<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/NCT03834415</url>
  </required_header>
  <id_info>
    <org_study_id>CSUB0153</org_study_id>
    <nct_id>NCT03834415</nct_id>
  </id_info>
  <brief_title>Lactobacillus Reuteri DSM17938 in C-Section Infants</brief_title>
  <official_title>Influence of Lactobacillus Reuteri DSM17938 on Early Gut Microbial Colonization in Infants Born by Caesarean Section: A Double-blinded, Randomized, Placebo-controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Innovacion y Desarrollo de Estrategias en Salud</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>BioGaia AB</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Innovacion y Desarrollo de Estrategias en Salud</source>
  <oversight_info>
    <has_dmc>Yes</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>
      RCT designed to evaluate the impact of Lactobacillus reuteri DSM17938 to modify gut&#xD;
      microbiota in children delivered by C-section&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      RCT designed to evaluate the safety and efficacy of L. reuteri DSM17938 administrated to&#xD;
      newborns babies to modify the fecal microbiome after 30 days of supplementation. Secondary&#xD;
      Secondary endpoints will be evaluate the occurrence and frequency of AEs Day 0 to Day 60; The&#xD;
      gut bacterial composition Day 7 and Day 30 as described in primary endpoint; the gut&#xD;
      bacterial composition in infants born by c-section and supplemented with L. reuteri DSM17938&#xD;
      compared to the gut bacterial composition in infants born vaginally and the salivary&#xD;
      concentration of IgA at 48h ±3h after birth and at Day 30.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 8, 2019</start_date>
  <completion_date type="Actual">June 18, 2019</completion_date>
  <primary_completion_date type="Actual">April 18, 2019</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>RCT two arms to evaluate the safety and efficacy of L. reuteri vs. placebo to modulate the microbiome gut profile in newborn babies delivered by C-section</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Blinding process will be structured centrally. The oil drops of active are contained in an ambar flask. Placebo consistency, smell, flavor and container are identical to active product</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Changes on fecal microbiome diversity at day 14</measure>
    <time_frame>14 days</time_frame>
    <description>Changes on diversity evaluated by Shannon Index of firmicutes, bacteroidetes and actinobacteria at day 14 after intervention</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes on fecal microbiome abundance at day 14</measure>
    <time_frame>14 days</time_frame>
    <description>Changes on abundance evaluated by Simpson Index of firmicutes, bacteroidetes and actinobacteria at day 14 after intervention</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes on fecal microbiome stability at day 14</measure>
    <time_frame>14 days</time_frame>
    <description>Changes on stability evaluated by Chao Index of firmicutes, bacteroidetes and actinobacteria at day 14 after intervention</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes on fecal microbiome diversity at day 7, 30 and 60</measure>
    <time_frame>7, 30 and 60 days</time_frame>
    <description>Changes on abundance evaluated by Channon Index of firmicutes, bacteroidetes and actinobacteria at day 7, 30 and 60 after intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes on fecal microbiome abundance at day 7, 30 and 60</measure>
    <time_frame>7, 30 and 60 days</time_frame>
    <description>Changes on abundance evaluated by Simpson Index of firmicutes, bacteroidetes and actinobacteria at day 7, 30 and 60 after intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes on fecal microbiome stability at day 7, 30 and 60</measure>
    <time_frame>7, 30 and 60 days</time_frame>
    <description>Changes on stability evaluated by Chao Index of firmicutes, bacteroidetes and actinobacteria at day 7, 30 and 60 after intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes on Salivary IgA levels</measure>
    <time_frame>7, 30 and 60 days</time_frame>
    <description>Levels of salivary IgA after 7,30 and 60 days after intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of Adverse Event</measure>
