<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/NCT03030703</url>
  </required_header>
  <id_info>
    <org_study_id>SPPhyticAcidTrial</org_study_id>
    <nct_id>NCT03030703</nct_id>
  </id_info>
  <brief_title>Cystatin SN Binds to Phytic Acid and Predicts Non-heme Iron Bioavailability</brief_title>
  <official_title>Salivary Cystatin SN Binds to Phytic Acid and is a Predictor of Non-heme Iron Bioavailability With Phytic Acid Supplementation</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>
    <collaborator>
      <agency>American Academy of Nurse Practitioners</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>
      Phytic acid is a known inhibitor of iron bioavailability, although long term studies have&#xD;
      suggested possibly exaggerated findings compared to single meal studies, pointing to phytic&#xD;
      acid adaptation over time. Salivary proline-rich proteins have been found to reduce&#xD;
      tannin-iron chelation, but studies have not explored changes in salivary proteins that may&#xD;
      result in phytic acid adaptation. The primary objectives of this study are: 1) To determine&#xD;
      whether phytic acid impacts iron bioavailability or status when consumed over time 2) to test&#xD;
      whether salivary protein production may impact iron bioavailability with phytic acid&#xD;
      supplementation, and 3) to explore in vitro phytic acid salivary binding. Secondary&#xD;
      objectives included assessment of the reliability of astringency as a measure of salivary&#xD;
      protein production and iron absorption.&#xD;
&#xD;
      The study was conducted in an iron absorption study of 7 women, aged 18-35 years old, to&#xD;
      determine iron bioavailability with supplementation of 350 mg phytic acid before and after&#xD;
      regular, three times daily supplementation for four weeks. Direct iron absorption was&#xD;
      measured using area under the curve. Iron status was measured by changes in hemoglobin and&#xD;
      ferritin, and was adjusted by participant c-reactive protein levels. Salivary samples were&#xD;
      collected before and after supplement consumption during meal challenges, and analyzed on&#xD;
      HPLC and by ELISA. Astringency testing was conducted at the end of each meal challenge. In&#xD;
      vitro saliva-phytic acid modeling was explored on HPLC, MALDI-TOF, and ELISA. Iron absorption&#xD;
      and status markers were analyzed by ANOVA, and mixed-modeling followed by pairwise comparison&#xD;
      by least significant differences. Pearson's correlations were used to correlated salivary&#xD;
      proteins and astringency with iron bioavailability.&#xD;
&#xD;
      The present study will provide important information regarding the approximate influence of&#xD;
      phytic acid consumption on iron bioavailability and storage over time in regards to salivary&#xD;
      proteins. It will also give context to the role of salivary proteins with phytic acid&#xD;
      consumption over time. Data will also help to delineate possible physiological mechanisms&#xD;
      underlying phytic acid adaptation and possible ways to detect individuals who better adapt&#xD;
      than others.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 11, 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>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</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 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 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 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 the intervention</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Iron-deficiency</condition>
  <condition>Iron Deficiency Anemia</condition>
  <arm_group>
    <arm_group_label>350 mg phytic acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>350 mg phytic acid (inositol hexaphosphate) at week 0 (before supplementation) and at week 4 (after supplementation)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>phytic acid</intervention_name>
    <description>350 mg phytic acid (inositol hexaphosphate) three times daily for four weeks</description>
    <arm_group_label>350 mg phytic acid</arm_group_label>
    <other_name>inositol hexaphosphate</other_name>
  </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>Phytic acid</keyword>
  <keyword>Cystatin</keyword>
  <keyword>Salivary proline-rich protein</keyword>
  <keyword>antinutrient</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>Inositol</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/NCT03030703
org study id: SPPhyticAcidTrial
nct id: NCT03030703
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Phytic acid is a known inhibitor of iron bioavailability, although long term studies have
      suggested possibly exaggerated findings compared to single meal studies, pointing to phytic
      acid adaptation over time. Salivary proline-rich proteins have been found to reduce
      tannin-iron chelation, but studies have not explored changes in salivary proteins that may
      result in phytic acid adaptation. The primary objectives of this study are: 1) To determine
      whether phytic acid impacts iron bioavailability or status when consumed over time 2) to test
      whether salivary protein production may impact iron bioavailability with phytic acid
      supplementation, and 3) to explore in vitro phytic acid salivary binding. Secondary
      objectives included assessment of the reliability of astringency as a measure of salivary
      protein production and iron absorption.

      The study was conducted in an iron absorption study of 7 women, aged 18-35 years old, to
      determine iron bioavailability with supplementation of 350 mg phytic acid before and after
      regular, three times daily supplementation for four weeks. 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 and by ELISA. Astringency testing was conducted at the end of each meal challenge. In
      vitro saliva-phytic acid modeling was explored on HPLC, MALDI-TOF, and ELISA. 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
      phytic acid consumption on iron bioavailability and storage over time in regards to salivary
      proteins. It will also give context to the role of salivary proteins with phytic acid
      consumption over time. Data will also help to delineate possible physiological mechanisms
      underlying phytic acid adaptation and possible ways to detect individuals who better adapt
      than others.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Change in baseline to endline area under the curve after meal challenge at weeks 0 and 4 of 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 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 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 the intervention
arm group label: 350 mg phytic acid
arm group type: Experimental
description: 350 mg phytic acid (inositol hexaphosphate) at week 0 (before supplementation) and at week 4 (after supplementation)
intervention type: Dietary Supplement
intervention name: phytic acid
description: 350 mg phytic acid (inositol hexaphosphate) three times daily for four weeks
arm group label: 350 mg phytic acid
other name: inositol hexaphosphate
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: Inositol
sharing ipd: No