Impact of EPA and DHA Supplementation on Plasma Biomarkers of Inflammation (n3)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Laval University
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Benoit Lamarche, Laval University
ClinicalTrials.gov Identifier:
NCT01810003
First received: March 4, 2013
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

Subclinical inflammation is now indisputably recognized as a key etiological factor in the development of atherosclerosis and subsequent cardiovascular disease. Obesity and related dysmetabolic states including metabolic syndrome (MetS) are highly prevalent causes of subclinical inflammation. Obesity and MetS are both diet and lifestyle-related and there is a growing body of literature suggesting that specific nutrients, such as long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA), may attenuate the pro-inflammatory state associated with these conditions. However, careful review of existing literature on this topic reveals important gaps in knowledge, the purported anti-inflammatory effects of LCn-3PUFA even being questioned by many. Significant confounding attributable to study design, sample size and biomarker selection may be responsible in part for inconsistencies in the literature on LCn-3PUFA and inflammation. We also found that evidence available to date (for and against) is based primarily on secondary analyses, as most of the studies published were not primarily designed to investigate inflammation as a primary outcome. It remains unclear whether the different LCn-3PUFA, primarily docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3), have similar effects on pro-inflammatory processes as almost all studies were undertaken using a mix of LCn-3PUFA. Whether efficacy of EPA and DHA is influenced by sex/gender is also unknown. Finally, a better understanding of the systemic and tissue-specific mechanisms underlying the anticipated anti-inflammatory effects of different LCn-3PUFA in MetS would also be of great value. Addressing these gaps has important public health implications, considering that LCn-3PUFA supplements are broadly and indiscriminately recommended for the prevention of cardiovascular disease.

The overarching objective of the proposed research is to compare the anti-inflammatory effects of EPA and DHA in men and women with MetS.


Condition Intervention
Cardiovascular Disease, Inflammation
Dietary Supplement: High DHA
Dietary Supplement: High EPA
Dietary Supplement: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Impact of EPA and DHA Supplementation on Plasma Biomarkers of Inflammation in Men and Women With Metabolic Syndrome

Further study details as provided by Laval University:

Primary Outcome Measures:
  • Change in plasma biomarkers of inflammation (CRP, IL-2, IL-6, IL-10, IL-18 and TNF-α) [ Time Frame: At the beginning and the end of each 10-week period ] [ Designated as safety issue: No ]
    Period 1: weeks 0 and 10 (week 10 minus week 0) Period 2 : weeks 18 and 28 (week 10 minus week 0) Period 3 : weeks 36 and 46 (week 46 minus week 36)


Secondary Outcome Measures:
  • Change in lipid concentrations (LDL-C, HDL-C, TG) [ Time Frame: At the beginning and the end of each 10-week period ] [ Designated as safety issue: No ]
    Period 1: weeks 0 and 10 (week 10 minus week 0) Period 2 : weeks 18 and 28 (week 10 minus week 0) Period 3 : weeks 36 and 46 (week 46 minus week 36)

  • Change in blood pressure [ Time Frame: At the beginning and the end of each 10-week period ] [ Designated as safety issue: No ]
    Period 1: weeks 0 and 10 (week 10 minus week 0) Period 2 : weeks 18 and 28 (week 10 minus week 0) Period 3 : weeks 36 and 46 (week 46 minus week 36)

  • Change in endogenous production and clearance rate of CRP (in a subsample of the entire study population) [ Time Frame: At the end of the three 10-week periods ] [ Designated as safety issue: No ]
    Change between results at weeks 10, 28, 46

  • Change in expression of inflammation genes in peripheral blood cells (in a subsample of the entire study population) [ Time Frame: At the end of the three 10-week periods ] [ Designated as safety issue: No ]
    Change between results at weeks 10, 28, 46

  • Change in anthropometric measures (waist and hip circumference) [ Time Frame: At the beginning and the end of each 10-week period ] [ Designated as safety issue: No ]
    Period 1: weeks 0 and 10 (week 10 minus week 0) Period 2 : weeks 18 and 28 (week 10 minus week 0) Period 3 : weeks 36 and 46 (week 46 minus week 36)


Estimated Enrollment: 170
Study Start Date: March 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High DHA
High DHA supplementation (3g/day)
Dietary Supplement: High DHA
10 week supplementation period
Experimental: High EPA
EPA supplementation (3g/day)
Dietary Supplement: High EPA
10 week supplementation period
Placebo Comparator: Placebo
Placebo (3g corn oil/day)
Dietary Supplement: Placebo
10 week supplementation period

