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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Diet/Exercise, Niacin, Fenofibrate for HIV Lipodystrophy

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

Intervention / Treatment
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* Behavioral: Diet
* Behavioral: Exercise
* Drug: Niacin
* Drug: Fenofibrate
* Other: Placebos


Participation Criteria
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Eligibility Criteria
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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: Omega-3 fatty acids L-Carnitine Soluble fiber supplements Guggul Garlic supplements Niacin greater than 25mg/d 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Subjects receive lifestyle advice and placebos for Niaspan and Tricor | Other: Placebos<br>* Placebos for Niaspan and Tricor<br>|
| Experimental: 2<br>Diet, exercise, and two placebos | Behavioral: Diet<br>* ATP-III diet<br>Behavioral: Exercise<br>* Supervised exercise in study gym<br>Other: Placebos<br>* Placebos for Niaspan and Tricor<br>|
| Experimental: 3<br>Diet, exercise, Niaspan, and placebo | Behavioral: Diet<br>* ATP-III diet<br>Behavioral: Exercise<br>* Supervised exercise in study gym<br>Drug: Niacin<br>* Niaspan, titrated up to 2 grams per day<br>Other: Placebos<br>* Placebos for Niaspan and Tricor<br>|
| Experimental: 4<br>Diet, exercise, placebo, and Tricor | Behavioral: Diet<br>* ATP-III diet<br>Behavioral: Exercise<br>* Supervised exercise in study gym<br>Drug: Fenofibrate<br>* Tricor, 120 mg per day<br>Other: Placebos<br>* Placebos for Niaspan and Tricor<br>|
| Experimental: 5<br>Diet, exercise, Niaspan, and Tricor | Behavioral: Diet<br>* ATP-III diet<br>Behavioral: Exercise<br>* Supervised exercise in study gym<br>Drug: Niacin<br>* Niaspan, titrated up to 2 grams per day<br>Drug: Fenofibrate<br>* Tricor, 120 mg per day<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity | Adiponectin (micrograms/ml) | Measured at 24 weeks | 
| Body Composition | Body cell mass (kg) Fat mass (kg) | Measured at 24 weeks |