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/NCT06014983</url>
    </required_header>
    <id_info>
      <org_study_id>H23-00016</org_study_id>
      <nct_id>NCT06014983</nct_id>
    </id_info>
    <brief_title>Efficacy and Adverse Side Effects of Two Forms of Iron in Pregnancy</brief_title>
    <acronym>EASE-Iron</acronym>
    <official_title>Efficacy and Adverse Side Effects of Two Forms of Iron in Prenatal Micronutrient Supplements (EASE-Iron): A Randomized Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of British Columbia</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of British Columbia</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>
        This two-arm, double-blind randomized clinical trial will recruit 208 generally healthy,&#xD;
        low-risk pregnant individuals aged 19-42 years living in Vancouver, Canada. Participants will&#xD;
        be randomized to receive one of two forms of iron (ferrous fumarate or ferrous bisglycinate)&#xD;
        in addition to a prenatal multivitamin (without iron) daily during their pregnancy until&#xD;
        delivery, with optional continuation until ~4 weeks postpartum for breastmilk sample&#xD;
        collection. Blood samples will be taken at baseline and again at 37 weeks gestation to assess&#xD;
        how different forms of iron impact body iron stores. Rectal swabs will also be taken at&#xD;
        baseline and 37 weeks gestation to detect presence of harmful bacteria in the gut and&#xD;
        quantify their abundance. This research will inform more specific guidelines for optimal iron&#xD;
        supplementation practices for the prevention and treatment of iron deficiency for both mother&#xD;
        and baby.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        To address our primary aim of determining the optimal form of iron in prenatal supplements,&#xD;
        we seek to answer the following research questions:&#xD;
  &#xD;
          1. Does providing a more bioavailable form of iron (24 mg elemental iron as ferrous&#xD;
             bisglycinate) effectively increase ferritin concentration in maternal venous blood and&#xD;
             umbilical cord blood, as compared to the standard 24 mg elemental iron as ferrous&#xD;
             fumarate?&#xD;
  &#xD;
          2. Does 12 weeks of 24 mg daily oral iron as ferrous fumarate increase biomarkers of&#xD;
             potential harm (gut inflammation, gut pathogen abundance, adverse side effects) in&#xD;
             pregnant individuals, as compared to 24 mg daily oral iron as ferrous bisglycinate?&#xD;
  &#xD;
        Pregnant individuals 13-25 weeks gestation will be randomized to one of two trial arms to&#xD;
        receive either 24 mg elemental iron as ferrous fumarate or 24 mg elemental iron as ferrous&#xD;
        bisglycinate for a minimum of 12 weeks during pregnancy until delivery, with optional&#xD;
        continuation until 4-weeks postpartum for breastmilk collection. All participants will also&#xD;
        receive the standard form and dose of other critical micronutrients during pregnancy (e.g.,&#xD;
        folate, calcium) through the provision of a prenatal multivitamin (not containing iron).&#xD;
  &#xD;
        Interested individuals may undergo the informed consent process anytime prior to 25 weeks&#xD;
        gestation. Once an individual indicates that they are interested in participating in the&#xD;
        trial, the individual will be assigned a unique study ID and a baseline visit will be&#xD;
        scheduled.&#xD;
  &#xD;
        The baseline visit will occur between 13-25 weeks gestation and will involve discontinuation&#xD;
        of current iron/prenatal vitamin supplementation, review and signing the informed consent&#xD;
        form (a scanned copy will be shared with the participant), randomization to an iron group,&#xD;
        provision of study supplements, completion of a baseline questionnaire, measurement of weight&#xD;
        and height, a small blood draw and collection of a rectal swab sample.&#xD;
  &#xD;
        The intervention period is a minimum of 12 weeks (from baseline at 13-25 weeks to delivery).&#xD;
        Participants will supplement daily with the iron and prenatal multivitamin supplements.&#xD;
        Monthly follow-up surveys will be sent to participants via email to check-in and receive&#xD;
        updates regarding any changes to medical history or medication use.&#xD;
  &#xD;
        The endline visit will occur at approximately 37 weeks gestation and will involve collecting&#xD;
        any remaining supplements (for capsule counts and assessment of adherence), a weight&#xD;
        measurement, a small blood draw, collection of a rectal swab sample, and completion of a&#xD;
        short endline questionnaire.&#xD;
  &#xD;
        Optional continuation of study: After the endline visit, participants who are planning to&#xD;
        breastfeed will have the option to continue supplementing with the study supplements until&#xD;
        approximately 4 weeks postpartum, at which time they will provide a small breastmilk sample.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">January 2026</completion_date>
    <primary_completion_date type="Anticipated">December 2025</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>Parallel Assignment</intervention_model>
      <primary_purpose>Other</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Maternal ferritin concentration</measure>
      <time_frame>Blood sample collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)</time_frame>
      <description>µg/L; reflects body iron stores</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Umbilical cord ferritin concentration</measure>
      <time_frame>Umbilical cord blood collected at time of delivery</time_frame>
      <description>µg/L; proxy measure for newborn iron stores</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Maternal hemoglobin concentration</measure>
      <time_frame>Maternal blood sample collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)</time_frame>
      <description>g/L; obtained through a complete blood count</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Umbilical cord hemoglobin concentration</measure>
      <time_frame>Umbilical cord blood collected at time of delivery</time_frame>
      <description>g/L; measured using a HemoCue device</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Placental iron concentration</measure>
      <time_frame>Placenta collected at time of delivery</time_frame>
      <description>µg/g; reflects iron transfer to fetus</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Gut pathogen abundance</measure>
      <time_frame>Flocked rectal swab collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)</time_frame>
      <description>Ct values; quantifies abundance of harmful bacteria in the gut</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fecal calprotectin</measure>
      <time_frame>Flocked rectal swab collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)</time_frame>
