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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
  Purpose

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 Intervention Phase
HIV Infections
AIDS
Dyslipidemia
Hypertriglyceridemia
Drug: Omega-3 fatty acid administration
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Brown, Todd, M.D., Ph.D.:

Primary Outcome Measures:
  • Change in Triglyceride Concentrations From Baseline in the LOVAZA Group Compared to the Placebo Group. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 48
Study Start Date: October 2006
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00346697

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.
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:
Responsible Party: Todd T. Brown, MD, PhD, Associate Professor of Medicine and Epidemiology, Brown, Todd, M.D., Ph.D.
ClinicalTrials.gov Identifier: NCT00346697     History of Changes
Other Study ID Numbers: K23 AT002862-01, K23AT002862-01
Study First Received: June 29, 2006
Results First Received: July 15, 2014
Last Updated: November 4, 2014
Health Authority: United States: Federal Government

Keywords provided by 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:
Acquired Immunodeficiency Syndrome
Dyslipidemias
HIV Infections
Hypertriglyceridemia
Hyperlipidemias
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Lipid Metabolism Disorders
Metabolic Diseases
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on November 20, 2014