<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/NCT03298334</url>
  </required_header>
  <id_info>
    <org_study_id>17-2694</org_study_id>
    <nct_id>NCT03298334</nct_id>
  </id_info>
  <brief_title>Vaginal Microbiome Seeding and Health Outcomes in Cesarean-delivered Neonates.</brief_title>
  <official_title>Vaginal Microbiome Seeding and Health Outcomes in Cesarean-delivered Neonates: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rutgers University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Inova Health Care Services</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Neonates delivered by scheduled Cesarean Section will be randomized to receive vaginal&#xD;
      seeding (exposing the infant to Mother's vaginal flora) or sham. Infants will be followed for&#xD;
      three years to examine health outcomes including microbiome development, immune development,&#xD;
      metabolic outcomes, and any adverse events.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cesarean section (CS) delivery is a common surgical procedure intended to increase the&#xD;
      chances of successful delivery and to protect the health of the mother and baby. Yet this&#xD;
      intervention is overused and has been associated with higher risk of immune and metabolic&#xD;
      disorders in the offspring. It is hypothesized that these associations are due to&#xD;
      CS-delivered newborns not receiving the full inoculum of maternal microbes at birth.&#xD;
&#xD;
      While restoring labor is not possible, restoring the microbes that colonize infants during&#xD;
      birth through exposure to vaginal flora, is feasible, and has been shown in a small pilot&#xD;
      study, to normalize the microbiota of the intestine, skin and mouth during the first month of&#xD;
      life.&#xD;
&#xD;
      The investigators hypothesize that the restoration of the vaginal microbiota to the infant at&#xD;
      birth will restore the infant microbiome and decrease the risk of obesity and other&#xD;
      immune-mediated diseases linked with CS. The investigators aim to test this hypothesis in a&#xD;
      randomized controlled trial by first examining the effect of vaginal seeding, in CS-delivered&#xD;
      newborns, on the gut microbiota composition, structure and function (Phase I of study; first&#xD;
      50 infants) and then on the BMI z score and other immune-mediated outcomes (Phase II of&#xD;
      study; 600 infants).&#xD;
&#xD;
      Methods: CS-delivered neonates will be randomized to either an experimental arm with exposure&#xD;
      to the maternal vaginal microbiota at birth, or a control arm with no exposure. Feces, skin,&#xD;
      saliva, breast milk, and vaginal swabs will be collected for microbiome analysis. The&#xD;
      investigators will obtain clinical information from in-person visits, surveys and the&#xD;
      electronic health record.&#xD;
&#xD;
      Implications: this randomized controlled clinical study will provide evidence of whether the&#xD;
      &quot;vaginal seeding&quot; procedure can safely transfer microbes from mom-to-baby, and whether these&#xD;
      microbes are beneficial for the metabolic and immune health of the child.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2018</start_date>
  <completion_date type="Anticipated">April 2029</completion_date>
  <primary_completion_date type="Anticipated">April 2027</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adiposity</measure>
    <time_frame>2 years</time_frame>
    <description>E.g. Body mass index z-score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>3 years</time_frame>
    <description>Monitoring for adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intestinal microbiota</measure>
    <time_frame>3 years</time_frame>
    <description>Intestinal microbiota development over the first three years of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune and inflammatory regulation</measure>
    <time_frame>3 years</time_frame>
    <description>E.g. Monitoring for immune and inflammatory mediated conditions</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">600</enrollment>
  <condition>Cesarean Delivery Affecting Newborn</condition>
  <condition>Obesity, Childhood</condition>
  <condition>Intestinal Microbiome</condition>
  <condition>Microbiota</condition>
  <condition>Host Microbial Interactions</condition>
  <condition>Gastrointestinal Microbiome</condition>
  <arm_group>
