Therapeutic Approaches to HAART-Induced Lipodystrophy

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Brief Title

Therapeutic Approaches to HAART-Induced Lipodystrophy

Official Title

Therapeutic Approaches to HAART-Induced Lipodystrophy

Brief Summary

      To determine the efficacy and safety of 4 therapeutic interventions on HAART-Induced
      lipodystrophy. The interventions are: 1) Dietary - the effect of a high carbohydrate vs.a
      high cis-monounsaturated fatty acid diet. 2) The effect of aerobic exercise with dietary
      advice. 3) The effect of Omega-3 Fish Oil Capsules. 4) The effect of leptin therapy. These
      interventions are aimed at improving the metabolic complications of HAART therapy such as
      elevated lipids, and insulin resistance or diabetes.

Detailed Description

      Patients with HAART-induced lipodystrophy report loss of subcutaneous (sc) fat from the
      extremities and face and excess fat accumulation in the neck and truncal region. They also
      are predisposed to metabolic complications of insulin resistance, such as, dyslipidemia and
      diabetes mellitus. The pathogenesis of HAART-induced lipodystrophy is not fully understood
      although PIs have been strongly implicated as the cause. The metabolic complications pose an
      increased risk of atherosclerosis and acute pancreatitis whereas changes in body fat
      distribution cause physical discomfort and psychological distress. Management of these
      problems poses a therapeutic challenge. We propose potentially safe therapeutic lifestyle
      changes as well as novel therapies for management of HAART-induced lipodystrophy and its
      metabolic complications. The hypotheses to be tested and the aims are:

      Hypothesis 1: A diet rich in cis-monounsaturated fatty acids improves HAART-induced glucose
      intolerance and dyslipidemia in HIV-infected patients.

      Aim 1: To compare acceptability and effects of isocaloric diets rich in carbohydrates and
      cis-monounsaturated fats, each given for 6 wk, on glucose and lipid metabolism in patients
      with HAART-induced dyslipidemia in a randomized, cross-over study.

      Hypothesis 2: A regimen of aerobic exercise improves insulin resistance, dyslipidemia and
      body fat distribution in HIV-infected patients with HAART-induced lipodystrophy.

      Aim 2: To determine the effects of a supervised aerobic exercise regimen and dietary advice
      on glucose and lipid metabolism, and body fat distribution in HIV-infected patients with
      HAART-induced lipodystrophy.

      Hypothesis 3: The n-3 polyunsaturated fats improve HAART-induced dyslipidemia in HIV-infected

      Aim 3: To determine the lipid-lowering effects of n-3 polyunsaturated fats in a randomized,
      double-blind, placebo-controlled, crossover trial in HIV-infected patients with HAART-induced

      Hypothesis 4: Leptin replacement improves insulin resistance, dyslipidemia and body fat
      distribution in patients with HAART-induced lipodystrophy and hypoleptinemia.

      Aim 4 To study efficacy and safety of recombinant methionyl leptin (r-metHuleptin) in
      improving insulin sensitivity, dyslipidemia and body fat distribution in patients with
      HAART-induced lipodystrophy and hypoleptinemia using a randomized, double-blind,
      placebo-controlled, parallel design.

      Results from these studies may help in designing therapeutic approaches to HAART-induced
      lipodystrophy and its metabolic complications as well as for prevention of these problems in
      HIV-infected patients being placed on HAART.

      We are only reporting the results of Aim 4 - (Leptin Study) here.

Study Phase

Phase 2

Study Type


Primary Outcome

Fasting Serum Triglycerides

Secondary Outcome

 Body Weight (kg)


HIV Infections



Study Arms / Comparison Groups

Description:  Leptin weight and gender based dose, sub-cutaneous, twice daily. Leptin versus placebo for entire 6 months double-blind.


* 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


Estimated Enrollment


Start Date

January 2003

Completion Date

September 2014

Primary Completion Date

September 2014

Eligibility Criteria

        Inclusion Criteria - General inclusion:

          -  Age > 14 years

          -  HIV infection being treated with HIV-1 protease inhibitors for >6 months currently, or
             previous protease inhibitor therapy of at least 2 years duration with development of
             lipodystrophy and current stable therapy preferably for past 4 months.

          -  Fasting serum triglycerides > 200 mg/dL

        Exclusion Criteria - General exclusion:

          -  Acute, ongoing AIDS-defining opportunistic infections.

          -  Blood CD4 positive lymphocyte count < 200/mm3

          -  Known liver disease due to causes other than nonalcoholic steatohepatitis with
             elevation of liver transaminases by more than two and a half times above the upper
             limits of normal (SGOT>105 U/L, SGPT>120 U/L) or total bilirubin (>1.5 mg/dL).

          -  Hematocrit of less than 30%.

          -  Current alcohol abuse (>7 drinks or 210 g per wk for women and >14 drinks or 420 g per
             wk for men).

          -  Current substance abuse.

          -  Uncontrolled diabetes mellitus with fasting plasma glucose > 180 mg/dL or hemoglobin
             A1c > 9%.

          -  History of weight loss during the last 3 months.

          -  Use of anorexiogenic drugs, thiazolidinediones, anabolic steroids and human growth

          -  Major Neuro-psychiatric illnesses impeding competence or compliance.

          -  Pregnant and lactating women.

          -  Cancer excluding skin cancer other than melanoma.

          -  Acute medical illnesses precluding participation in the studies.

          -  Chronic renal insufficiency with serum creatinine > 2 mg/dL.

          -  Untreated thyroid disorders such as hypothyroidism and hyperthyroidism. Each of the 4
             treatment arms has additional specific inclusion and exclusion criteria




14 Years - 65 Years

Accepts Healthy Volunteers



Abhimanyu Garg, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party

Principal Investigator

Study Sponsor

University of Texas Southwestern Medical Center


 Amylin Pharmaceuticals, LLC.

Study Sponsor

Abhimanyu Garg, M.D., Principal Investigator, Univeristy of Texas Southwestern Medical Center

Verification Date

May 2019