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

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Brief Title

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

Official Title

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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Insulin Resistance (HOMA Index)

Secondary Outcome

 Cholesterol Levels

Condition

HIV Lipodystrophy

Intervention

Leptin

Study Arms / Comparison Groups

 Leptin
Description:  Leptin replacement therapy

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

9

Start Date

August 2006

Completion Date

June 2011

Primary Completion Date

May 2011

Eligibility Criteria

        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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Christos Mantzoros, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00362440

Organization ID

2005P000159


Responsible Party

Principal Investigator

Study Sponsor

Beth Israel Deaconess Medical Center

Collaborators

 American Diabetes Association

Study Sponsor

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


Verification Date

February 2017