xml: <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/NCT06021171</url>
    </required_header>
    <id_info>
      <org_study_id>2021-44-0701</org_study_id>
      <nct_id>NCT06021171</nct_id>
    </id_info>
    <brief_title>Improving the Iron Status of Athletes With Pre-, Pro- and Synbiotics</brief_title>
    <official_title>Improving the Iron Status of Athletes With Pre-, Pro- and Synbiotics</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>King's College</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>King's College</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>
        Iron deficiency (ID) is the most common micronutrient deficiency worldwide, and poor iron&#xD;
        bioavailability is a major cause. While 30% of female athletes are affected by ID, and its&#xD;
        consequences are highly relevant to athletic performance, ID affects women and children&#xD;
        around the world with consequences just as relevant, if not more so (e.g. school performance,&#xD;
        work capacity and thus wage earning). With poor iron absorption being a cause of ID in active&#xD;
        women, it is especially important to discover simple ways to improve iron (Fe) uptake. While&#xD;
        some studies have suggested that consumption of prebiotic fiber may improve Fe absorption in&#xD;
        animal models, there have been few studies examining the effects of synbiotic supplementation&#xD;
        (consumption of both a prebiotic and probiotic that work together) on Fe uptake in adult&#xD;
        females (athletes and non-athletes).&#xD;
  &#xD;
        A recent pilot study demonstrated a substantial improvement in Fe uptake in female athletes&#xD;
        after 4 and 8 weeks of synbiotic supplementation compared to placebo during Fe repletion with&#xD;
        a low dose of ferrous sulfate (FeSO4). If synbiotic supplementation can improve the Fe&#xD;
        bioavailability of FeSO4 (which is ~30%) in ID women during repletion of Fe status, it could&#xD;
        possibly improve the Fe bioavailability of non-heme Fe sources, as well as mixed meals.&#xD;
  &#xD;
        Research Question: What is the effect of synbiotic supplementation (a supplement containing a&#xD;
        prebiotic + a probiotic), compared to prebiotic supplementation or a placebo, on Fe uptake&#xD;
        and the gut microbiome in ID athletes during low-dose Fe repletion?&#xD;
  &#xD;
        Hypothesis: In the proposed study, we hypothesize that synbiotic supplementation along with&#xD;
        Fe repletion with a low dose of FeSO4 will have greatest impact on athletes' Fe uptake due to&#xD;
        alterations in the microbiome, which will be assessed.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The following Specific Aims will help us to answer this research question: To screen the iron&#xD;
        status of athletes at the beginning of training season and determine the prevalence of anemia&#xD;
        and iron depletion on our NCAA Division III campus. To determine the differences in Fe uptake&#xD;
        with consumption of a synbiotic, prebiotic, and placebo supplements along with low-dose Fe&#xD;
        supplementation in ID athletes. To determine the differences in the microbiome with&#xD;
        consumption of a synbiotic, prebiotic, and placebo supplements along with low-dose Fe&#xD;
        supplementation in ID female athletes. This aim will help us mechanism behind change in iron&#xD;
        status with a functional fiber (e.g. synbiotic supplementation).&#xD;
  &#xD;
        This data is essential to advance our understanding of how Fe uptake in active persons can be&#xD;
        enhanced by functional fiber supplementation, as well as by REAL foods containing functional&#xD;
        fibers, which could help ameliorate ID not only for athletes here in the US but for people&#xD;
        around the globe.&#xD;
  &#xD;
        The design is a randomized, placebo-controlled crossover trial, which will use each&#xD;
        participant as her/his own control, in addition to a placebo treatment being administered in&#xD;
        a counter-balanced order with the other treatments.&#xD;
  &#xD;
        Participants: King's is a Division III College and currently has &gt;85 eligible female athletes&#xD;
        on the rosters of a variety of competitive sports teams. During a recent RCT, about 30 active&#xD;
        women were screened and &gt;30% were ID (1). For the proposed study, given the effect size&#xD;
        observed in previous work (6), we need n=10 to complete the 18-week randomized crossover&#xD;
        trial (e.g. so recruiting n=13 would allow for a &quot;normal&quot; 20% attrition rate during the trial&#xD;
        due to injuries, illnesses, etc).&#xD;
  &#xD;
        Iron Status Screening: Athletes from King's will be asked to volunteer via recruitment email.&#xD;
        To address Aim 1, at baseline (and after NCAA health clearance), athletes will have their&#xD;
        iron status screened via venous blood sample at the beginning of their season in the Human&#xD;
        Performance Lab in the Alley Center (Complete Blood Count, which includes Hgb); Serum&#xD;
        ferritin; C-Reactive Protein for inflammation adjustment of ferritin). Anthropometrics and&#xD;
        body composition will be measured and health, dietary and training information will also be&#xD;
        collected. Standard demographic information, and medical history will be self-reported by&#xD;
        each participant using computer-based questionnaires. All athletes with normal iron status&#xD;
        (Hgb &gt;12.0 g/dL AND sFer&gt;30.0 µg/L) will be given their iron status results and offered a&#xD;
        Nutrition Consultation by a MS Nutrition Student under the supervision of the PI. Athletes&#xD;
        will not be eligible to participate in the study if pregnant, wishing to become pregnant,&#xD;
        breastfeeding, having a condition or taking medication impacting Fe status, or not healthy&#xD;
        enough to train/participate in their sport.&#xD;
  &#xD;
        Crossover Trial: To address Aims 2 and 3, women athletes identified as ID (sFer&lt;30.0 µg/L)&#xD;
        will be invited to participate in a 18-week double-blind, randomized, crossover trial with&#xD;
        concurrent daily Fe supplementation (100 mg FeSO4/d, Puritan's Pride). Participating ID&#xD;
