Acipimox to Improve Hyperlipidemia and Insulin Sensitivity Associated With HIV

HIV Infections Clinical Trial

Official title:

Anti-Lipolytic Strategy for HIV Lipodystrophy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00246402
• Other study ID #: 337
• Secondary ID: R21HL073675
• Status: Completed
• Phase: N/A
• First received: October 27, 2005
• Last updated: May 14, 2014
• Start date: September 2002
• Est. completion date: August 2006

Study information

• Verified date: December 2007
• Source: National Heart, Lung, and Blood Institute (NHLBI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Heart Diseases
• HIV Infections
• Hyperlipidemia
• Hyperlipidemias
• Hypertriglyceridemia
• Insulin Resistance

Intervention

Drug:
• Acipimox

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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):4438-4 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fasting Triglyceride Concentration (Initial, after 3 months)
Secondary	Insulin Sensitivity (Initial, after 3 months)