    <time_frame>30 days</time_frame>
    <description>Frequency of adverse events reported after randomization and until finish the treatment (day 30)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">69</enrollment>
  <condition>C-section</condition>
  <arm_group>
    <arm_group_label>Lactobacillus reuteri DSM17038</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lactobacillus reuteri DSM17038, 1x108 CFU once a day for 30 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo probiotics</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo for probiotics, pols drops similar in consistency and flavor as experimental product</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Lactobacillus reuteri DSM17038</intervention_name>
    <description>Oil drops of L. reuteri containing 1x10&gt;8 CFU</description>
    <arm_group_label>Lactobacillus reuteri DSM17038</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo for Probiotics</intervention_name>
    <description>Oil drops mimicking in consistency and flavor to experimental product</description>
    <arm_group_label>Placebo probiotics</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Gestational age &gt;37weeks +0 days and &lt;39 weeks +0 days&#xD;
&#xD;
          -  Birth weight appropriate for gestational age (AGA) or Large for Gestational Age (LGA)&#xD;
&#xD;
          -  Apgar score 8 or greater&#xD;
&#xD;
          -  Children will receive more than 50% of the feeding occasions with human breastmilk&#xD;
&#xD;
          -  Mothers will have the intention to exclusively or predominantly breastfeed the&#xD;
             subject. On the diary report form mother will report day by day the frequency of human&#xD;
             lactation and the frequency and amount of infant formula.&#xD;
&#xD;
          -  Readiness and the opportunity for parents to fill out a study diary, questionnaires.&#xD;
&#xD;
          -  Parent(s) are willing to postpone major changes in the infant feeding mode, and&#xD;
&#xD;
          -  Written informed consent from parents&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Older than 24 hours after birth when given the first dose of investigational product&#xD;
&#xD;
          -  Any kind of chronic or acute diseases during pregnancy that can modify fecal&#xD;
             microbiota in children, e.g. gestational diabetes, pre-clampsia, gastrointestinal&#xD;
             disease&#xD;
&#xD;
          -  Congenital malformations or anomalies&#xD;
&#xD;
          -  Maternal use of antibiotics from gestational week 33 and throughout the study period.&#xD;
&#xD;
          -  Maternal use of probiotics from gestational week 33 and throughout the study period.&#xD;
&#xD;
          -  Maternal severe obesity at inclusion or at delivery evaluated using Rosso Madrones&#xD;
             centiles&#xD;
&#xD;
          -  Infant use of antibiotics throughout the study period.&#xD;
&#xD;
          -  Infant use of probiotics throughout the study period, including infant formula and/or&#xD;
             supplementation.&#xD;
&#xD;
          -  Infants carrying out general anesthesia&#xD;
&#xD;
          -  Meconium aspiration syndrome&#xD;
&#xD;
          -  History of premature disruption of membranes for &gt;24h&#xD;
&#xD;
          -  Participation in other clinical trials&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Hours</minimum_age>
    <maximum_age>36 Hours</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pedro Gutierrez Castrellon, MD, MSc, DSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital General Dr. Manuel Gea Gonzalez</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital General Dr. Manuel Gea Gonzalez</name>
      <address>
        <city>Mexico city</city>
        <state>Tlalpan</state>
        <zip>14080</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <reference>
    <citation>Chandel DS, Perez-Munoz ME, Yu F, Boissy R, Satpathy R, Misra PR, Sharma N, Chaudhry R, Parida S, Peterson DA, Gewolb IH, Panigrahi P. Changes in the Gut Microbiota After Early Administration of Oral Synbiotics to Young Infants in India. J Pediatr Gastroenterol Nutr. 2017 Aug;65(2):218-224. doi: 10.1097/MPG.0000000000001522.</citation>
    <PMID>28121648</PMID>
  </reference>
