<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01692431</url>
  </required_header>
  <id_info>
    <org_study_id>12/EE/011</org_study_id>
    <nct_id>NCT01692431</nct_id>
  </id_info>
  <brief_title>The Impact of Fish-oil Fatty Acids on Postprandial Vascular Reactivity</brief_title>
  <acronym>FOFA</acronym>
  <official_title>The Impact of Fish-oil Fatty Acids on Postprandial Vascular Reactivity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of East Anglia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of East Anglia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary aim of this study is to determine the impact of individual fish oil fatty acids&#xD;
      on vascular reactivity and to identify underlying physiological and molecular mechanism of&#xD;
      any observed effects. In addition response to intervention according to genotype will be&#xD;
      determined retrospectively.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A loss of vascular reactivity and increased vascular tone is being increasingly recognised as&#xD;
      a significant cardiovascular disease (CVD) risk factor and highly predictive of future CVD&#xD;
      events. A previous study by our group has shown the inclusion of a fish oil mixture&#xD;
      administered alongside a high fat meal preserves postprandial vascular function in healthy&#xD;
      men [1]. In this three arm, placebo controlled cross over study, the impact of individual&#xD;
      fatty acids contained within fish-oil on postprandial vascular reactivity (measured at 4 hour&#xD;
      post test meal) will be assessed for the first time. Clinical measurements of vascular&#xD;
      function which correlate with CVD risk factors and are predictive of future CVD events will&#xD;
      be undertaken in order to assess any potentially beneficial effects. In addition plasma&#xD;
      samples will be taken at 0 and 4 hours to determine the change in concentration of modulators&#xD;
      of vascular tone. Accordingly, our nutrients of interest which will be administered in the&#xD;
      intervention arms of the study, will be present in this lipoprotein rich fraction. By&#xD;
      exposing cells in culture to these EPA- and DHA-enriched lipoproteins, mechanisms underlying&#xD;
      the vascular response in our human volunteers will be investigated. Finally we will measure&#xD;
      the plasma fatty acid profile to confirm that circulating concentrations of EPA and DHA are&#xD;
      increasing postprandially according to intake.&#xD;
&#xD;
      As it is now recognised that genetic variation, in addition to being an important determinant&#xD;
      of the risk of all known chronic diseases, plays a large part in determining an individual's&#xD;
      response to dietary change, DNA will be extracted from whole blood taken at the clinical&#xD;
      screening and stored for subsequent genotyping for variants likely to be important in the&#xD;
      regulation of EPA and DHA metabolism and vascular tone. Although the current study will not&#xD;
      be fully powered to generate definite conclusion regarding genotype*diet interactions, it&#xD;
      will serve to generate pilot data for future studies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Endopat</measure>
    <time_frame>Change from baseline at 4 hours postprandially</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pulse Wave Velocity</measure>
    <time_frame>Change from baseline at 4 hours postprandially</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Cardiovascular Physiological Phenomena</condition>
  <condition>Endothelial Nitric Oxide Synthase</condition>
  <condition>Eicosapentaenoic Acid</condition>
  <condition>Docosahexaenoic Acid (All-Z Isomer)</condition>
  <arm_group>
    <arm_group_label>DHA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High fat meal containing DHA rich oil.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EPA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High fat meal containing EPA.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>High fat meal with no/negligable omega-3 fatty acid content.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>EPA</intervention_name>
    <description>High fat meal containing EPA</description>
    <arm_group_label>EPA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>DHA</intervention_name>
    <description>High fat meal containing DHA</description>
    <arm_group_label>DHA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>High fat meal containing negligible EPA/DHA content</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        In order to recruit a population at a relative risk of developing CVD of &gt;1.5 males aged&#xD;
        35-55 years, who possess one of the following risk factors for CVD will be recruited&#xD;
        through local advertisement:&#xD;
&#xD;
          -  Total cholesterol &gt; 6mmol/L&#xD;
&#xD;
          -  High density lipoprotein cholesterol (HDLC) &lt; 1.0mmol/L&#xD;
&#xD;
          -  Systolic blood pressure &gt; 140 mmHg&#xD;
