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

HIV Infections Clinical Trial

— Heart Positive  

Official title:

Diet/Exercise, Niacin, Fenofibrate for HIV Lipodystrophy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00246376
• Other study ID #: 340
• Secondary ID: R01HL073696
• Status: Completed
• Phase: N/A
• First received: October 27, 2005
• Last updated: April 25, 2012
• Start date: January 2004
• Est. completion date: February 2012

Study information

• Verified date: April 2012
• Source: National Heart, Lung, and Blood Institute (NHLBI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 221
• Est. completion date: February 2012
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis
• Cardiovascular Diseases
• Heart Diseases
• HIV Infections
• Hyperlipidemia
• Hyperlipidemias
• Hypertriglyceridemia
• Insulin Resistance
• Lipodystrophy

Intervention

Behavioral:
• Diet
ATP-III diet
• Exercise
Supervised exercise in study gym

Drug:
• Niacin
Niaspan, titrated up to 2 grams per day
• Fenofibrate
Tricor, 120 mg per day

Other:
• Placebos
Placebos for Niaspan and Tricor

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)	Legacy Community Health Center

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 hyp — View 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. Epub 2006 Jul 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fasting serum triglyceride level		Measured at 24 hours	Yes
Secondary	Insulin sensitivity		Measured at 24 hours	No
Secondary	Body composition		Measured at 24 hours	No
Secondary	Lipoprotein fractions		Measured at 4 days	No