Leptin replacement therapy
Drug: Leptin
Drug: Pioglitazone or metformin
Placebo Comparator: Pioglitazone or metformin
Diabetes treatment therapy
Drug: Placebo
Drug: Pioglitazone or metformin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Insulin Resistance (HOMA Index)
Time Frame: At the end of each 3 month intervention
At the end of each 3 month intervention

Secondary Outcome Measures

Outcome Measure
Time Frame
Cholesterol Levels
Time Frame: At the end of each 3 month intervention
At the end of each 3 month intervention
Body Composition (Fat Mass)
Time Frame: At the end of each 3 month intervention
At the end of each 3 month intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beth Israel Deaconess Medical Center

Collaborators

American Diabetes Association

Investigators

  • Principal Investigator: Christos Mantzoros, MD, Beth Israel Deaconess Medical Center

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

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

August 1, 2006

Primary Completion (Actual)

May 1, 2011

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

August 9, 2006

First Submitted That Met QC Criteria

August 9, 2006

First Posted (Estimate)

August 10, 2006

Study Record Updates

Last Update Posted (Actual)

March 23, 2017

Last Update Submitted That Met QC Criteria

February 2, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2005P000159

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.

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