<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/NCT03030664</url>
  </required_header>
  <id_info>
    <org_study_id>BIOWELL</org_study_id>
    <secondary_id>2016-A00419-42</secondary_id>
    <nct_id>NCT03030664</nct_id>
  </id_info>
  <brief_title>Effect of L. Reuteri on Bowel Movements in Children (BIOWELL Study)</brief_title>
  <acronym>BIOWELL</acronym>
  <official_title>Randomised Controlled Trial With Two Parallel Arms Testing the Effect of L. Reuteri on Bowel Movements in Children Aged 6 Months to 4 Years</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Intercommunal Creteil</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>BioGaia AB</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre Hospitalier Intercommunal Creteil</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>
      A randomized, multicenter, placebo-controlled, double blind study in two parallel groups&#xD;
      testing the efficacy of daily oral supplementation with the probiotic L.reuteri DSM17938&#xD;
      compared to placebo in increasing the number of spontaneous bowel movements in infants and&#xD;
      children with functional constipation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Functional constipation in infants up to 4 years of age is defined according to Rome III&#xD;
      criteria (Hyman 2006). The diagnose must include 1 month of at least two of the following&#xD;
      criteria: two or fewer defecations per week; at least 1 episode per week of incontinence&#xD;
      after the acquisition of toilet skills; history of excessive stool retention; history of&#xD;
      painful or hard bowel movements; presence of a large faecal mass in the rectum; history of&#xD;
      large-diameter stools that may obstruct the toilet.&#xD;
&#xD;
      Accompanying symptoms may include irritability, decreased appetite and/or early satiety. The&#xD;
      accompanying symptoms disappear immediately following passage of a large stool.&#xD;
&#xD;
      There is a growing interest for the use of probiotics in functional constipation as research&#xD;
      suggests that probiotics could provide beneficial support in the traditional treatment&#xD;
      arsenal although the mechanisms of actions are not completely understood.&#xD;
&#xD;
      Wu et al have demonstrated that Lactobacillus reuteri DSM 17938 may have a region-specific&#xD;
      intestinal effect on gut motility and therefore could be beneficial in treatment of&#xD;
      constipation&#xD;
&#xD;
      Lactobacillus reuteri DSM 17938 has shown significant favourable effects in adults (Ojetti&#xD;
      2014) and young children as described above (Coccorullo 2010, Olgac 2013). These studies&#xD;
      require confirmation however. The present clinical study has been designed to strengthen the&#xD;
      current available data that L. reuteri DSM 17938 has beneficial effects in infants and young&#xD;
      children with functional constipation.&#xD;
&#xD;
      We hypothesize that daily oral supplementation with the probiotic Lactobacillus reuteri DSM&#xD;
      17938 will effectively increase the number of spontaneous bowel movements in infants/children&#xD;
      diagnosed with functional constipation according to Rome IV.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Actual">July 30, 2021</completion_date>
  <primary_completion_date type="Actual">June 30, 2021</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>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in number of spontaneous bowel movements</measure>
    <time_frame>Week 4</time_frame>
    <description>Change in number of spontaneous bowel movements at week 4 compared to baseline evaluated by a bowel habit questionnaire (BQH)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>rescue medication</measure>
    <time_frame>week 4</time_frame>
    <description>Total number of rescue medication during the intervention period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fecal retention</measure>
    <time_frame>week 4</time_frame>
    <description>number of subjects with 3 or more than 3 stools per week and without fecal retention at the last week of the intervention period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>weekly number of spontaneous bowel movements</measure>
    <time_frame>week 1</time_frame>
    <description>weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>weekly number of spontaneous bowel movements</measure>
    <time_frame>week 2</time_frame>
    <description>weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>weekly number of spontaneous bowel movements</measure>
    <time_frame>week 3</time_frame>
    <description>weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>weekly number of spontaneous bowel movements</measure>
    <time_frame>week 4</time_frame>
    <description>weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>weekly number of spontaneous bowel movements</measure>
    <time_frame>week 8</time_frame>
    <description>weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Score of QOL</measure>
    <time_frame>baseline</time_frame>
    <description>Score of quality of life measured using the PedsQL Parent family acute version</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Score of QOL</measure>
    <time_frame>week 4</time_frame>
    <description>Score of quality of life measured using the PedsQL Parent family acute version</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Score of QOL</measure>
    <time_frame>week 8</time_frame>
    <description>Score of quality of life measured using the PedsQL Parent family acute version</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain during defecation</measure>
