<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/NCT02228291</url>
  </required_header>
  <id_info>
    <org_study_id>13-3-019</org_study_id>
    <nct_id>NCT02228291</nct_id>
  </id_info>
  <brief_title>The Effect of Citric Flavonoid on Endothelial Function</brief_title>
  <official_title>The Effect of Citric Flavonoid Administration on Endothelial Function and Gut Barrier Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maastricht University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized, double-blind, placebo-controlled, parallel study aims to determine the&#xD;
      6-week and acute effects of daily administration of a citrus flavonoid on cardiovascular and&#xD;
      intestinal health as assessed by investigation of endothelial function, blood pressure and&#xD;
      heart rate, glucose/insulin metabolism, lipid profile and gut barrier function in overweigh&#xD;
      subjects.&#xD;
&#xD;
      Futhermore we aim to relate the specific intestinal (microbial) metabolism with final serum&#xD;
      levels of specific metabolites of the study product.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Endothelial function</measure>
    <time_frame>6 weeks</time_frame>
    <description>The primary objective of this study is to evaluate the efficacy on endothelial function, as assessed by flow mediated dilatation (FMD) measurements, after 6 weeks of administration of study product.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Endothelial function</measure>
    <time_frame>6 weeks</time_frame>
    <description>The second secondary objective of this study is to determine the 6-week effect on plasma biomarkers of endothelial dysfunction and low-grade inflammation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure &amp; heart rate</measure>
    <time_frame>6 weeks</time_frame>
    <description>The third objective of this study is to assess the 6-week effect on blood pressure and heart rate by measuring systolic and diastolic blood pressure and heart rate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose / insulin metabolism</measure>
    <time_frame>6 weeks</time_frame>
    <description>The fourth secondary objective of this study is to determine the 6-week effect on glucose / insulin metabolism by blood measurements.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>6 weeks</time_frame>
    <description>The fourth secondary objective of this study is to determine the 6-week effect on lipid profile by blood measurements.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gut barrier function</measure>
    <time_frame>6 weeks</time_frame>
    <description>The fifth secondary objective of this study is to assess the acute and 6-week effect on gut barrier function by measuring plasma and fecal endotoxin (LPS) and zonulin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gut barrier function</measure>
    <time_frame>6 weeks</time_frame>
    <description>The sixth secondary objective of this study is to assess the 6-week effect of on gut barrier function by performing a gut sugar permeability test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Colonic inflammation</measure>
    <time_frame>6 weeks</time_frame>
    <description>The seventh secondary objective of this study is to assess the 6-week effect on colonic inflammation, by measuring fecal calprotectin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bioavailability and metabolism</measure>
    <time_frame>5 days</time_frame>
    <description>The eight secondary objective of this study is to enlarge the understanding of the bioavailability and metabolism of this study product in human beings, by relating specific intestinal (microbial) metabolism with serum levels of its metabolites.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">68</enrollment>
  <condition>Obesity</condition>
  <condition>Overweight</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Cellulose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Citric flavonoid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Citric flavonoid</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Capsule containing citrus flavonoid</intervention_name>
    <arm_group_label>Citric flavonoid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Overweight men/women (BMI 25-35 kg/m2)&#xD;
&#xD;
          -  Healthy individuals&#xD;
&#xD;
          -  Age between 18 and 70 years&#xD;
&#xD;
          -  Fasting glucose &lt; 7.0 mmol/L&#xD;
&#xD;
          -  Normal HbA1c (4.4 to 6.2%)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Type 2 diabetes mellitus (defined as fasting plasma glucose ≥ 7.0 mmol/L)&#xD;
&#xD;
          -  Gastroenterological diseases or abdominal surgery&#xD;
&#xD;
          -  Cardiovascular diseases, cancer, liver or kidney malfunction, thyroid disorders,&#xD;
             disease with a life expectancy shorter than 5 years&#xD;
&#xD;
          -  Self-admitted HIV-positive status&#xD;
&#xD;
          -  Abuse of products; alcohol (&gt; 20 alcoholic consumptions per week) and drugs&#xD;
&#xD;
          -  Smoking&#xD;
&#xD;
          -  Plans to lose weight or following a hypocaloric diet during the study period&#xD;
&#xD;
          -  Weight gain or loss &gt; 3 kg in previous 3 months&#xD;
&#xD;
          -  Use of medication interfering with endpoints&#xD;
&#xD;
          -  Intake of antihypertensive medication, statins, corticosteroids, NSAIDs, ciclosporin&#xD;
             A, rifampicin are strictly forbidden&#xD;
&#xD;
          -  Use of antioxidants, minerals and vitamin supplements available in pharmacies,&#xD;
             drugstores, food markets or in alternative medicine&#xD;
