<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/NCT02221791</url>
  </required_header>
  <id_info>
    <org_study_id>FLAVO2</org_study_id>
    <nct_id>NCT02221791</nct_id>
  </id_info>
  <brief_title>Comparison of Pure Epicatechin and Cocoa on Markers of Vascular Function</brief_title>
  <acronym>FLAVO2</acronym>
  <official_title>Comparison of Pure Epicatechin and Cocoa on Markers of Vascular Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wageningen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Top Institute Food and Nutrition</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Wageningen University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Intervention studies support a protective effect of flavonoid-rich foods such as chocolate&#xD;
      and tea on cardiovascular disease risk. In a previous study we found that pure epicatechin&#xD;
      improves markers of vascular function and insulin resistance although the results were less&#xD;
      pronounced than the majority of chocolate intervention studies.&#xD;
&#xD;
      The food matrix of chocolate or other compounds present in chocolate could play a role in the&#xD;
      bioavailability of flavonoids, resulting in these heightened improvements in vascular&#xD;
      function.&#xD;
&#xD;
      In this study we aim to compare the acute effects of pure epicatechin and high-flavonoid&#xD;
      chocolate on markers of vascular function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Twenty male participants between the ages of 40 and 80 will visit the university on three&#xD;
      days, separated by a 2-week washout. During each visit the participants will, in random&#xD;
      order, be allocated to one of the three interventions:&#xD;
&#xD;
        1. High flavan-3-ol chocolate (70g) plus placebo capsule;&#xD;
&#xD;
        2. White chocolate (70g) plus 100mg of epicatechin in capsule form;&#xD;
&#xD;
        3. White chocolate (70g) plus placebo capsule; Measurements of vascular function will be&#xD;
           taken before, and 2 hours after consumption of the supplements. In order to determine&#xD;
           flavonoid bioavailability, 24-hour urine samples will be collected and 7 blood samples&#xD;
           will be taken over a period of 8 hours.&#xD;
&#xD;
      The primary study parameter is the percentage change in Flow-Mediated Dilation (FMD) as a&#xD;
      result of a high-flavonoid cocoa or epicatechin challenge. Additional study parameters&#xD;
      include plasma flavonoid and nitric oxide concentrations as well as pulse wave analysis&#xD;
      parameters.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">October 2014</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>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Endothelium-dependent flow-mediated dilation as a result of high flavan-3-ol cocoa or pure epicatechin consumption.</measure>
    <time_frame>Baseline and 2 hours after consumption</time_frame>
    <description>Change in arterial diameter as a result of 5 minute arterial occlusion (200mmHg). Arterial diameter will be measured by means of ultrasonography.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in nitric oxide as a result of high flavan-3-ol cocoa or pure epicatechin consumption</measure>
    <time_frame>Baseline and 1 hr, 2hr, 3hr, 4hr, 6hr and 8hr after consumption</time_frame>
    <description>Plasma analysis of nitric oxide</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in arterial augmentation index as measured by Pulse Wave Analysis</measure>
    <time_frame>Baseline and 2 hours after consumption</time_frame>
    <description>Measured in triplicate using a SphygmoCor device at baseline and 2 hours after consumption</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bioavailability of plasma epicatechin metabolites</measure>
    <time_frame>Baseline and 1hr, 2hr, 3hr, 4hr, 6hr and 8hr after consumption</time_frame>
    <description>Plasma analysis of epicatechin metabolites will be measured up to 8 hours after consumption of high flavan-3-ol cocoa or pure epicatechin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bioavailability of urine epicatechin metabolites</measure>
    <time_frame>24 hour urine samples</time_frame>
    <description>Urinary epicatechin metabolites will be measured in 24-hour urine samples</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Endothelial Dysfunction</condition>
  <condition>Bioavailability</condition>
  <arm_group>
