The Impact of Fish-oil Fatty Acids on Postprandial Vascular Reactivity (FOFA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of East Anglia
ClinicalTrials.gov Identifier:
NCT01692431
First received: September 17, 2012
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

The primary aim of this study is to determine the impact of individual fish oil fatty acids on vascular reactivity and to identify underlying physiological and molecular mechanism of any observed effects. In addition response to intervention according to genotype will be determined retrospectively.


Condition Intervention
Cardiovascular Physiological Phenomena
Endothelial Nitric Oxide Synthase
Eicosapentaenoic Acid
Docosahexaenoic Acid (All-Z Isomer)
Dietary Supplement: EPA
Dietary Supplement: DHA
Dietary Supplement: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Impact of Fish-oil Fatty Acids on Postprandial Vascular Reactivity

Resource links provided by NLM:


Further study details as provided by University of East Anglia:

Primary Outcome Measures:
  • Endopat [ Time Frame: Change from baseline at 4 hours postprandially ] [ Designated as safety issue: No ]
    EndoPat is an easy to use and rapid technique which has been validated against other clinically accepted measures of endothelial function such as Flow Mediated Dilation and Coronary Blood Flow measured by angiography alongside acetylcholine infusion. EndoPat has also been shown to correlate with multiple known CVD risk factors and to be predictive of future cardiovascular events. In addition, EndoPat will be utilised alongside oral administration of nitroglycerin in order to establish if peripheral arterial tone is altered in response to EPA or DHA in a non-Nitric Oxide dependent manner. EndoPAT produces a reactive hyperaemic index score which is indicative of the endothelial's capacity to produce NO, which itself is indicative of general endothelial function. EndoPAT will be assessed using a standardised methodology developed by Itamar Medical, which involves measuring changes in dilation in response to induced hyperaemia.


Secondary Outcome Measures:
  • Pulse Wave Velocity [ Time Frame: Change from baseline at 4 hours postprandially ] [ Designated as safety issue: No ]
    Pulse Wave Velocity (PWV) analysis will also be utilised in order to measure arterial stiffness. PWV analysis will allow several non-invasive measurements to be taken simultaneously including PWV, which is an established index of arterial stiffness, and augmentation index, an indirect measure of arterial stiffness which is dependent on wave-reflections and independent of pulse pressure. PWV and associated measures will be measured using methodology developed by Skidmore medical. PWV is measured in m/sec while augmentation index is measured as a % of augmentation (of central aortic pressure by a reflected pulse wave).


Enrollment: 28
Study Start Date: September 2012
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DHA
High fat meal containing DHA rich oil.
Dietary Supplement: DHA
High fat meal containing DHA
Experimental: EPA
High fat meal containing EPA.
Dietary Supplement: EPA
High fat meal containing EPA
Placebo Comparator: Control
High fat meal with no/negligable omega-3 fatty acid content.
Dietary Supplement: Placebo
High fat meal containing negligible EPA/DHA content

Detailed Description:

A loss of vascular reactivity and increased vascular tone is being increasingly recognised as a significant cardiovascular disease (CVD) risk factor and highly predictive of future CVD events. A previous study by our group has shown the inclusion of a fish oil mixture administered alongside a high fat meal preserves postprandial vascular function in healthy men [1]. In this three arm, placebo controlled cross over study, the impact of individual fatty acids contained within fish-oil on postprandial vascular reactivity (measured at 4 hour post test meal) will be assessed for the first time. Clinical measurements of vascular function which correlate with CVD risk factors and are predictive of future CVD events will be undertaken in order to assess any potentially beneficial effects. In addition plasma samples will be taken at 0 and 4 hours to determine the change in concentration of modulators of vascular tone. Accordingly, our nutrients of interest which will be administered in the intervention arms of the study, will be present in this lipoprotein rich fraction. By exposing cells in culture to these EPA- and DHA-enriched lipoproteins, mechanisms underlying the vascular response in our human volunteers will be investigated. Finally we will measure the plasma fatty acid profile to confirm that circulating concentrations of EPA and DHA are increasing postprandially according to intake.

As it is now recognised that genetic variation, in addition to being an important determinant of the risk of all known chronic diseases, plays a large part in determining an individual's response to dietary change, DNA will be extracted from whole blood taken at the clinical screening and stored for subsequent genotyping for variants likely to be important in the regulation of EPA and DHA metabolism and vascular tone. Although the current study will not be fully powered to generate definite conclusion regarding genotype*diet interactions, it will serve to generate pilot data for future studies.

  Eligibility

Ages Eligible for Study:   35 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

In order to recruit a population at a relative risk of developing CVD of >1.5 males aged 35-55 years, who possess one of the following risk factors for CVD will be recruited through local advertisement:

  • Total cholesterol > 6mmol/L
  • High density lipoprotein cholesterol (HDLC) < 1.0mmol/L
  • Systolic blood pressure > 140 mmHg
  • Diastolic blood pressure > 90 mmHg
  • Waist circumference > 102cm

Exclusion Criteria:

Current smokers, or ex-smokers ceasing < 3 months ago

Subjects with existing or significant past medical history of vascular disease or any medical condition likely to affect the study measures e.g. vascular disease, circulatory (i.e. Reynaud's), diabetes, systemic lupus erythematosus, hepatic, renal, digestive, haematological, neurological, cancer or thyroidal disease.

Those with known allergies to the intervention foods / commercially available supplements.

Those unprepared to adhere to dietary restrictions during the trial i.e. for 3 days preceding each assessment visit (and for a 3 day run-in period) or unwilling to comply with the assessments per protocol.

Parallel participation in another research project which involves concurrent dietary intervention and/or sampling of biological fluids/material.

Having vaccinations (excluding the flu vaccination) or antibiotics within 3 months of start of trial, and those with vaccinations scheduled for during the trial.

Taking EPA or DHA containing food / dietary supplements likely to affect the study results e.g. supplements derived from marine organisms which equate to a greater than 1 gram of EPA and DHA per daily serving. Prospective participants who are willing to cease supplementation 2 month preceding, and during, the trial will be considered on a case by case basis.

Habitual consumption of more than one portion of oily fish per week (as defined as 140g of any oil fish, including salmon, trout, mackerel, sardines, pilchards, herring, kipper, eel, whitebait, etc).

Prescribed lipid lowering, medicine affecting lipoprotein metabolism or blood blotting, hypertension, vasodilators (e.g. Viagra) or antibiotic medication.

Assessed from the clinical screening.

Unsatisfactory biochemical or haematological assessment assessed by the studies clinical advisor

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01692431

Locations
United Kingdom
Norwich Medical School
Norwich, United Kingdom, NR47TJ
Sponsors and Collaborators
University of East Anglia
Investigators
Principal Investigator: Anne Marie Minihane, PhD University of East Anglia
  More Information

Publications:
Responsible Party: University of East Anglia
ClinicalTrials.gov Identifier: NCT01692431     History of Changes
Other Study ID Numbers: 12/EE/011
Study First Received: September 17, 2012
Last Updated: October 14, 2013
Health Authority: United Kingdom: National Health Service

ClinicalTrials.gov processed this record on April 23, 2014