Exercise and Pioglitazone for HIV-Metabolic Syndromes
Condition: HIV Infections; Type 2 Diabetes; Obesity; HIV; AIDS; Cardiovascular Disease; Lipodystrophy
MeSH terms: Cardiovascular Diseases; Lipodystrophy; Metabolic Syndrome
Study type: Interventional

Summary: 
      The purpose is to examine the safety and efficacy of 16wks of pioglitazone (Actos; 30mg/d)
      with and without aerobic and strength exercise training for reducing glucose intolerance and
      central adiposity in HIV-infected people. We anticipate that pioglitazone + exercise training
      will improve glucose metabolism and insulin sensitivity, and reduce central adiposity more
      than pioglitazone alone. These improvements should translate into reduced cardiovascular
      disease risk in HIV-infected people.
    

Detailed description: 
      Our prior research has examined the pathogenesis and potential treatments for metabolic
      complications in people living with HIV. We have adopted the "lipotoxicity" hypothesis for
      Metabolic Syndrome X to explain the pathogenesis of impaired glucose tolerance (IGT) and fat
      redistribution in HIV: increased lipolysis and mobilization of lipids and free fatty acids
      from subcutaneous adipose depots leads to their excessive deposition in muscle and liver
      which contributes to dyslipidemia, insulin resistance, increased hepatic glucose output, and
      possibly visceral fat accumulation. Effective treatments have not been identified. Consensus
      groups recommend regular exercise and dietary modifications as primary and pharmacologic
      interventions as secondary treatments for the syndromes. We propose to test the efficacy of
      aerobic and weight lifting exercise training and an oral insulin-sensitizing agent
      (pioglitazone) as treatments for HIV-associated IGT and fat redistribution. We propose a
      4-month, 2-group randomized study to evaluate the efficacy of pioglitazone and exercise +
      pioglitazone in 40 men and 40 women living with HIV and IGT and fat redistribution. We will
      measure: insulin sensitivity, glucose disposal rate, hepatic glucose production rate
      (5hr-hyperinsulinemic euglycemic clamp with 6,6-[2H2]-glucose); whole-body and regional fat
      and muscle content (1H-MRI of the abdomen and thigh & DEXA), soleus muscle and liver lipid
      content (1H-MRS), muscle and fat PPARgamma/alpha mRNA and protein expression, serum lipid
      profiles, and serum adiponectin levels before and at the end of 4 months of treatment. We
      hypothesize that exercise training + pioglitazone will be more effective than pioglitazone
      alone at improving insulin sensitivity, reducing visceral fat, liver and muscle lipid
      content, and increasing peripheral subcutaneous fat content in HIV-infected people. We
      hypothesize that combined treatment will be more effective because exercise training will
      activate PPARalpha expression in muscle and pioglitazone will activate PPARy expression in
      fat and muscle. We anticipate that this project will provide direct evidence that supports
      the combined use of exercise training and pioglitazone in people living with HIV and
      experiencing metabolic and anthropomorphic disorders that increase cardiovascular disease
      risk.
    

Intervention name(s): Pioglitazone; Exercise training
Intervention type(s): Drug; Behavioral
Intervention description(s): Oral 30mg/day for 16 weeks; Supervised aerobic and resistance exercise training (1.5hrs/day x 3 days/wk) for 16 weeks
Other intervention name(s): Actos; Physical activity
Intervention MeSH terms: Pioglitazone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: PPAR-gamma agonist; glucose metabolism; inflammation; adipose tissue distribution; cardiac function; vascular function; mass spectrometry; Treatment Experienced