    <arm_group_label>Pure Epicatechin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will consume 100mg of epicatechin (capsule) + 70g white chocolate</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High flavan-3-ol cocoa</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will consume 70g high flavan-3-ol cocoa (100mg epicatechin) + placebo capsule</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will consume 70g white chocolate + placebo capsules</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Pure Epicatechin</intervention_name>
    <description>Participants will consume 100mg of epicatechin (capsule) + 70g white chocolate</description>
    <arm_group_label>Pure Epicatechin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>High flavan-3-ol cocoa</intervention_name>
    <description>Participants will consume 70g high flavan-3-ol cocoa (100mg epicatechin) + placebo capsule</description>
    <arm_group_label>High flavan-3-ol cocoa</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will consume 70g white chocolate + placebo capsules</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 40 and 80 years,&#xD;
&#xD;
          -  BMI between &gt; 20 and ≤ 30&#xD;
&#xD;
          -  No reported current or previous metabolic diseases,&#xD;
&#xD;
          -  No history of cardiovascular diseases,&#xD;
&#xD;
          -  No history of renal, liver or thyroid diseases,&#xD;
&#xD;
          -  No history of gastrointestinal diseases,&#xD;
&#xD;
          -  No diagnosed diabetes mellitus,&#xD;
&#xD;
          -  Fasting laboratory parameters within normal range as judged by the study physician:&#xD;
             renal function (serum creatinine, ureum), liver function (ALAT, ASAT, GGT), serum&#xD;
             glucose and HDL, LDL and total cholesterol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Body mass index &gt;30 or ≤20 kg/m2&#xD;
&#xD;
          -  Usage of CVD medication (e.g. anti-hypertensive and/or lipid-modifying medication,&#xD;
             non-steroidal anti-inflammatory drugs, acetylsalicylic acid), antibiotics,&#xD;
             corticosteroids or opioids and not able or willing to stop taking them from at least 4&#xD;
             weeks prior to the study&#xD;
&#xD;
          -  Taking nutritional supplements and unwilling to discontinue&#xD;
&#xD;
          -  Reported dietary habits: medically prescribed diet, slimming diet&#xD;
&#xD;
          -  Reported average alcohol consumption greater than or equal to 3 glasses/d&#xD;
&#xD;
          -  Reported intense sporting activities &gt; 10 h/w&#xD;
&#xD;
          -  Weight loss or weight gain of 5 kg or more during the last 2 months&#xD;
&#xD;
          -  Smokers&#xD;
&#xD;
          -  Vegetarians&#xD;
&#xD;
          -  Problems with consuming the supplements or following the study guidelines&#xD;
&#xD;
          -  Recent blood donation (i.e. 1 month) prior to the study and/or planned donation during&#xD;
             and shortly after the study period&#xD;
&#xD;
          -  Not agreeing to be informed about unexpected and medically relevant personal&#xD;
             test-results, or not agreeing that their general practitioner will be informed about&#xD;
             these results&#xD;
&#xD;
          -  Participation in another biomedical trial less than 2 months before the start of the&#xD;
             study or at the same time&#xD;
&#xD;
          -  No signed informed consent form&#xD;
&#xD;
          -  Unable to comply with the study procedure (e.g. holidays, urine collection, blood&#xD;
             sampling)&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter Hollman, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wageningen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Wageningen University</name>
      <address>
        <city>Wageningen</city>
        <zip>6703 HD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <link>
    <url>http://voedingsonderzoek.wur.nl/flavo2</url>
    <description>Website for the study (in dutch)</description>
  </link>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>October 14, 2014</last_update_submitted>
  <last_update_submitted_qc>October 14, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 15, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Flavan-3-ol</keyword>
  <keyword>Flavonoids</keyword>
  <keyword>Epicatechin</keyword>
  <keyword>Cocoa</keyword>
  <keyword>Chocolate</keyword>
  <keyword>Endothelial function</keyword>
  <keyword>Bioavailability</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/NCT02221791
org study id: FLAVO2
nct id: NCT02221791
lead sponsor: 
collaborator: 
has dmc: No
Intervention studies support a protective effect of flavonoid-rich foods such as chocolate
      and tea on cardiovascular disease risk. In a previous study we found that pure epicatechin
      improves markers of vascular function and insulin resistance although the results were less
      pronounced than the majority of chocolate intervention studies.

