High Triglyceride Level, HIV Infection
Conditions
Keywords
HIV infection, Dyslipidemia, Elevated Triglyceride level, vascular function (BART), arterial stiffness, omega three fatty acids, complementary therapies
Brief summary
The study seeks to determine if the use of omega three fatty acids in individuals infected with HIV and with high triglycerides leads to improved triglyceride levels, better blood vessel function and decrease in the amount of obstruction in blood vessels.
Detailed description
While omega-three fatty acids have been shown to be beneficial for triglycerides (TG) and HDL-C levels in HIV uninfected individuals and in some small, short duration studies in HIV-infected individuals, there are no data that extend these observations to determine whether intake of omega-three fats over a more prolonged time period will also have a beneficial impact on functional outcomes such as vascular endothelial function and anatomic surrogate markers of cardiovascular disease (CVD) in HIV-infected patients. We propose a randomized, double blind trial of purified omega-three fatty acids in HIV-infected individuals with elevated levels of triglycerides. While the impact of omega-three fatty acids on lipid profiles should be evident early (within 12 weeks); we propose to conduct this trial for a full 24 months to test our overall hypothesis that this intervention will not only improve triglyceride and HDL-C levels, improve HDL-subpopulations, plasma and membrane phospholipids and decrease inflammation, but will also improve brachial artery reactivity testing (BART) as a measure of vascular endothelial function at 24 weeks and 24 months and arterial stiffness measured by a pulse wave velocity test as a surrogate marker of CVD risk at 24 months when compared to controls. The specific aims of this proposal include: 1. To conduct a randomized, placebo controlled trial of omega-three fatty acids over 24 months in HIV-infected individuals with elevated levels of triglycerides (\> 150 mg/dl). 2. To demonstrate the impact of omega-three fatty acid intake on TG levels and on HDL-C levels, HDL subpopulations, composition of plasma and membrane phospholipids, and chronic inflammation as measured by c-reactive protein (CRP), sPLA2 and by levels of arachidonic acid. 3. To demonstrate the impact of omega-three fatty acid intake on BART at 24 weeks and 24 months and on arterial stiffness at 24 months.
Interventions
DRUGLovaza
Lovaza at a dose of 4g per day with each 1g capsule containing approximately 465 mg of eicosapentaenoic acid (EPA) and 375 docosahexaenoic acid (DHA) for 24 months
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Tufts University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-infected men and women at least 18 years of age, * On stable HAART for the previous two months and without anticipated changes in their HAART regimen throughout the duration of the study, * Fasting triglycerides \> 150 mg/dl and \< 2,500 mg/dl * Participants may be on lipid lowering therapy; if on lipid lowering therapy, therapy must be stable for 8 weeks and cannot be changed during the course of the study. * Participants may be on beta blockers (e.g., Atenolol, Metoprolol, Propranolol), and Estrogens (e.g., Estinyl; Estrace; Estraderm), however therapy with these agents must be stable for 8 weeks before starting the study and cannot be altered while on study unless deemed medically necessary by the participant's medical provider and approved by Dr. Wanke. * Female participants of reproductive age must not be pregnant (negative test) or lactating at screening and throughout the trial and agree to use contraception for the course of the trial and 2 months after the trial unless they are surgically sterilized (tubal ligation or hysterectomy), or post-menopausal with no menses for \> 1 year. * Ability to provide consent.
Exclusion criteria
* plasma HIV-1 RNA \> 10,000 copies/ml * change in HAART regimen over two months prior to study entry * change in lipid lowering therapy within 2 months (8 weeks) * Pregnancy in female participants * Evidence of liver or renal disease with values of liver enzymes \> 5 X upper limit of normal or creatinine \> 1.5 X upper limit of normal * presence of active opportunistic infection or malignancy * presence of other inflammatory or end organ disease (, rheumatoid arthritis, active treatment for hepatitis c, or other diseases that may alter inflammatory markers) * routine ingestion of fish oil (individuals who have used fish oil would be reconsidered for study participation if they discontinue use of fish oil for 8 weeks and TG levels remain elevated). * Allergic to fish or Lovaza * BMI \>35
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Triglyceride Level | 24 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vascular Function | 24 months | Carotid-femoral pulse wave velocity is a measure of arterial stiffness, with lower values indicating less arterial stiffness. |
Countries
United States
Participant flow
Pre-assignment details
12 participants were enrolled but the did not participate due to 1) declining to participate, 2) inability of study team to locate participant, or 3) moving out of state.
Participants by arm
| Arm | Count |
|---|---|
| Lovaza (Omega Three Fatty Acid) Lovaza at a dose of 4g per day with each 1g capsule containing approximately 465 mg of eicosapentaenoic acid (EPA) and 375 docosahexaenoic acid (DHA) for 12 weeks.
Other Names:
Lovaza was previously known as Omacor (omega-3-acid ethyl esters) capsules
Lovaza: Lovaza at a dose of 4g per day with each 1g capsule containing approximately 465 mg of eicosapentaenoic acid (EPA) and 375 docosahexaenoic acid (DHA) for 24 months | 61 |
| Sugar Pill Dietary Supplement: sugar pill
2 capsules given twice daily Arms: sugar pill | 56 |
| Total | 117 |
Baseline characteristics
| Characteristic | Lovaza (Omega Three Fatty Acid) | Sugar Pill | Total |
|---|---|---|---|
| Age, Continuous | 53 years STANDARD_DEVIATION 9 | 50 years STANDARD_DEVIATION 9 | 51 years STANDARD_DEVIATION 9 |
| Body mass index (BMI) | 28 kg/meters squared STANDARD_DEVIATION 6 | 28 kg/meters squared STANDARD_DEVIATION 6 | 28 kg/meters squared STANDARD_DEVIATION 6 |
| CD4+ cell count | 652 cells/cubic mL STANDARD_DEVIATION 394 | 644 cells/cubic mL STANDARD_DEVIATION 309 | 648 cells/cubic mL STANDARD_DEVIATION 354 |
| Current smoker | 24 Participants | 16 Participants | 40 Participants |
| Region of Enrollment United States | 61 participants | 56 participants | 117 participants |
| Sex: Female, Male Female | 15 Participants | 10 Participants | 25 Participants |
| Sex: Female, Male Male | 46 Participants | 46 Participants | 92 Participants |
| Undetectable HIV viral load | 58 Participants | 52 Participants | 110 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 61 | 16 / 56 |
| serious Total, serious adverse events | 22 / 61 | 21 / 56 |
Outcome results
Primary
Triglyceride Level
Time frame: 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza (Omega Three Fatty Acid) | Triglyceride Level | 130 mg/dL |
| Sugar Pill | Triglyceride Level | 159 mg/dL |
Secondary
Vascular Function
Carotid-femoral pulse wave velocity is a measure of arterial stiffness, with lower values indicating less arterial stiffness.
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lovaza (Omega Three Fatty Acid) | Vascular Function | 833 m/s | Standard Deviation 238 |
| Sugar Pill | Vascular Function | 832 m/s | Standard Deviation 152 |