AIDS, Dyslipidemia, HIV Infections, Hypertriglyceridemia
Conditions
Keywords
AIDS, HIV, HAART, Lipids, Triglycerides, Cholesterol, omega-3 fatty acids, bone turnover, inflammation, insulin resistance
Brief summary
The purpose of this study is to evaluate the efficacy and safety of omega-3-fatty acids in HIV-infected patients with hypertriglyceridemia. In addition, we, the researchers, will evaluate the effect of omega-3 fatty acid administration of markers of bone turnover and inflammation.
Detailed description
Hypertriglyceridemia is common among HIV-infected patients receiving Highly Active Antiretroviral Therapy (HAART). Although fibrates, statins, and niacin have all been used in the management of hypertriglyceridemia in HIV-infected patients, optimal control is difficult to achieve and other agents are needed. Omega-3 fatty acids are effective for lowering triglycerides in patients without HIV infection, but experience in HIV-infected patients is limited. In addition, omega-3 fatty acids may also have secondary benefits in decreasing bone resorption and decreasing markers of systemic inflammation. The purpose of this study is to evaluate the efficacy and safety of omega-3-fatty acids in HIV-infected patients with hypertriglyceridemia. In addition, we will evaluate the effect of omega-3 fatty acid administration of markers of bone turnover and inflammation. It is 8- week randomized, double-blind trial of omega-3 fatty acids (LOVAZA, GSK, Inc) compared to placebo in 48 HAART-treated HIV-infected patients with triglycerides between 250 and 1000 mg/dl receiving dietary counseling. Subjects will be recruited from three centers (Johns Hopkins, Georgetown, and Los Angeles VAMC). The primary endpoint will be the change in triglyceride concentrations from baseline in the LOVAZA group compared to the placebo group. Secondary endpoints include the effect of LOVAZA on other lipid targets (total cholesterol, LDL cholesterol, HDL-cholesterol), markers of systemic inflammation, markers of bone turnover, markers of insulin resistance, HIV-disease control (CD4+ counts, HIV viral loads), measures of hepatotoxicity (ALT), platelet function, and patient reports of adverse events. Omega-3 fatty acids may be a useful adjunct in the treatment of hypertriglyceridemia in HIV-infected patients, but additional controlled studies are needed to assess its safety and efficacy using a purified, standardized preparation.
Interventions
LOVAZA 1 gram capsules, 4 capsules daily
DRUGPlacebo
Corn-oil placebo
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
GlaxoSmithKline
Brown, Todd, M.D., Ph.D.
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
* Ability and willingness to give informed consent * Age ≥ 18 years * HIV-1 infection documented at any time prior to study entry * Fasting plasma triglyceride value between 200 and 1000 mg/dL on two occasions within 4 weeks * Subjects must be receiving a stable antiretroviral medication regimen for \> 3 months without any anticipated changes during the study interval * Females must not be pregnant or lactating. Females of childbearing potential and males must use a reliable means of contraception * On stable lipid modification pharmacotherapy for at least 8 weeks prior to study entry
Exclusion criteria
* Hemoglobin A1C \> 8.5 % * Uncontrolled hypothyroidism (TSH \> 4.5) * HIV viral load \> 5,000 copies/ml (cpm), * Active liver disease and/or liver transaminases greater than 2.0 X upper limit of normal * Active kidney disease or serum creatinine \> 2.5 mg/dL * Myocardial infarction, unstable ischemic heart disease, stroke, or coronary revascularization procedure * Uncontrolled hypertension within 4 weeks of study entry (SBP \> 180 mmHg or DBP \> 100 mmHg) * Use of systemic cancer chemotherapy within 8 weeks of study entry * Pregnancy or breastfeeding * Drug or alcohol dependence, or other conditions which may affect study compliance * History of coagulopathy or use of anticoagulants such as warfarin * Use of omega-3 fatty acid preparation in the 12 weeks prior to randomization * Significant changes in clinical status from the Screening Visit which would preclude the patient from being an appropriate candidate. * Any of the following laboratory parameters: hematocrit \< 25%, absolute neutrophil count \< 1.5 x 10\^9/L, platelets \< 100 x 10\^9/L or hemoglobin \< 8.0 gm/dL
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Triglyceride Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | 8 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change in Total Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group | 8 weeks |
| Change in Non-HDL Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group | 8 weeks |
| Change in HDL Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group | 8 weeks |
| Change in HOMA-IR From Baseline in the LOVAZA Group Compared to the Placebo Group | 8 weeks |
| Change in CD4+ T-cell Counts From Baseline in the LOVAZA Group Compared to the Placebo Group | 8 weeks |
| Change in hsCRP Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | 8 weeks |
| Change in IL-6 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | 8 weeks |
| Change in TNF-a Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | 8 weeks |
| Change in sTNFR1 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | 8 weeks |
| Change in sTNFR2 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | 8 weeks |
| Change in CTX Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | 8 weeks |
| Change in P1NP Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | 8 weeks |
| Change in Collagen ADP From Baseline in the LOVAZA Group Compared to the Placebo Group. | 8 weeks |
| Change in Collagen Epinephrine From Baseline in the LOVAZA Group Compared to the Placebo Group. | 8 weeks |
Countries
United States
Participant flow
Recruitment details
Recruitment took plave between November 2006 and September 2010 at 3 sites (Johns Hopkins University, Baltimore, MD;Veteran's Administration Greater Los Angeles Healthcare System (Los Angeles, CA), and the Georgetown University Hospital (Washington, DC). Participants were recruited from the HIV Clinics at these institutions.
Participants by arm
| Arm | Count |
|---|---|
| LOVAZA 4 g/d of omega-3 fatty acid esters, plus dietary counseling | 24 |
| Placebo Corn oil placebo, plus dietary counselling | 24 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | LOVAZA | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 48 Participants | 24 Participants |
| Age, Continuous | 50.3 years STANDARD_DEVIATION 5.2 | 49.5 years | 48 years |
| Region of Enrollment United States | 24 participants | 48 participants | 24 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 21 Participants | 43 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 24 | 8 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Change in Triglyceride Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group.
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in Triglyceride Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | -34 mg/dl |
| Placebo | Change in Triglyceride Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | 40 mg/dl |
p-value: 0.01Wilcoxon (Mann-Whitney)
Secondary
Change in CD4+ T-cell Counts From Baseline in the LOVAZA Group Compared to the Placebo Group
Time frame: 8 weeks
Population: Analysis done on all participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in CD4+ T-cell Counts From Baseline in the LOVAZA Group Compared to the Placebo Group | 20 cells/cc |
| Placebo | Change in CD4+ T-cell Counts From Baseline in the LOVAZA Group Compared to the Placebo Group | 7 cells/cc |
p-value: 0.7Wilcoxon (Mann-Whitney)
Secondary
Change in Collagen ADP From Baseline in the LOVAZA Group Compared to the Placebo Group.
Time frame: 8 weeks
Population: Analysis done on all participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in Collagen ADP From Baseline in the LOVAZA Group Compared to the Placebo Group. | 6.5 seconds |
| Placebo | Change in Collagen ADP From Baseline in the LOVAZA Group Compared to the Placebo Group. | -6 seconds |
p-value: 0.12Wilcoxon (Mann-Whitney)
Secondary
Change in Collagen Epinephrine From Baseline in the LOVAZA Group Compared to the Placebo Group.
Time frame: 8 weeks
Population: Analysis done on all participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in Collagen Epinephrine From Baseline in the LOVAZA Group Compared to the Placebo Group. | 5.5 seconds |
| Placebo | Change in Collagen Epinephrine From Baseline in the LOVAZA Group Compared to the Placebo Group. | -18 seconds |
p-value: 0.3Wilcoxon (Mann-Whitney)
Secondary
Change in CTX Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group.
Time frame: 8 weeks
Population: Analysis done on all participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in CTX Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | -0.02 ng/mL |
| Placebo | Change in CTX Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | 0.03 ng/mL |
p-value: 0.25Wilcoxon (Mann-Whitney)
Secondary
Change in HDL Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in HDL Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group | 1.5 mg/dl |
| Placebo | Change in HDL Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group | -1 mg/dl |
p-value: 0.16Wilcoxon (Mann-Whitney)
Secondary
Change in HOMA-IR From Baseline in the LOVAZA Group Compared to the Placebo Group
Time frame: 8 weeks
Population: Analysis done on all participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in HOMA-IR From Baseline in the LOVAZA Group Compared to the Placebo Group | 0.56 units on a scale |
| Placebo | Change in HOMA-IR From Baseline in the LOVAZA Group Compared to the Placebo Group | 0.94 units on a scale |
p-value: 0.96Wilcoxon (Mann-Whitney)
Secondary
Change in hsCRP Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group.
Time frame: 8 weeks
Population: Analysis done on all participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in hsCRP Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | -0.04 ng/ml |
| Placebo | Change in hsCRP Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | 0.17 ng/ml |
p-value: 0.2Wilcoxon (Mann-Whitney)
Secondary
Change in IL-6 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group.
Time frame: 8 weeks
Population: Analysis done on all participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in IL-6 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | -0.62 pg/mL |
| Placebo | Change in IL-6 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | 0.19 pg/mL |
p-value: 0.006Wilcoxon (Mann-Whitney)
Secondary
Change in Non-HDL Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in Non-HDL Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group | -12.5 mg/dl |
| Placebo | Change in Non-HDL Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group | -9 mg/dl |
p-value: 0.72Wilcoxon (Mann-Whitney)
Secondary
Change in P1NP Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group.
Time frame: 8 weeks
Population: Analysis done on all participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in P1NP Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | -5.23 mcg/L |
| Placebo | Change in P1NP Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | -2.12 mcg/L |
p-value: 0.14Wilcoxon (Mann-Whitney)
Secondary
Change in sTNFR1 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group.
Time frame: 8 weeks
Population: Analysis done on all participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in sTNFR1 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | -0.90 pg/mL |
| Placebo | Change in sTNFR1 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | -66.3 pg/mL |
p-value: 0.89Wilcoxon (Mann-Whitney)
Secondary
Change in sTNFR2 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group.
Time frame: 8 weeks
Population: Analysis done on all participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in sTNFR2 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | -63.5 pg/mL |
| Placebo | Change in sTNFR2 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | 118 pg/mL |
p-value: 0.89Wilcoxon (Mann-Whitney)
Secondary
Change in TNF-a Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group.
Time frame: 8 weeks
Population: Analysis done on all participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in TNF-a Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | -0.36 pg/mL |
| Placebo | Change in TNF-a Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. | 0.58 pg/mL |
p-value: 0.04Wilcoxon (Mann-Whitney)
Secondary
Change in Total Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOVAZA | Change in Total Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group | -16 mg/dl |
| Placebo | Change in Total Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group | -5 mg/dl |
p-value: 0.8Wilcoxon (Mann-Whitney)