<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/NCT01691404</url>
  </required_header>
  <id_info>
    <org_study_id>NL4077208112</org_study_id>
    <nct_id>NCT01691404</nct_id>
  </id_info>
  <brief_title>Study on the Effects of Epicatechin and Quercetin Supplementation on Vascular Function and Blood Pressure (FLAVO)</brief_title>
  <official_title>Study on the Effects of Epicatechin and Quercetin Supplementation on Vascular Function and Blood Pressure in Untreated (Pre)Hypertensive Subjects</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>
      Flavonoid-rich foods such as tea and cocoa have been identified as having a blood&#xD;
      pressure-lowering effect. Part of this effect is thought to be due to the flavonoid content&#xD;
      of these foods although it is currently unknown which flavonoids play a role. Epicatechin is&#xD;
      one the major flavonoids in cocoa while quercetin is largely found in tea.&#xD;
&#xD;
      During this study the investigators plan to investigate the effects of pure epicatechin and&#xD;
      quercetin supplementation on vascular function and blood pressure in untreated&#xD;
      (prehypertensive) subjects by way of a three-armed double-blind crossover intervention.&#xD;
      Participants will sequentially consume supplements containing quercetin, epicatechin or&#xD;
      placebo for a period of 4 weeks. Before and after this 4 week period, measurements of&#xD;
      vascular function and blood pressure will be taken.&#xD;
&#xD;
      The investigators hypothesize that the supplementation of epicatechin and quercetin will&#xD;
      improve vascular function and blood pressure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      By means of a three-armed double-blind crossover intervention, the effects of pure flavonoid&#xD;
      supplementation will be investigated. The products under investigation will be epicatechin&#xD;
      and quercetin-3-glucoside. Subjects will be asked to consume either 160mg of&#xD;
      quercetin-3-glucoside, 100mg of epicatechin or a placebo capsule for a period of 4 weeks.&#xD;
      Measurements of vascular function and blood pressure will be taken before and after each&#xD;
      4-week intervention period. A 4-week washout period will be planned between each&#xD;
      intervention.&#xD;
&#xD;
      Measurements of vascular function will include flow-mediated dilation, pulse wave analysis,&#xD;
      pulse wave velocity and vasomotion as well as biomarkers of inflammation and vascular&#xD;
      function.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">March 2013</completion_date>
  <primary_completion_date type="Actual">March 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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Endothelium-dependent flow-mediated dilation as a result of epicatechin and quercetin-3-glucoside supplementation</measure>
    <time_frame>Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)</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 blood pressure as a result of epicatechin and quercetin-3-glucoside supplementation</measure>
    <time_frame>Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)</time_frame>
    <description>Office BP (Dinamap, 4 consecutive measurements with 2-min intervals)and 24-hour ABPM (Spacelab; 1x24h)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in pulse wave velocity as a result of epicatechin and quercetin supplementation</measure>
    <time_frame>Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)</time_frame>
    <description>Measured using a SphygmoCor device at baseline and the end of each intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in vasomotion as a result of epicatechin and quercetin supplementation</measure>
    <time_frame>Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)</time_frame>
    <description>Measured using a PeriFlux 5001 device at baseline and the end of each intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in biomarkers of endothelial function as a result of epicatechin and quercetin supplementation</measure>
    <time_frame>Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)</time_frame>
    <description>Plasma analysis of endothelin-1, ADMA, MCP-1, sVCAM-1, sICAM-1, sE-selectin, sTM, CRP, SAA, IL-6, IL-8, TNF-α, vWF, nitric oxide</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in peripheral blood mononuclear cell gene expression of markers of inflammation as a result of epicatechin and quercetin supplementation</measure>
    <time_frame>Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)</time_frame>
    <description>PBMC gene expression of markers of inflammation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cardiovascular parameters in plasma as a result of epicatechin and quercetin supplementation</measure>
    <time_frame>Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)</time_frame>
    <description>Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, insulin and glucose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in pulse wave analysis as a result of epicatechin and quercetin supplementation</measure>
    <time_frame>Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)</time_frame>
    <description>Measured using a SphygmoCor device at baseline and the end of each intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Baseline and every 2 weeks thereafter (weeks 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20)</time_frame>
