<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/NCT01735357</url>
  </required_header>
  <id_info>
    <org_study_id>EDT</org_study_id>
    <nct_id>NCT01735357</nct_id>
  </id_info>
  <brief_title>Differential Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Platelet, Endothelial and Vascular Function</brief_title>
  <official_title>Investigation Into Incorporation of (n-3) Polyunsaturated Fatty Acids Into Erythrocyte Membranes and Clearance, and Effects on Platelet Function, Arterial Function and Endothelial Repair</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King's College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>King's College London</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study was to determine whether supplementation with oils enriched with&#xD;
      long chain n-3 PUFA, either EPA or DHA, had a differential effect on platelet, endothelial&#xD;
      and vascular function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Relatively few studies have made a head-to-head comparison of DHA (22:6n-3) with EPA&#xD;
      (20:5n-3). The understanding of this differential effect may be of great interest in&#xD;
      populations with low EPA intake such as vegetarians, who may choose to supplement their&#xD;
      dietary intake of long-chain n-3 PUFA in the form of DHA-rich algal oil.&#xD;
&#xD;
      This study aimed to investigate the effect of supplementation with oils rich in either EPA or&#xD;
      DHA (3g/day, 6 weeks) in healthy young males on platelet, endothelial and vascular function,&#xD;
      as well as other CVD risk factors. The primary outcomes were platelet monocyte aggregates and&#xD;
      endothelial progenitor cells - novel markers of platelet and endothelial function, measured&#xD;
      by flow cytometry, Secondary outcomes included capillary density, measured by capillaroscopy&#xD;
      to assess changes in microvascular function, pulse wave analysis, digital volume pulse and&#xD;
      ambulatory blood pressure. Other secondary outcomes included lipid profiles (TAG,&#xD;
      cholesterol, NEFA), glycaemic control (HOMA, QUICKI) and oxidative stress (isoprostane). The&#xD;
      omega-3 index (erythrocyte EPA+DHA) was used as a marker of compliance.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2009</start_date>
  <completion_date type="Actual">April 2010</completion_date>
  <primary_completion_date type="Actual">April 2010</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>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Platelet Monocyte Aggregates (PMA)</measure>
    <time_frame>6 weeks</time_frame>
    <description>The endothelium plays a vital role in the regulation of blood flow, thrombosis and inflammation. Endothelium-derived anti-adhesive and anti-aggregant substances, including prostacyclin and nitric oxide, are known to inhibit platelet activation. Endothelial dysfunction or vessel wall injury lead to the activation of platelets, of which platelet-monocyte-aggregates (PMA) are a sensitive marker, and were shown to inversely correlate with markers of EF in patients with stable CHD. The measurement of PMA by flow cytometry is a method which reduces ex vivo platelet activation to its minimum and is believed to represent platelet activation in vivo.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Endothelial Progenitor Cell (EPC) counts</measure>
    <time_frame>6 weeks</time_frame>
    <description>EPCs are a subgroup of circulating progenitor cells that are recruited from the bone marrow to repair the injured vasculature. They have been associated with a reduced CVD risk and may serve as markers of endothelial function because they represent a greater capacity for the endothelium to repair itself. Two populations of EPCs were measured by flow cytometry, described as 'early EPC' (KDR+/CD34+/CD133+) and 'late EPCs' (KDR+/CD34+/CD31+).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Capillary density</measure>
    <time_frame>6 weeks</time_frame>
    <description>Capillary rarefaction has been associated to CVD risk factors such as hypertension, smoking and obesity. The cutaneous circulation has emerged as an accessible and representative vascular bed to look at microvascular dysfunction. Capillary density was measured by a Capiscope (kk technologies)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arterial stiffness</measure>
    <time_frame>6 weeks</time_frame>
    <description>Pulse wave analysis (PWA) was used to measure indices of arterial stiffness, including peripheral and central augmentation index, as well as central systolic and diastolic blood pressure. Digital volume pulse (DVP) was used to measure reflection and stiffness indices.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood Pressure (BP) and Heart Rate (HR)</measure>
    <time_frame>6 weeks</time_frame>
    <description>Resting HR and BP were measured in the seated and supine position after 15 minute rest, on the days of both baseline and endpoint visits. In addition, ambulatory BP and HR (24h, daytime, nighttime) was measured 2-3 days prior to each visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma isoprostane concentrations</measure>
    <time_frame>6 weeks</time_frame>
    <description>8-iso-prostaglandin-F2α (8-IsoP-F2α), a prostaglandin F2-like compound biosynthesized nonenzymatically by a free-radical oxygenation of arachidonic acid, was measured in plasma in order to assess oxidative stress.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Nitrate and Nitrites (NOx) concentrations</measure>
    <time_frame>6 weeks</time_frame>
