<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/NCT03266315</url>
  </required_header>
  <id_info>
    <org_study_id>REB16-2401</org_study_id>
    <nct_id>NCT03266315</nct_id>
  </id_info>
  <brief_title>Probiotics Supplementation and Intestinal Microbiome in Neonates With Gastrointestinal Surgery</brief_title>
  <acronym>ProPS</acronym>
  <official_title>Probiotics Supplementation and Intestinal Microbiome in Neonates With Gastrointestinal Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Calgary</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Calgary</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>
      Congenital defects of the gastrointestinal tract commonly require surgical intervention in&#xD;
      the neonatal period. Intestinal surgery during this critical period of microbiome acquisition&#xD;
      results in aberrant colonization of the gastrointestinal tract by several pathways. Surgical&#xD;
      stress is known to cause disruption of the gut barrier and increase intestinal permeability&#xD;
      and bacterial translocation. This process triggers exaggerated immune responses that lead to&#xD;
      inflammation and sometimes infectious complications. Post-operative use of antibiotics has&#xD;
      been shown to potentiate the growth of pathogenic bacterial species Adults with abdominal&#xD;
      surgery who received post-op probiotics reported a significant reduction in surgical site&#xD;
      infection, urinary tract infection, and combined infection. Currently, probiotics used only&#xD;
      in the non-surgical population of infants.&#xD;
&#xD;
      The main objective of this study is to determine the impact of probiotics administration on&#xD;
      the intestinal microbiome in neonates undergoing intestinal surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Research Objectives/Question:&#xD;
&#xD;
      The main objective of this study is to determine the impact of probiotics administration on&#xD;
      the intestinal microbiome in neonates undergoing gastrointestinal surgery.&#xD;
&#xD;
      Primary question:&#xD;
&#xD;
      Diversity and abundance of stool microbiome at after 1 and 3 weeks of initiation of&#xD;
      probiotics&#xD;
&#xD;
      Secondary outcomes:&#xD;
&#xD;
      1. Length of hospital stay&#xD;
&#xD;
      Methodology:&#xD;
&#xD;
      Study design This study will be a randomized controlled double-blinded trial in the NICU at&#xD;
      Alberta Children's Hospital. Probiotics or placebo will be administered orally or via naso-&#xD;
      or orogastric feeding tube. Intestinal microbiome data will be compared between the two&#xD;
      groups. The study duration will be 24 months.&#xD;
&#xD;
      Study Population Infants born between 23 - 41 weeks of gestation, admitted to NICU at Alberta&#xD;
      Children's Hospital for gastrointestinal surgery.&#xD;
&#xD;
        1. Inclusion Criteria:&#xD;
&#xD;
             1. Infants born between 23 - 41 weeks of gestation&#xD;
&#xD;
             2. Required gastrointestinal surgery in the first week of life (including spontaneous&#xD;
                intestinal perforation, bowel atresia, mechanical bowel obstruction, volvulus,&#xD;
                gastroschisis)&#xD;
&#xD;
             3. Ready to start enteral feeding&#xD;
&#xD;
        2. Exclusion Criteria:&#xD;
&#xD;
           1. Infants with major congenital anomalies excluding gastrointestinal tract 3.&#xD;
           Palliative care patients 4. Septic babies with positive blood, CSF or urine culture&#xD;
&#xD;
           Sample Size and feasibility:&#xD;
&#xD;
           Connivant sample of 20 patients (10 in each group)&#xD;
&#xD;
           Study protocol. Infants will be identified within 48 hours of surgery and parents will&#xD;
           be approached for informed consent. Once consent is obtained, subjects will be randomly&#xD;
           assigned to receive either probiotics or placebo. Investigators will conduct the&#xD;
           randomization using a computer-generated table of random numbers generated at the&#xD;
           University of Calgary.&#xD;
&#xD;
           Preparation and Administration of Study Drug The study supplementation will be started&#xD;
           at the when oral feeds will reach 24 mL/kg/day after surgery after collecting a&#xD;
           stool/ostomy sample. The decision to start feeding will be made by the neonatal and&#xD;
           surgical team. After the first stool/ostomy sample is obtained, one study sachet to a&#xD;
           minimum of 1 mL of Expressed Breast Milk (EBM) (mothers own milk or donor human milk)&#xD;
           once a day.&#xD;
&#xD;
           Placebo sachet will be made of 0.3 g maltodextrin and be administered to the control&#xD;
           group in the same manner. If the infant is placed NPO, the study drug will be stopped&#xD;
           and restarted together with refeeding. Both probiotics and placebo will be packaged as a&#xD;
           single-dose sachet. The study probiotic/placebo will be given till discharge. If the&#xD;
           infant is transferred outside NICU, the study drug will be dispensed with the infant and&#xD;