        athletes will receive the following treatments for 4 weeks each, in a randomized,&#xD;
        counter-balanced order: a) synbiotic supplement (RegularGirl), b) prebiotic supplement&#xD;
        (SunFiber), and c) placebo (maltodextrin). There will be a 3-week wash-out period between&#xD;
        treatments (see Figure 1). In our pilot study, we observed a strong response within a 4-week&#xD;
        time period.&#xD;
  &#xD;
        Volunteers will be asked to mix the supplemental functional fiber source (or placebo) packet,&#xD;
        all identically packaged and only visible as white powder, with any food or beverage once&#xD;
        daily. They will also asked to consume 100 mg FeSO4 per day as a single low-dose Fe tablet&#xD;
        once per day, either in the morning or in the evening, avoiding consumption with coffee/tea&#xD;
        or supplemental calcium source. Throughout the 18-week study, athletes will be asked to&#xD;
        complete a daily training, medication, compliance, stool (using the Bristol Stool Scale, BSS)&#xD;
        and GI symptom log. Compliance will also be measured by research staff via weekly pill and&#xD;
        packet counts.&#xD;
  &#xD;
        Iron status (as described in Screening above) and dietary intake (via 24-h recall and FFQ)&#xD;
        will be measured at the beginning and end of each treatment point of the trial (see &quot;X&quot; in&#xD;
        Figure 1). Fecal samples will be collected at beginning and end of each timepoint for&#xD;
        analysis of the microbiome (see &quot;X&quot; in Figure 1) using self-collection vials provided&#xD;
        (OMNIgene-GUT, OMG-200, DNA GenoTek). Volunteers will not be asked to alter their usual food/&#xD;
        dietary intake in any way during the trial. At the end of the study, athletes will be given&#xD;
        their endpoint lab results and offered a Nutrition Consultation by a MS Nutrition Student&#xD;
        under the supervision of the PI.&#xD;
  &#xD;
        Iron status (as described in Screening above) and dietary intake (via 24-h recall and FFQ)&#xD;
        will be measured at the beginning and end of each treatment point of the trial (see &quot;X&quot; in&#xD;
        Figure 1). Fecal samples will be collected at beginning and end of each timepoint for&#xD;
        analysis of the microbiome (see &quot;X&quot; in Figure 1) using self-collection vials provided&#xD;
        (OMNIgene-GUT, OMG-200, DNA GenoTek). Volunteers will not be asked to alter their usual food/&#xD;
        dietary intake in any way during the trial. At the end of the study, athletes will be given&#xD;
        their endpoint lab results and offered a Nutrition Consultation by a MS Nutrition Student&#xD;
        under the supervision of the PI.&#xD;
  &#xD;
        Time and effort: 15.5 hours over the 18 week study Blood sampling and body measurements will&#xD;
        take about 15 min, 6x during the trial (1.5 h total) Completion of forms will take about 15&#xD;
        min 6 x during the trial (1.5 h total) Stool collection will take about 5 min, 6 times during&#xD;
        trial (0.5 h total) Meeting at the Alley Center Human Performance Lab weekly will take ~ 5&#xD;
        min, 18x over the course of the study (1.5 h total) Consumption of iron supplement and packet&#xD;
        every day and daily record-keeping will take &lt;5 min/day * 126 days during 18 week study&#xD;
        (&lt;10.5 h total)&#xD;
  &#xD;
        Data analysis plan: All analyses of sFer will be adjusted for inflammation. Briefly, GLM&#xD;
        Repeated measures ANOVA will be used to assess the effect of the treatments on iron status,&#xD;
        GI symptoms, etc. (Time-by-Tx effects will be examined). All statistical analyses will be&#xD;
        performed using SPSS (most recent version), and results will be considered statistically&#xD;
        significant at p&lt;0.05 for main effects.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">August 15, 2021</start_date>
    <completion_date type="Actual">May 15, 2022</completion_date>
    <primary_completion_date type="Actual">May 15, 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>
      <intervention_model_description>This is a double-blind, randomized, placebo-controlled crossover trial.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>Volunteers will be asked to mix the powder packet (e.g. supplemental functional fiber source or placebo), with any food or beverage once daily. All 3 powders are identically packaged and only visible as white powder, and all 3 powders are colorless, odorless and tasteless when mixed in a liquid or semi-solid food. Instructions and education to both groups will be identical. Packets were sent to the Researcher pre-packaged and pre-labeled as A, B, C by the product company.&#xD;
  Subject randomization to treatment order was completed using random number generator by a Research Assistant not involved in direct contact with subjects.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Blood serum level of ferritin</measure>
      <time_frame>baseline (0), 4, 8, 12, 16, 18 weeks</time_frame>
      <description>biomarker of iron status, iron stores, use to calculate Total body iron</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Blood level of hemoglobin</measure>
      <time_frame>baseline (0), 4, 8, 12, 16, 18 weeks</time_frame>
      <description>biomarker of iron status</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Blood serum level of soluble transferrin receptor</measure>
      <time_frame>baseline (0), 4, 8, 12, 16, 18 weeks</time_frame>
      <description>biomarker of iron status, tissue iron status, use to calculate Total body iron</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Gut microbiome data</measure>
      <time_frame>baseline (0), 4, 8, 12, 16, 18 weeks</time_frame>
      <description>Fecal samples to yield gut bacterial taxa</description>
    </primary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Actual">10</enrollment>
    <condition>Iron-deficiency</condition>
    <condition>Iron Deficiency Anemia</condition>
    <condition>Iron Deficiency (Without Anemia)</condition>
    <arm_group>
      <arm_group_label>Regular Girl (Sunfiber + Bifidobacterium lactis)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Regular Girl, a synbiotic supplement containing the Prebiotic Sunfiber + Bifidobacterium Lactis</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Maltodextrin</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Maltodextrin</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sunfiber</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>SunFiber, a prebiotic fiber supplement</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Partially hydrolyzed guar gum + bifidobacterium lactis</intervention_name>
      <description>Synbiotic Supplement: Contains 5 grams of prebiotic fiber (Sunfiber®) and 8 billion active probiotics (Bifidobacterium lactis).</description>
      <arm_group_label>Regular Girl (Sunfiber + Bifidobacterium lactis)</arm_group_label>
      <other_name>RegularGirl</other_name>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Partially hydrolyzed guar gum</intervention_name>
      <description>5 g Partially hydrolyzed guar gum</description>
      <arm_group_label>Sunfiber</arm_group_label>
      <other_name>SunFiber</other_name>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Maltodextrin</intervention_name>
      <description>5 g Maltodextrin</description>
      <arm_group_label>Maltodextrin</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  18 years of age or older&#xD;
  &#xD;
            -  currently participating in or training for their sport&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnant, or wishing to become pregnant&#xD;
  &#xD;
            -  Breastfeeding&#xD;
  &#xD;
            -  Having a condition or taking medication impacting iron status&#xD;
  &#xD;
            -  Not healthy enough to train for/participate in their sport.&#xD;
        </textblock>
      </criteria>
      <gender>All</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>Diane M. DellaValle</last_name>
      <role>Principal Investigator</role>
      <affiliation>King's College</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>King's College</name>
        <address>
          <city>Wilkes-Barre</city>
          <state>Pennsylvania</state>
          <zip>18711</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>https://sunfiber.com/products/</url>
      <description>Website for SunFiber Product</description>
    </link>
    <reference>
      <citation>DellaValle DM, Haas JD. Impact of iron depletion without anemia on performance in trained endurance athletes at the beginning of a training season: a study of female collegiate rowers. Int J Sport Nutr Exerc Metab. 2011 Dec;21(6):501-6. doi: 10.1123/ijsnem.21.6.501.</citation>
      <PMID>22089308</PMID>
    </reference>
    <reference>
      <citation>Dellavalle DM, Haas JD. Iron status is associated with endurance performance and training in female rowers. Med Sci Sports Exerc. 2012 Aug;44(8):1552-9. doi: 10.1249/MSS.0b013e3182517ceb.</citation>
      <PMID>22382172</PMID>
    </reference>
    <reference>
      <citation>Sandroni A, House E, Howard L, DellaValle DM. Synbiotic Supplementation Improves Response to Iron Supplementation in Female Athletes during Training. J Diet Suppl. 2022;19(3):366-380. doi: 10.1080/19390211.2021.1887423. Epub 2021 Feb 22.</citation>
      <PMID>33615951</PMID>
    </reference>
    <reference>
      <citation>DellaValle DM, Glahn RP, Shaff JE, O'Brien KO. Iron Absorption from an Intrinsically Labeled Lentil Meal Is Low but Upregulated in Women with Poor Iron Status. J Nutr. 2015 Oct;145(10):2253-7. doi: 10.3945/jn.115.217273. Epub 2015 Sep 2.</citation>
      <PMID>26338889</PMID>
    </reference>
    <reference>
      <citation>Scholz-Ahrens KE, Schrezenmeir J. Inulin and oligofructose and mineral metabolism: the evidence from animal trials. J Nutr. 2007 Nov;137(11 Suppl):2513S-2523S. doi: 10.1093/jn/137.11.2513S.</citation>
      <PMID>17951495</PMID>
    </reference>
    <reference>
      <citation>Freitas Kde C, Amancio OM, de Morais MB. High-performance inulin and oligofructose prebiotics increase the intestinal absorption of iron in rats with iron deficiency anaemia during the growth phase. Br J Nutr. 2012 Sep 28;108(6):1008-16. doi: 10.1017/S0007114511006301. Epub 2011 Dec 15.</citation>
      <PMID>22172251</PMID>
    </reference>
    <reference>
      <citation>Laparra JM, Diez-Municio M, Herrero M, Moreno FJ. Structural differences of prebiotic oligosaccharides influence their capability to enhance iron absorption in deficient rats. Food Funct. 2014 Oct;5(10):2430-7. doi: 10.1039/c4fo00504j. Epub 2014 Aug 11.</citation>
      <PMID>25109275</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 25, 2021</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>August 30, 2023</last_update_submitted>
    <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>King's College</investigator_affiliation>
      <investigator_full_name>Diane DellaValle, PhD, RDN, LDN</investigator_full_name>
      <investigator_title>Associate Professor, Research Dietitian</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anemia</mesh_term>
      <mesh_term>Anemia, Iron-Deficiency</mesh_term>
      <mesh_term>Iron Deficiencies</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>IPD that underlie the results reported, after deidentification (text, tables, figures, appendices).</ipd_description>
      <ipd_time_frame>Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.</ipd_time_frame>
      <ipd_access_criteria>Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact dianedellavalle@kings.edu.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06021171
  org study id: 2021-44-0701
  nct id: NCT06021171
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Iron deficiency (ID) is the most common micronutrient deficiency worldwide, and poor iron
        bioavailability is a major cause. While 30% of female athletes are affected by ID, and its
        consequences are highly relevant to athletic performance, ID affects women and children
        around the world with consequences just as relevant, if not more so (e.g. school performance,
        work capacity and thus wage earning). With poor iron absorption being a cause of ID in active
        women, it is especially important to discover simple ways to improve iron (Fe) uptake. While
        some studies have suggested that consumption of prebiotic fiber may improve Fe absorption in
        animal models, there have been few studies examining the effects of synbiotic supplementation
        (consumption of both a prebiotic and probiotic that work together) on Fe uptake in adult
        females (athletes and non-athletes).
  
