<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/NCT02264223</url>
  </required_header>
  <id_info>
    <org_study_id>KLBIO 07-10-14</org_study_id>
    <nct_id>NCT02264223</nct_id>
  </id_info>
  <brief_title>The Bioavailability of Red Clover Isoflavones</brief_title>
  <acronym>KLBIO</acronym>
  <official_title>The Effects of Processing and Matrices on Bioavailability of Red Clover Isoflavones in Healthy Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Southern Danish University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Herrens Mark A/S</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Natur Drogeriet A/S</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Future Food Innovation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Previous literature has shown that the molecular form of isoflavones (as aglycones or&#xD;
      glycosides) and food matrices can influence the bioavailability of these compounds in humans&#xD;
      and hence their efficacy. To determine the effects of processing and food matrices on the&#xD;
      bioavailability of active compounds derived from red clover the investigators will execute a&#xD;
      5 phase, cross-over design, open label, RCT using 20 healthy women aged between 18 to 40&#xD;
      years. Participants will receive 5 different formulations of red clover and bioavailability&#xD;
      will be monitored in blood plasma using LC-MS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of this study is to elucidate the effects food matrices and processing on the&#xD;
      bioavailability of active compounds on the bioavailability of red clover derived isoflavones.&#xD;
      20 healthy participants will receive red clover derived isoflavones in five different&#xD;
      formulations. The five formulations are split up into five phases:&#xD;
&#xD;
      Phase 1) Fermented extract in liquid form Phase 2) Fermented extract (freeze-dried) in&#xD;
      capsule form Phase 3) Fermented extract (freeze-dried) in tablet form Phase 4) Fermented&#xD;
      extract (concentrated) mixed in yogurt Phase 5) Un-fermented red clover in capsule or tablet&#xD;
      form The trial will last 5-6 weeks for each participant. Plasma sample collection will take&#xD;
      place both pre-and post- ingestion of a formulation, participants will receive blood tests at&#xD;
      intervals -15 min, 0 min, 2hr, 4hr, 6hr, 8hr and 12hr (on the day of ingestion) and on the&#xD;
      subsequent two mornings (24hr and 48hr) following the initiation of a phase. There will be a&#xD;
      minimum. 5 day intervals between all phases (washout periods). Isoflavones biochanin A,&#xD;
      formononetin, genistein and daidzein present in plasma will be detected using HPLC-MS for&#xD;
      each phase, thus creating a bioavailability curve that can be compared to each of the other&#xD;
      phases. The primary endpoint is to determine whether fermented extract is more bioavailable&#xD;
      than unfermented extract.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">May 2022</completion_date>
  <primary_completion_date type="Actual">May 2022</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Bioavailability of isoflavones in terms of fermented vs unfermented formulations</measure>
    <time_frame>-15min, 0hr, 2hr, 4hr, 6hr, 8hr, 12hr, 24hr, 48hr</time_frame>
    <description>As measured by iAUC plasma concentrations of isoflavones over 48 hours</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bioavailability of isoflavones in terms of matrices (tablet, capsule, yoghurt and liquid)</measure>
    <time_frame>-15min, 0hr, 2hr, 4hr, 6hr, 8hr, 12hr, 24hr, 48hr</time_frame>
    <description>As measured by iAUC plasma concentrations of isoflavones over 48 hours</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Capsule (aglycone)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>single bolus 40mg isoflavone formulation of fermented extract in freeze-dried capsule.&#xD;
Fermented red clover isoflavones in aglycone form</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tablet (aglycone)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>single bolus 40mg isoflavone aglycone formulation of fermented extract in freeze-dried tablet.&#xD;
Fermented red clover isoflavones in aglycone form</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Yoghurt (aglycone)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>single bolus 40mg isoflavone aglycone formulation of fermented extract mixed with yoghurt&#xD;
Fermented red clover isoflavones in aglycone form</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Liquid extract (aglycone)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>single bolus 40mg isoflavone aglycone formulation of fermented extract in liquid&#xD;
Fermented red clover isoflavones in aglycone form</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tablet unfermented (glycoside)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>single bolus 40mg isoflavone aglycone equivalent tablet formulation of unfermented red clover isoflavones&#xD;
Unfermented glycosides (as aglycone equivalents)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Fermented red clover isoflavones in aglycone form</intervention_name>
    <description>Fermented isoflavones in aglycone form</description>
    <arm_group_label>Capsule (aglycone)</arm_group_label>
    <arm_group_label>Liquid extract (aglycone)</arm_group_label>
    <arm_group_label>Tablet (aglycone)</arm_group_label>
    <arm_group_label>Yoghurt (aglycone)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Unfermented glycosides (as aglycone equivalents)</intervention_name>
    <description>Unfermented aglycone equivalents in glycoside form</description>
    <arm_group_label>Tablet unfermented (glycoside)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Healthy women&#xD;
&#xD;
          -  Age: 18-40 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Habitual intake of soy products, chickpeas or other supplements with a high content of&#xD;
             isoflavones&#xD;
&#xD;
          -  Hormone therapy&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Taking drugs affecting uptake&#xD;
&#xD;
          -  Participation in other clinical trials within the last 3 months&#xD;
&#xD;
          -  Severe cardiovascular, psychiatric, neurological and / or kidney disease&#xD;
&#xD;
          -  Alcohol or substance abuse&#xD;
&#xD;
          -  Acute illness&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Per B Jeppesen, Prof. PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Aarhus</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <state>Central Jutland Region</state>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>October 8, 2014</study_first_submitted>
  <study_first_submitted_qc>October 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>May 17, 2022</last_update_submitted>
  <last_update_submitted_qc>May 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Aarhus</investigator_affiliation>
    <investigator_full_name>Per Bendix Jeppesen</investigator_full_name>
    <investigator_title>Associate Prof., PhD</investigator_title>
  </responsible_party>
  <keyword>Bioavailability</keyword>
  <keyword>Isoflavones</keyword>
  <keyword>Plasma</keyword>
  <keyword>Human</keyword>
  <keyword>Processing</keyword>
  <keyword>Cross-over</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/NCT02264223
org study id: KLBIO 07-10-14
nct id: NCT02264223
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Previous literature has shown that the molecular form of isoflavones (as aglycones or
      glycosides) and food matrices can influence the bioavailability of these compounds in humans
      and hence their efficacy. To determine the effects of processing and food matrices on the
      bioavailability of active compounds derived from red clover the investigators will execute a
      5 phase, cross-over design, open label, RCT using 20 healthy women aged between 18 to 40
      years. Participants will receive 5 different formulations of red clover and bioavailability
      will be monitored in blood plasma using LC-MS.
