Acipimox to Improve Hyperlipidemia and Insulin Sensitivity Associated With HIV

Sponsor

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00246402

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Insulin Resistance Cardiovascular Diseases Heart Diseases HIV Infections Hypertriglyceridemia Hyperlipidemia	Drug: Acipimox	N/A

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Masking:

Double

Primary Purpose:

Prevention

Official Title:

Anti-Lipolytic Strategy for HIV Lipodystrophy

Study Start Date :

Sep 1, 2002

Actual Study Completion Date :

Aug 1, 2006

Outcome Measures

Primary Outcome Measures

Fasting Triglyceride Concentration (Initial, after 3 months) []

Secondary Outcome Measures

Insulin Sensitivity (Initial, after 3 months) []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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