Acipimox to Improve Hyperlipidemia and Insulin Sensitivity Associated With HIV
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.
|Study Design:||Allocation: Randomized
Primary Purpose: Prevention
|Official Title:||Anti-Lipolytic Strategy for HIV Lipodystrophy|
- Fasting Triglyceride Concentration (Initial, after 3 months)
- Insulin Sensitivity (Initial, after 3 months)
|Study Start Date:||September 2002|
|Study Completion Date:||August 2006|
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00246402
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Colleen M. Hadigan, MD||Massachusetts General Hospital|