    <description>During the study subjects will be asked to maintain a diary in which they can report any adverse events they may have a result of the supplements. Diaries will be checked every 2 weeks. Study subjects will also be asked to contact the research team if they experience repeated adverse events.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Hypertension</condition>
  <condition>Endothelial Dysfunction</condition>
  <arm_group>
    <arm_group_label>Epicatechin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will be asked to consume supplements containing 100mg of epicatechin daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Quercetin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will be asked to consume supplements containing 160mg of quercetin-3-glucoside daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will be asked to consume capsules containing a placebo (cellulose) daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Epicatechin</intervention_name>
    <description>Subjects will be asked to consume supplements containing 100mg of epicatechin daily</description>
    <arm_group_label>Epicatechin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Quercetin</intervention_name>
    <description>Subjects will be asked to consume 160mg of quercetin-3-glucoside daily</description>
    <arm_group_label>Quercetin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects will be asked to consume capsules containing placebo (cellulose) daily</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Systolic Blood Pressure between 125 and 160 mmHg&#xD;
&#xD;
          -  Age between 30 and 80 years&#xD;
&#xD;
          -  BMI &gt; 20 and ≤ 40&#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 diabetes mellitus&#xD;
&#xD;
          -  Fasting laboratory parameters within normal range: complete blood count (RBC, WBC,&#xD;
             PLT, HB, HT), renal function (serum creatinine, urea), liver function (ALAT, ASAT,&#xD;
             ɣ-GT), and serum glucose.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Body mass index &gt; 40 and ≤20&#xD;
&#xD;
          -  Secondary hypertension&#xD;
&#xD;
          -  Weight loss or weight gain of 5 kg or more during the last 2 months&#xD;
&#xD;
          -  Usage of non-steroidal anti-inflammatory drugs (acetylsalicylic acid, ibuprofen,&#xD;
             naproxen) and not able or willing to stop taking them from at least 4 weeks prior to&#xD;
             the study&#xD;
&#xD;
          -  Usage of cholesterol-lowering medication&#xD;
&#xD;
          -  Daily usage of corticosteroids&#xD;
&#xD;
          -  Medical treatment that may affect blood pressure and not able (or willing) to stop&#xD;
&#xD;
          -  Taking nutritional supplements and unwilling to discontinue&#xD;
&#xD;
          -  Lactating, pregnant or intention to become pregnant during study&#xD;
&#xD;
          -  Reported dietary habits, medically prescribed diet, slimming diet&#xD;
&#xD;
          -  Reported average alcohol consumption &gt; 2 glasses/d (men) or &gt;1 glass/d (women)&#xD;
&#xD;
          -  Problems with consuming the supplements or following the study guidelines&#xD;
&#xD;
          -  Unwilling to undergo home or office blood pressure measurements&#xD;
&#xD;
          -  Recent blood donation i.e. 1 month (male subjects) or 2 months (female subjects) prior&#xD;
             to the study and planned donation during the study period&#xD;
&#xD;
          -  Reported intense sporting activities &gt; 10 h/w&#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;
          -  Clinical disorders that could interfere with the intervention&#xD;
&#xD;
          -  Unable to comply with the study procedure (e.g. holidays, urine collection, blood&#xD;
             sampling)&#xD;
&#xD;
          -  Smokers&#xD;
&#xD;
          -  Difficulty imaging brachial artery by ultrasonography&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter Hollman, PhD</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/flavo</url>
    <description>Website for the study (in dutch)</description>
  </link>
  <link>
    <url>http://www.hne.wur.nl/UK</url>
    <description>Website of Division of Human Nutrition, Wageningen University, The Netherlands</description>
  </link>
  <verification_date>November 2012</verification_date>
  <study_first_submitted>September 12, 2012</study_first_submitted>
  <study_first_submitted_qc>September 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 24, 2012</study_first_posted>
  <last_update_submitted>April 22, 2013</last_update_submitted>
  <last_update_submitted_qc>April 22, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 23, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Flavonoids</keyword>
  <keyword>Quercetin</keyword>
  <keyword>Epicatechin</keyword>
  <keyword>Vascular function</keyword>
  <keyword>Blood pressure</keyword>
  <keyword>Endothelial function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Quercetin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01691404
org study id: NL4077208112
nct id: NCT01691404
lead sponsor: 
collaborator: 
has dmc: No
Flavonoid-rich foods such as tea and cocoa have been identified as having a blood
      pressure-lowering effect. Part of this effect is thought to be due to the flavonoid content
      of these foods although it is currently unknown which flavonoids play a role. Epicatechin is
      one the major flavonoids in cocoa while quercetin is largely found in tea.

      During this study the investigators plan to investigate the effects of pure epicatechin and
      quercetin supplementation on vascular function and blood pressure in untreated
      (prehypertensive) subjects by way of a three-armed double-blind crossover intervention.
      Participants will sequentially consume supplements containing quercetin, epicatechin or
      placebo for a period of 4 weeks. Before and after this 4 week period, measurements of
      vascular function and blood pressure will be taken.

      The investigators hypothesize that the supplementation of epicatechin and quercetin will
      improve vascular function and blood pressure.
By means of a three-armed double-blind crossover intervention, the effects of pure flavonoid
      supplementation will be investigated. The products under investigation will be epicatechin
      and quercetin-3-glucoside. Subjects will be asked to consume either 160mg of
      quercetin-3-glucoside, 100mg of epicatechin or a placebo capsule for a period of 4 weeks.
      Measurements of vascular function and blood pressure will be taken before and after each
      4-week intervention period. A 4-week washout period will be planned between each
      intervention.

      Measurements of vascular function will include flow-mediated dilation, pulse wave analysis,
      pulse wave velocity and vasomotion as well as biomarkers of inflammation and vascular
      function.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in Endothelium-dependent flow-mediated dilation as a result of epicatechin and quercetin-3-glucoside supplementation
time frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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 blood pressure as a result of epicatechin and quercetin-3-glucoside supplementation
time frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
description: Office BP (Dinamap, 4 consecutive measurements with 2-min intervals)and 24-hour ABPM (Spacelab; 1x24h)
measure: Change in pulse wave velocity as a result of epicatechin and quercetin supplementation
time frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
description: Measured using a SphygmoCor device at baseline and the end of each intervention
measure: Change in vasomotion as a result of epicatechin and quercetin supplementation
time frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
description: Measured using a PeriFlux 5001 device at baseline and the end of each intervention.
measure: Changes in biomarkers of endothelial function as a result of epicatechin and quercetin supplementation
time frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
description: Plasma analysis of endothelin-1, ADMA, MCP-1, sVCAM-1, sICAM-1, sE-selectin, sTM, CRP, SAA, IL-6, IL-8, TNF-α, vWF, nitric oxide
measure: Changes in peripheral blood mononuclear cell gene expression of markers of inflammation as a result of epicatechin and quercetin supplementation
time frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
description: PBMC gene expression of markers of inflammation
measure: Change in cardiovascular parameters in plasma as a result of epicatechin and quercetin supplementation
time frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
description: Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, insulin and glucose
measure: Changes in pulse wave analysis as a result of epicatechin and quercetin supplementation
time frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
description: Measured using a SphygmoCor device at baseline and the end of each intervention
measure: Adverse events
time frame: Baseline and every 2 weeks thereafter (weeks 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20)
description: During the study subjects will be asked to maintain a diary in which they can report any adverse events they may have a result of the supplements. Diaries will be checked every 2 weeks. Study subjects will also be asked to contact the research team if they experience repeated adverse events.
arm group label: Epicatechin
arm group type: Active Comparator
description: Subjects will be asked to consume supplements containing 100mg of epicatechin daily
arm group label: Quercetin
arm group type: Active Comparator
description: Subjects will be asked to consume supplements containing 160mg of quercetin-3-glucoside daily
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects will be asked to consume capsules containing a placebo (cellulose) daily
intervention type: Dietary Supplement
intervention name: Epicatechin
description: Subjects will be asked to consume supplements containing 100mg of epicatechin daily
arm group label: Epicatechin
intervention type: Dietary Supplement
intervention name: Quercetin
description: Subjects will be asked to consume 160mg of quercetin-3-glucoside daily
arm group label: Quercetin
intervention type: Dietary Supplement
intervention name: Placebo
description: Subjects will be asked to consume capsules containing placebo (cellulose) daily
arm group label: Placebo
criteria: 
gender: All
minimum age: 30 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Peter Hollman, PhD
role: Principal Investigator
affiliation: Wageningen University
facility: 
country: Netherlands
url: http://voedingsonderzoek.wur.nl/flavo
description: Website for the study (in dutch)
url: http://www.hne.wur.nl/UK
description: Website of Division of Human Nutrition, Wageningen University, The Netherlands
responsible party type: Sponsor
mesh term: Hypertension
mesh term: Quercetin