      The food matrix of chocolate or other compounds present in chocolate could play a role in the
      bioavailability of flavonoids, resulting in these heightened improvements in vascular
      function.

      In this study we aim to compare the acute effects of pure epicatechin and high-flavonoid
      chocolate on markers of vascular function.
Twenty male participants between the ages of 40 and 80 will visit the university on three
      days, separated by a 2-week washout. During each visit the participants will, in random
      order, be allocated to one of the three interventions:

        1. High flavan-3-ol chocolate (70g) plus placebo capsule;

        2. White chocolate (70g) plus 100mg of epicatechin in capsule form;

        3. White chocolate (70g) plus placebo capsule; Measurements of vascular function will be
           taken before, and 2 hours after consumption of the supplements. In order to determine
           flavonoid bioavailability, 24-hour urine samples will be collected and 7 blood samples
           will be taken over a period of 8 hours.

      The primary study parameter is the percentage change in Flow-Mediated Dilation (FMD) as a
      result of a high-flavonoid cocoa or epicatechin challenge. Additional study parameters
      include plasma flavonoid and nitric oxide concentrations as well as pulse wave analysis
      parameters.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Single (Investigator)
measure: Change in Endothelium-dependent flow-mediated dilation as a result of high flavan-3-ol cocoa or pure epicatechin consumption.
time frame: Baseline and 2 hours after consumption
description: Change in arterial diameter as a result of 5 minute arterial occlusion (200mmHg). Arterial diameter will be measured by means of ultrasonography.
measure: Change in nitric oxide as a result of high flavan-3-ol cocoa or pure epicatechin consumption
time frame: Baseline and 1 hr, 2hr, 3hr, 4hr, 6hr and 8hr after consumption
description: Plasma analysis of nitric oxide
measure: Changes in arterial augmentation index as measured by Pulse Wave Analysis
time frame: Baseline and 2 hours after consumption
description: Measured in triplicate using a SphygmoCor device at baseline and 2 hours after consumption
measure: Bioavailability of plasma epicatechin metabolites
time frame: Baseline and 1hr, 2hr, 3hr, 4hr, 6hr and 8hr after consumption
description: Plasma analysis of epicatechin metabolites will be measured up to 8 hours after consumption of high flavan-3-ol cocoa or pure epicatechin
measure: Bioavailability of urine epicatechin metabolites
time frame: 24 hour urine samples
description: Urinary epicatechin metabolites will be measured in 24-hour urine samples
arm group label: Pure Epicatechin
arm group type: Active Comparator
description: Participants will consume 100mg of epicatechin (capsule) + 70g white chocolate
arm group label: High flavan-3-ol cocoa
arm group type: Active Comparator
description: Participants will consume 70g high flavan-3-ol cocoa (100mg epicatechin) + placebo capsule
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will consume 70g white chocolate + placebo capsules
intervention type: Dietary Supplement
intervention name: Pure Epicatechin
description: Participants will consume 100mg of epicatechin (capsule) + 70g white chocolate
arm group label: Pure Epicatechin
intervention type: Dietary Supplement
intervention name: High flavan-3-ol cocoa
description: Participants will consume 70g high flavan-3-ol cocoa (100mg epicatechin) + placebo capsule
arm group label: High flavan-3-ol cocoa
intervention type: Dietary Supplement
intervention name: Placebo
description: Participants will consume 70g white chocolate + placebo capsules
arm group label: Placebo
criteria: 
gender: Male
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Peter Hollman, Dr
role: Principal Investigator
affiliation: Wageningen University
facility: 
country: Netherlands
url: http://voedingsonderzoek.wur.nl/flavo2
description: Website for the study (in dutch)
responsible party type: Sponsor