<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/NCT03751137</url>
  </required_header>
  <id_info>
    <org_study_id>822736</org_study_id>
    <nct_id>NCT03751137</nct_id>
  </id_info>
  <brief_title>GI Tract Biomarkers in Infants With Different Diets</brief_title>
  <official_title>Longitudinal, Prospective Comparison of the Gastrointestinal Tract of Breastfed and Formula Fed Infants Via Fecal Analysis of the Microbiome, Intestinal Epithelial Cell Expression of Gut Hormones, and Fecal Analysis of the Metabolome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nemours Children's Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Delaware</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nemours Children's Clinic</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>
      Childhood obesity is increasing with more than one-third of adolescents currently overweight&#xD;
      and one in five with obesity. The lifelong incidence of obesity-related morbidities is also&#xD;
      increasing with childhood obesity. It is not yet known how obesity develops in an individual,&#xD;
      specifically in early childhood. Further, it is unclear what mechanistic role a child's&#xD;
      earliest nutrition or changing intestinal flora has in the etiology of obesity. Very young&#xD;
      children are developing appetite and satiety patterns early in life. Nutrition and gut&#xD;
      microbial flora have impact on how these processes unfold, but specific mechanisms are not&#xD;
      yet well understood. The investigators hypothesize that formula-fed infants with changes in&#xD;
      their microbial flora are more likely to have altered carbohydrate metabolism, evidenced by&#xD;
      greater imbalances of fatty acid production, and are more likely to have accelerated growth&#xD;
      trajectory due to satiety disruption. The investigators further hypothesize that altered&#xD;
      carbohydrate metabolism, e.g. imbalances of short- and long-chain fatty acid levels in the&#xD;
      gut, stimulate cellular stress and affect specific gut hormones. This study will compare the&#xD;
      microbiome of the intestinal microbial flora in two groups of infants, one breast fed and the&#xD;
      other formula fed, using longitudinally collected fecal samples from both groups. Samples&#xD;
      will be subjected to shotgun metagenomic analysis and simultaneous metabolomic analysis. A&#xD;
      bioinformatics approach will elucidate key differences among and between sample groups, and&#xD;
      will further analyze bacterial gene expression levels related to carbohydrate metabolism.&#xD;
      This study will compare the expression of human proteins involved in cellular stress response&#xD;
      and gut peptide signaling by applying quantitative Reverse Transcriptase-Polymerase Chain&#xD;
      Reaction to human messenger RNA isolated from the longitudinally collected samples from both&#xD;
      groups. Finally, this study will monitor the trajectory of growth and feeding over the first&#xD;
      2 years of life. The project's focus on the influence of different early feeding types,&#xD;
      microbial flora changes, and altered carbohydrate metabolism leading to disruption of&#xD;
      gut-brain signaling will provide critical data for host:microbiome interactions and&#xD;
      translational therapeutic targets.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 10, 2016</start_date>
  <completion_date type="Anticipated">June 30, 2023</completion_date>
  <primary_completion_date type="Actual">July 31, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Microbiome</measure>
    <time_frame>Enrollment</time_frame>
    <description>Metagenomic analysis of microbial organisms in infant's feces</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Microbiome</measure>
    <time_frame>6 months</time_frame>
    <description>Metagenomic analysis of microbial organisms in infant's feces</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Microbiome</measure>
    <time_frame>12 months</time_frame>
    <description>Metagenomic analysis of microbial organisms in infant's feces</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Microbiome</measure>
    <time_frame>18 months</time_frame>
    <description>Metagenomic analysis of microbial organisms in infant's feces</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Metabolome</measure>
    <time_frame>Enrollment</time_frame>
    <description>Metabolic products present in infant's feces</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolome</measure>
    <time_frame>6 months</time_frame>
    <description>Metabolic products present in infant's feces</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolome</measure>
    <time_frame>12 months</time_frame>
    <description>Metabolic products present in infant's feces</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolome</measure>
    <time_frame>18 months</time_frame>
    <description>Metabolic products present in infant's feces</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gut hormone gene expression</measure>
    <time_frame>Enrollment</time_frame>
    <description>Transcriptional output of human epithelial cells in infant's feces</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gut hormone gene expression</measure>
    <time_frame>6 months</time_frame>
    <description>Transcriptional output of human epithelial cells in infant's feces</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gut hormone gene expression</measure>
    <time_frame>12 months</time_frame>
    <description>Transcriptional output of human epithelial cells in infant's feces</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gut hormone gene expression</measure>
    <time_frame>18 months</time_frame>