    <arm_group_label>Receives Vaginal Seeding</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>No Vaginal Seeding</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Vaginal Seeding</intervention_name>
    <description>A gauze containing the Mother's vaginal flora will be swabbed over the face and body of the neonate shortly after cesarean delivery.</description>
    <arm_group_label>Receives Vaginal Seeding</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No Vaginal Seeding</intervention_name>
    <description>A gauze carrying sterile saline will be swabbed over the face and body of the neonate shortly after cesarean delivery.</description>
    <arm_group_label>No Vaginal Seeding</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria for Mother:&#xD;
&#xD;
          -  Scheduled for cesarean delivery at ≥ 37 weeks&#xD;
&#xD;
          -  Pregnant with single fetus, in good general health, age 18 years or older&#xD;
&#xD;
          -  Negative maternal testing for infections transmitted through vaginal and/or other body&#xD;
             fluids performed as standard of care tests in early pregnancy&#xD;
&#xD;
          -  Negative testing for Group B strep at 35-37 weeks gestation&#xD;
&#xD;
          -  Vaginal pH ≤ 4.5 indicative of Lactobacillus-dominated vaginal microbiota&#xD;
&#xD;
          -  No maternal or fetal complications that may inhibit the ability to perform microbiome&#xD;
             restoration per protocol&#xD;
&#xD;
          -  English or Spanish speaking&#xD;
&#xD;
          -  Negative maternal testing for Gonorrhea, Chlamydia, Hepatitis B, Hepatitis C,&#xD;
             Syphilis, and HIV at 35 weeks gestation or later&#xD;
&#xD;
          -  Women aged 18-29 years must have a normal Pap test within 3 years&#xD;
&#xD;
          -  Women aged 30-65 years must have a normal Pap test and an HPV test (co-testing) within&#xD;
             5 years or FDA-approved primary hrHPV testing alone within 5 years or a normal Pap&#xD;
             test alone within 3 years&#xD;
&#xD;
          -  Negative maternal testing for SARS-CoV-2 for the delivery admission performed as&#xD;
             standard of care test at the Inova Health System.&#xD;
&#xD;
        Inclusion Criteria for Infant:&#xD;
&#xD;
          -  Infant condition after delivery requires no more than standard neonatal resuscitation*&#xD;
             or is otherwise medically unable to receive the full VMT procedure&#xD;
&#xD;
        [*] Standard neonatal resuscitation may include: tactile stimulation, bulb suction, oxygen&#xD;
        without positive pressure, or drying&#xD;
&#xD;
        Exclusion Criteria for Mother:&#xD;
&#xD;
          -  Delivery at a hospital other than Inova Health System&#xD;
&#xD;
          -  Cesarean delivery scheduled for active infection that would have interfered with&#xD;
             vaginal delivery such as genital herpetic lesions&#xD;
&#xD;
          -  Rupture of membranes prior to scheduled cesarean delivery&#xD;
&#xD;
          -  Bacterial vaginosis within 30 days of cesarean delivery&#xD;
&#xD;
          -  Symptomatic urinary tract infection within 30 days of cesarean delivery&#xD;
&#xD;
          -  Antibiotic therapy within 30 days of cesarean delivery (exclusive of medication use&#xD;
             for prophylaxis at the time of surgery)&#xD;
&#xD;
          -  Symptoms on admission suggesting Chorioamnionitis, e.g. maternal fever, fundal&#xD;
             tenderness&#xD;
&#xD;
          -  Symptoms on delivery admission of possible vaginal infection such as genital herpetic&#xD;
             lesions&#xD;
&#xD;
          -  History of genital HSV&#xD;
&#xD;
          -  History positive testing for Group B strep infection&#xD;
&#xD;
          -  History of a child with a diagnosis of Group B strep sepsis&#xD;
&#xD;
          -  Pregnancy a result of donor egg or surrogacy&#xD;
&#xD;
          -  Preexisting history of Type I or Type II Diabetes&#xD;
&#xD;
          -  Maternal history of documented genital HPV infection, positive HPV testing or genital&#xD;
             warts on physician examination&#xD;
&#xD;
          -  Positive maternal testing for SARS-CoV-2 within 30 days of delivery or symptoms on&#xD;
             admission suggesting potential Covid-19 infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Days</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Suchitra Hourigan, MD, Chief, Clinical Microbiome Unit, NIAID, Pediatric Gastroenterologist</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Allergy and Infectious Diseases (NIAID), Inova Children's Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Noel Mueller, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Maria Gloria Dominguez Bello, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rutgers University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lawrence Appel, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Suchitra Hourigan, MD</last_name>