  <reference>
    <citation>Garcia Rodenas CL, Lepage M, Ngom-Bru C, Fotiou A, Papagaroufalis K, Berger B. Effect of Formula Containing Lactobacillus reuteri DSM 17938 on Fecal Microbiota of Infants Born by Cesarean-Section. J Pediatr Gastroenterol Nutr. 2016 Dec;63(6):681-687. doi: 10.1097/MPG.0000000000001198.</citation>
    <PMID>27035371</PMID>
  </reference>
  <reference>
    <citation>Nitert MD, Barrett HL, Foxcroft K, Tremellen A, Wilkinson S, Lingwood B, Tobin JM, McSweeney C, O'Rourke P, McIntyre HD, Callaway LK. SPRING: an RCT study of probiotics in the prevention of gestational diabetes mellitus in overweight and obese women. BMC Pregnancy Childbirth. 2013 Feb 25;13:50. doi: 10.1186/1471-2393-13-50.</citation>
    <PMID>23442391</PMID>
  </reference>
  <reference>
    <citation>Jansman AJ, Zhang J, Koopmans SJ, Dekker RA, Smidt H. Effects of a simple or a complex starter microbiota on intestinal microbiota composition in caesarean derived piglets. J Anim Sci. 2012 Dec;90 Suppl 4:433-5. doi: 10.2527/jas.53850.</citation>
    <PMID>23365401</PMID>
  </reference>
  <reference>
    <citation>Kuitunen M, Kukkonen K, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, Haahtela T, Savilahti E. Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. J Allergy Clin Immunol. 2009 Feb;123(2):335-41. doi: 10.1016/j.jaci.2008.11.019. Epub 2009 Jan 8.</citation>
    <PMID>19135235</PMID>
  </reference>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>February 5, 2019</study_first_submitted>
  <study_first_submitted_qc>February 5, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <last_update_submitted>June 18, 2019</last_update_submitted>
  <last_update_submitted_qc>June 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Innovacion y Desarrollo de Estrategias en Salud</investigator_affiliation>
    <investigator_full_name>Pedro Gutierrez Castrellon</investigator_full_name>
    <investigator_title>Head of Translational Research Center for Mother-Child Health</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Protocol documents and data base results will be available at international sites</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>January 2019, for 12 months</ipd_time_frame>
    <ipd_access_criteria>IPD sharing access will be available for all investigators who want to do secondary analysis, always giving credits to principal investigators and owner of this research</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/NCT03834415
org study id: CSUB0153
nct id: NCT03834415
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
RCT designed to evaluate the impact of Lactobacillus reuteri DSM17938 to modify gut
      microbiota in children delivered by C-section
RCT designed to evaluate the safety and efficacy of L. reuteri DSM17938 administrated to
      newborns babies to modify the fecal microbiome after 30 days of supplementation. Secondary
      Secondary endpoints will be evaluate the occurrence and frequency of AEs Day 0 to Day 60; The
      gut bacterial composition Day 7 and Day 30 as described in primary endpoint; the gut
      bacterial composition in infants born by c-section and supplemented with L. reuteri DSM17938
      compared to the gut bacterial composition in infants born vaginally and the salivary
      concentration of IgA at 48h ±3h after birth and at Day 30.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: RCT two arms to evaluate the safety and efficacy of L. reuteri vs. placebo to modulate the microbiome gut profile in newborn babies delivered by C-section
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Blinding process will be structured centrally. The oil drops of active are contained in an ambar flask. Placebo consistency, smell, flavor and container are identical to active product
measure: Changes on fecal microbiome diversity at day 14
time frame: 14 days
description: Changes on diversity evaluated by Shannon Index of firmicutes, bacteroidetes and actinobacteria at day 14 after intervention
measure: Changes on fecal microbiome abundance at day 14
time frame: 14 days
description: Changes on abundance evaluated by Simpson Index of firmicutes, bacteroidetes and actinobacteria at day 14 after intervention
measure: Changes on fecal microbiome stability at day 14
time frame: 14 days
