Diet, Exercise, Niacin, and Fenofibrate to Reduce Heart Disease Risk Factors in Individuals With HIV Lipodystrophy or Dyslipidemia

Overview

This study will evaluate the efficacy of diet and exercise (DE), with and without niacin and fenofibrate, in reducing the cardiovascular risk of patients with HIV lipodystrophy or dyslipidemia.

Full Title of Study: “Diet/Exercise, Niacin, Fenofibrate for HIV Lipodystrophy”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: September 2009

Detailed Description

BACKGROUND: HIV lipodystrophy syndrome is associated with both metabolic (e.g., dyslipidemia and insulin resistance) and anthropomorphic (e.g., lipoatrophy and central obesity) abnormalities. These defects are likely to predispose HIV patients on highly active antiretroviral therapy (HAART) to accelerated cardiovascular morbidity. Based on studies of key mechanisms of altered lipid kinetics in these patients, evidence that DE patterns of patients with HIV lipodystrophy are inadequate to manage cardiovascular risk factors, and current recommendations for treatment of atherosclerosis and insulin resistance, the following is hypothesized: 1) an intensive lifestyle intervention with DE will improve the plasma lipid profile, decrease visceral fat mass, and improve hormonal, metabolic, and lipoprotein markers associated with insulin resistance; and 2) adding niacin, fenofibrate, or a combination of the two drugs to the intensive lifestyle intervention will result in further improvement in the cardiovascular risk profile. DESIGN NARRATIVE: This randomized, placebo-controlled study of 200 hypertriglyceridemic HIV patients on stable HAART treatment has the following specific aims: 1) to compare the effects of usual care, intensive DE, DE plus niacin, DE plus fenofibrate, and DE plus niacin plus fenofibrate on fasting plasma lipid concentrations (primary endpoint); 2) to compare the effects of the five treatment protocols on body fat distribution; and 3) to compare the effects of the five treatment protocols on hormonal, lipoprotein, and metabolic markers of insulin resistance. The collaborative team has expertise in lipid and lipoprotein metabolism, innovative and effective diet modification programs, intensive exercise programs in HIV patients, and studies of antilipidemic and antiretroviral agents. Therefore, this study will determine the efficacy of DE, with and without niacin and fenofibrate, in reducing the cardiovascular risk of patients with HIV lipodystrophy or dyslipidemia.

Interventions

  • Behavioral: Diet
    • ATP-III diet
  • Behavioral: Exercise
    • Supervised exercise in study gym
  • Drug: Niacin
    • Niaspan, titrated up to 2 grams per day
  • Drug: Fenofibrate
    • Tricor, 120 mg per day
  • Other: Placebos
    • Placebos for Niaspan and Tricor

Arms, Groups and Cohorts

  • Placebo Comparator: 1
    • Subjects receive lifestyle advice and placebos for Niaspan and Tricor
  • Experimental: 2
    • Diet, exercise, and two placebos
  • Experimental: 3
    • Diet, exercise, Niaspan, and placebo
  • Experimental: 4
    • Diet, exercise, placebo, and Tricor
  • Experimental: 5
    • Diet, exercise, Niaspan, and Tricor

Clinical Trial Outcome Measures

Primary Measures

  • Triglycerides
    • Time Frame: Measured at 24 weeks
    • Triglycerides (mg/dL): Fasting lipid levels
  • Non-HDL-C
    • Time Frame: Measured at 24 weeks
    • non-HDL-C (mg/dL): Fasting lipid levels
  • HDL-C
    • Time Frame: Measured at 24 weeks
    • HDL-C (mg/dL): Fasting lipid levels
  • Total Cholesterol
    • Time Frame: Measured at 24 weeks
    • Total cholesterol (mg/dL): Fasting lipid levels
  • Total Cholesterol : HDL-C Ratio
    • Time Frame: Measured at 24 weeks
    • Total cholesterol : HDL-C ratio: Fasting lipid levels

Secondary Measures

  • Insulin Sensitivity
    • Time Frame: Measured at 24 weeks
    • Adiponectin (micrograms/ml)
  • Body Composition
    • Time Frame: Measured at 24 weeks
    • Body cell mass (kg) Fat mass (kg)

Participating in This Clinical Trial

Inclusion Criteria

  • HIV positive – On stable HAART regimen for at least 6 months prior to study entry – T-cell count greater than 100 and viral load less than 1,000 for at least 6 months prior to study entry – Fasting triglyceride level greater than 150 mg/dl – Body mass index (BMI) greater than 18.5 and less than 30 – Uses barrier contraception Exclusion Criteria:

  • Fasting triglyceride level greater than 1000 mg/dl – BMI less than 18.5 or greater than 30 – Taking diabetic medication or HbA1c less than 7.0 – Use of lipid lowering medication in the 30 days prior to study entry – Unable to exercise – T-cell count less than 100 – Current medical condition that makes exercise unadvisable – History of coronary artery disease (CAD) – Use of dietary supplements (within 30 days of study entry) that may affect lipid levels including, but not limited to, the following: 1. Omega-3 fatty acids 2. L-Carnitine 3. Soluble fiber supplements 4. Guggul 5. Garlic supplements 6. Niacin greater than 25mg/d 7. Oral liquid supplements – Use of steroids, hormones, or testosterone (without diagnosis of hypogonadism, testosterone less than 300 ng/dl) – Irregular periods – Depo-Provera – Hypo- or Hyperthyroidism – Adrenal insufficiency – Serum alanine or aspartate aminotransferase level greater than 3 times the upper limit of normal – Alcohol abuse – Renal insufficiency (creatinine level greater than 1.5 mg/dl) – Coumadin therapy – Pregnancy – Peptic ulcer disease – Cholelithiasis – History of hyperuricemia – History of myositis or rhabdomyolysis – Known adverse reaction to niacin or fibrates – Hepatitis C therapy

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Baylor College of Medicine
  • Collaborator
    • National Heart, Lung, and Blood Institute (NHLBI)
  • Provider of Information About this Clinical Study
    • Principal Investigator: Ashok Balasubramanyam, Principal Investigator – Baylor College of Medicine
  • Overall Official(s)
    • Ashok Balasubramanyam, MD, Principal Investigator, Baylor College of Medicine

References

Samson SL, Pownall HJ, Scott LW, Ballantyne CM, Smith EO, Sekhar RV, Balasubramanyam A. Heart positive: design of a randomized controlled clinical trial of intensive lifestyle intervention, niacin and fenofibrate for HIV lipodystrophy/dyslipidemia. Contemp Clin Trials. 2006 Dec;27(6):518-30. doi: 10.1016/j.cct.2006.07.002. Epub 2006 Jul 21.

Citations Reporting on Results

Balasubramanyam A, Coraza I, Smith EO, Scott LW, Patel P, Iyer D, Taylor AA, Giordano TP, Sekhar RV, Clark P, Cuevas-Sanchez E, Kamble S, Ballantyne CM, Pownall HJ. Combination of niacin and fenofibrate with lifestyle changes improves dyslipidemia and hypoadiponectinemia in HIV patients on antiretroviral therapy: results of "heart positive," a randomized, controlled trial. J Clin Endocrinol Metab. 2011 Jul;96(7):2236-47. doi: 10.1210/jc.2010-3067. Epub 2011 May 11.

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