The Effect of Omega-3 Polyunsaturated Fatty Acids in Congestive Heart Failure

Salutary Effects of Dietary Supplementation With OMEGA 3 on Exercise Performance and Endothelial Function in Patients With Congestive Heart Failure. A Matter of Lipid Oxidation ?

A diet rich in Omega-3 (fish oil) reduces plasma triglycerides and the risk for ischemic heart disease. Recently, a large trial evaluating treatment with Omega 3 in heart failure patients suggested that omega 3 may lower the risk of death from CHF. The mechanism of this potential benefit is not well understood.

Methods:

Forty patients will be enrolled in the study. Twenty patients will receive Omega 3 (lovaza 4 gm a day) and 20 patients will receive placebo. All subjects will have assessment of their exercise capacity and blood vessel function before and after an 8 week treatment period. About 4 table spoons of blood will be drawn throughout the study.

Expected results:

The investigators believe that omega 3 may improve the ability to exercise and improve blood vessel function.

Study Overview

• Status: Terminated
• Conditions: Heart Failure
• Intervention / Treatment: Drug: LOVAZA (Omega-3); Drug: Placebo

Detailed Description

A diet rich in Omega-3 polyunsaturated fatty acids Omega 3 reduces plasma triglycerides and the risk for ischemic heart disease1, and may exert direct antiarrhythmic effect on the myocardium 2-9. A post-hoc analysis of the GISSI-Prevenzione trial demonstrated a reduction in all-cause and sudden mortality in a subgroup of nearly 2000 post-infarction patients with left ventricular dysfunction 10. This provocative finding has now been prospectively studied in a large-scale, randomized, double-blind study designed to investigate the effects of Omega 3 on mortality and morbidity in patients with symptomatic heart failure (the GISSI Heart Failure project). The results of the GISSI-HF trial demonstrate that 1 g per day of Omega 3 is associated with 9% reduction in mortality and cardiovascular admissions in patients with predominantly systolic heart failure, when added to optimal medical therapy11.

The mechanism(s) underlying these beneficial effects remains to be elucidated and will be critical in fully exhausting the therapeutic benefits of Omega 3 in CHF. We have recently demonstrated that lipid oxidation during acute exercise is altered in patients with CHF 12 and that the degree of this alteration carries prognostic significance. It is conceivable that Omega 3 modulates lipid oxidation during exercise and thereby favorably effect outcome. Accordingly we propose to study the effect of Omega 3 on lipid oxidation during exercise in CHF. We will further examine VO2 and endothelial function at present the principal surrogate markers for survival in CHF 13.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

All subjects with CHF due to systolic dysfunction followed at the outpatient facilities of Columbia University Medical Center will be screened and subjects will be asked to participate if the following criteria are met:

• Older than 18 years.
• Symptomatic heart failure (New York Heart Association functional class II-III).
• Ischemic or non-ischemic cardiomyopathy.
• Left ventricular ejection fraction (EF) 40% or lower.
• Peak oxygen uptake (VO2, peak) between 10 and 17 mL O2/min/kg.
• Be on appropriate, stable medical treatments for heart failure, including (unless shown to be intolerant) a diuretic, an angiotensin-converting enzyme inhibitor and/or angiotensin-receptor blocker and a beta-blocker, pacemaker or ICD or CRT.

Exclusion Criteria:

• Unable to perform treadmill exercise
• Pregnancy
• Recent myocardial infarction (within 3 months).
• Clinically significant angina.
• Hospitalization for heart failure requiring intravenous treatments within 30 days.
• Allergy to fish

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1 Drug Treatment - LOVAZA; Drug Treatment - LOVAZA 4 gm q24 for 8 weeks	Drug: LOVAZA (Omega-3); LOVAZA 4 gm q24 for 8 weeks Each 1-gram capsule of LOVAZA (omega-3-acid ethyl esters) contains at least 900 mg of the ethyl esters of omega-3 fatty acids. These are predominantly a combination of ethyl esters of eicosapentaenoic acid (EPA - approximately 465 mg) and docosahexaenoic acid (DHA - approximately 375 mg).
Placebo Comparator: 2 placebo; Placebo 4 capsules q24 for 8 weeks	Drug: Placebo; 4 capsules of placebo every 24 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Peak VO2	0, 1 and 8 weeks of Omega 3 supplementation.
Change in Reactive Hyperemia Peripheral Arterial Tonometry (RH-PAT) After 8 Weeks of Omega 3 Supplementation.	0 and after 8 weeks of Omega 3 supplementation.
Change in Base Line Oxidized Low Density Lipoprotein (LDL) Level and in Response to Exercise	0, 1 and 8 weeks of Omega 3 supplementation.

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Ulrich Jorde, MD, Columbia University

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: February 12, 2009
• First Submitted That Met QC Criteria: July 22, 2009
• First Posted (Estimate): July 23, 2009

Study Record Updates

• Last Update Posted (Estimate): May 25, 2016
• Last Update Submitted That Met QC Criteria: April 26, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Heart Failure; omega 3; VO2 max; lovaza
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: AAAD7501; LVZ112854 (Other Identifier: GSK protocol #)