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

• ClinicalTrials.gov Identifier: NCT00346697
• Recruitment Status: Completed
• First Posted: June 30, 2006
• Results First Posted: November 5, 2014
• Last Update Posted: November 5, 2014
• Sponsor: Brown, Todd, M.D., Ph.D.
• Collaborators: National Center for Complementary and Integrative Health (NCCIH); GlaxoSmithKline
• Information provided by (Responsible Party): Todd T. Brown, MD, PhD, Brown, Todd, M.D., Ph.D.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV Infections; AIDS; Dyslipidemia; Hypertriglyceridemia	Drug: Omega-3 fatty acid administration; Drug: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: October 2006
• Actual Primary Completion Date: April 2010
• Actual Study Completion Date: April 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: LOVAZA; 4 g/d of omega-3 fatty acid esters, plus dietary counseling	Drug: Omega-3 fatty acid administration; LOVAZA 1 gram capsules, 4 capsules daily
Placebo Comparator: Placebo; Corn oil placebo, plus dietary counselling	Drug: Placebo; Corn-oil placebo

Outcome Measures

Primary Outcome Measures :

1. Change in Triglyceride Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ]

Secondary Outcome Measures :

1. Change in Total Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group [ Time Frame: 8 weeks ]
2. Change in Non-HDL Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group [ Time Frame: 8 weeks ]
3. Change in HDL Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group [ Time Frame: 8 weeks ]
4. Change in HOMA-IR From Baseline in the LOVAZA Group Compared to the Placebo Group [ Time Frame: 8 weeks ]
5. Change in CD4+ T-cell Counts From Baseline in the LOVAZA Group Compared to the Placebo Group [ Time Frame: 8 weeks ]
6. Change in hsCRP Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ]
7. Change in IL-6 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ]
8. Change in TNF-a Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ]
9. Change in sTNFR1 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ]
10. Change in sTNFR2 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ]
11. Change in CTX Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ]
12. Change in P1NP Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ]
13. Change in Collagen ADP From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ]
14. Change in Collagen Epinephrine From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Veterans Administration of Greater Los Angeles Health System

Los Angeles, California, United States, 90073

United States, District of Columbia

Georgetown University

Washington, District of Columbia, United States, 20007

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

Brown, Todd, M.D., Ph.D.

National Center for Complementary and Integrative Health (NCCIH)

GlaxoSmithKline

Investigators

• Principal Investigator: Todd T. Brown, MD; Johns Hopkins University
• Principal Investigator: David Leaf, MD; Veterans Adminstration of Greater Los Angeles Health System
• Principal Investigator: Mattew Goetz, MD; Veterans Adminstration of Greater Los Angeles Health System
• Principal Investigator: Adrian S Dobs, MD; Johns Hopkins University
• Principal Investigator: Joseph Timpone, MD; Georgetown University

More Information

Publications of Results:

Metkus TS, Timpone J, Leaf D, Bidwell Goetz M, Harris WS, Brown TT. Omega-3 fatty acid therapy reduces triglycerides and interleukin-6 in hypertriglyeridemic HIV patients. HIV Med. 2013 Oct;14(9):530-9. doi: 10.1111/hiv.12046. Epub 2013 May 19.

• Responsible Party: Todd T. Brown, MD, PhD, Associate Professor of Medicine and Epidemiology, Brown, Todd, M.D., Ph.D.
• ClinicalTrials.gov Identifier: NCT00346697
• Other Study ID Numbers: K23AT002862-01 ( U.S. NIH Grant/Contract ); K23AT002862-01 ( U.S. NIH Grant/Contract )
• First Posted: June 30, 2006
• Results First Posted: November 5, 2014
• Last Update Posted: November 5, 2014
• Last Verified: November 2014

Keywords provided by Todd T. Brown, MD, PhD, Brown, Todd, M.D., Ph.D.:

AIDS; HIV; HAART; Lipids; Triglycerides; Cholesterol; omega-3 fatty acids; bone turnover; inflammation; insulin resistance

Additional relevant MeSH terms:

Dyslipidemias; Hypertriglyceridemia; Lipid Metabolism Disorders; Metabolic Diseases; Hyperlipidemias