<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/NCT03229967</url>
  </required_header>
  <id_info>
    <org_study_id>17-05311-XP</org_study_id>
    <nct_id>NCT03229967</nct_id>
  </id_info>
  <brief_title>Gastrointestinal Microbiome Influence on the Development of Bronchopulmonary Dysplasia</brief_title>
  <acronym>MiBPD</acronym>
  <official_title>Gastrointestinal Microbiota Influence on the Pathogenesis of Bronchopulmonary Dysplasia in Very Low Birthweight Neonates</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Tennessee</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Tennessee</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>
      The purpose of this study is to advance our knowledge of the factors that contribute to the&#xD;
      development of bronchopulmonary dysplasia (BPD), a chronic lung affecting premature infants.&#xD;
      Specifically, the investigators will determine the complexity of the gut microbiota, the&#xD;
      genera of the bacteria that naturally live in the gut, and determine if the relative&#xD;
      diversity of the gut bacteria is a prognostic indicator of BPD. To accomplish this, the&#xD;
      investigators propose to characterize the microbiota of human premature newborns with BPD,&#xD;
      then validate this potential mechanism in mice. The investigators will enroll very low&#xD;
      birthweight premature infants admitted to the neonatal intensive care units (NICU) at Le&#xD;
      Bonheur Children's Hospital and Regional One Health that are at high risk to develop BPD. A&#xD;
      cohort of well full term newborns will also be enrolled. Non-invasive stool samples will be&#xD;
      obtained weekly over the first month of life. Infants that eventually develop BPD will be&#xD;
      paired with infants that did not develop BPD. Stool samples from these infants will be sent&#xD;
      for analysis. The investigators expect that reduced complexity of the gut microbiome is&#xD;
      associated with BPD. The investigators will model the contribution of reduced microbiome&#xD;
      complexity to the risk to develop BPD or death, as well as the association with disease&#xD;
      severity. The project investigates important factors leading to the development of BPD, and&#xD;
      has the potential to directly translate to therapy for the most significant pulmonary&#xD;
      complication of prematurity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 5, 2017</start_date>
  <completion_date type="Actual">December 30, 2020</completion_date>
  <primary_completion_date type="Actual">December 30, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Bronchopulmonary dysplasia (BPD)</measure>
    <time_frame>36 weeks corrected gestational age, until the date of death or initial hospital discharge whichever occurs first, assessed up to up to 3 months</time_frame>
    <description>National Institute of Child Health and Disease (NICHD) consensus definition</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Death</measure>
    <time_frame>from the date of enrollment until the date of death or initial hospital discharge, whichever occurs first, assessed up to up to 3 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Necrotizing Enterocolitis (NEC)</measure>
    <time_frame>from the date of enrollment until the date of initial hospital discharge or death, whichever occurs first, assessed up to up to 3 months</time_frame>
    <description>Modified Bell's staging for NEC &gt; Stage 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal Chorioamnionitis</measure>
    <time_frame>presence on admission</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Maternal perinatal antibiotic exposure</measure>
    <time_frame>from hospital admission until birth of infant</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Infant antibiotic exposure</measure>
    <time_frame>birth until 36 weeks corrected gestational age</time_frame>
  </other_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">197</enrollment>
  <condition>Bronchopulmonary Dysplasia</condition>
  <arm_group>
    <arm_group_label>Exploration Cohort</arm_group_label>
    <description>Up to 150 VLBW (very low birthweight) infants enrolled from the Regional One Health NICU (neonatal intensive care unit). Weekly stool samples will be obtained. After 36 weeks infants diagnosed with BPD per NIH guidelines, will be matched with infants without BPD. Stool samples from these infants will be sent for 16s rRNA (ribosomal ribonucleic acid) sequencing after conclusion of initial enrollment period. ITS (internal transcribed spacer) DNA may also be used to characterize fungal communities.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Validation Cohort</arm_group_label>
