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

This study has been completed.
Sponsor:
Collaborators:
GlaxoSmithKline
Information provided by (Responsible Party):
Todd T. Brown, MD, PhD, Brown, Todd, M.D., Ph.D.
ClinicalTrials.gov Identifier:
NCT00346697
First received: June 29, 2006
Last updated: November 4, 2014
Last verified: November 2014

June 29, 2006
November 4, 2014
October 2006
April 2010   (final data collection date for primary outcome measure)
Change in Triglyceride Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • patients
  • To understand the association between the metabolic and skeletal abnormalities in HIV-infected subjects
  • and their relationship to inflammation
  • To determine whether treatment with w-3 fatty acids will have hypotriglyceridemic, anti-inflammatory, and anti-bone resorptive effects in a randomized trial of HIV-infected
  • To clarify the mechanisms of action of u>-3 fatty acids, namely the effect on lipolysis and
  • bone turnover using stable isotope infusion techniques.
Complete list of historical versions of study NCT00346697 on ClinicalTrials.gov Archive Site
  • Change in Total Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in Non-HDL Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in HDL Cholesterol Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in HOMA-IR From Baseline in the LOVAZA Group Compared to the Placebo Group [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in CD4+ T-cell Counts From Baseline in the LOVAZA Group Compared to the Placebo Group [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Change in hsCRP Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in IL-6 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in TNF-a Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in sTNFR1 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in sTNFR2 Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in CTX Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in P1NP Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in Collagen ADP From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Change in Collagen Epinephrine From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
Not Provided
 
Omega-3 Fatty Acids for High Triglycerides in HIV-infected Patients
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

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • HIV Infections
  • AIDS
  • Dyslipidemia
  • Hypertriglyceridemia
  • Drug: Omega-3 fatty acid administration
    LOVAZA 1 gram capsules, 4 capsules daily
  • Drug: Placebo
    Corn-oil placebo
  • Experimental: LOVAZA
    4 g/d of omega-3 fatty acid esters, plus dietary counseling
    Intervention: Drug: Omega-3 fatty acid administration
  • Placebo Comparator: Placebo
    Corn oil placebo, plus dietary counselling
    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
48
April 2010
April 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00346697
K23 AT002862-01, K23AT002862-01
No
Todd T. Brown, MD, PhD, Brown, Todd, M.D., Ph.D.
Brown, Todd, M.D., Ph.D.
  • National Center for Complementary and Integrative Health (NCCIH)
  • GlaxoSmithKline
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
Brown, Todd, M.D., Ph.D.
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP