<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/NCT01690676</url>
  </required_header>
  <id_info>
    <org_study_id>Epi2012</org_study_id>
    <nct_id>NCT01690676</nct_id>
  </id_info>
  <brief_title>Effect of an Apple Polyphenol Extract on Brachial Artery Flow-mediated Vasodilatory Function</brief_title>
  <official_title>The Effect of an Apple Polyphenol Extract Rich in Epicatechin and Flavan-3-ol Oligomers (Evesse™ EPC) on Brachial Artery Flow-mediated Vasodilatory Function (FMD)in Volunteer Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Danisco</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Turku</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>4Pharma Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Danisco</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Effect of apple polyphenols on FMD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of this single centre, repeated-dose, double-blind, placebo-controlled, crossover&#xD;
      study is to test the hypothesis that an orally ingested apple polyphenol extract rich in&#xD;
      epicatechin and flavan-3-ol oligomers improves brachial artery endothelium-dependent&#xD;
      vasodilation function (FMD) in volunteer subjects with borderline hypertension. FMD and&#xD;
      endothelium-independent nitrate-mediated vasodilatation (NMD) of the left brachial artery&#xD;
      will be investigated with ultrasonography at the start and end of both treatment periods.&#xD;
      Biomarkers of vascular function and epicatechin (and metabolite) concentrations will be&#xD;
      determined from blood samples taken at the start and end of both treatment periods. Diet&#xD;
      diary data will be collected for the evaluation of the possible effects of diet on the study&#xD;
      results. Adverse events data will be collected throughout the study. Safety laboratory&#xD;
      determinations will be performed at the last visit of both treatment periods.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">May 2013</completion_date>
  <primary_completion_date type="Actual">May 2013</primary_completion_date>
  <phase>Phase 2</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>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Brachial flow-mediated dilation test (FMD)</measure>
    <time_frame>At first visits of both periods baseline FMD will be recorded followed by FMD recording 1.5 hours after first dose. After 4 weeks intervention, at last visits of both periods FMD will be recorded, last dose will be taken and FMD recorded 1.5 hours after.</time_frame>
    <description>ultrasonography, FMDmax%</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Nitrate-mediated vasodilatation response (NMD)</measure>
    <time_frame>At the first and last visits of both periods, approximately 10 minutes after FMD.</time_frame>
    <description>ultrasonography, NMDmax%</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Circulating biomarkers of vascular function</measure>
    <time_frame>Once at the first visit of both periods and once at the last visit of both periods. Blood sampling prior to the morning dose and appr. 2 h thereafter</time_frame>
    <description>depends on the biomarker</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BP</measure>
    <time_frame>Once at the first visit of both periods and once at the last visit of both periods. Blood pressure will be recorded twice prior to the morning dose.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma epicatechin concentration</measure>
    <time_frame>At the first visit of both periods and at the last visit of both periods. Blood sampling prior to the morning dose and appr. 2 h thereafter</time_frame>
    <description>HPLC</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">57</enrollment>
  <condition>Borderline Hypertension</condition>
  <arm_group>
    <arm_group_label>Epicatechin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The subjects will receive the study product and corresponding placebo once a day for 4 weeks in randomised order. There will be a four to five-weeks wash-out between the treatment periods.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Microcrystalline cellulose</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The subjects will receive the study product and corresponding placebo once a day for 4 weeks in randomised order. There will be a four to five-weeks wash-out between the treatment periods.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Epicatechin</intervention_name>
    <arm_group_label>Epicatechin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Microcrystalline cellulose</intervention_name>
    <arm_group_label>Microcrystalline cellulose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Borderline hypertension&#xD;
&#xD;
          -  Otherwise healthy&#xD;
&#xD;
          -  Aged 40-65 years (inclusive)&#xD;
&#xD;
          -  Not consuming high amounts (over 20 mg daily) of flavonoids&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  BMI &gt;32 kg/m2&#xD;
&#xD;
          -  Total serum cholesterol ≥ 8 mmol/l&#xD;
&#xD;
          -  Any abnormal safety laboratory parameter or abnormal finding in ECG evaluated to be&#xD;
             clinically significant&#xD;
&#xD;
          -  Coronary artery disease&#xD;
&#xD;
          -  Pregnancy or lactating&#xD;
&#xD;
          -  Alcohol abuse as evaluated by medical history&#xD;
&#xD;
          -  Regular smoking/using nicotine products&#xD;
&#xD;
          -  Diabetes mellitus&#xD;
&#xD;
          -  Apple allergy&#xD;
&#xD;
          -  Use of lipid lowering medications&#xD;
&#xD;
          -  Regular use of any medication that is known or believed to affect endothelial function&#xD;
             or blood vessel constriction&#xD;
&#xD;
          -  Any other condition or medication that in the opinion of the investigator would&#xD;
             interfere with the evaluation of the study results or constitute a health risk for the&#xD;
             subject&#xD;
&#xD;
          -  High consumption of vitamin products, herbal remedies or products containing&#xD;
             flavonoids&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kirsti Tiihonen, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Danisco</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Olli Raitakari, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Turku, Turku, Finland, The Research Centre of Applied and Preventive Cardiovascular Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pia Salo, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Turku, Turku, Finland, The Research Centre of Applied and Preventive Cardiovascular Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anne Lithonius</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clinical Research Services Turku</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mika Scheinin, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Clinical Research Services Turku</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jari Turunen, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>4Pharma Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Turku</name>
      <address>
        <city>Turku</city>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Finland</country>
  </location_countries>
  <verification_date>April 2014</verification_date>
  <study_first_submitted>September 14, 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 7, 2014</last_update_submitted>
  <last_update_submitted_qc>April 7, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 8, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>FMD</keyword>
  <keyword>epicatechin</keyword>
  <keyword>apple polyphenol</keyword>
  <keyword>borderline hypertension</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</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/NCT01690676
org study id: Epi2012
nct id: NCT01690676
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Effect of apple polyphenols on FMD.
