Clinical trial NCT00246376: Diet, Exercise, Niacin, and Fenofibrate to Reduce Heart Disease Risk Factors in Individuals With HIV Lipodystrophy or Dyslipidemia
Official title: Diet/Exercise, Niacin, Fenofibrate for HIV Lipodystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Diseases
Heart Diseases
HIV Infections
Hyperlipidemia
Hypertriglyceridemia
Insulin Resistance
Atherosclerosis
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Legacy Community Health Center
First posted: 2005-10-30
Enrollment: 221
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Triglycerides
timeFrame: Measured at 24 weeks
measure: Non-HDL-C
timeFrame: Measured at 24 weeks
measure: HDL-C
timeFrame: Measured at 24 weeks
measure: Total Cholesterol
timeFrame: Measured at 24 weeks
measure: Total Cholesterol : HDL-C Ratio
timeFrame: Measured at 24 weeks
Secondary outcomes:
measure: Insulin Sensitivity
timeFrame: Measured at 24 weeks
measure: Body Composition
timeFrame: Measured at 24 weeks
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Ashok Balasubramanyam, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: Gillard BK, Raya JL, Ruiz-Esponda R, Iyer D, Coraza I, Balasubramanyam A, Pownall HJ. Impaired lipoprotein processing in HIV patients on antiretroviral therapy: aberrant high-density lipoprotein lipids, stability, and function. Arterioscler Thromb Vasc Biol. 2013 Jul;33(7):1714-21. doi: 10.1161/ATVBAHA.113.301538. Epub 2013 May 2.
citation: Vu CN, Ruiz-Esponda R, Yang E, Chang E, Gillard B, Pownall HJ, Hoogeveen RC, Coraza I, Balasubramanyam A. Altered relationship of plasma triglycerides to HDL cholesterol in patients with HIV/HAART-associated dyslipidemia: further evidence for a unique form of metabolic syndrome in HIV patients. Metabolism. 2013 Jul;62(7):1014-20. doi: 10.1016/j.metabol.2013.01.020. Epub 2013 Mar 19.
citation: Wooten JS, Nambi P, Gillard BK, Pownall HJ, Coraza I, Scott LW, Nambi V, Ballantyne CM, Balasubramanyam A. Intensive lifestyle modification reduces Lp-PLA2 in dyslipidemic HIV/HAART patients. Med Sci Sports Exerc. 2013 Jun;45(6):1043-50. doi: 10.1249/MSS.0b013e3182843961.