<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/NCT03828708</url>
  </required_header>
  <id_info>
    <org_study_id>18-1317</org_study_id>
    <nct_id>NCT03828708</nct_id>
  </id_info>
  <brief_title>Early Iron Exposure on the Gut Microbiota in Young Infants</brief_title>
  <acronym>IF</acronym>
  <official_title>Different Iron Exposure on the Development of Gut Microbiota From Birth to Four Months</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</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 study will look at the amount of iron in infant formula and how that affects a child's&#xD;
      gut development. The children of mothers who plan to formula feed their children will be&#xD;
      randomized to receive either high iron or low iron formula from birth until 4 months of age.&#xD;
      Infants will consume only the study provided formula during enrollment. Blood and stool&#xD;
      samples will be collected at birth and end of study to measure the effects of the iron&#xD;
      exposure. The overall object is to compare high iron versus low iron exposure in formula-fed&#xD;
      infants during the first months of life. Aims include determining the types of bacteria that&#xD;
      are present in the infants' fecal microbiome, determining the effect of high iron exposure on&#xD;
      gut microbiome and sleep patterns, and comparing iron status and homeostasis between the low&#xD;
      and high iron formula groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Disturbance of the gut microbial colonization during infancy may result in long-term&#xD;
      programming impact of metabolism and disease risks of the host. The early gut microbial&#xD;
      colonization coincides with the maturation of the infant's mucosal innate immune system and&#xD;
      research showed that the gut microbial dysbiosis is associated with impaired innate immune&#xD;
      development. Thus, ensuring proper microbial colonization early in life is critical to the&#xD;
      maturation of the immune system and long-term health.&#xD;
&#xD;
      Iron fortification can increase the abundance of pathogenic bacteria and induce inflammation&#xD;
      in older infants. However, it is still not known what the effect of iron is on a more&#xD;
      vulnerable population: the newborn infant, who has immature immune system. Infants 0-4 months&#xD;
      are at a low risk for iron deficiency due to the iron endowment at birth, which is compatible&#xD;
      with the very low iron content (&lt;0.5mg Fe/L) in breastmilk. However, commercial infant&#xD;
      formulas are all fortified with ≥12mg Fe/L. Whether this striking difference drives adverse&#xD;
      health effects is unknown/unexamined, especially on early colonization and immune&#xD;
      homeostasis. The overall objective is to determine the impact of high vs. low iron exposure&#xD;
      in formula-fed infants during the early post-natal months on gut microbiome.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 28, 2021</start_date>
  <completion_date type="Anticipated">May 2024</completion_date>
  <primary_completion_date type="Anticipated">May 2024</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>
    <intervention_model_description>Participants will be randomized to one of the two groups with different amount of iron consumed.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Gut microbiota</measure>
    <time_frame>birth to 4 months of age</time_frame>
    <description>the gut microbial structure of the participants, by stool samples collected</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Iron status: soluble transferrin receptor</measure>
    <time_frame>at baseline (birth) and end of intervention (4 months)</time_frame>
    <description>Soluble transferrin receptors are proteins found in blood that can be elevated with iron deficiency.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Iron status: ferritin</measure>
    <time_frame>at baseline (birth) and end of intervention (4 months)</time_frame>
    <description>A ferritin blood test shows how much iron is stored in your body.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Iron status: hepcidin</measure>
    <time_frame>at baseline (birth) and end of intervention (4 months)</time_frame>
    <description>Hepcidin is a regulator of iron metabolism.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammation: c-reactive protein</measure>
    <time_frame>at baseline (birth) and end of intervention (4 months)</time_frame>
    <description>C-reactive protein (CRP) is a substance produced by the liver in response to inflammation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunity: soluble CD14</measure>
    <time_frame>at baseline (birth) and end of intervention (4 months)</time_frame>
    <description>biomarker of innate immunity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep patterns: duration</measure>
    <time_frame>end of intervention (4 months)</time_frame>
    <description>Participants will wear a device (Micro Motionlogger Watch version 734) to provide objective measurements of duration.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Infant Development</condition>
  <arm_group>
    <arm_group_label>Standard iron arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to this arm will consume infant formula containing 12 mg/L of iron, equivalent to the standard iron content in U.S. infant formula</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low iron arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to this arm will consume infant formula containing 5 mg/L of iron, equivalent to the standard iron content in European infant formula</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Iron in infant formula</intervention_name>
    <description>Participants will receive the same low-iron (5 mg/L) infant formula. Infants in the standard iron group will add iron supplement to pre-made infant formula so the iron content will be 12 mg/L.</description>
    <arm_group_label>Low iron arm</arm_group_label>
    <arm_group_label>Standard iron arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy new born infants&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Newborn infants with conditions that prohibit cow-milk based formula consumption&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>4 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Minghua Tang, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Minghua Tang, PhD</last_name>
    <phone>7653377572</phone>
    <email>minghua.tang@ucdenver.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Julie Long, MS</last_name>
    <phone>303-724-9377</phone>
    <email>julie.long@ucdenver.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Colorado Anschutz Medical Campus</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Minghua Tang, PhD</last_name>
      <phone>303-724-3248</phone>
      <email>minghua.tang@ucdenver.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>February 1, 2023</last_update_submitted>
  <last_update_submitted_qc>February 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>the gut microbiome sequencing data will be shared</ipd_description>
  </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/NCT03828708
org study id: 18-1317
nct id: NCT03828708
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will look at the amount of iron in infant formula and how that affects a child's
      gut development. The children of mothers who plan to formula feed their children will be
      randomized to receive either high iron or low iron formula from birth until 4 months of age.
      Infants will consume only the study provided formula during enrollment. Blood and stool
      samples will be collected at birth and end of study to measure the effects of the iron
      exposure. The overall object is to compare high iron versus low iron exposure in formula-fed
      infants during the first months of life. Aims include determining the types of bacteria that
      are present in the infants' fecal microbiome, determining the effect of high iron exposure on
      gut microbiome and sleep patterns, and comparing iron status and homeostasis between the low
      and high iron formula groups.
Disturbance of the gut microbial colonization during infancy may result in long-term
      programming impact of metabolism and disease risks of the host. The early gut microbial
      colonization coincides with the maturation of the infant's mucosal innate immune system and
      research showed that the gut microbial dysbiosis is associated with impaired innate immune
      development. Thus, ensuring proper microbial colonization early in life is critical to the
      maturation of the immune system and long-term health.

      Iron fortification can increase the abundance of pathogenic bacteria and induce inflammation
      in older infants. However, it is still not known what the effect of iron is on a more
      vulnerable population: the newborn infant, who has immature immune system. Infants 0-4 months
      are at a low risk for iron deficiency due to the iron endowment at birth, which is compatible
      with the very low iron content (<0.5mg Fe/L) in breastmilk. However, commercial infant
      formulas are all fortified with ≥12mg Fe/L. Whether this striking difference drives adverse
      health effects is unknown/unexamined, especially on early colonization and immune
      homeostasis. The overall objective is to determine the impact of high vs. low iron exposure
      in formula-fed infants during the early post-natal months on gut microbiome.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will be randomized to one of the two groups with different amount of iron consumed.
primary purpose: Basic Science
masking: None (Open Label)
measure: Gut microbiota
time frame: birth to 4 months of age
description: the gut microbial structure of the participants, by stool samples collected
measure: Iron status: soluble transferrin receptor
time frame: at baseline (birth) and end of intervention (4 months)
description: Soluble transferrin receptors are proteins found in blood that can be elevated with iron deficiency.
measure: Iron status: ferritin
time frame: at baseline (birth) and end of intervention (4 months)
description: A ferritin blood test shows how much iron is stored in your body.
measure: Iron status: hepcidin
time frame: at baseline (birth) and end of intervention (4 months)
description: Hepcidin is a regulator of iron metabolism.
measure: Inflammation: c-reactive protein
time frame: at baseline (birth) and end of intervention (4 months)
description: C-reactive protein (CRP) is a substance produced by the liver in response to inflammation.
measure: Immunity: soluble CD14
time frame: at baseline (birth) and end of intervention (4 months)
description: biomarker of innate immunity
measure: Sleep patterns: duration
time frame: end of intervention (4 months)
description: Participants will wear a device (Micro Motionlogger Watch version 734) to provide objective measurements of duration.
arm group label: Standard iron arm
arm group type: Experimental
description: Participants randomized to this arm will consume infant formula containing 12 mg/L of iron, equivalent to the standard iron content in U.S. infant formula
arm group label: Low iron arm
arm group type: Experimental
description: Participants randomized to this arm will consume infant formula containing 5 mg/L of iron, equivalent to the standard iron content in European infant formula
intervention type: Other
intervention name: Iron in infant formula
description: Participants will receive the same low-iron (5 mg/L) infant formula. Infants in the standard iron group will add iron supplement to pre-made infant formula so the iron content will be 12 mg/L.
arm group label: Low iron arm
arm group label: Standard iron arm
criteria: 
gender: All
minimum age: 1 Day
maximum age: 4 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Minghua Tang, PhD
role: Principal Investigator
affiliation: University of Colorado, Denver
last name: Minghua Tang, PhD
phone: 7653377572
email: minghua.tang@ucdenver.edu
last name: Julie Long, MS
phone: 303-724-9377
email: julie.long@ucdenver.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
sharing ipd: Undecided
ipd description: the gut microbiome sequencing data will be shared