        A recent pilot study demonstrated a substantial improvement in Fe uptake in female athletes
        after 4 and 8 weeks of synbiotic supplementation compared to placebo during Fe repletion with
        a low dose of ferrous sulfate (FeSO4). If synbiotic supplementation can improve the Fe
        bioavailability of FeSO4 (which is ~30%) in ID women during repletion of Fe status, it could
        possibly improve the Fe bioavailability of non-heme Fe sources, as well as mixed meals.
  
        Research Question: What is the effect of synbiotic supplementation (a supplement containing a
        prebiotic + a probiotic), compared to prebiotic supplementation or a placebo, on Fe uptake
        and the gut microbiome in ID athletes during low-dose Fe repletion?
  
        Hypothesis: In the proposed study, we hypothesize that synbiotic supplementation along with
        Fe repletion with a low dose of FeSO4 will have greatest impact on athletes' Fe uptake due to
        alterations in the microbiome, which will be assessed.
  The following Specific Aims will help us to answer this research question: To screen the iron
        status of athletes at the beginning of training season and determine the prevalence of anemia
        and iron depletion on our NCAA Division III campus. To determine the differences in Fe uptake
        with consumption of a synbiotic, prebiotic, and placebo supplements along with low-dose Fe
        supplementation in ID athletes. To determine the differences in the microbiome with
        consumption of a synbiotic, prebiotic, and placebo supplements along with low-dose Fe
        supplementation in ID female athletes. This aim will help us mechanism behind change in iron
        status with a functional fiber (e.g. synbiotic supplementation).
  