    <description>Plasma NOx was measured as a circulating marker of endothelial function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum total cholesterol concentration</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Triacylglycerol concentrations</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum high density lipoprotein concentration</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum low density lipoprotein concentration</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum non esterified fatty acids (NEFA) concentration</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Apolipoprotein B concentration</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma glucose concentration</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma insulin concentration</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum adiponectin concentration</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum resistin concentration</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Erythrocyte phospholipid fatty acid profiles</measure>
    <time_frame>6 weeks</time_frame>
    <description>The EPA and DHA content of erythrocyte lipids were used as a marker of compliance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fatty acid profile of plasma non esterified fatty acid fraction</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Olive oil (BP specification)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>5g per day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DHA-rich oil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fish oil supplement (total = 5g/day) providing 3.1g/day of DHA triacylglycerol, blended with olive oil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EPA-rich oil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fish oil supplement (total = 5g/day) providing 2.9g/day of EPA triacylglycerol, blended with olive oil</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>EPA-rich triacylglycerol oil</intervention_name>
    <arm_group_label>EPA-rich oil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo - olive oil (BP specification)</intervention_name>
    <arm_group_label>Olive oil (BP specification)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>DHA-rich triacylglycerol oil</intervention_name>
    <arm_group_label>DHA-rich oil</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males&#xD;
&#xD;
          -  No smokers&#xD;
&#xD;
          -  Aged 18-45y old&#xD;
&#xD;
          -  Able to understand the information sheet and comply with all the trial procedures&#xD;
&#xD;
          -  Having given written consent to take part in the study prior to participation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Reported history of CVD (myocardial infarction, angina, venous thrombosis, stroke,&#xD;
             dyslipidemia), diabetes (or fasting glucose ≥ 6.1 mmol/L), cancer, kidney, liver or&#xD;
             bowel disease.&#xD;
&#xD;
          -  Presence of gastrointestinal disorder or use of drug, which is likely to alter&#xD;
             gastrointestinal motility or nutrient absorption.&#xD;
&#xD;
          -  Current smokers; history of substance abuse or alcoholism (previous weekly alcohol&#xD;
             intake &gt;60 units/week); current self-reported weekly alcohol intake exceeding 28 units&#xD;
&#xD;
          -  Recent use of hypolipidaemic, antihypertensive, antiplatelet or antithrombotic&#xD;
             mediations&#xD;
&#xD;
          -  Platelet count above or below the normal range or any history indicative of a&#xD;
             congenital or acquired platelet or haemostatic defect.&#xD;
&#xD;
          -  Allergy or intolerance to any component of study capsules&#xD;
&#xD;
          -  Unwilling to restrict consumption of any source of fish oil for the length of the&#xD;
             study&#xD;
&#xD;
          -  Subjects reporting consumption of &gt;1 portion oily fish per week&#xD;
&#xD;
          -  Weight change of &gt;3 kg in preceding 2 months; BMI &lt;18 and &gt;32 kg/m2&#xD;
&#xD;
          -  Blood pressure&gt;160/90 mmHg&#xD;
&#xD;
          -  Fasting blood cholesterol &gt; 6.5 mmol/L; fasting triacylglycerol concentrations &gt; 2.0&#xD;
             mmol/L&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wendy L Hall, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>King's College London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Diabetes &amp; Nutritional Sciences Division, King's College London</name>
      <address>
        <city>London</city>
        <zip>SE1 9NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://www.ncbi.nlm.nih.gov/pubmed/27105870</url>
    <description>Related Info</description>
  </link>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>November 20, 2012</study_first_submitted>
  <study_first_submitted_qc>November 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2012</study_first_posted>
  <last_update_submitted>September 12, 2019</last_update_submitted>
  <last_update_submitted_qc>September 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>King's College London</investigator_affiliation>
    <investigator_full_name>Dr Wendy Hall</investigator_full_name>
    <investigator_title>Lecturer in Nutritional Sciences</investigator_title>
  </responsible_party>
  <keyword>Eicosapentaenoic acid</keyword>
  <keyword>Docosahexaenoic acid</keyword>
  <keyword>Cardiovascular risk</keyword>
  <keyword>Platelet function</keyword>
  <keyword>Endothelial function</keyword>
  <keyword>Vascular function</keyword>
  <keyword>young males</keyword>
  <!-- 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/NCT01735357
org study id: EDT
nct id: NCT01735357
lead sponsor: 
has dmc: No
The purpose of this study was to determine whether supplementation with oils enriched with
      long chain n-3 PUFA, either EPA or DHA, had a differential effect on platelet, endothelial
      and vascular function.
Relatively few studies have made a head-to-head comparison of DHA (22:6n-3) with EPA
      (20:5n-3). The understanding of this differential effect may be of great interest in
      populations with low EPA intake such as vegetarians, who may choose to supplement their
      dietary intake of long-chain n-3 PUFA in the form of DHA-rich algal oil.