&#xD;
          -  Hormone replacement therapy (women)&#xD;
&#xD;
          -  Use of antibiotics in the 90 days prior to the start of study&#xD;
&#xD;
          -  Administration of investigational drugs or participation in any scientific&#xD;
             intervention study which may interfere with this study (to be decided by the principle&#xD;
             investigator) in the 180 days prior to the study&#xD;
&#xD;
          -  Known pregnancy (assessed by a pregnancy test before start of study), lactation&#xD;
&#xD;
          -  Blood donation within 3 months before study period&#xD;
&#xD;
          -  Failure to comply prohibited intake of hesperidin containing food products during&#xD;
             study period and prohibited intake of food products that are able to influence the FMD&#xD;
             measurements one day prior to test days.&#xD;
&#xD;
          -  History of any side effects towards the intake of flavonoids or citrus fruits&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>A.A.M. Masclee, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Internal Medicine, Division of Gastroenterology-Hepatology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maastricht University Medical Center</name>
      <address>
        <city>Maastricht</city>
        <state>Limburg</state>
        <zip>6229HX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>August 27, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2014</study_first_posted>
  <last_update_submitted>July 6, 2015</last_update_submitted>
  <last_update_submitted_qc>July 6, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 8, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Maastricht University Medical Center</investigator_affiliation>
    <investigator_full_name>Bouke Salden</investigator_full_name>
    <investigator_title>Coordinating Investigator</investigator_title>
  </responsible_party>
  <keyword>Polyphenols</keyword>
  <keyword>Endothelial function</keyword>
  <keyword>Gut barrier function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Overweight</mesh_term>
  </condition_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/NCT02228291
org study id: 13-3-019
nct id: NCT02228291
lead sponsor: 
has dmc: Yes
This randomized, double-blind, placebo-controlled, parallel study aims to determine the
      6-week and acute effects of daily administration of a citrus flavonoid on cardiovascular and
      intestinal health as assessed by investigation of endothelial function, blood pressure and
      heart rate, glucose/insulin metabolism, lipid profile and gut barrier function in overweigh
      subjects.

      Futhermore we aim to relate the specific intestinal (microbial) metabolism with final serum
      levels of specific metabolites of the study product.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Endothelial function
time frame: 6 weeks
description: The primary objective of this study is to evaluate the efficacy on endothelial function, as assessed by flow mediated dilatation (FMD) measurements, after 6 weeks of administration of study product.
measure: Endothelial function
time frame: 6 weeks
description: The second secondary objective of this study is to determine the 6-week effect on plasma biomarkers of endothelial dysfunction and low-grade inflammation.
measure: Blood pressure & heart rate
time frame: 6 weeks
description: The third objective of this study is to assess the 6-week effect on blood pressure and heart rate by measuring systolic and diastolic blood pressure and heart rate.
measure: Glucose / insulin metabolism
time frame: 6 weeks
description: The fourth secondary objective of this study is to determine the 6-week effect on glucose / insulin metabolism by blood measurements.
measure: Lipid profile
time frame: 6 weeks
description: The fourth secondary objective of this study is to determine the 6-week effect on lipid profile by blood measurements.
measure: Gut barrier function
time frame: 6 weeks
description: The fifth secondary objective of this study is to assess the acute and 6-week effect on gut barrier function by measuring plasma and fecal endotoxin (LPS) and zonulin.
measure: Gut barrier function
time frame: 6 weeks
description: The sixth secondary objective of this study is to assess the 6-week effect of on gut barrier function by performing a gut sugar permeability test.
measure: Colonic inflammation
time frame: 6 weeks
description: The seventh secondary objective of this study is to assess the 6-week effect on colonic inflammation, by measuring fecal calprotectin.
measure: Bioavailability and metabolism
time frame: 5 days
description: The eight secondary objective of this study is to enlarge the understanding of the bioavailability and metabolism of this study product in human beings, by relating specific intestinal (microbial) metabolism with serum levels of its metabolites.
arm group label: Placebo
arm group type: Placebo Comparator
description: Cellulose
arm group label: Citric flavonoid
arm group type: Experimental
description: Citric flavonoid
intervention type: Dietary Supplement
intervention name: Capsule containing citrus flavonoid
arm group label: Citric flavonoid
intervention type: Dietary Supplement
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: A.A.M. Masclee, MD, PhD
role: Principal Investigator
affiliation: Department of Internal Medicine, Division of Gastroenterology-Hepatology
facility: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Maastricht University Medical Center
investigator full name: Bouke Salden
investigator title: Coordinating Investigator
mesh term: Overweight