The aim of this single centre, repeated-dose, double-blind, placebo-controlled, crossover
      study is to test the hypothesis that an orally ingested apple polyphenol extract rich in
      epicatechin and flavan-3-ol oligomers improves brachial artery endothelium-dependent
      vasodilation function (FMD) in volunteer subjects with borderline hypertension. FMD and
      endothelium-independent nitrate-mediated vasodilatation (NMD) of the left brachial artery
      will be investigated with ultrasonography at the start and end of both treatment periods.
      Biomarkers of vascular function and epicatechin (and metabolite) concentrations will be
      determined from blood samples taken at the start and end of both treatment periods. Diet
      diary data will be collected for the evaluation of the possible effects of diet on the study
      results. Adverse events data will be collected throughout the study. Safety laboratory
      determinations will be performed at the last visit of both treatment periods.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Supportive Care
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Brachial flow-mediated dilation test (FMD)
time frame: At first visits of both periods baseline FMD will be recorded followed by FMD recording 1.5 hours after first dose. After 4 weeks intervention, at last visits of both periods FMD will be recorded, last dose will be taken and FMD recorded 1.5 hours after.
description: ultrasonography, FMDmax%
measure: Nitrate-mediated vasodilatation response (NMD)
time frame: At the first and last visits of both periods, approximately 10 minutes after FMD.
description: ultrasonography, NMDmax%
measure: Circulating biomarkers of vascular function
time frame: Once at the first visit of both periods and once at the last visit of both periods. Blood sampling prior to the morning dose and appr. 2 h thereafter
description: depends on the biomarker
measure: BP
time frame: Once at the first visit of both periods and once at the last visit of both periods. Blood pressure will be recorded twice prior to the morning dose.
measure: Plasma epicatechin concentration
time frame: At the first visit of both periods and at the last visit of both periods. Blood sampling prior to the morning dose and appr. 2 h thereafter
description: HPLC
arm group label: Epicatechin
arm group type: Active Comparator
description: The subjects will receive the study product and corresponding placebo once a day for 4 weeks in randomised order. There will be a four to five-weeks wash-out between the treatment periods.
arm group label: Microcrystalline cellulose
arm group type: Placebo Comparator
description: The subjects will receive the study product and corresponding placebo once a day for 4 weeks in randomised order. There will be a four to five-weeks wash-out between the treatment periods.
intervention type: Dietary Supplement
intervention name: Epicatechin
arm group label: Epicatechin
intervention type: Dietary Supplement
intervention name: Microcrystalline cellulose
arm group label: Microcrystalline cellulose
criteria: 
gender: All
minimum age: 40 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kirsti Tiihonen, PhD
role: Study Director
affiliation: Danisco
last name: Olli Raitakari, MD
role: Principal Investigator
affiliation: University of Turku, Turku, Finland, The Research Centre of Applied and Preventive Cardiovascular Medicine
last name: Pia Salo, MD, PhD
role: Principal Investigator
affiliation: University of Turku, Turku, Finland, The Research Centre of Applied and Preventive Cardiovascular Medicine
last name: Anne Lithonius
role: Principal Investigator
affiliation: Clinical Research Services Turku
last name: Mika Scheinin, MD, PhD
role: Study Chair
affiliation: Clinical Research Services Turku
last name: Jari Turunen, MSc
role: Principal Investigator
affiliation: 4Pharma Ltd.
facility: 
country: Finland
responsible party type: Sponsor
mesh term: Hypertension