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Acipimox to Improve Hyperlipidemia and Insulin Sensitivity Associated With HIV

This study has been completed.
Sponsor:
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00246402
First received: October 27, 2005
Last updated: May 14, 2014
Last verified: December 2007
  Purpose

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 Intervention
Insulin Resistance
Cardiovascular Diseases
Heart Diseases
HIV Infections
Hypertriglyceridemia
Hyperlipidemia
Drug: Acipimox

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: Anti-Lipolytic Strategy for HIV Lipodystrophy

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • Fasting Triglyceride Concentration (Initial, after 3 months)

Secondary Outcome Measures:
  • Insulin Sensitivity (Initial, after 3 months)

Estimated Enrollment: 30
Study Start Date: September 2002
Study Completion Date: August 2006
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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00246402

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Investigators
Principal Investigator: Colleen M. Hadigan, MD Massachusetts General Hospital
  More Information

Publications:
Responsible Party: Colleen Hadigan, MD MPH, Harvard Medical School, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00246402     History of Changes
Other Study ID Numbers: 337, R21 HL73675
Study First Received: October 27, 2005
Last Updated: May 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Cardiovascular Diseases
HIV Infections
Heart Diseases
Hyperlipidemias
Hypertriglyceridemia
Insulin Resistance
Dyslipidemias
Glucose Metabolism Disorders
Hyperinsulinism
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Lipid Metabolism Disorders
Metabolic Diseases
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Acipimox
Antimetabolites
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014