    <description>Up to 10 VLBW infants enrolled from the Le Bonheur Children's Hospital NICU. Weekly stool samples will be obtained. After 36 weeks infants diagnosed with BPD per NIH guidelines willl be matched with infants without BPD. Stool samples from these infants will be sent for 16s rRNA sequencing after conclusion of initial enrollment period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Well Baby Cohort</arm_group_label>
    <description>40 Well Baby Infants have been enrolled and may be used for secondary analysis of microbial community composition of the meconium.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>16S rRNA stool microbiome sequencing.</intervention_name>
    <description>This is an observational cohort that will undergo gut microbiome sequencing.</description>
    <arm_group_label>Exploration Cohort</arm_group_label>
    <arm_group_label>Validation Cohort</arm_group_label>
    <arm_group_label>Well Baby Cohort</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Fecal Stool Sample (contains bacterial and fungal DNA)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Study Population will be composed of VLBW infants (birthweight less than 1500 grams) and&#xD;
        their mothers (Including 40 term infants and their mothers)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Newborn humans less than 1 week of age with a birthweight less than 1,500 g, or&#xD;
             fetuses with impending delivery and estimated birthweight of less than 1,500 grams. No&#xD;
             individuals will be excluded on the basis of sex or ethnicity.&#xD;
&#xD;
          2. Parents can understand and comply with planned study procedures.&#xD;
&#xD;
          3. Parents provide assent/permission prior to any study procedures.&#xD;
&#xD;
        Inclusion criteria mothers:&#xD;
&#xD;
        1. The mother's of infants meeting the infant inclusion criteria above.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diagnosed immunodeficiency disorder.&#xD;
&#xD;
          2. Currently receiving investigational immunomodulatory, probiotic or antiviral agent.&#xD;
&#xD;
          3. Infants whose mothers meet the exclusion criteria below.&#xD;
&#xD;
        Exclusion criteria mothers:&#xD;
&#xD;
          1. Diagnosed immunodeficiency disorder&#xD;
&#xD;
          2. Currently receiving investigational immunomodulatory, probiotic or antiviral agents&#xD;
&#xD;
          3. Lacking the mental capacity (e.g. due to pain, anesthesia, mental impairment) to&#xD;
             provide informed consent for themselves or assent for the participation of their&#xD;
             infant.&#xD;
&#xD;
          4. Having an infant that meets the infant exclusion criteria.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Days</minimum_age>
    <maximum_age>7 Days</maximum_age>
  </eligibility>
  <location>
    <facility>
      <name>LeBonheur Children's Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional One Health</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Willis KA, Purvis JH, Myers ED, Aziz MM, Karabayir I, Gomes CK, Peters BM, Akbilgic O, Talati AJ, Pierre JF. Fungi form interkingdom microbial communities in the primordial human gut that develop with gestational age. FASEB J. 2019 Nov;33(11):12825-12837. doi: 10.1096/fj.201901436RR. Epub 2019 Aug 31.</citation>
    <PMID>31480903</PMID>
  </results_reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 11, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>May 8, 2023</last_update_submitted>
  <last_update_submitted_qc>May 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Tennessee</investigator_affiliation>
    <investigator_full_name>Kent Avery Willis, MD</investigator_full_name>
    <investigator_title>Neonatal-Perinatal Medicine Fellow</investigator_title>
  </responsible_party>
  <keyword>Bronchopulmonary dysplasia</keyword>
  <keyword>Microbiome</keyword>
  <keyword>Microbiota</keyword>
  <keyword>Premature infant</keyword>
  <keyword>Observational cohort study</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchopulmonary Dysplasia</mesh_term>
    <mesh_term>Hyperplasia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>MiSeq data will be placed in a public repository</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 30, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT03229967/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03229967
org study id: 17-05311-XP
nct id: NCT03229967
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to advance our knowledge of the factors that contribute to the
      development of bronchopulmonary dysplasia (BPD), a chronic lung affecting premature infants.