Detailed Description:

The proposed study will be undertaken according to a double-blind randomized placebo controlled cross-over design with 3 treatment phases: 1- high DHA, 2- High EPA, 3- Control. Each treatment phase will last 10 weeks and will be separated by 8-week washouts. Participants will be randomized to one of 6 treatment sequences while stratifying for sex. Treatments will provide 3 identical 1g capsules per day. During the 3 treatment periods, subjects will receive in random order 0g/d EPA+DHA (3g corn oil placebo), 3g/d EPA (>90% EPA), and 3g/d DHA (>90% DHA). Long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) will be provided in their re-esterified triacylglycerol form as studies have shown that bioavailability was greater when EPA and DHA were consumed as TG rather than as ethyl esters. The therapeutic dose that maximizes the anti-inflammatory effects of LCn-3PUFA in patients with inflammation has not been established, although data suggest that they may be dose-dependent. However, studies in healthy human volunteers suggest that an intake > 2 g EPA + DHA/day is required to affect inflammatory processes. Many of the available studies have used a dose of EPA+DHA that was lower than 2g/d, with no apparent anti-inflammatory effects. A study has shown that a dose of 1.8g/d of EPA+DHA induced significant changes in peripheral blood cell (PBC) inflammation gene expression, with no change in plasma CRP concentrations. In the present study, we propose to use a dose of 3 g/d for each individual LCn-3PUFA tested, which is at the higher end of the recommended intake for patients with high plasma TG, but which will maximize our chance to observe changes in inflammatory markers and to differentiate the effects of EPA and DHA, if they exist. Participants will be instructed to maintain a constant body weight during the course of the study. They will also be counselled on how to exclude fatty fish meals (including salmon, tuna, mackerel, and herring), fish-oil supplements, flax products, walnuts, and omega-3-enriched eggs during the study. Vitamin supplements and natural health products will be strictly forbidden during the entire experimental period, with the exception of calcium, which will be allowed at a stable dose. Although alcohol consumption will be permitted during the study with intakes not exceeding one serving (12-15 g alcohol) per day, it will be forbidden for the 4 days that precede the various tests at the end of each treatment phase. Subjects will also be instructed to maintain their usual physical activity except for the 4 days that precede blood sampling at the various stages of the study, during which they will be asked to remain sedentary.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men and women aged between 18 and 70 years with metabolic syndrome as defined by the International Diabetes Federation (IDF) criteria
  • Stable body weight for at least 3 months prior to randomization.
  • Pre-menopausal women with regular menstrual cycle (25-35 days)

Exclusion Criteria:

  • Plasma CRP > 10 g/ml at screening
  • Extreme dyslipidemias such as familial hypercholesterolemia
  • Previous history of cardiovascular disease (coronary heart disease, cerebrovascular disease or peripheral arterial disease) and type 1 or 2 diabetes or patients having received or being treated with insulin or a thiazolidinedione within the past 6 months
  • Subjects taking medications known to affect inflammation and blood lipids (e.g. steroids, beta blockers, thiazide diuretics, lipid lowering agents, hormone replacement, binging alcohol)
  • Subjects taking LCn-3PUFA supplements within 6 months of study onset.
  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: NCT01810003

Contacts
Contact: Benoît Lamarche, PhD 418-656-2131 ext 4355 Benoit.lamarche@inaf.ulaval.ca

Locations
Canada
Institute of Nutrition and Functional Foods (INAF), Laval University Recruiting
Quebec, Canada, G1V 0A6
Contact: Amélie Charest, MSc    418-656-2131 ext 11467    Amelie.charest@inaf.ulaval.ca   
Principal Investigator: Benoît Lamarche, PhD         
Sub-Investigator: Patrick Couture, MD, FRCP (C, PhD)         
Sub-Investigator: André Tchernof, PhD         
Sponsors and Collaborators
Laval University
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Benoît Lamarche, PhD Laval University
  More Information

No publications provided

Responsible Party: Benoit Lamarche, Professor, Laval University
ClinicalTrials.gov Identifier: NCT01810003     History of Changes
Other Study ID Numbers: INAF-2012-143
Study First Received: March 4, 2013
Last Updated: April 1, 2014
Health Authority: Canada: Health Canada

Keywords provided by Laval University:
Cardiovascular disease
Inflammation
EPA/DHA supplementation

Additional relevant MeSH terms:
Cardiovascular Diseases
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on October 21, 2014