      <description>µg/g; reflects gut inflammation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse side effects</measure>
      <time_frame>Endline (37 weeks gestation)</time_frame>
      <description>Includes reported gastrointestinal side effects (e.g., constipation, diarrhea, nausea) and any other side effects experienced</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Markers of inflammation</measure>
      <time_frame>Maternal blood sample collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation); umbilical cord blood sample collected at time of delivery</time_frame>
      <description>Includes alpha-1 acid glycoprotein (AGP; g/L) and C-reactive protein (CRP; mg/L), used in combination to adjust ferritin concentration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hepcidin concentration</measure>
      <time_frame>Maternal blood sample collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation); umbilical cord blood sample collected at time of delivery</time_frame>
      <description>nmol/L; hormone that influences iron regulation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Breastmilk iron stores</measure>
      <time_frame>Breastmilk sample collected at 4-weeks postpartum</time_frame>
      <description>Includes measurement of breastmilk iron content (mg/mL) and lactoferrin (mg/mL)</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">208</enrollment>
    <condition>Pregnancy</condition>
    <condition>Iron Deficiency</condition>
    <arm_group>
      <arm_group_label>Ferrous fumarate</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>24 mg elemental iron/day</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Ferrous bisglycinate</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>24 mg elemental iron/day</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Ferrous fumarate</intervention_name>
      <description>Participants will supplement with 24 mg elemental iron in the form of ferrous fumarate daily for a minimum of 12 weeks.</description>
      <arm_group_label>Ferrous fumarate</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Ferrous bisglycinate</intervention_name>
      <description>Participants will supplement with 24 mg elemental iron in the form of ferrous bisglycinate daily for a minimum of 12 weeks.</description>
      <arm_group_label>Ferrous bisglycinate</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Pregnant individual (singleton pregnancy)&#xD;
  &#xD;
            -  19-42 years of age&#xD;
  &#xD;
            -  Planning to deliver at BC Women's Hospital&#xD;
  &#xD;
            -  Living in the greater Vancouver area and willing to travel to the University of&#xD;
               British Columbia for study visits&#xD;
  &#xD;
            -  13-25 weeks gestation&#xD;
  &#xD;
            -  Willing to participate and able to provide informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Having a pre-existing medical condition known to impact iron status (e.g., inherited&#xD;
               hemoglobin disorder (i.e., sickle cell, hemochromatosis, thalassemia or other&#xD;
               structural hemoglobin variant), malabsorptive disorders (i.e., chronic pancreatitis,&#xD;
               cystic fibrosis, celiac disease) and inflammatory bowel disease (i.e., Crohn's&#xD;
               disease, ulcerative colitis), gastric bypass surgery, atrophic gastritis, advanced&#xD;
               liver disease, kidney dialysis)&#xD;
  &#xD;
            -  Using medications known to interfere with iron metabolism or the gut pathogen&#xD;
               equilibrium (e.g., chronic use of proton pump inhibitors, anti-inflammatory agents,&#xD;
               non-steroidal anti-inflammatory drugs, antibiotics)&#xD;
  &#xD;
            -  Having a personal neural tube defect (NTD) history or a previous NTD pregnancy&#xD;
  &#xD;
            -  Receiving ongoing blood transfusions&#xD;
  &#xD;
            -  Currently smoking or having smoked in the past 3 months&#xD;
  &#xD;
            -  Pre-pregnancy body mass index (BMI) ≥30 kg/m^2&#xD;
  &#xD;
            -  Allergy to any study supplement ingredients&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>19 Years</minimum_age>
      <maximum_age>42 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Crystal Karakochuk, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of British Columbia</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Crystal Karakochuk, PhD</last_name>
      <phone>604-822-0421</phone>
      <email>crystal.karakochuk@ubc.ca</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Lulu Pei, MSc</last_name>
      <phone>604-822-0421</phone>
      <email>lulu.pei@ubc.ca</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University of British Columbia, Food, Nutrition and Health Building</name>
        <address>
          <city>Vancouver</city>
          <state>British Columbia</state>
          <zip>V6T 1Z4</zip>
          <country>Canada</country>
        </address>
      </facility>
      <contact>
        <last_name>Lulu Pei, MSc</last_name>
        <phone>604-822-0421</phone>
        <email>lulu.pei@ubc.ca</email>
      </contact>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of British Columbia</investigator_affiliation>
      <investigator_full_name>Crystal Karakochuk</investigator_full_name>
      <investigator_title>Assistant Professor</investigator_title>
    </responsible_party>
    <keyword>Iron</keyword>
    <keyword>Pregnancy</keyword>
    <keyword>Nutrition</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Iron Deficiencies</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Ferrous fumarate</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>Upon reasonable request, the Principal Investigator will share de-identified individual participant data.</ipd_description>
    </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/NCT06014983
  org study id: H23-00016
  nct id: NCT06014983
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This two-arm, double-blind randomized clinical trial will recruit 208 generally healthy,
        low-risk pregnant individuals aged 19-42 years living in Vancouver, Canada. Participants will
        be randomized to receive one of two forms of iron (ferrous fumarate or ferrous bisglycinate)
        in addition to a prenatal multivitamin (without iron) daily during their pregnancy until
        delivery, with optional continuation until ~4 weeks postpartum for breastmilk sample
        collection. Blood samples will be taken at baseline and again at 37 weeks gestation to assess
        how different forms of iron impact body iron stores. Rectal swabs will also be taken at
        baseline and 37 weeks gestation to detect presence of harmful bacteria in the gut and
        quantify their abundance. This research will inform more specific guidelines for optimal iron
        supplementation practices for the prevention and treatment of iron deficiency for both mother
        and baby.
  To address our primary aim of determining the optimal form of iron in prenatal supplements,
        we seek to answer the following research questions:
  
          1. Does providing a more bioavailable form of iron (24 mg elemental iron as ferrous
             bisglycinate) effectively increase ferritin concentration in maternal venous blood and
             umbilical cord blood, as compared to the standard 24 mg elemental iron as ferrous
             fumarate?
  
          2. Does 12 weeks of 24 mg daily oral iron as ferrous fumarate increase biomarkers of
             potential harm (gut inflammation, gut pathogen abundance, adverse side effects) in
             pregnant individuals, as compared to 24 mg daily oral iron as ferrous bisglycinate?
  
        Pregnant individuals 13-25 weeks gestation will be randomized to one of two trial arms to
        receive either 24 mg elemental iron as ferrous fumarate or 24 mg elemental iron as ferrous
        bisglycinate for a minimum of 12 weeks during pregnancy until delivery, with optional
        continuation until 4-weeks postpartum for breastmilk collection. All participants will also
        receive the standard form and dose of other critical micronutrients during pregnancy (e.g.,
        folate, calcium) through the provision of a prenatal multivitamin (not containing iron).
  
        Interested individuals may undergo the informed consent process anytime prior to 25 weeks
        gestation. Once an individual indicates that they are interested in participating in the
        trial, the individual will be assigned a unique study ID and a baseline visit will be
        scheduled.
  
        The baseline visit will occur between 13-25 weeks gestation and will involve discontinuation
        of current iron/prenatal vitamin supplementation, review and signing the informed consent
        form (a scanned copy will be shared with the participant), randomization to an iron group,
        provision of study supplements, completion of a baseline questionnaire, measurement of weight
        and height, a small blood draw and collection of a rectal swab sample.
  
        The intervention period is a minimum of 12 weeks (from baseline at 13-25 weeks to delivery).
        Participants will supplement daily with the iron and prenatal multivitamin supplements.
        Monthly follow-up surveys will be sent to participants via email to check-in and receive
        updates regarding any changes to medical history or medication use.
  
        The endline visit will occur at approximately 37 weeks gestation and will involve collecting
        any remaining supplements (for capsule counts and assessment of adherence), a weight
        measurement, a small blood draw, collection of a rectal swab sample, and completion of a
        short endline questionnaire.
  
        Optional continuation of study: After the endline visit, participants who are planning to
        breastfeed will have the option to continue supplementing with the study supplements until
        approximately 4 weeks postpartum, at which time they will provide a small breastmilk sample.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Other
  masking: Double (Participant, Investigator)
  measure: Maternal ferritin concentration
  time frame: Blood sample collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)
  description: µg/L; reflects body iron stores
  measure: Umbilical cord ferritin concentration
  time frame: Umbilical cord blood collected at time of delivery
  description: µg/L; proxy measure for newborn iron stores
  measure: Maternal hemoglobin concentration
  time frame: Maternal blood sample collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)
  description: g/L; obtained through a complete blood count
  measure: Umbilical cord hemoglobin concentration
  time frame: Umbilical cord blood collected at time of delivery
  description: g/L; measured using a HemoCue device
  measure: Placental iron concentration
  time frame: Placenta collected at time of delivery
  description: µg/g; reflects iron transfer to fetus
  measure: Gut pathogen abundance
  time frame: Flocked rectal swab collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)
  description: Ct values; quantifies abundance of harmful bacteria in the gut
  measure: Fecal calprotectin
  time frame: Flocked rectal swab collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)
  description: µg/g; reflects gut inflammation
  measure: Adverse side effects
  time frame: Endline (37 weeks gestation)
  description: Includes reported gastrointestinal side effects (e.g., constipation, diarrhea, nausea) and any other side effects experienced
  measure: Markers of inflammation
  time frame: Maternal blood sample collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation); umbilical cord blood sample collected at time of delivery
  description: Includes alpha-1 acid glycoprotein (AGP; g/L) and C-reactive protein (CRP; mg/L), used in combination to adjust ferritin concentration
  measure: Hepcidin concentration
  time frame: Maternal blood sample collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation); umbilical cord blood sample collected at time of delivery
  description: nmol/L; hormone that influences iron regulation
  measure: Breastmilk iron stores
  time frame: Breastmilk sample collected at 4-weeks postpartum
  description: Includes measurement of breastmilk iron content (mg/mL) and lactoferrin (mg/mL)
  arm group label: Ferrous fumarate
  arm group type: Active Comparator
  description: 24 mg elemental iron/day
  arm group label: Ferrous bisglycinate
  arm group type: Experimental
  description: 24 mg elemental iron/day
  intervention type: Dietary Supplement
  intervention name: Ferrous fumarate
  description: Participants will supplement with 24 mg elemental iron in the form of ferrous fumarate daily for a minimum of 12 weeks.
  arm group label: Ferrous fumarate
  intervention type: Dietary Supplement
  intervention name: Ferrous bisglycinate
  description: Participants will supplement with 24 mg elemental iron in the form of ferrous bisglycinate daily for a minimum of 12 weeks.
  arm group label: Ferrous bisglycinate
  criteria: 
  gender: Female
  minimum age: 19 Years
  maximum age: 42 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Crystal Karakochuk, PhD
  role: Principal Investigator
  affiliation: University of British Columbia
  last name: Crystal Karakochuk, PhD
  phone: 604-822-0421
  email: crystal.karakochuk@ubc.ca
  last name: Lulu Pei, MSc
  phone: 604-822-0421
  email: lulu.pei@ubc.ca
  facility: 
  contact: 
  country: Canada
  responsible party type: Principal Investigator
  investigator affiliation: University of British Columbia
  investigator full name: Crystal Karakochuk
  investigator title: Assistant Professor
  mesh term: Iron Deficiencies
  mesh term: Ferrous fumarate
  sharing ipd: No
  ipd description: Upon reasonable request, the Principal Investigator will share de-identified individual participant data.