Omega-3 Fatty Acids for High Triglycerides in HIV-infected Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study of N-3 Fatty Acid on Plasma Triglyceride Levels in Hypertriglyceridemic HIV Patients Receiving Highly Active Antiretroviral Therapy

Conditions
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HIV Infections, AIDS, Dyslipidemia, Hypertriglyceridemia

Intervention / Treatment
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* Drug: Omega-3 fatty acid administration
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LOVAZA<br>4 g/d of omega-3 fatty acid esters, plus dietary counseling | Drug: Omega-3 fatty acid administration<br>* LOVAZA 1 gram capsules, 4 capsules daily<br>|
| Placebo Comparator: Placebo<br>Corn oil placebo, plus dietary counselling | Drug: Placebo<br>* Corn-oil placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Triglyceride Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AIDS, HIV, HAART, Lipids, Triglycerides, Cholesterol, omega-3 fatty acids, bone turnover, inflammation, insulin resistance