      This study aimed to investigate the effect of supplementation with oils rich in either EPA or
      DHA (3g/day, 6 weeks) in healthy young males on platelet, endothelial and vascular function,
      as well as other CVD risk factors. The primary outcomes were platelet monocyte aggregates and
      endothelial progenitor cells - novel markers of platelet and endothelial function, measured
      by flow cytometry, Secondary outcomes included capillary density, measured by capillaroscopy
      to assess changes in microvascular function, pulse wave analysis, digital volume pulse and
      ambulatory blood pressure. Other secondary outcomes included lipid profiles (TAG,
      cholesterol, NEFA), glycaemic control (HOMA, QUICKI) and oxidative stress (isoprostane). The
      omega-3 index (erythrocyte EPA+DHA) was used as a marker of compliance.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Participant)
measure: Platelet Monocyte Aggregates (PMA)
time frame: 6 weeks
description: The endothelium plays a vital role in the regulation of blood flow, thrombosis and inflammation. Endothelium-derived anti-adhesive and anti-aggregant substances, including prostacyclin and nitric oxide, are known to inhibit platelet activation. Endothelial dysfunction or vessel wall injury lead to the activation of platelets, of which platelet-monocyte-aggregates (PMA) are a sensitive marker, and were shown to inversely correlate with markers of EF in patients with stable CHD. The measurement of PMA by flow cytometry is a method which reduces ex vivo platelet activation to its minimum and is believed to represent platelet activation in vivo.
measure: Endothelial Progenitor Cell (EPC) counts
time frame: 6 weeks
description: EPCs are a subgroup of circulating progenitor cells that are recruited from the bone marrow to repair the injured vasculature. They have been associated with a reduced CVD risk and may serve as markers of endothelial function because they represent a greater capacity for the endothelium to repair itself. Two populations of EPCs were measured by flow cytometry, described as 'early EPC' (KDR+/CD34+/CD133+) and 'late EPCs' (KDR+/CD34+/CD31+).
measure: Capillary density
time frame: 6 weeks
description: Capillary rarefaction has been associated to CVD risk factors such as hypertension, smoking and obesity. The cutaneous circulation has emerged as an accessible and representative vascular bed to look at microvascular dysfunction. Capillary density was measured by a Capiscope (kk technologies)
measure: Arterial stiffness
time frame: 6 weeks
description: Pulse wave analysis (PWA) was used to measure indices of arterial stiffness, including peripheral and central augmentation index, as well as central systolic and diastolic blood pressure. Digital volume pulse (DVP) was used to measure reflection and stiffness indices.
measure: Blood Pressure (BP) and Heart Rate (HR)
time frame: 6 weeks
description: Resting HR and BP were measured in the seated and supine position after 15 minute rest, on the days of both baseline and endpoint visits. In addition, ambulatory BP and HR (24h, daytime, nighttime) was measured 2-3 days prior to each visit.
measure: Plasma isoprostane concentrations
time frame: 6 weeks
description: 8-iso-prostaglandin-F2α (8-IsoP-F2α), a prostaglandin F2-like compound biosynthesized nonenzymatically by a free-radical oxygenation of arachidonic acid, was measured in plasma in order to assess oxidative stress.
measure: Plasma Nitrate and Nitrites (NOx) concentrations
time frame: 6 weeks
description: Plasma NOx was measured as a circulating marker of endothelial function.
measure: Serum total cholesterol concentration
time frame: 6 weeks
measure: Serum Triacylglycerol concentrations
time frame: 6 weeks
measure: Serum high density lipoprotein concentration
time frame: 6 weeks
measure: Serum low density lipoprotein concentration
time frame: 6 weeks
measure: Serum non esterified fatty acids (NEFA) concentration
time frame: 6 weeks
measure: Serum Apolipoprotein B concentration
time frame: 6 weeks
measure: Plasma glucose concentration
time frame: 6 weeks
measure: Plasma insulin concentration
time frame: 6 weeks
measure: Serum adiponectin concentration
time frame: 6 weeks
measure: Serum resistin concentration
time frame: 6 weeks
measure: Erythrocyte phospholipid fatty acid profiles
time frame: 6 weeks
description: The EPA and DHA content of erythrocyte lipids were used as a marker of compliance.
measure: Fatty acid profile of plasma non esterified fatty acid fraction
time frame: 6 weeks
arm group label: Olive oil (BP specification)
arm group type: Placebo Comparator
description: 5g per day
arm group label: DHA-rich oil
arm group type: Experimental
description: Fish oil supplement (total = 5g/day) providing 3.1g/day of DHA triacylglycerol, blended with olive oil
arm group label: EPA-rich oil
arm group type: Experimental
description: Fish oil supplement (total = 5g/day) providing 2.9g/day of EPA triacylglycerol, blended with olive oil
intervention type: Dietary Supplement
intervention name: EPA-rich triacylglycerol oil
arm group label: EPA-rich oil
intervention type: Dietary Supplement
intervention name: Placebo - olive oil (BP specification)
arm group label: Olive oil (BP specification)
intervention type: Dietary Supplement
intervention name: DHA-rich triacylglycerol oil
arm group label: DHA-rich oil
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Wendy L Hall, PhD
role: Principal Investigator
affiliation: King's College London
facility: 
country: United Kingdom
url: http://www.ncbi.nlm.nih.gov/pubmed/27105870
description: Related Info
responsible party type: Principal Investigator
investigator affiliation: King's College London
investigator full name: Dr Wendy Hall
investigator title: Lecturer in Nutritional Sciences