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

Diet/Exercise, Niacin, Fenofibrate for HIV Lipodystrophy

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00246376

Acronym

HeartPositive

Enrollment

221

Registered

2005-10-31

Start date

2004-01-31

Completion date

2012-02-29

Last updated

2016-03-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

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.

Interventions

BEHAVIORALDiet

ATP-III diet

BEHAVIORALExercise

Supervised exercise in study gym

DRUGNiacin

Niaspan, titrated up to 2 grams per day

DRUGFenofibrate

Tricor, 120 mg per day

OTHERPlacebos

Placebos for Niaspan and Tricor

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Non-HDL-C	Measured at 24 weeks	non-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
Triglycerides	Measured at 24 weeks	Triglycerides (mg/dL): Fasting lipid levels
HDL-C	Measured at 24 weeks	HDL-C (mg/dL): Fasting lipid levels

Secondary

Measure	Time frame	Description
Body Composition	Measured at 24 weeks	1. Body cell mass (kg) 2. Fat mass (kg)
Insulin Sensitivity	Measured at 24 weeks	Adiponectin (micrograms/ml)

Countries

United States

Participant flow

Recruitment details

Subjects were recruited mainly from the Legacy Community Health Center and Thomas Street Clinic of the Harris County Hospital District and from Houston Area Community Services and private clinics. Recruitment period: January 2004 to September 2009.

Pre-assignment details

If potential subjects were taking nutritional supplements or lipid-lowering drugs, these were discontinued for washout for 6 weeks - baseline fasting lipid levels were then measured to determine eligibility prior to randomization.

Participants by arm

Arm	Count
Group 1: Usual Care Subjects receive lifestyle advice and placebos for Niaspan and Tricor	41
Group 2: Diet / Exercise Diet, exercise, and two placebos	43
Group 3: Diet / Exercise + Fenofibrate Diet, exercise, Fenofibrate, and Niaspan placebo	45
Group 4: Diet / Exercise + Niacin Diet, exercise, Fenofibrate placebo, and Niaspan	47
Group 5: Diet / Exercise + Niacin + Fenofibrate Diet, exercise, Fenofibrate and Niaspan	45
Total	221

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Adverse Event	2	3	1	3	1
Overall Study	Dropped/withdrew during dietary run-in	11	5	4	7	3
Overall Study	Lost to Follow-up	2	11	11	16	13

Baseline characteristics

Characteristic	Group 1: Usual Care	Group 2: Diet / Exercise	Group 3: Diet / Exercise + Fenofibrate	Group 4: Diet / Exercise + Niacin	Group 5: Diet / Exercise + Niacin + Fenofibrate	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Age, Categorical Between 18 and 65 years	40 Participants	43 Participants	45 Participants	47 Participants	45 Participants	220 Participants
Region of Enrollment United States	41 participants	43 participants	45 participants	47 participants	45 participants	221 participants
Sex: Female, Male Female	4 Participants	4 Participants	9 Participants	5 Participants	7 Participants	29 Participants
Sex: Female, Male Male	37 Participants	39 Participants	36 Participants	42 Participants	38 Participants	192 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	17 / 30	11 / 38	12 / 41	33 / 40	25 / 42
serious Total, serious adverse events	7 / 30	10 / 38	6 / 41	4 / 40	5 / 42