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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00362440
Recruitment Status : Completed
First Posted : August 10, 2006
Results First Posted : March 23, 2017
Last Update Posted : March 23, 2017
American Diabetes Association
Information provided by (Responsible Party):
Christos Mantzoros, Beth Israel Deaconess Medical Center

Tracking Information
First Submitted Date  ICMJE August 9, 2006
First Posted Date  ICMJE August 10, 2006
Results First Submitted Date  ICMJE December 22, 2015
Results First Posted Date  ICMJE March 23, 2017
Last Update Posted Date March 23, 2017
Study Start Date  ICMJE August 2006
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 2, 2017)
Insulin Resistance (HOMA Index) [ Time Frame: At the end of each 3 month intervention ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 9, 2006)
  • Insulin Resistance
  • Cholesteral Levels
  • Body Composition
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2017)
  • Cholesterol Levels [ Time Frame: At the end of each 3 month intervention ]
  • Body Composition (Fat Mass) [ Time Frame: At the end of each 3 month intervention ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Combination of Insulin Sensitizer and Leptin as Treatment for the HAART -Induced Metabolic Syndrome
Official Title  ICMJE A Combination of Insulin Sensitizer and Leptin as Treatment for the HAART -Induced Metabolic Syndrome: A Randomized, Double-blind, Placebo-controlled Clinical Trial
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE HIV Lipodystrophy
Intervention  ICMJE
  • Drug: Leptin
  • Drug: Pioglitazone or metformin
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: Leptin
    Leptin replacement therapy
    • Drug: Leptin
    • Drug: Pioglitazone or metformin
  • Placebo Comparator: Pioglitazone or metformin
    Diabetes treatment therapy
    • Drug: Pioglitazone or metformin
    • Drug: Placebo
Publications * Lee JH, Chan JL, Sourlas E, Raptopoulos V, Mantzoros CS. Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy. J Clin Endocrinol Metab. 2006 Jul;91(7):2605-11. Epub 2006 Apr 24.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 2, 2017)
Original Enrollment  ICMJE
 (submitted: August 9, 2006)
Actual Study Completion Date  ICMJE June 2011
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00362440
Other Study ID Numbers  ICMJE 2005P000159
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Christos Mantzoros, Beth Israel Deaconess Medical Center
Study Sponsor  ICMJE Beth Israel Deaconess Medical Center
Collaborators  ICMJE American Diabetes Association
Investigators  ICMJE
Principal Investigator: Christos Mantzoros, MD Beth Israel Deaconess Medical Center
PRS Account Beth Israel Deaconess Medical Center
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP