Cardiovascular Disease, HIV Infection
Conditions
Keywords
HIV, cardiovascular risk, atherogenic lipid profile, brachial artery reactivity, omega three fatty acids
Brief summary
The purpose of this study is to determine whether fish oil supplementation with Lovaza, formally known as Omacor will result in a significant reduction in serum triglyceride (TG), an increase in high density lipoproteins(HDL), and an improvement of endothelial dysfunction.
Detailed description
This is a randomized, double blind, placebo controlled, cross-over, clinical trial to determine the effect of fish oil supplementation with Lovaza® on triglyceride levels in HIV-infected subjects on HAART with elevated serum triglycerides. The sample size is 40 subjects. The total duration of the study is 28 weeks, with 12-week treatment periods separated by a 4-week washout. This study will be conducted at the Clinical Research Center at Tufts Medical Center.
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 12 weeks.
DRUGPlacebo
2 capsules given twice daily
Sponsors
Tufts University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* HIV-infected men and women at least 18 years of age * On stable HAART for previous three months and without anticipated changes in their HAART regimen throughout the duration of the study * Fasting triglycerides \> 150 mg/dl and \< 1,500 mg/dl * Participants may be on lipid lowering therapy; if on lipid lowering therapy, therapy must be stable for 8 weeks and cannot be changes during the course of the study * Participants may be on beta blockers (e.g., Atenolol, Metoprolol, Propranolol), Estrogens (e.g.,Estinyl;Estrace;Estraderm) and Thiazides (water pills), however therapy with these agents must be stable for 8 weeks before starting the study and cannot be altered while on the 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 2 methods of barrier 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 * Previous history of atherosclerotic disease or diabetes mellitus * Change in HAART regimen over three months prior to study entry * Change in lipid lowering therapy within 2 months * On chronic anticoagulants such as heparin or coumadin * On fish oil, omega 3 supplements, or Omacor currently or during the past month
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Baseline Mean Serum Triglyceride Level at Study End | Baseline and 12 weeks | Change in Baseline (time 0) Mean Serum Triglyceride levels after 12 weeks of treatment or placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum HDL Level | 12 weeks | — |
| Brachial Artery Reactivity | 12 weeks | To demonstrate the impact of omega-three fatty acid intake on BART (Brachial Artery Reactivity Test) at 12 weeks. Brachial artery ultrasound measurements Brachial artery reactivity will be assessed by ultrasound and FMD will be calculated as the change in brachial artery diameter after release of suprasystolic blood pressure cuff inflation. A blood pressure cuff will be inflated on the upper arm to induce increase in blood flow, termed reactive hyperemia, which increases arterial diameter. The change in vessel diameter is determined by high-resolution ultrasound imaging. The endothelium-dependent FMD of the brachial artery is quantified as the maximum percent change in arterial diameter, expressed in units of % of brachial artery. |
Countries
United States
Participant flow
Recruitment details
Phone contact n=109 Screening n=51 Eligible n=42 Screen failed n=9 Declined participation n=1 Randomized to treatment first n=20 Randomized to placebo first n=21
Participants by arm
| Arm | Count |
|---|---|
| Lovaza Then Placebo Lovaza, dietary counseling
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 12 weeks. | 20 |
| Placebo Then Lovaza Placebo or Corn oil pill, dietary counseling
Corn oil pill : 2 capsules given twice daily for 12 weeks | 21 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase I Followed by Wash Out x 4 Weeks | Adverse Event | 1 | 1 |
| Phase I Followed by Wash Out x 4 Weeks | alcohol treatment | 1 | 0 |
| Phase I Followed by Wash Out x 4 Weeks | Lost to Follow-up | 0 | 1 |
| Phase II | too busy | 0 | 1 |
Baseline characteristics
| Characteristic | Lovaza Then Placebo | Placebo Then Lovaza | Total |
|---|---|---|---|
| Age, Continuous | 51.5 years | 55.0 years | 52.0 years |
| Region of Enrollment United States | 20 participants | 21 participants | 41 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 17 Participants | 18 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 41 | 29 / 41 |
| serious Total, serious adverse events | 0 / 41 | 0 / 41 |
Outcome results
Primary
Change in Baseline Mean Serum Triglyceride Level at Study End
Change in Baseline (time 0) Mean Serum Triglyceride levels after 12 weeks of treatment or placebo
Time frame: Baseline and 12 weeks
Population: Randomized, cross over design
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lovaza | Change in Baseline Mean Serum Triglyceride Level at Study End | -103.0 mg/dl | Standard Deviation 92.2 |
| Placebo | Change in Baseline Mean Serum Triglyceride Level at Study End | -23.4 mg/dl | Standard Deviation 60.8 |
Secondary
Brachial Artery Reactivity
To demonstrate the impact of omega-three fatty acid intake on BART (Brachial Artery Reactivity Test) at 12 weeks. Brachial artery ultrasound measurements Brachial artery reactivity will be assessed by ultrasound and FMD will be calculated as the change in brachial artery diameter after release of suprasystolic blood pressure cuff inflation. A blood pressure cuff will be inflated on the upper arm to induce increase in blood flow, termed reactive hyperemia, which increases arterial diameter. The change in vessel diameter is determined by high-resolution ultrasound imaging. The endothelium-dependent FMD of the brachial artery is quantified as the maximum percent change in arterial diameter, expressed in units of % of brachial artery.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lovaza | Brachial Artery Reactivity | 6.4 % of brachial artery diameter | Standard Deviation 5.9 |
| Placebo | Brachial Artery Reactivity | 7.5 % of brachial artery diameter | Standard Deviation 3.1 |
Secondary
Serum HDL Level
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lovaza | Serum HDL Level | 39 mg/dl | Standard Deviation 12 |
| Placebo | Serum HDL Level | 36 mg/dl | Standard Deviation 10 |