Omacor and Placebo in Carotid Plaque Stability

A Double Blind Comparison of Omacor and Placebo in Patients Awaiting Endarterectomy to Investigate the Effect on Carotid Plaque Stability

The purpose of this study is to investigate the effect of intake of Omacor (Omega-3-acid ethyl ester 90) 2g/day on specified parameters related to the stability of carotid plaque in patients awaiting endarterectomy.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease
• Intervention / Treatment: Drug: Omega-3-acid ethyl ester 90 (n-3 PUFA)

Detailed Description

There is evidence both from epidemiological studies and large clinical trials that consumption of long-chain Omega-3 polyunsaturated fatty acids (PUFA) found in oily fish and fish oils, protects against cardiovascular disease in Western Populations. The large clinical trial GISSI-Prevention showed radical reductions in Cardiovascular Disease and Sudden Cardiac Death after the intake of Omega-3 PUFA, and statistically significant effects were seen after only a few months of use.

One of the models for explaining this markedly effect hypothesizes that Omega-3 PUFA, with its anti inflammatory effects, might act to stabilize atherosclerotic plaques by decreasing infiltration of inflammatory cells into the plaques and/or by decreasing the activity of these cells once resident in the plaque. A previous clinical study has showed increased incorporation of the Omega-3 fatty acids EPA and DHA in carotid plaque after intake of Omega-3 PUFA. The morphological properties of the plaque was also altered, showing thicker fibrous caps and less inflammation determined by the AHA and modified AHA classification.

These findings are important to confirm. Secondly additional indicators of plaque stability are required to strengthen the hypothesis. Also the mechanisms by which the morphological changes come about need to be identified. The model that is being used assesses structural changes associated with plaque rupture and instability through different important variables.

Comparisons: Double blind comparison of Omacor 2g/day and placebo in patients awaiting endarterectomy.

• Study Type: Interventional
• Enrollment: 121
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Southampton, United Kingdom, SO17 1BJ
    • University of Southampton, School of medicine

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:

• Males of females above 18 years of age
• Patients awaiting carotid endarterectomy
• Written Informed Consent

Exclusion Criteria:

• Patients consuming fish oil or evening primrose oil preparations
• Patients eating > 2 oily fish meals per week
• Patients requiring operation within 7 days
• Pregnant or breastfeeding
• Patients participating in other clinical studies involving treatment with drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The primary objective is to compare the carotid plaque stability after placebo versus Omega-3 fatty acid treatment by assessing structural changes associated with plaque rupture and instability. The composite endpoint includes changes in
(1) the size of the lipid pool,
(2) the number of foam cells,
(3) the presence of haemorrhage,
(4) the number of macrophages in lesions and
(5) the overall density of inflammation in the plaque as a whole and
(6) in fibrous caps of lesions.

Secondary Outcome Measures

Outcome Measure
(1) the size of the lipid pool,
(2) the number of foam cells,
(3) the presence of haemorrhage,
(4) the number of macrophages in lesions and
(5) the overall density of inflammation in the plaque as a whole and
(6) in fibrous caps of lesions.

Collaborators and Investigators

• Sponsor: Pronova BioPharma
• Investigators: Principal Investigator: Philip C. Calder, PhD, University of Southampton, School of Medicine, Institute of Human Nutrition

Publications and helpful links

General Publications

• Thies F, Garry JM, Yaqoob P, Rerkasem K, Williams J, Shearman CP, Gallagher PJ, Calder PC, Grimble RF. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet. 2003 Feb 8;361(9356):477-85. doi: 10.1016/S0140-6736(03)12468-3.
• Cawood AL, Ding R, Napper FL, Young RH, Williams JA, Ward MJ, Gudmundsen O, Vige R, Payne SP, Ye S, Shearman CP, Gallagher PJ, Grimble RF, Calder PC. Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. Atherosclerosis. 2010 Sep;212(1):252-9. doi: 10.1016/j.atherosclerosis.2010.05.022. Epub 2010 May 20.

Study record dates

Study Major Dates

• Study Start: August 1, 2003
• Study Completion: July 1, 2005

Study Registration Dates

• First Submitted: February 17, 2006
• First Submitted That Met QC Criteria: February 17, 2006
• First Posted (Estimate): February 20, 2006

Study Record Updates

• Last Update Posted (Estimate): February 20, 2006
• Last Update Submitted That Met QC Criteria: February 17, 2006
• Last Verified: February 1, 2006

More Information

Terms related to this study

• Keywords: inflammation; Endarterectomy; Omacor; Omega-3 PUFA; Carotid Plaque stability; Structural changes
• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: CTN K85 02025