      Specifically, the investigators will determine the complexity of the gut microbiota, the
      genera of the bacteria that naturally live in the gut, and determine if the relative
      diversity of the gut bacteria is a prognostic indicator of BPD. To accomplish this, the
      investigators propose to characterize the microbiota of human premature newborns with BPD,
      then validate this potential mechanism in mice. The investigators will enroll very low
      birthweight premature infants admitted to the neonatal intensive care units (NICU) at Le
      Bonheur Children's Hospital and Regional One Health that are at high risk to develop BPD. A
      cohort of well full term newborns will also be enrolled. Non-invasive stool samples will be
      obtained weekly over the first month of life. Infants that eventually develop BPD will be
      paired with infants that did not develop BPD. Stool samples from these infants will be sent
      for analysis. The investigators expect that reduced complexity of the gut microbiome is
      associated with BPD. The investigators will model the contribution of reduced microbiome
      complexity to the risk to develop BPD or death, as well as the association with disease
      severity. The project investigates important factors leading to the development of BPD, and
      has the potential to directly translate to therapy for the most significant pulmonary
      complication of prematurity.
observational model: Cohort
time perspective: Prospective
measure: Bronchopulmonary dysplasia (BPD)
time frame: 36 weeks corrected gestational age, until the date of death or initial hospital discharge whichever occurs first, assessed up to up to 3 months
description: National Institute of Child Health and Disease (NICHD) consensus definition
measure: Death
time frame: from the date of enrollment until the date of death or initial hospital discharge, whichever occurs first, assessed up to up to 3 months
measure: Necrotizing Enterocolitis (NEC)
time frame: from the date of enrollment until the date of initial hospital discharge or death, whichever occurs first, assessed up to up to 3 months
description: Modified Bell's staging for NEC > Stage 2
measure: Maternal Chorioamnionitis
time frame: presence on admission
measure: Maternal perinatal antibiotic exposure
time frame: from hospital admission until birth of infant
measure: Infant antibiotic exposure
time frame: birth until 36 weeks corrected gestational age
arm group label: Exploration Cohort
description: Up to 150 VLBW (very low birthweight) infants enrolled from the Regional One Health NICU (neonatal intensive care unit). Weekly stool samples will be obtained. After 36 weeks infants diagnosed with BPD per NIH guidelines, will be matched with infants without BPD. Stool samples from these infants will be sent for 16s rRNA (ribosomal ribonucleic acid) sequencing after conclusion of initial enrollment period. ITS (internal transcribed spacer) DNA may also be used to characterize fungal communities.
arm group label: Validation Cohort
description: Up to 10 VLBW infants enrolled from the Le Bonheur Children's Hospital NICU. Weekly stool samples will be obtained. After 36 weeks infants diagnosed with BPD per NIH guidelines willl be matched with infants without BPD. Stool samples from these infants will be sent for 16s rRNA sequencing after conclusion of initial enrollment period.
arm group label: Well Baby Cohort
description: 40 Well Baby Infants have been enrolled and may be used for secondary analysis of microbial community composition of the meconium.
intervention type: Diagnostic Test
intervention name: 16S rRNA stool microbiome sequencing.
description: This is an observational cohort that will undergo gut microbiome sequencing.
arm group label: Exploration Cohort
arm group label: Validation Cohort
arm group label: Well Baby Cohort
Fecal Stool Sample (contains bacterial and fungal DNA)
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 0 Days
maximum age: 7 Days
facility: 
facility: 
country: United States
citation: Willis KA, Purvis JH, Myers ED, Aziz MM, Karabayir I, Gomes CK, Peters BM, Akbilgic O, Talati AJ, Pierre JF. Fungi form interkingdom microbial communities in the primordial human gut that develop with gestational age. FASEB J. 2019 Nov;33(11):12825-12837. doi: 10.1096/fj.201901436RR. Epub 2019 Aug 31.
PMID: 31480903
responsible party type: Principal Investigator
investigator affiliation: University of Tennessee
investigator full name: Kent Avery Willis, MD
investigator title: Neonatal-Perinatal Medicine Fellow
mesh term: Bronchopulmonary Dysplasia
mesh term: Hyperplasia
sharing ipd: No
ipd description: MiSeq data will be placed in a public repository
provided document: 