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

Not Applicable

Completed

Conditions: Cardiovascular Diseases
Heart Diseases
HIV Infections
Hyperlipidemia
Hypertriglyceridemia
Insulin Resistance
Atherosclerosis

Interventions: Behavioral: Diet
Behavioral: Exercise
Other: Placebos
Drug: Niacin
Drug: Fenofibrate

Registration Number: NCT00246376

Lead Sponsor: Baylor College of Medicine

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 221

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Placebos	Diet, exercise, and two placebos
1	Placebos	Subjects receive lifestyle advice and placebos for Niaspan and Tricor
2	Diet	Diet, exercise, and two placebos
2	Exercise	Diet, exercise, and two placebos
3	Diet	Diet, exercise, Niaspan, and placebo
3	Exercise	Diet, exercise, Niaspan, and placebo
3	Placebos	Diet, exercise, Niaspan, and placebo
4	Placebos	Diet, exercise, placebo, and Tricor
4	Diet	Diet, exercise, placebo, and Tricor
4	Exercise	Diet, exercise, placebo, and Tricor
5	Diet	Diet, exercise, Niaspan, and Tricor
5	Exercise	Diet, exercise, Niaspan, and Tricor
3	Niacin	Diet, exercise, Niaspan, and placebo
4	Fenofibrate	Diet, exercise, placebo, and Tricor
5	Fenofibrate	Diet, exercise, Niaspan, and Tricor
5	Niacin	Diet, exercise, Niaspan, and Tricor

Primary Outcome Measures

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