    <description>Transcriptional output of human epithelial cells in infant's feces</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Obesity, Childhood</condition>
  <arm_group>
    <arm_group_label>Breast Feeding</arm_group_label>
    <description>Infants who, when enrolled, are exclusively breast feeding.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Formula Feeding</arm_group_label>
    <description>Infants who, when enrolled, are exclusively formula feeding.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Fecal samples containing microbial genetic material and, to a lesser degree, human intestinal&#xD;
      epithelial cells with human genetic material.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Infants who are either exclusively breast feeding or exclusively formula feeding are&#xD;
        eligible to enroll if meeting other criteria.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Otherwise healthy, male or female term infants&#xD;
&#xD;
          -  Exclusively breast or formula feeding&#xD;
&#xD;
          -  Never been exposed to oral or intravenous antibiotics or probiotics&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Maternal antibiotic use while breast-feeding&#xD;
&#xD;
          -  Infant or maternal use of probiotics&#xD;
&#xD;
          -  Current or recent (&lt;14 days) gastrointestinal infection (viral, bacterial, or fungal)&#xD;
&#xD;
          -  Gastrointestinal mucosal disease, or significant constipation&#xD;
&#xD;
          -  Consuming formula that is not standard cow's milk formula&#xD;
&#xD;
          -  Infants on acid suppression medications or infants receiving high-density formula (&gt;20&#xD;
             calories/ounce) may be enrolled and will be analyzed separately&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Weeks</minimum_age>
    <maximum_age>3 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Matthew Di Guglielmo, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nemours</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nemours Children's Hospital - Delaware</name>
      <address>
        <city>Wilmington</city>
        <state>Delaware</state>
        <zip>19803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Di Guglielmo MD, Franke KR, Robbins A, Crowgey EL. Impact of Early Feeding: Metagenomics Analysis of the Infant Gut Microbiome. Front Cell Infect Microbiol. 2022 Mar 4;12:816601. doi: 10.3389/fcimb.2022.816601. eCollection 2022.</citation>
    <PMID>35310842</PMID>
  </results_reference>
  <results_reference>
    <citation>Di Guglielmo MD, Franke K, Cox C, Crowgey EL. Whole genome metagenomic analysis of the gut microbiome of differently fed infants identifies differences in microbial composition and functional genes, including an absent CRISPR/Cas9 gene in the formula-fed cohort. Hum Microb J. 2019 Jun;12:100057. doi: 10.1016/j.humic.2019.100057. Epub 2019 May 25.</citation>
    <PMID>34278055</PMID>
  </results_reference>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>November 16, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>December 8, 2022</last_update_submitted>
  <last_update_submitted_qc>December 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Microbiome</keyword>
  <keyword>Gut-brain axis</keyword>
  <keyword>Satiety</keyword>
  <keyword>Hormone</keyword>
  <keyword>Obesity</keyword>
  <keyword>Metabolome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pediatric Obesity</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>We will release deidentified metagenomic sequencing data from each participant to either database of Genotypes and Phenotypes (dbGaP) or Sequence Read Archive (SRA).</ipd_description>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>At the conclusion of the study</ipd_time_frame>
    <ipd_access_criteria>To be determined</ipd_access_criteria>
  </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/NCT03751137
org study id: 822736
nct id: NCT03751137
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Childhood obesity is increasing with more than one-third of adolescents currently overweight
      and one in five with obesity. The lifelong incidence of obesity-related morbidities is also
      increasing with childhood obesity. It is not yet known how obesity develops in an individual,
      specifically in early childhood. Further, it is unclear what mechanistic role a child's
      earliest nutrition or changing intestinal flora has in the etiology of obesity. Very young
      children are developing appetite and satiety patterns early in life. Nutrition and gut
      microbial flora have impact on how these processes unfold, but specific mechanisms are not
      yet well understood. The investigators hypothesize that formula-fed infants with changes in
      their microbial flora are more likely to have altered carbohydrate metabolism, evidenced by
      greater imbalances of fatty acid production, and are more likely to have accelerated growth
      trajectory due to satiety disruption. The investigators further hypothesize that altered
      carbohydrate metabolism, e.g. imbalances of short- and long-chain fatty acid levels in the
      gut, stimulate cellular stress and affect specific gut hormones. This study will compare the
      microbiome of the intestinal microbial flora in two groups of infants, one breast fed and the
      other formula fed, using longitudinally collected fecal samples from both groups. Samples
      will be subjected to shotgun metagenomic analysis and simultaneous metabolomic analysis. A
      bioinformatics approach will elucidate key differences among and between sample groups, and
      will further analyze bacterial gene expression levels related to carbohydrate metabolism.