        This data is essential to advance our understanding of how Fe uptake in active persons can be
        enhanced by functional fiber supplementation, as well as by REAL foods containing functional
        fibers, which could help ameliorate ID not only for athletes here in the US but for people
        around the globe.
  
        The design is a randomized, placebo-controlled crossover trial, which will use each
        participant as her/his own control, in addition to a placebo treatment being administered in
        a counter-balanced order with the other treatments.
  
        Participants: King's is a Division III College and currently has >85 eligible female athletes
        on the rosters of a variety of competitive sports teams. During a recent RCT, about 30 active
        women were screened and >30% were ID (1). For the proposed study, given the effect size
        observed in previous work (6), we need n=10 to complete the 18-week randomized crossover
        trial (e.g. so recruiting n=13 would allow for a "normal" 20% attrition rate during the trial
        due to injuries, illnesses, etc).
  
        Iron Status Screening: Athletes from King's will be asked to volunteer via recruitment email.
        To address Aim 1, at baseline (and after NCAA health clearance), athletes will have their
        iron status screened via venous blood sample at the beginning of their season in the Human
        Performance Lab in the Alley Center (Complete Blood Count, which includes Hgb); Serum
        ferritin; C-Reactive Protein for inflammation adjustment of ferritin). Anthropometrics and
        body composition will be measured and health, dietary and training information will also be
        collected. Standard demographic information, and medical history will be self-reported by
        each participant using computer-based questionnaires. All athletes with normal iron status
        (Hgb >12.0 g/dL AND sFer>30.0 µg/L) will be given their iron status results and offered a
        Nutrition Consultation by a MS Nutrition Student under the supervision of the PI. Athletes
        will not be eligible to participate in the study if pregnant, wishing to become pregnant,
        breastfeeding, having a condition or taking medication impacting Fe status, or not healthy
        enough to train/participate in their sport.
  
        Crossover Trial: To address Aims 2 and 3, women athletes identified as ID (sFer<30.0 µg/L)
        will be invited to participate in a 18-week double-blind, randomized, crossover trial with
        concurrent daily Fe supplementation (100 mg FeSO4/d, Puritan's Pride). Participating ID
        athletes will receive the following treatments for 4 weeks each, in a randomized,
        counter-balanced order: a) synbiotic supplement (RegularGirl), b) prebiotic supplement
        (SunFiber), and c) placebo (maltodextrin). There will be a 3-week wash-out period between
        treatments (see Figure 1). In our pilot study, we observed a strong response within a 4-week
        time period.
  
        Volunteers will be asked to mix the supplemental functional fiber source (or placebo) packet,
        all identically packaged and only visible as white powder, with any food or beverage once
        daily. They will also asked to consume 100 mg FeSO4 per day as a single low-dose Fe tablet
        once per day, either in the morning or in the evening, avoiding consumption with coffee/tea
        or supplemental calcium source. Throughout the 18-week study, athletes will be asked to
        complete a daily training, medication, compliance, stool (using the Bristol Stool Scale, BSS)
        and GI symptom log. Compliance will also be measured by research staff via weekly pill and
        packet counts.
  
        Iron status (as described in Screening above) and dietary intake (via 24-h recall and FFQ)
        will be measured at the beginning and end of each treatment point of the trial (see "X" in
        Figure 1). Fecal samples will be collected at beginning and end of each timepoint for
        analysis of the microbiome (see "X" in Figure 1) using self-collection vials provided
        (OMNIgene-GUT, OMG-200, DNA GenoTek). Volunteers will not be asked to alter their usual food/
        dietary intake in any way during the trial. At the end of the study, athletes will be given
        their endpoint lab results and offered a Nutrition Consultation by a MS Nutrition Student
        under the supervision of the PI.
  
        Iron status (as described in Screening above) and dietary intake (via 24-h recall and FFQ)
        will be measured at the beginning and end of each treatment point of the trial (see "X" in
        Figure 1). Fecal samples will be collected at beginning and end of each timepoint for
        analysis of the microbiome (see "X" in Figure 1) using self-collection vials provided
        (OMNIgene-GUT, OMG-200, DNA GenoTek). Volunteers will not be asked to alter their usual food/
        dietary intake in any way during the trial. At the end of the study, athletes will be given
        their endpoint lab results and offered a Nutrition Consultation by a MS Nutrition Student
        under the supervision of the PI.
  
        Time and effort: 15.5 hours over the 18 week study Blood sampling and body measurements will
        take about 15 min, 6x during the trial (1.5 h total) Completion of forms will take about 15
        min 6 x during the trial (1.5 h total) Stool collection will take about 5 min, 6 times during
        trial (0.5 h total) Meeting at the Alley Center Human Performance Lab weekly will take ~ 5
        min, 18x over the course of the study (1.5 h total) Consumption of iron supplement and packet
        every day and daily record-keeping will take <5 min/day * 126 days during 18 week study
        (<10.5 h total)
  