    <time_frame>baseline</time_frame>
    <description>Score of pain during defecation measured using Hick or Wong baker faces</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain during defecation</measure>
    <time_frame>week 4</time_frame>
    <description>Score of pain during defecation measured using Hick or Wong baker faces</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain during defecation</measure>
    <time_frame>week 8</time_frame>
    <description>Score of pain during defecation measured using Hick or Wong baker faces</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">52</enrollment>
  <condition>Constipation</condition>
  <arm_group>
    <arm_group_label>L.reuteri</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>probiotics: L.reuteri produced by Biogaia 5 drops per day: 10exp(8) colony forming unit will be delivered</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Same formulation as probiotics, without active substance. 5 drops per day will be delivered</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>L.reuteri</intervention_name>
    <description>Each day, at about the same time, the subjects will be given 5 drops (1x10^8 CFU) of the study product in connection with feeding</description>
    <arm_group_label>L.reuteri</arm_group_label>
    <other_name>Lactobacillus reuteri</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Same formulation as study product, without probiotics.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: 6 months up to 4 years&#xD;
&#xD;
          -  Suffering from functional constipation, as defined by modified Rome III criteria for&#xD;
             children aged 4 years or less (Hyman 2006)&#xD;
&#xD;
          -  Parent(s) willingness to postpone major changes in the infant feeding mode&#xD;
&#xD;
          -  Parent(s) willingness and ability to fill in diary and questionnaires&#xD;
&#xD;
          -  Written informed consent from parents&#xD;
&#xD;
          -  Stated availability throughout the study period&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic illness or major medical problem&#xD;
&#xD;
          -  Gastrointestinal disease (including organic cause of constipation and dyschezia or&#xD;
             history of severe fecalome)&#xD;
&#xD;
          -  Intractable constipation (not responding to conventional treatment for more than 3&#xD;
             months)&#xD;
&#xD;
          -  Gastrointestinal surgery (in the year before enrolment)&#xD;
&#xD;
          -  Food allergy, lactose or gluten intolerance, as declared by parents&#xD;
&#xD;
          -  Use of L. reuteri two weeks before randomisation and throughout the intervention&#xD;
             period. If fed with infant formula, it cannot contain L. reuteri.&#xD;
&#xD;
          -  Use of antibiotics two weeks before randomisation and throughout the intervention&#xD;
             period, both infant/child and lactating mother&#xD;
&#xD;
          -  If breastfeeding, use of L reuteri by the mother 2 weeks prior to enrolment&#xD;
&#xD;
          -  Conventional treatment for constipation within 2 weeks before enrolment&#xD;
&#xD;
          -  Medication that influences gastrointestinal motility&#xD;
&#xD;
          -  Mental or behavioral disorders as judged by the investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>4 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marc BELLAICHE, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hopital Universitaire Robert-Debre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CH Sud francilien</name>
      <address>
        <city>Corbeil-Essonnes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHI Creteil</name>
      <address>
        <city>Créteil</city>
        <zip>94000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital J. Monod - Pavillon Femme Mère Enfant - Le Havre</name>
      <address>
        <city>Le Havre</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint Vincent-de-Paul</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Robert Debré</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>January 23, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>June 9, 2022</last_update_submitted>
  <last_update_submitted_qc>June 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centre Hospitalier Intercommunal Creteil</investigator_affiliation>
    <investigator_full_name>Camille JUNG</investigator_full_name>
    <investigator_title>Head of the clinical research department</investigator_title>
  </responsible_party>
  <keyword>constipation</keyword>
  <keyword>Lactobacillus reuteri</keyword>
  <keyword>probiotics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Constipation</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/NCT03030664
org study id: BIOWELL
secondary id: 2016-A00419-42
nct id: NCT03030664
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A randomized, multicenter, placebo-controlled, double blind study in two parallel groups
      testing the efficacy of daily oral supplementation with the probiotic L.reuteri DSM17938
      compared to placebo in increasing the number of spontaneous bowel movements in infants and
      children with functional constipation.
Functional constipation in infants up to 4 years of age is defined according to Rome III
      criteria (Hyman 2006). The diagnose must include 1 month of at least two of the following
      criteria: two or fewer defecations per week; at least 1 episode per week of incontinence
      after the acquisition of toilet skills; history of excessive stool retention; history of
      painful or hard bowel movements; presence of a large faecal mass in the rectum; history of
      large-diameter stools that may obstruct the toilet.