      This study will compare the expression of human proteins involved in cellular stress response
      and gut peptide signaling by applying quantitative Reverse Transcriptase-Polymerase Chain
      Reaction to human messenger RNA isolated from the longitudinally collected samples from both
      groups. Finally, this study will monitor the trajectory of growth and feeding over the first
      2 years of life. The project's focus on the influence of different early feeding types,
      microbial flora changes, and altered carbohydrate metabolism leading to disruption of
      gut-brain signaling will provide critical data for host:microbiome interactions and
      translational therapeutic targets.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Microbiome
time frame: Enrollment
description: Metagenomic analysis of microbial organisms in infant's feces
measure: Microbiome
time frame: 6 months
description: Metagenomic analysis of microbial organisms in infant's feces
measure: Microbiome
time frame: 12 months
description: Metagenomic analysis of microbial organisms in infant's feces
measure: Microbiome
time frame: 18 months
description: Metagenomic analysis of microbial organisms in infant's feces
measure: Metabolome
time frame: Enrollment
description: Metabolic products present in infant's feces
measure: Metabolome
time frame: 6 months
description: Metabolic products present in infant's feces
measure: Metabolome
time frame: 12 months
description: Metabolic products present in infant's feces
measure: Metabolome
time frame: 18 months
description: Metabolic products present in infant's feces
measure: Gut hormone gene expression
time frame: Enrollment
description: Transcriptional output of human epithelial cells in infant's feces
measure: Gut hormone gene expression
time frame: 6 months
description: Transcriptional output of human epithelial cells in infant's feces
measure: Gut hormone gene expression
time frame: 12 months
description: Transcriptional output of human epithelial cells in infant's feces
measure: Gut hormone gene expression
time frame: 18 months
description: Transcriptional output of human epithelial cells in infant's feces
arm group label: Breast Feeding
description: Infants who, when enrolled, are exclusively breast feeding.
arm group label: Formula Feeding
description: Infants who, when enrolled, are exclusively formula feeding.
Fecal samples containing microbial genetic material and, to a lesser degree, human intestinal
      epithelial cells with human genetic material.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Weeks
maximum age: 3 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Matthew Di Guglielmo, MD PhD
role: Principal Investigator
affiliation: Nemours
facility: 
country: United States
citation: Di Guglielmo MD, Franke KR, Robbins A, Crowgey EL. Impact of Early Feeding: Metagenomics Analysis of the Infant Gut Microbiome. Front Cell Infect Microbiol. 2022 Mar 4;12:816601. doi: 10.3389/fcimb.2022.816601. eCollection 2022.
PMID: 35310842
citation: Di Guglielmo MD, Franke K, Cox C, Crowgey EL. Whole genome metagenomic analysis of the gut microbiome of differently fed infants identifies differences in microbial composition and functional genes, including an absent CRISPR/Cas9 gene in the formula-fed cohort. Hum Microb J. 2019 Jun;12:100057. doi: 10.1016/j.humic.2019.100057. Epub 2019 May 25.
PMID: 34278055
responsible party type: Sponsor
mesh term: Pediatric Obesity
sharing ipd: Yes
ipd description: We will release deidentified metagenomic sequencing data from each participant to either database of Genotypes and Phenotypes (dbGaP) or Sequence Read Archive (SRA).
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Analytic Code
ipd time frame: At the conclusion of the study
ipd access criteria: To be determined