Clinical trial NCT00246402: Acipimox to Improve Hyperlipidemia and Insulin Sensitivity Associated With HIV
Official title: Anti-Lipolytic Strategy for HIV Lipodystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insulin Resistance
Cardiovascular Diseases
Heart Diseases
HIV Infections
Hypertriglyceridemia
Hyperlipidemia
Lead sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Sponsor class: NIH
First posted: 2005-10-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: PREVENTION

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Documented HIV infection
* Stable antiretroviral regimen for greater than 3 months
* Hypertriglyceridemia (fasting triglycerides greater than 150mg/dl)
* Evidence of fat redistribution (e.g., increased abdominal or cervical fat, and/or decreased subcutaneous fat of the face, arms, or legs) on physical exam

Exclusion Criteria:

* Current therapy with a lipid lowering medication (e.g., fibrates, HMG CoA reductase inhibitors, resins) or treatment with these agents in the 3 months prior to study entry
* Current use of hormone replacement therapy, oral contraceptives for women, or supraphysiologic testosterone therapy in men
* Fasting triglycerides greater than 1000mg/dl
* Active alcohol or substance abuse
* Active peptic ulcer disease
* History of renal failure or serum creatinine greater than 2.0
* Serious opportunistic infection within the 3 months prior to study entry
* Hemoglobin less than 11.0 mg/dl
* Elevated transaminase levels (AST or ALT greater than 2.5x the upper limit of normal)
* Previously diagnosed diabetes mellitus or patients receiving current treatment for diabetes

Primary outcomes:
measure: Fasting Triglyceride Concentration (Initial, after 3 months)
Secondary outcomes:
measure: Insulin Sensitivity (Initial, after 3 months)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Colleen M. Hadigan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hadigan C, Liebau J, Torriani M, Andersen R, Grinspoon S. Improved triglycerides and insulin sensitivity with 3 months of acipimox in human immunodeficiency virus-infected patients with hypertriglyceridemia. J Clin Endocrinol Metab. 2006 Nov;91(11):4438-44. doi: 10.1210/jc.2006-1174. Epub 2006 Aug 29.