<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/NCT03030716</url>
  </required_header>
  <id_info>
    <org_study_id>PRPTanninTrial</org_study_id>
    <nct_id>NCT03030716</nct_id>
  </id_info>
  <brief_title>Multiple Daily Condensed Tannin Supplementation and Iron Bioavailability: The Tannin Dose Response Trial</brief_title>
  <official_title>Long-term, Multiple Daily Condensed Tannin Supplementation in Increasing Concentrations Does Not Affect Iron Status or Bioavailability: Results From the Tannin-dose Response Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kansas State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>United States Department of Agriculture Foreign Agricultural Service</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Kansas State University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Tannins are known to inhibit iron absorption through formation of insoluble tannin-mineral&#xD;
      complexes, and have thus been termed 'antinutritional.' Despite this, there is evidence that&#xD;
      adaptation to similar antinutritional factors is possible when consumed over time.&#xD;
      Limitations in current studies include short (single meal) duration, and use of incongruent&#xD;
      tannin types from the condensed tannins that are commonly consumed. If adaptation to tannins&#xD;
      does happen, it may be due to salivary proline-rich proteins, which have been found to be&#xD;
      protective of iron status in animal models. The primary objectives of this study are: 1) To&#xD;
      determine whether condensed tannins impact iron bioavailability or status when consumed in&#xD;
      multi-dose, multiple daily supplements and 2) to test whether salivary protein production may&#xD;
      impact iron bioavailability with tannin supplementation. Secondary objectives included&#xD;
      assessment of the reliability of astringency as a measure of salivary protein production and&#xD;
      iron absorption.&#xD;
&#xD;
      The study has been conducted in an iron absorption study of 11 women, aged 18-35 years old,&#xD;
      to determine iron bioavailability with supplementation of 0.03, 0.25, and 1.5 g 95%&#xD;
      proanthocyanidin rich grape seed extract before and after regular, three times daily&#xD;
      supplementation for four weeks. Each participant consumed all three concentrations of&#xD;
      supplement over the 26-week study, with a two-week washout between interventions. Direct iron&#xD;
      absorption was measured using area under the curve. Iron status was measured by changes in&#xD;
      hemoglobin and ferritin, and was adjusted by participant c-reactive protein levels. Salivary&#xD;
      samples were collected before and after supplement consumption during meal challenges, and&#xD;
      analyzed on HPLC. Astringency testing was conducted at the end of each meal challenge. Iron&#xD;
      absorption and status markers were analyzed by ANOVA, and mixed-modeling followed by pairwise&#xD;
      comparison by least significant differences. Pearson's correlations were used to correlated&#xD;
      salivary proteins and astringency with iron bioavailability.&#xD;
&#xD;
      The present study will provide important information regarding the approximate influence of&#xD;
      condensed tannin consumption on iron bioavailability and storage over time, at different&#xD;
      doses. Data will also help to delineate possible physiological mechanisms underlying tannin&#xD;
      adaptation and possible ways to detect individuals who better adapt than others.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 25, 2016</start_date>
  <completion_date type="Actual">December 10, 2016</completion_date>
  <primary_completion_date type="Actual">December 10, 2016</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in baseline to endline area under the curve after meal challenge at weeks 0 and 4 of each intervention</measure>
    <time_frame>Baseline and 4 weeks</time_frame>
    <description>Change in area under the curve will be measured after administration of test meal including ferrous sulfate and condensed tannin supplementation at weeks 0 and 4</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in baseline to endline hemoglobin and serum ferritin at weeks 0 and 4 of each intervention</measure>
    <time_frame>Baseline and 4 weeks</time_frame>
    <description>Change in ferritin and hemoglobin will be measured before administration of test meals at weeks 0 and 4</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in salivary proteins at weeks 0 and 4 of each intervention</measure>
    <time_frame>Baseline and 4 weeks</time_frame>
    <description>HPLC determination of salivary proteins will be analyzed from saliva collected before and after test meals at weeks 0 and 4 of each intervention</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Iron Deficiency Anemia</condition>
  <condition>Iron-deficiency</condition>
  <arm_group>
    <arm_group_label>0.03 mg 95% condensed proanthocyanidin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.03 g 95% condensed proanthocyanidins from grape seed extract at week 0 0.03 g 95% condensed proanthocyanidins from grape seed extract at week 4</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.25 g 95% condensed proanthocyanidin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.25 g 95% condensed proanthocyanidins from grape seed extract at week 0 0.25 g 95% condensed proanthocyanidins from grape seed extract at week 4</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1.5 g 95% condensed proanthocyanidin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1.5 g 95% condensed proanthocyanidins from grape seed extract at week 0 1.5 g 95% condensed proanthocyanidins from grape seed extract at week 4</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>95% condensed proanthocyanidins from grape seed extract</intervention_name>
    <description>0.03, 0.25, and 1.5 g 95% condensed proanthocyanidins from grape seed extract consumed three times daily for 4 weeks each</description>
    <arm_group_label>0.03 mg 95% condensed proanthocyanidin</arm_group_label>
    <arm_group_label>0.25 g 95% condensed proanthocyanidin</arm_group_label>
    <arm_group_label>1.5 g 95% condensed proanthocyanidin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female, 18-35 years old&#xD;
&#xD;
          -  Non-obese BMI (18-29.9)&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Oral disease&#xD;
&#xD;
          -  Gastrointestinal disease&#xD;
&#xD;
          -  Tobacco user&#xD;
&#xD;
          -  Heavy alcohol user&#xD;
&#xD;
          -  Pregnancy (assessed by pregnancy test)&#xD;
&#xD;
          -  Lactation&#xD;
&#xD;
          -  Medications affecting iron bioavailability&#xD;
&#xD;
          -  Vitamin or mineral supplementation (other than vitamin B12)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Brian L Lindshield, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kansas State University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Physical Activity and Nutrition Research Consortium</name>
      <address>
        <city>Manhattan</city>
        <state>Kansas</state>
        <zip>66502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 23, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>January 24, 2017</last_update_submitted>
  <last_update_submitted_qc>January 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Kansas State University</investigator_affiliation>
    <investigator_full_name>Brian Lindshield</investigator_full_name>
    <investigator_title>Ph.D., Associate Professor</investigator_title>
  </responsible_party>
  <keyword>antinutrients</keyword>
  <keyword>tannins</keyword>
  <keyword>proanthocyanidins</keyword>
  <keyword>salivary proline-rich proteins</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Iron-Deficiency</mesh_term>
    <mesh_term>Iron Deficiencies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Proanthocyanidin</mesh_term>
    <mesh_term>Grape Seed Extract</mesh_term>
    <mesh_term>Procyanidin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03030716
org study id: PRPTanninTrial
nct id: NCT03030716
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Tannins are known to inhibit iron absorption through formation of insoluble tannin-mineral
      complexes, and have thus been termed 'antinutritional.' Despite this, there is evidence that
      adaptation to similar antinutritional factors is possible when consumed over time.
