Acipimox to Improve Hyperlipidemia and Insulin Sensitivity Associated With HIV
Condition: Insulin Resistance; Cardiovascular Diseases; Heart Diseases; HIV Infections; Hypertriglyceridemia; Hyperlipidemia
MeSH terms: Cardiovascular Diseases; Heart Diseases; Insulin Resistance; Hyperlipidemias; Hyperlipoproteinemias; Hypertriglyceridemia
Study type: Interventional

Summary: 
      The purpose of this study is to test whether chronic administration of the drug acipimox will
      improve hyperlipidemia and insulin sensitivity among HIV infected patients experiencing
      highly active antiretroviral therapy (HAART) associated metabolic disturbances.
    

Detailed description: 
      BACKGROUND:

      HIV infected patients treated with HAART are at increased risk for developing significant
      dyslipidemia, insulin resistance, and abnormal patterns of fat distribution. While the exact
      mechanism responsible for these changes is not known, there is increasing evidence that
      patients with HIV infection and fat redistribution have increased basal rates of lipolysis
      and elevated circulating free fatty acids (FFA). Patients with HIV associated lipodystrophy
      have increased FFA levels that correlated directly with impaired glucose metabolism and
      triglyceride concentrations. Furthermore, acute inhibition of lipolysis in patients with HIV
      lipodystrophy and insulin resistance results in improvement in insulin sensitivity. However,
      long-term administration of lipolytic blocking agents has not been evaluated in this patient
      population. Acipimox, a nicotinic acid analogue and a potent inhibitor of lipolysis, is an
      established therapy for dyslipidemia. In addition, through effects on lowering circulating
      FFA, acute administration of acipimox has been shown to improve insulin sensitivity in other
      populations, including lean and obese individuals and patients with type II diabetes. This
      study will test the hypothesis that chronic administration of acipimox will improve
      hyperlipidemia and insulin sensitivity among HIV infected patients experiencing HAART
      associated metabolic disturbances.

      DESIGN NARRATIVE:

      The study will be a 3-month double-blind placebo-controlled trial of 250 mg of acipimox three
      times daily in 30 patients with HAART lipodystrophy. The primary clinical endpoint of this
      study will be the change in fasting triglyceride concentration, comparing baseline values to
      those obtained after 3 months of acipimox or placebo. Insulin sensitivity, an important
      secondary endpoint, will be determined by hyperinsulinemic euglycemic clamp studies. Rates of
      lipolysis in the fasting state will be quantified by a 3-hour infusion of stable
      isotope-labeled glycerol. Indirect calorimetry will be used to assess changes in resting
      energy expenditure. Cross-sectional computed tomography (CT) imaging of the thigh and abdomen
      will allow for measurement of visceral and subcutaneous fat areas. Dual energy x-ray
      absorptiometry (DEXA) will be used to determine whole body fat mass.
    

Intervention name(s): Acipimox
Intervention type(s): Drug
Intervention MeSH terms: Acipimox
Allocation: Randomized
Masking: Double
Primary purpose: Prevention