&#xD;
          -  Diastolic blood pressure &gt; 90 mmHg&#xD;
&#xD;
          -  Waist circumference &gt; 102cm&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Current smokers, or ex-smokers ceasing &lt; 3 months ago&#xD;
&#xD;
        Subjects with existing or significant past medical history of vascular disease or any&#xD;
        medical condition likely to affect the study measures e.g. vascular disease, circulatory&#xD;
        (i.e. Reynaud's), diabetes, systemic lupus erythematosus, hepatic, renal, digestive,&#xD;
        haematological, neurological, cancer or thyroidal disease.&#xD;
&#xD;
        Those with known allergies to the intervention foods / commercially available supplements.&#xD;
&#xD;
        Those unprepared to adhere to dietary restrictions during the trial i.e. for 3 days&#xD;
        preceding each assessment visit (and for a 3 day run-in period) or unwilling to comply with&#xD;
        the assessments per protocol.&#xD;
&#xD;
        Parallel participation in another research project which involves concurrent dietary&#xD;
        intervention and/or sampling of biological fluids/material.&#xD;
&#xD;
        Having vaccinations (excluding the flu vaccination) or antibiotics within 3 months of start&#xD;
        of trial, and those with vaccinations scheduled for during the trial.&#xD;
&#xD;
        Taking EPA or DHA containing food / dietary supplements likely to affect the study results&#xD;
        e.g. supplements derived from marine organisms which equate to a greater than 1 gram of EPA&#xD;
        and DHA per daily serving. Prospective participants who are willing to cease&#xD;
        supplementation 2 month preceding, and during, the trial will be considered on a case by&#xD;
        case basis.&#xD;
&#xD;
        Habitual consumption of more than one portion of oily fish per week (as defined as 140g of&#xD;
        any oil fish, including salmon, trout, mackerel, sardines, pilchards, herring, kipper, eel,&#xD;
        whitebait, etc).&#xD;
&#xD;
        Prescribed lipid lowering, medicine affecting lipoprotein metabolism or blood blotting,&#xD;
        hypertension, vasodilators (e.g. Viagra) or antibiotic medication.&#xD;
&#xD;
        Assessed from the clinical screening.&#xD;
&#xD;
        Unsatisfactory biochemical or haematological assessment assessed by the studies clinical&#xD;
        advisor&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anne Marie Minihane, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of East Anglia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Norwich Medical School</name>
      <address>
        <city>Norwich</city>
        <zip>NR47TJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Armah CK, Jackson KG, Doman I, James L, Cheghani F, Minihane AM. Fish oil fatty acids improve postprandial vascular reactivity in healthy men. Clin Sci (Lond). 2008 Jun;114(11):679-86. doi: 10.1042/CS20070277.</citation>
    <PMID>18052925</PMID>
  </reference>
  <verification_date>October 2013</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <last_update_submitted>October 14, 2013</last_update_submitted>
  <last_update_submitted_qc>October 14, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 16, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01692431
org study id: 12/EE/011
nct id: NCT01692431
lead sponsor: 
has dmc: No
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.
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.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Endopat
time frame: Change from baseline at 4 hours postprandially
description: 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.
measure: Pulse Wave Velocity
time frame: Change from baseline at 4 hours postprandially
description: 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).
arm group label: DHA
arm group type: Experimental
description: High fat meal containing DHA rich oil.
arm group label: EPA
arm group type: Experimental
description: High fat meal containing EPA.
arm group label: Control
arm group type: Placebo Comparator
description: High fat meal with no/negligable omega-3 fatty acid content.
intervention type: Dietary Supplement
intervention name: EPA
description: High fat meal containing EPA
arm group label: EPA
intervention type: Dietary Supplement
intervention name: DHA
description: High fat meal containing DHA
arm group label: DHA
intervention type: Dietary Supplement
intervention name: Placebo
description: High fat meal containing negligible EPA/DHA content
arm group label: Control
criteria: 
gender: Male
minimum age: 35 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Anne Marie Minihane, PhD
role: Principal Investigator
affiliation: University of East Anglia
facility: 
country: United Kingdom
citation: Armah CK, Jackson KG, Doman I, James L, Cheghani F, Minihane AM. Fish oil fatty acids improve postprandial vascular reactivity in healthy men. Clin Sci (Lond). 2008 Jun;114(11):679-86. doi: 10.1042/CS20070277.
PMID: 18052925
responsible party type: Sponsor