      Accompanying symptoms may include irritability, decreased appetite and/or early satiety. The
      accompanying symptoms disappear immediately following passage of a large stool.

      There is a growing interest for the use of probiotics in functional constipation as research
      suggests that probiotics could provide beneficial support in the traditional treatment
      arsenal although the mechanisms of actions are not completely understood.

      Wu et al have demonstrated that Lactobacillus reuteri DSM 17938 may have a region-specific
      intestinal effect on gut motility and therefore could be beneficial in treatment of
      constipation

      Lactobacillus reuteri DSM 17938 has shown significant favourable effects in adults (Ojetti
      2014) and young children as described above (Coccorullo 2010, Olgac 2013). These studies
      require confirmation however. The present clinical study has been designed to strengthen the
      current available data that L. reuteri DSM 17938 has beneficial effects in infants and young
      children with functional constipation.

      We hypothesize that daily oral supplementation with the probiotic Lactobacillus reuteri DSM
      17938 will effectively increase the number of spontaneous bowel movements in infants/children
      diagnosed with functional constipation according to Rome IV.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in number of spontaneous bowel movements
time frame: Week 4
description: Change in number of spontaneous bowel movements at week 4 compared to baseline evaluated by a bowel habit questionnaire (BQH)
measure: rescue medication
time frame: week 4
description: Total number of rescue medication during the intervention period
measure: fecal retention
time frame: week 4
description: number of subjects with 3 or more than 3 stools per week and without fecal retention at the last week of the intervention period
measure: weekly number of spontaneous bowel movements
time frame: week 1
description: weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire
measure: weekly number of spontaneous bowel movements
time frame: week 2
description: weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire
measure: weekly number of spontaneous bowel movements
time frame: week 3
description: weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire
measure: weekly number of spontaneous bowel movements
time frame: week 4
description: weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire
measure: weekly number of spontaneous bowel movements
time frame: week 8
description: weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire
measure: Score of QOL
time frame: baseline
description: Score of quality of life measured using the PedsQL Parent family acute version
measure: Score of QOL
time frame: week 4
description: Score of quality of life measured using the PedsQL Parent family acute version
measure: Score of QOL
time frame: week 8
description: Score of quality of life measured using the PedsQL Parent family acute version
measure: Pain during defecation
time frame: baseline
description: Score of pain during defecation measured using Hick or Wong baker faces
measure: Pain during defecation
time frame: week 4
description: Score of pain during defecation measured using Hick or Wong baker faces
measure: Pain during defecation
time frame: week 8
description: Score of pain during defecation measured using Hick or Wong baker faces
arm group label: L.reuteri
arm group type: Active Comparator
description: probiotics: L.reuteri produced by Biogaia 5 drops per day: 10exp(8) colony forming unit will be delivered
arm group label: Placebo
arm group type: Placebo Comparator
description: Same formulation as probiotics, without active substance. 5 drops per day will be delivered
intervention type: Dietary Supplement
intervention name: L.reuteri
description: Each day, at about the same time, the subjects will be given 5 drops (1x10^8 CFU) of the study product in connection with feeding
arm group label: L.reuteri
other name: Lactobacillus reuteri
intervention type: Drug
intervention name: Placebo
description: Same formulation as study product, without probiotics.
arm group label: Placebo
criteria: 
gender: All
minimum age: 6 Months
maximum age: 4 Years
healthy volunteers: No
last name: Marc BELLAICHE, MD
role: Principal Investigator
affiliation: Hopital Universitaire Robert-Debre
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Principal Investigator
investigator affiliation: Centre Hospitalier Intercommunal Creteil
investigator full name: Camille JUNG
investigator title: Head of the clinical research department
mesh term: Constipation
sharing ipd: No