The aim of this study is to elucidate the effects food matrices and processing on the
      bioavailability of active compounds on the bioavailability of red clover derived isoflavones.
      20 healthy participants will receive red clover derived isoflavones in five different
      formulations. The five formulations are split up into five phases:

      Phase 1) Fermented extract in liquid form Phase 2) Fermented extract (freeze-dried) in
      capsule form Phase 3) Fermented extract (freeze-dried) in tablet form Phase 4) Fermented
      extract (concentrated) mixed in yogurt Phase 5) Un-fermented red clover in capsule or tablet
      form The trial will last 5-6 weeks for each participant. Plasma sample collection will take
      place both pre-and post- ingestion of a formulation, participants will receive blood tests at
      intervals -15 min, 0 min, 2hr, 4hr, 6hr, 8hr and 12hr (on the day of ingestion) and on the
      subsequent two mornings (24hr and 48hr) following the initiation of a phase. There will be a
      minimum. 5 day intervals between all phases (washout periods). Isoflavones biochanin A,
      formononetin, genistein and daidzein present in plasma will be detected using HPLC-MS for
      each phase, thus creating a bioavailability curve that can be compared to each of the other
      phases. The primary endpoint is to determine whether fermented extract is more bioavailable
      than unfermented extract.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Bioavailability of isoflavones in terms of fermented vs unfermented formulations
time frame: -15min, 0hr, 2hr, 4hr, 6hr, 8hr, 12hr, 24hr, 48hr
description: As measured by iAUC plasma concentrations of isoflavones over 48 hours
measure: Bioavailability of isoflavones in terms of matrices (tablet, capsule, yoghurt and liquid)
time frame: -15min, 0hr, 2hr, 4hr, 6hr, 8hr, 12hr, 24hr, 48hr
description: As measured by iAUC plasma concentrations of isoflavones over 48 hours
arm group label: Capsule (aglycone)
arm group type: Active Comparator
description: single bolus 40mg isoflavone formulation of fermented extract in freeze-dried capsule.
Fermented red clover isoflavones in aglycone form
arm group label: Tablet (aglycone)
arm group type: Active Comparator
description: single bolus 40mg isoflavone aglycone formulation of fermented extract in freeze-dried tablet.
Fermented red clover isoflavones in aglycone form
arm group label: Yoghurt (aglycone)
arm group type: Active Comparator
description: single bolus 40mg isoflavone aglycone formulation of fermented extract mixed with yoghurt
Fermented red clover isoflavones in aglycone form
arm group label: Liquid extract (aglycone)
arm group type: Active Comparator
description: single bolus 40mg isoflavone aglycone formulation of fermented extract in liquid
Fermented red clover isoflavones in aglycone form
arm group label: Tablet unfermented (glycoside)
arm group type: Active Comparator
description: single bolus 40mg isoflavone aglycone equivalent tablet formulation of unfermented red clover isoflavones
Unfermented glycosides (as aglycone equivalents)
intervention type: Dietary Supplement
intervention name: Fermented red clover isoflavones in aglycone form
description: Fermented isoflavones in aglycone form
arm group label: Capsule (aglycone)
arm group label: Liquid extract (aglycone)
arm group label: Tablet (aglycone)
arm group label: Yoghurt (aglycone)
intervention type: Dietary Supplement
intervention name: Unfermented glycosides (as aglycone equivalents)
description: Unfermented aglycone equivalents in glycoside form
arm group label: Tablet unfermented (glycoside)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Per B Jeppesen, Prof. PhD
role: Principal Investigator
affiliation: University of Aarhus
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: University of Aarhus
investigator full name: Per Bendix Jeppesen
investigator title: Associate Prof., PhD