      Limitations in current studies include short (single meal) duration, and use of incongruent
      tannin types from the condensed tannins that are commonly consumed. If adaptation to tannins
      does happen, it may be due to salivary proline-rich proteins, which have been found to be
      protective of iron status in animal models. The primary objectives of this study are: 1) To
      determine whether condensed tannins impact iron bioavailability or status when consumed in
      multi-dose, multiple daily supplements and 2) to test whether salivary protein production may
      impact iron bioavailability with tannin supplementation. Secondary objectives included
      assessment of the reliability of astringency as a measure of salivary protein production and
      iron absorption.

      The study has been conducted in an iron absorption study of 11 women, aged 18-35 years old,
      to determine iron bioavailability with supplementation of 0.03, 0.25, and 1.5 g 95%
      proanthocyanidin rich grape seed extract before and after regular, three times daily
      supplementation for four weeks. Each participant consumed all three concentrations of
      supplement over the 26-week study, with a two-week washout between interventions. Direct iron
      absorption was measured using area under the curve. Iron status was measured by changes in
      hemoglobin and ferritin, and was adjusted by participant c-reactive protein levels. Salivary
      samples were collected before and after supplement consumption during meal challenges, and
      analyzed on HPLC. Astringency testing was conducted at the end of each meal challenge. Iron
      absorption and status markers were analyzed by ANOVA, and mixed-modeling followed by pairwise
      comparison by least significant differences. Pearson's correlations were used to correlated
      salivary proteins and astringency with iron bioavailability.

      The present study will provide important information regarding the approximate influence of
      condensed tannin consumption on iron bioavailability and storage over time, at different
      doses. Data will also help to delineate possible physiological mechanisms underlying tannin
      adaptation and possible ways to detect individuals who better adapt than others.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in baseline to endline area under the curve after meal challenge at weeks 0 and 4 of each intervention
time frame: Baseline and 4 weeks
description: Change in area under the curve will be measured after administration of test meal including ferrous sulfate and condensed tannin supplementation at weeks 0 and 4
measure: Change in baseline to endline hemoglobin and serum ferritin at weeks 0 and 4 of each intervention
time frame: Baseline and 4 weeks
description: Change in ferritin and hemoglobin will be measured before administration of test meals at weeks 0 and 4
measure: Change in salivary proteins at weeks 0 and 4 of each intervention
time frame: Baseline and 4 weeks
description: HPLC determination of salivary proteins will be analyzed from saliva collected before and after test meals at weeks 0 and 4 of each intervention
arm group label: 0.03 mg 95% condensed proanthocyanidin
arm group type: Experimental
description: 0.03 g 95% condensed proanthocyanidins from grape seed extract at week 0 0.03 g 95% condensed proanthocyanidins from grape seed extract at week 4
arm group label: 0.25 g 95% condensed proanthocyanidin
arm group type: Experimental
description: 0.25 g 95% condensed proanthocyanidins from grape seed extract at week 0 0.25 g 95% condensed proanthocyanidins from grape seed extract at week 4
arm group label: 1.5 g 95% condensed proanthocyanidin
arm group type: Experimental
description: 1.5 g 95% condensed proanthocyanidins from grape seed extract at week 0 1.5 g 95% condensed proanthocyanidins from grape seed extract at week 4
intervention type: Dietary Supplement
intervention name: 95% condensed proanthocyanidins from grape seed extract
description: 0.03, 0.25, and 1.5 g 95% condensed proanthocyanidins from grape seed extract consumed three times daily for 4 weeks each
arm group label: 0.03 mg 95% condensed proanthocyanidin
arm group label: 0.25 g 95% condensed proanthocyanidin
arm group label: 1.5 g 95% condensed proanthocyanidin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Brian L Lindshield, Ph.D.
role: Principal Investigator
affiliation: Kansas State University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Kansas State University
investigator full name: Brian Lindshield
investigator title: Ph.D., Associate Professor
mesh term: Anemia, Iron-Deficiency
mesh term: Iron Deficiencies
mesh term: Proanthocyanidin
mesh term: Grape Seed Extract
mesh term: Procyanidin
sharing ipd: No