        Data analysis plan: All analyses of sFer will be adjusted for inflammation. Briefly, GLM
        Repeated measures ANOVA will be used to assess the effect of the treatments on iron status,
        GI symptoms, etc. (Time-by-Tx effects will be examined). All statistical analyses will be
        performed using SPSS (most recent version), and results will be considered statistically
        significant at p<0.05 for main effects.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: This is a double-blind, randomized, placebo-controlled crossover trial.
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: Volunteers will be asked to mix the powder packet (e.g. supplemental functional fiber source or placebo), with any food or beverage once daily. All 3 powders are identically packaged and only visible as white powder, and all 3 powders are colorless, odorless and tasteless when mixed in a liquid or semi-solid food. Instructions and education to both groups will be identical. Packets were sent to the Researcher pre-packaged and pre-labeled as A, B, C by the product company.
  Subject randomization to treatment order was completed using random number generator by a Research Assistant not involved in direct contact with subjects.
  measure: Blood serum level of ferritin
  time frame: baseline (0), 4, 8, 12, 16, 18 weeks
  description: biomarker of iron status, iron stores, use to calculate Total body iron
  measure: Blood level of hemoglobin
  time frame: baseline (0), 4, 8, 12, 16, 18 weeks
  description: biomarker of iron status
  measure: Blood serum level of soluble transferrin receptor
  time frame: baseline (0), 4, 8, 12, 16, 18 weeks
  description: biomarker of iron status, tissue iron status, use to calculate Total body iron
  measure: Gut microbiome data
  time frame: baseline (0), 4, 8, 12, 16, 18 weeks
  description: Fecal samples to yield gut bacterial taxa
  arm group label: Regular Girl (Sunfiber + Bifidobacterium lactis)
  arm group type: Active Comparator
  description: Regular Girl, a synbiotic supplement containing the Prebiotic Sunfiber + Bifidobacterium Lactis
  arm group label: Maltodextrin
  arm group type: Placebo Comparator
  description: Maltodextrin
  arm group label: Sunfiber
  arm group type: Active Comparator
  description: SunFiber, a prebiotic fiber supplement
  intervention type: Dietary Supplement
  intervention name: Partially hydrolyzed guar gum + bifidobacterium lactis
  description: Synbiotic Supplement: Contains 5 grams of prebiotic fiber (Sunfiber®) and 8 billion active probiotics (Bifidobacterium lactis).
  arm group label: Regular Girl (Sunfiber + Bifidobacterium lactis)
  other name: RegularGirl
  intervention type: Dietary Supplement
  intervention name: Partially hydrolyzed guar gum
  description: 5 g Partially hydrolyzed guar gum
  arm group label: Sunfiber
  other name: SunFiber
  intervention type: Dietary Supplement
  intervention name: Maltodextrin
  description: 5 g Maltodextrin
  arm group label: Maltodextrin
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 35 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Diane M. DellaValle
  role: Principal Investigator
  affiliation: King's College
  facility: 
  country: United States
  url: https://sunfiber.com/products/
  description: Website for SunFiber Product
  citation: DellaValle DM, Haas JD. Impact of iron depletion without anemia on performance in trained endurance athletes at the beginning of a training season: a study of female collegiate rowers. Int J Sport Nutr Exerc Metab. 2011 Dec;21(6):501-6. doi: 10.1123/ijsnem.21.6.501.
  PMID: 22089308
  citation: Dellavalle DM, Haas JD. Iron status is associated with endurance performance and training in female rowers. Med Sci Sports Exerc. 2012 Aug;44(8):1552-9. doi: 10.1249/MSS.0b013e3182517ceb.
  PMID: 22382172
  citation: Sandroni A, House E, Howard L, DellaValle DM. Synbiotic Supplementation Improves Response to Iron Supplementation in Female Athletes during Training. J Diet Suppl. 2022;19(3):366-380. doi: 10.1080/19390211.2021.1887423. Epub 2021 Feb 22.
  PMID: 33615951
  citation: DellaValle DM, Glahn RP, Shaff JE, O'Brien KO. Iron Absorption from an Intrinsically Labeled Lentil Meal Is Low but Upregulated in Women with Poor Iron Status. J Nutr. 2015 Oct;145(10):2253-7. doi: 10.3945/jn.115.217273. Epub 2015 Sep 2.
  PMID: 26338889
  citation: Scholz-Ahrens KE, Schrezenmeir J. Inulin and oligofructose and mineral metabolism: the evidence from animal trials. J Nutr. 2007 Nov;137(11 Suppl):2513S-2523S. doi: 10.1093/jn/137.11.2513S.
  PMID: 17951495
  citation: Freitas Kde C, Amancio OM, de Morais MB. High-performance inulin and oligofructose prebiotics increase the intestinal absorption of iron in rats with iron deficiency anaemia during the growth phase. Br J Nutr. 2012 Sep 28;108(6):1008-16. doi: 10.1017/S0007114511006301. Epub 2011 Dec 15.
  PMID: 22172251
  citation: Laparra JM, Diez-Municio M, Herrero M, Moreno FJ. Structural differences of prebiotic oligosaccharides influence their capability to enhance iron absorption in deficient rats. Food Funct. 2014 Oct;5(10):2430-7. doi: 10.1039/c4fo00504j. Epub 2014 Aug 11.
  PMID: 25109275
  responsible party type: Principal Investigator
  investigator affiliation: King's College
  investigator full name: Diane DellaValle, PhD, RDN, LDN
  investigator title: Associate Professor, Research Dietitian
  mesh term: Anemia
  mesh term: Anemia, Iron-Deficiency
  mesh term: Iron Deficiencies
  sharing ipd: Yes
  ipd description: IPD that underlie the results reported, after deidentification (text, tables, figures, appendices).
  ipd time frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
  ipd access criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact dianedellavalle@kings.edu.