description: Changes on stability evaluated by Chao Index of firmicutes, bacteroidetes and actinobacteria at day 14 after intervention
measure: Changes on fecal microbiome diversity at day 7, 30 and 60
time frame: 7, 30 and 60 days
description: Changes on abundance evaluated by Channon Index of firmicutes, bacteroidetes and actinobacteria at day 7, 30 and 60 after intervention
measure: Changes on fecal microbiome abundance at day 7, 30 and 60
time frame: 7, 30 and 60 days
description: Changes on abundance evaluated by Simpson Index of firmicutes, bacteroidetes and actinobacteria at day 7, 30 and 60 after intervention
measure: Changes on fecal microbiome stability at day 7, 30 and 60
time frame: 7, 30 and 60 days
description: Changes on stability evaluated by Chao Index of firmicutes, bacteroidetes and actinobacteria at day 7, 30 and 60 after intervention
measure: Changes on Salivary IgA levels
time frame: 7, 30 and 60 days
description: Levels of salivary IgA after 7,30 and 60 days after intervention
measure: Frequency of Adverse Event
time frame: 30 days
description: Frequency of adverse events reported after randomization and until finish the treatment (day 30)
arm group label: Lactobacillus reuteri DSM17038
arm group type: Experimental
description: Lactobacillus reuteri DSM17038, 1x108 CFU once a day for 30 days
arm group label: Placebo probiotics
arm group type: Placebo Comparator
description: Placebo for probiotics, pols drops similar in consistency and flavor as experimental product
intervention type: Dietary Supplement
intervention name: Lactobacillus reuteri DSM17038
description: Oil drops of L. reuteri containing 1x10>8 CFU
arm group label: Lactobacillus reuteri DSM17038
intervention type: Other
intervention name: Placebo for Probiotics
description: Oil drops mimicking in consistency and flavor to experimental product
arm group label: Placebo probiotics
criteria: 
gender: All
minimum age: 12 Hours
maximum age: 36 Hours
healthy volunteers: No
last name: Pedro Gutierrez Castrellon, MD, MSc, DSc
role: Principal Investigator
affiliation: Hospital General Dr. Manuel Gea Gonzalez
facility: 
country: Mexico
citation: Chandel DS, Perez-Munoz ME, Yu F, Boissy R, Satpathy R, Misra PR, Sharma N, Chaudhry R, Parida S, Peterson DA, Gewolb IH, Panigrahi P. Changes in the Gut Microbiota After Early Administration of Oral Synbiotics to Young Infants in India. J Pediatr Gastroenterol Nutr. 2017 Aug;65(2):218-224. doi: 10.1097/MPG.0000000000001522.
PMID: 28121648
citation: Garcia Rodenas CL, Lepage M, Ngom-Bru C, Fotiou A, Papagaroufalis K, Berger B. Effect of Formula Containing Lactobacillus reuteri DSM 17938 on Fecal Microbiota of Infants Born by Cesarean-Section. J Pediatr Gastroenterol Nutr. 2016 Dec;63(6):681-687. doi: 10.1097/MPG.0000000000001198.
PMID: 27035371
citation: Nitert MD, Barrett HL, Foxcroft K, Tremellen A, Wilkinson S, Lingwood B, Tobin JM, McSweeney C, O'Rourke P, McIntyre HD, Callaway LK. SPRING: an RCT study of probiotics in the prevention of gestational diabetes mellitus in overweight and obese women. BMC Pregnancy Childbirth. 2013 Feb 25;13:50. doi: 10.1186/1471-2393-13-50.
PMID: 23442391
citation: Jansman AJ, Zhang J, Koopmans SJ, Dekker RA, Smidt H. Effects of a simple or a complex starter microbiota on intestinal microbiota composition in caesarean derived piglets. J Anim Sci. 2012 Dec;90 Suppl 4:433-5. doi: 10.2527/jas.53850.
PMID: 23365401
citation: Kuitunen M, Kukkonen K, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, Haahtela T, Savilahti E. Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. J Allergy Clin Immunol. 2009 Feb;123(2):335-41. doi: 10.1016/j.jaci.2008.11.019. Epub 2009 Jan 8.
PMID: 19135235
responsible party type: Principal Investigator
investigator affiliation: Innovacion y Desarrollo de Estrategias en Salud
investigator full name: Pedro Gutierrez Castrellon
investigator title: Head of Translational Research Center for Mother-Child Health
sharing ipd: Yes
ipd description: Protocol documents and data base results will be available at international sites
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: January 2019, for 12 months
ipd access criteria: IPD sharing access will be available for all investigators who want to do secondary analysis, always giving credits to principal investigators and owner of this research