    <phone>703-776-8489</phone>
    <email>suchitra.hourigan@inova.org, suchitra.hourigan@nih.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Shira Levy</last_name>
    <phone>703-776-8489</phone>
    <email>shira.levy@inova.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Inova Health System</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <zip>22042</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Suchitra Hourigan, MD</last_name>
      <phone>703-776-8489</phone>
      <email>suchitra.hourigan@inova.org, suchitra.hourigan@nih.gov</email>
    </contact>
    <contact_backup>
      <last_name>General Information</last_name>
      <email>microbiome@inova.org</email>
    </contact_backup>
    <investigator>
      <last_name>Ankit Shah, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, Bokulich NA, Song SJ, Hoashi M, Rivera-Vinas JI, Mendez K, Knight R, Clemente JC. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med. 2016 Mar;22(3):250-3. doi: 10.1038/nm.4039. Epub 2016 Feb 1.</citation>
    <PMID>26828196</PMID>
  </reference>
  <reference>
    <citation>Song SJ, Wang J, Martino C, Jiang L, Thompson WK, Shenhav L, McDonald D, Marotz C, Harris PR, Hernandez CD, Henderson N, Ackley E, Nardella D, Gillihan C, Montacuti V, Schweizer W, Jay M, Combellick J, Sun H, Garcia-Mantrana I, Gil Raga F, Collado MC, Rivera-Vinas JI, Campos-Rivera M, Ruiz-Calderon JF, Knight R, Dominguez-Bello MG. Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding. Med. 2021 Aug 13;2(8):951-964.e5. doi: 10.1016/j.medj.2021.05.003. Epub 2021 Jun 17.</citation>
    <PMID>35590169</PMID>
  </reference>
  <reference>
    <citation>Hourigan SK, Dominguez-Bello MG, Mueller NT. Can maternal-child microbial seeding interventions improve the health of infants delivered by Cesarean section? Cell Host Microbe. 2022 May 11;30(5):607-611. doi: 10.1016/j.chom.2022.02.014.</citation>
    <PMID>35550663</PMID>
  </reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 2, 2017</study_first_posted>
  <last_update_submitted>January 18, 2023</last_update_submitted>
  <last_update_submitted_qc>January 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Individual participant data will be shared with co-principal investigators (Maria Gloria Dominguez-Bello at Rutgers University and Noel Mueller at Johns Hopkins School of Medicine).</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
  </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/NCT03298334
org study id: 17-2694
nct id: NCT03298334
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Neonates delivered by scheduled Cesarean Section will be randomized to receive vaginal
      seeding (exposing the infant to Mother's vaginal flora) or sham. Infants will be followed for
      three years to examine health outcomes including microbiome development, immune development,
      metabolic outcomes, and any adverse events.
Cesarean section (CS) delivery is a common surgical procedure intended to increase the
      chances of successful delivery and to protect the health of the mother and baby. Yet this
      intervention is overused and has been associated with higher risk of immune and metabolic
      disorders in the offspring. It is hypothesized that these associations are due to
      CS-delivered newborns not receiving the full inoculum of maternal microbes at birth.

      While restoring labor is not possible, restoring the microbes that colonize infants during
      birth through exposure to vaginal flora, is feasible, and has been shown in a small pilot
      study, to normalize the microbiota of the intestine, skin and mouth during the first month of
      life.

      The investigators hypothesize that the restoration of the vaginal microbiota to the infant at
      birth will restore the infant microbiome and decrease the risk of obesity and other
      immune-mediated diseases linked with CS. The investigators aim to test this hypothesis in a
      randomized controlled trial by first examining the effect of vaginal seeding, in CS-delivered
      newborns, on the gut microbiota composition, structure and function (Phase I of study; first
      50 infants) and then on the BMI z score and other immune-mediated outcomes (Phase II of
      study; 600 infants).

      Methods: CS-delivered neonates will be randomized to either an experimental arm with exposure
      to the maternal vaginal microbiota at birth, or a control arm with no exposure. Feces, skin,
      saliva, breast milk, and vaginal swabs will be collected for microbiome analysis. The
      investigators will obtain clinical information from in-person visits, surveys and the
      electronic health record.

      Implications: this randomized controlled clinical study will provide evidence of whether the
      "vaginal seeding" procedure can safely transfer microbes from mom-to-baby, and whether these
      microbes are beneficial for the metabolic and immune health of the child.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
measure: Adiposity
time frame: 2 years
description: E.g. Body mass index z-score
measure: Adverse events
time frame: 3 years
description: Monitoring for adverse events
measure: Intestinal microbiota
time frame: 3 years
description: Intestinal microbiota development over the first three years of life
measure: Immune and inflammatory regulation
time frame: 3 years
description: E.g. Monitoring for immune and inflammatory mediated conditions
arm group label: Receives Vaginal Seeding
arm group type: Active Comparator
arm group label: No Vaginal Seeding
arm group type: Sham Comparator
intervention type: Biological
intervention name: Vaginal Seeding
description: A gauze containing the Mother's vaginal flora will be swabbed over the face and body of the neonate shortly after cesarean delivery.
arm group label: Receives Vaginal Seeding
intervention type: Other
intervention name: No Vaginal Seeding
description: A gauze carrying sterile saline will be swabbed over the face and body of the neonate shortly after cesarean delivery.
arm group label: No Vaginal Seeding
criteria: 
gender: All
minimum age: 0 Days
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Suchitra Hourigan, MD, Chief, Clinical Microbiome Unit, NIAID, Pediatric Gastroenterologist
role: Principal Investigator
affiliation: National Institute of Allergy and Infectious Diseases (NIAID), Inova Children's Hospital
last name: Noel Mueller, PhD
role: Principal Investigator
affiliation: Johns Hopkins University
last name: Maria Gloria Dominguez Bello, PhD
role: Principal Investigator
affiliation: Rutgers University
last name: Lawrence Appel, MD, MPH
role: Principal Investigator
affiliation: Johns Hopkins University
last name: Suchitra Hourigan, MD
phone: 703-776-8489
email: suchitra.hourigan@inova.org, suchitra.hourigan@nih.gov
last name: Shira Levy
phone: 703-776-8489
email: shira.levy@inova.org
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
citation: Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, Bokulich NA, Song SJ, Hoashi M, Rivera-Vinas JI, Mendez K, Knight R, Clemente JC. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med. 2016 Mar;22(3):250-3. doi: 10.1038/nm.4039. Epub 2016 Feb 1.
PMID: 26828196
citation: Song SJ, Wang J, Martino C, Jiang L, Thompson WK, Shenhav L, McDonald D, Marotz C, Harris PR, Hernandez CD, Henderson N, Ackley E, Nardella D, Gillihan C, Montacuti V, Schweizer W, Jay M, Combellick J, Sun H, Garcia-Mantrana I, Gil Raga F, Collado MC, Rivera-Vinas JI, Campos-Rivera M, Ruiz-Calderon JF, Knight R, Dominguez-Bello MG. Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding. Med. 2021 Aug 13;2(8):951-964.e5. doi: 10.1016/j.medj.2021.05.003. Epub 2021 Jun 17.
PMID: 35590169
citation: Hourigan SK, Dominguez-Bello MG, Mueller NT. Can maternal-child microbial seeding interventions improve the health of infants delivered by Cesarean section? Cell Host Microbe. 2022 May 11;30(5):607-611. doi: 10.1016/j.chom.2022.02.014.
PMID: 35550663
responsible party type: Sponsor
mesh term: Pediatric Obesity
sharing ipd: Yes
ipd description: Individual participant data will be shared with co-principal investigators (Maria Gloria Dominguez-Bello at Rutgers University and Noel Mueller at Johns Hopkins School of Medicine).
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code