           clinical outcomes will be ascertained in collaboration with the local Pediatrician at&#xD;
           the time of infants' discharge home.&#xD;
&#xD;
           Sample collection Nurses will collect the stool samples at 3-time points: prior to&#xD;
           initiation, 1 week after and 3 weeks after probiotic or placebo administration is&#xD;
           commenced. &quot;Stool&quot; will be collected directly from the infant's ostomy bag and diaper&#xD;
           with a sterile spatula. As soon as a sample is collected, the nurse will contact the&#xD;
           investigators. The samples will then be placed in a laboratory freezer (-80°C) within 24&#xD;
           hours of collection. Batched samples will be transported to the University of Calgary&#xD;
           Genomics laboratory for subsequent microbiome processing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Anticipated">December 3, 2022</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Intestinal microbiome</measure>
    <time_frame>3 weeks after surgury</time_frame>
    <description>Stool microbiome</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>6 months</time_frame>
    <description>Time between birth and hospital discharge</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Probiotics</condition>
  <condition>Infant, Newborn</condition>
  <condition>Surgical Procedures, Operative</condition>
  <condition>Gastro-Intestinal Disorder</condition>
  <arm_group>
    <arm_group_label>Probiotics</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>subjects will be randomly assigned to receive FloraBaby</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>subjects will be randomly assigned to receive placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>FloraBaby</intervention_name>
    <description>1 sachet will be added to a minimum of 1 mL of brest milk, sterile water or formula (in formula fed babies) once a day</description>
    <arm_group_label>Probiotics</arm_group_label>
    <other_name>Probiotics</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>1 sachet will be added to a minimum of 1 mL of brest milk, sterile water or formula (in formula fed babies) once a day</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Infants born between 23 - 41 weeks of gestation&#xD;
&#xD;
          2. Required gastrointestinal surgery (including spontaneous intestinal perforation, bowel&#xD;
             atresia, mechanical bowel obstruction, volvulus, gastroschisis)&#xD;
&#xD;
          3. Ready to start enteral feeding&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Infants with major congenital anomalies excluding gastrointestinal tract&#xD;
&#xD;
          2. Palliative care patients&#xD;
&#xD;
        4. Septic babies with positive blood, CSF or urine culture&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alixe Howlett, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Calgary</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Belal N Alshaikh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Calgary</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Belal Alshaikh, MD, MSc</last_name>
    <phone>4039561588</phone>
    <email>balshaik@ucalgary.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Belal M ALshaikh, MD</last_name>
      <phone>4039561588</phone>
      <email>balshaik@ucalgary.ca</email>
    </contact>
    <contact_backup>
      <last_name>Alixe M Howlett, MD</last_name>
      <email>alixe.howlett@ahs.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Belal M Alshaikh, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>November 4, 2022</last_update_submitted>
  <last_update_submitted_qc>November 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Calgary</investigator_affiliation>
    <investigator_full_name>Belal Alshaikh</investigator_full_name>
    <investigator_title>Clinical Associate Professor, Department of Pediatrics</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intestinal Diseases</mesh_term>
    <mesh_term>Gastrointestinal Diseases</mesh_term>
    <mesh_term>Digestive System Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03266315
org study id: REB16-2401
nct id: NCT03266315
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Congenital defects of the gastrointestinal tract commonly require surgical intervention in
      the neonatal period. Intestinal surgery during this critical period of microbiome acquisition
      results in aberrant colonization of the gastrointestinal tract by several pathways. Surgical
      stress is known to cause disruption of the gut barrier and increase intestinal permeability
      and bacterial translocation. This process triggers exaggerated immune responses that lead to
      inflammation and sometimes infectious complications. Post-operative use of antibiotics has
      been shown to potentiate the growth of pathogenic bacterial species Adults with abdominal
      surgery who received post-op probiotics reported a significant reduction in surgical site
      infection, urinary tract infection, and combined infection. Currently, probiotics used only
      in the non-surgical population of infants.

      The main objective of this study is to determine the impact of probiotics administration on
      the intestinal microbiome in neonates undergoing intestinal surgery.
Research Objectives/Question:

      The main objective of this study is to determine the impact of probiotics administration on
      the intestinal microbiome in neonates undergoing gastrointestinal surgery.

      Primary question:

      Diversity and abundance of stool microbiome at after 1 and 3 weeks of initiation of
      probiotics

      Secondary outcomes:

      1. Length of hospital stay

      Methodology:

      Study design This study will be a randomized controlled double-blinded trial in the NICU at
      Alberta Children's Hospital. Probiotics or placebo will be administered orally or via naso-
      or orogastric feeding tube. Intestinal microbiome data will be compared between the two
      groups. The study duration will be 24 months.

      Study Population Infants born between 23 - 41 weeks of gestation, admitted to NICU at Alberta
      Children's Hospital for gastrointestinal surgery.

        1. Inclusion Criteria:

             1. Infants born between 23 - 41 weeks of gestation

             2. Required gastrointestinal surgery in the first week of life (including spontaneous
                intestinal perforation, bowel atresia, mechanical bowel obstruction, volvulus,
                gastroschisis)

             3. Ready to start enteral feeding

        2. Exclusion Criteria:

           1. Infants with major congenital anomalies excluding gastrointestinal tract 3.
           Palliative care patients 4. Septic babies with positive blood, CSF or urine culture

           Sample Size and feasibility:

           Connivant sample of 20 patients (10 in each group)

           Study protocol. Infants will be identified within 48 hours of surgery and parents will
           be approached for informed consent. Once consent is obtained, subjects will be randomly
           assigned to receive either probiotics or placebo. Investigators will conduct the
           randomization using a computer-generated table of random numbers generated at the
           University of Calgary.

           Preparation and Administration of Study Drug The study supplementation will be started
           at the when oral feeds will reach 24 mL/kg/day after surgery after collecting a
           stool/ostomy sample. The decision to start feeding will be made by the neonatal and
           surgical team. After the first stool/ostomy sample is obtained, one study sachet to a
           minimum of 1 mL of Expressed Breast Milk (EBM) (mothers own milk or donor human milk)
           once a day.

           Placebo sachet will be made of 0.3 g maltodextrin and be administered to the control
           group in the same manner. If the infant is placed NPO, the study drug will be stopped
           and restarted together with refeeding. Both probiotics and placebo will be packaged as a
           single-dose sachet. The study probiotic/placebo will be given till discharge. If the
           infant is transferred outside NICU, the study drug will be dispensed with the infant and
           clinical outcomes will be ascertained in collaboration with the local Pediatrician at
           the time of infants' discharge home.

           Sample collection Nurses will collect the stool samples at 3-time points: prior to
           initiation, 1 week after and 3 weeks after probiotic or placebo administration is
           commenced. "Stool" will be collected directly from the infant's ostomy bag and diaper
           with a sterile spatula. As soon as a sample is collected, the nurse will contact the
           investigators. The samples will then be placed in a laboratory freezer (-80°C) within 24
           hours of collection. Batched samples will be transported to the University of Calgary
           Genomics laboratory for subsequent microbiome processing.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Intestinal microbiome
time frame: 3 weeks after surgury
description: Stool microbiome
measure: Length of hospital stay
time frame: 6 months
description: Time between birth and hospital discharge
arm group label: Probiotics
arm group type: Experimental
description: subjects will be randomly assigned to receive FloraBaby
arm group label: Placebo
arm group type: Placebo Comparator
description: subjects will be randomly assigned to receive placebo
intervention type: Biological
intervention name: FloraBaby
description: 1 sachet will be added to a minimum of 1 mL of brest milk, sterile water or formula (in formula fed babies) once a day
arm group label: Probiotics
other name: Probiotics
intervention type: Other
intervention name: Placebo
description: 1 sachet will be added to a minimum of 1 mL of brest milk, sterile water or formula (in formula fed babies) once a day
arm group label: Placebo
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Alixe Howlett, MD
role: Principal Investigator
affiliation: University of Calgary
last name: Belal N Alshaikh, MD
role: Principal Investigator
affiliation: University of Calgary
last name: Belal Alshaikh, MD, MSc
phone: 4039561588
email: balshaik@ucalgary.ca
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of Calgary
investigator full name: Belal Alshaikh
investigator title: Clinical Associate Professor, Department of Pediatrics
mesh term: Intestinal Diseases
mesh term: Gastrointestinal Diseases
mesh term: Digestive System Diseases
sharing ipd: No