Clinical trial NCT01046604: Pilot Study of Lovaza (Omega 3 Fatty Acids) to Improve Cardiac Antioxidant/Anti-inflammatory Profile Before Cardiac Surgery
Official title: Mitigating Cardiac Inflammation and Oxidative Stress in Atrial Myocardium Via Short-term Lovaza Treatment Prior to Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Mitral Valve Regurgitation
Left Atrium Dilatation and Hypertrophy
Mitochondrial Dysfunction in the Heart
Cardiomyocyte Apoptosis
Cardiac Inflammation
Keywords: mitral valve regurgitation
omega 3 fatty acids
fish oil
cardiac
mitochondria
apoptosis
human heart
Lead sponsor: East Carolina University
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2010-01-12
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: In the absence of treatment, severe mitral valve regurgitation (MR) results in left atrium (LA) dilatation and hypertrophy, followed ultimately by left ventricular dysfunction and heart failure. One promising intervention for the prevention of the deleterious effects of pressure overload-induced cardiac hypertrophy and heart failure is dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs). However, the molecular targets and mechanisms by which n-3 PUFAs exert their effects are not completely defined. A possible target of n-3 PUFAs is the mitochondrial membrane which has broad implications given that mitochondrial dysfunction and altered metabolism have been associated with cardiac hypertrophy and heart failure. The investigators have recently identified significant mitochondrial dysfunction in the LA of patients with severe MR, as compared to their non-hypertrophied right atrium (RA). However, the investigators have not addressed the possibility that intervention with purified n-3 PUFAs (Lovaza) could improve mitochondrial function. From a mechanistic perspective, the investigators have observed in vitro that n-3 PUFAs accumulate predominately into the mitochondrial membrane of cardiomyocytes where the investigators believe they exert their effects on the biophysical organization of the membrane. Therefore, the CENTRAL HYPOTHESIS is that administering Lovaza to patients with severe MR will reduce apoptosis and improve mitochondrial function in LA (Aim 1). This change in mitochondrial function will be driven by significant biochemical and biophysical remodeling of the mitochondrial membrane (Aim 2).


Eligibility criteria: Inclusion Criteria:

* Patients age 18+ undergoing minimally invasive mitral valve repair surgery will be enrolled in this study.

Exclusion Criteria:

* Patients with chronic renal insufficiency
* Chronic obstructive pulmonary disease
* Previous myocardial infarction
* Left ventricular dysfunction (ejection fraction \<40%)
* Use of anti-arrhythmic drugs other than beta blockers, and the presence of an implantable defibrillator.
* In addition, patients that have a high dietary intake of fish (≥ 2 servings/week) or have been taking n-3 PUFA supplements will be excluded.
* Also, patients that are allergic to fish or shellfish, or taking any anticoagulant/antiplatelet medications other than aspirin (e.g. Plavix, Coumadin) will be excluded from this study.
* Patients under the age of 18, and women who are pregnant will be excluded from this study.

Primary outcomes:
measure: Specific Aim 1: To determine if Lovaza treatment reduces markers of inflammation and improves mitochondrial function in atrial myocardium
timeFrame: 15 months
Secondary outcomes:
measure: Specific Aim 2: To determine if Lovaza treatment alters the biophysical and biochemical organization of cardiac mitochondrial membranes. The following questions will be addressed using the blood and cardiac tissue samples collected as described above:
timeFrame: 15 months
Other outcomes:
Locations:
city: Greenville
country: United States
facility: Brody School of Medicine
state: North Carolina
Study officials:
affiliation: Assistant Professor, Department of Pharmacology and Toxicology, East Carolina University
name: Ethan J Anderson, PhD
role: PRINCIPAL_INVESTIGATOR
References: