Therapeutic Approaches to HAART-Induced Lipodystrophy
Condition: HIV Infections; Lipodystrophy
MeSH terms: Lipodystrophy
Study type: Interventional
Phase: Phase 2

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
      patients.

      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
      dyslipidemia.

      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.
    

Intervention name(s): Leptin; Placebo
Intervention type(s): Drug; Other
Intervention description(s): weight based, sub-cutaneous injection, twice daily; weight based, sub-cutaneous injection, twice daily
Other intervention name(s): Metreleptin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Lipodystrophy; HIV; HAART; HIV Lipodystrophy Syndrome; Lipodystrophy syndrome; HIV-Associated Lipodystrophy; HIV-Associated Lipodystrophy Syndrome; Treatment Experienced