<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/NCT01719107</url>
  </required_header>
  <id_info>
    <org_study_id>CSUB0003</org_study_id>
    <nct_id>NCT01719107</nct_id>
  </id_info>
  <brief_title>Efficacy of Dietary Supplementation With Lactobacilllus Reuteri DSM 17938 on Functional Abdominal Pain (FAP) in Children</brief_title>
  <official_title>Efficacy of Dietary Supplementation With Lactobacilllus Reuteri DSM 17938 on Functional Abdominal Pain (FAP) in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aghia Sophia Children's Hospital of Athens</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>BioGaia AB</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Aghia Sophia Children's Hospital of Athens</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to investigate the effect of L. reuteri DSM 17938 on pain frequency&#xD;
      and severity in children of 5-16 years old and with diagnosis of FAP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, placebo-controlled study. Subjects between of 5-16 years&#xD;
      of age with FAP as defined in the Rome III criteria and with pain severity of at least 40 mm&#xD;
      on a 100 mm VAS scale and pain frequency of at least 1 episode per week over the preceding 8&#xD;
      weeks will be recruited. In accordance to the specific Rome III criteria for inclusion, FAP&#xD;
      is defined as a variable combination of chronic or recurrent gastrointestinal symptoms not&#xD;
      explained by structural or biochemical abnormalities.&#xD;
&#xD;
      A study questionnaire to record pain and other gastrointestinal symptoms will be used.&#xD;
&#xD;
      One-hundred and six (106) Subjects will be randomized to receive either dietary&#xD;
      supplementation with L. reuteri DSM 17938 (2 chewable tablets with breakfast), or the same&#xD;
      number of comparable placebo tablets, for 4 weeks. Supplementation will be stopped after 4&#xD;
      weeks, and the subjects will be followed up for an additional 4 weeks. The subjects will&#xD;
      complete a diary to record frequency and intensity of pain, use of medication, deviation from&#xD;
      the usual diet, physical activities, and absence from school and other activities.&#xD;
      Gastrointestinal symptoms are assessed by the GSRS (Gastrointestinal Symptom Rating Score).&#xD;
&#xD;
      Subjects/caregivers will be instructed to maintain the usual diet throughout the study, but&#xD;
      not to consume other probiotics (foods or supplements) during the entire study period.&#xD;
&#xD;
      The symptoms diary will be completed daily by the parents and will report information on the&#xD;
      frequency of pain episodes, location of pain, presence or absence of associated symptoms,&#xD;
      need to take medication for pain and interference with normal activities. The intensity of&#xD;
      the symptoms will be assessed by using the Wong-Baker Faces scale.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Abdominal pain frequency and severity over the 4-week treatment period.</measure>
    <time_frame>4 weeks</time_frame>
    <description>Reduction in pain frequency measured by a subject diary, in the L. reuteri DSM 17938 group and the placebo group, expressed as area under the pain-frequency curve and comparing L. reuteri DSM 17938 vs placebo over the treatment period.&#xD;
Reduction in pain severity is assessed using the face score system of Wong-Baker at day 14 and at the end of treatment (day 28)vs. baseline. Area under the pain-intensity curve will be assessed for Weeks 1-4 and Weeks 1-2</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Reduction in pain frequency and intensity over the 8-week study period</measure>
    <time_frame>8 weeks</time_frame>
    <description>Reduction in pain frequency measured by a subject diary in the L. reuteri group expressed as area under the L. reuteri pain-frequency curve compared to placebo over the initial 2 weeks of the treatment period as well as over the whole study period.&#xD;
Reduction in pain intensity, measured by the face score system of Wong-Baker at day 14, end of treatment (day 28), and end of follow-up period (day 56) vs baseline. Area under the pain-intensity curve for Weeks 1-4 and Weeks 1-2 will be compared.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in other GI symptoms over the whole study period</measure>
    <time_frame>8 weeks</time_frame>
    <description>Reduction in other GI symptoms as measured by Gastrointestinal Symptom Rating Scoring system. Time points: baseline, day 14, end of treatment and end of follow-up, in the L. reuteri group vs. placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days of absence from school and other activities due to abdominal pain over the whole study period</measure>
    <time_frame>8 weeks</time_frame>
    <description>The number of days of absence from school and other activities due to abdominal pain will be compared between the L. reuteri group vs placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in absence from work by parents over the whole study period</measure>
    <time_frame>8 weeks</time_frame>
    <description>he number of days of absence from work by parents due to abdominal pain of the child will be compared between the L. reuteri group vs placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety outcome over the whole study period</measure>
    <time_frame>8 weeks</time_frame>
    <description>The number of adverse events will be observed and recorded during the entire study period</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Functional Abdominal Pain (FAP) in Children</condition>
  <arm_group>
    <arm_group_label>L. reuteri DSM 17938 chewable tablets</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The active study product consists of a citrus flavored 450 mg chewable tablet containing freeze-dried L. reuteri DSM 17938. The study product is a convex tablet 10.3 mm in diameter, plain on both sides and with faint spots. It is composed of freeze-dried L. reuteri, isomalt, xylitol, sucrose distearate, hydrogenated palm oil, lemon-lime flavoring and anhydrous citric acid. The total viable count of L. reuteri DSM 17938 is 1x108 live bacteria (CFU)/tablet.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo chewable tablets</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo study product consists of an identical formulation in all respects except that the live bacteria are excluded.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>L. reuteri DSM 17938 chewable tablets</intervention_name>
    <description>2 chewable tablets with breakfast for 4 weeks</description>
    <arm_group_label>L. reuteri DSM 17938 chewable tablets</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo chewable tablets</intervention_name>
    <description>2 chewable tablets with breakfast for 4 weeks</description>
    <arm_group_label>Placebo chewable tablets</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects will be recruited according to the following inclusion criteria:&#xD;
&#xD;
          -  FAP (Functional Abdominal Pain) according to Rome III criteria for Child/Adolescent; 1&#xD;
             or more abdominal pain episodes per week over the past 8 weeks&#xD;
&#xD;
          -  Informed consent by study participant and at least one parent/legal guardian;&#xD;
&#xD;
          -  Age of 5-16 years;&#xD;
&#xD;
          -  Pain severity at study entry must be at least 40 mm on a 100 mm VAS scale;&#xD;
&#xD;
          -  Pain frequency of at least 1 or more episodes per week over the preceding 8 weeks;&#xD;
&#xD;
          -  Ability to understand and comply with the requirements of the trial;&#xD;
&#xD;
          -  Stated availability throughout the study period&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects presenting with one or more of the following criteria will be excluded from&#xD;
        participation in the study:&#xD;
&#xD;
          -  Chronic illness;&#xD;
&#xD;
          -  Surgery of gastrointestinal tract&#xD;
&#xD;
          -  Any symptoms/signs of organic disease and/or any abnormal results of laboratory assays&#xD;
             (total blood count, serum glucose, urea, electrolytes, amylase, SGOT, SGPT, anti tTG&#xD;
             antibodies, breath H2 test, suggesting disease other than FAP;&#xD;
&#xD;
          -  Weight loss of 5% or more in body weight over the preceding 3 months;&#xD;
&#xD;
          -  Exposure to any drugs for FAP in the past 2 weeks.&#xD;
&#xD;
          -  Exposure to probiotics or antibiotics within 4 weeks prior to study; subjects can be&#xD;
             included following a wash-out period of 4 weeks.&#xD;
&#xD;
          -  Participation in other interventional clinical trials in the past 3 months;&#xD;
&#xD;
          -  Subjects with special dietary needs&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>16 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexandra Papadopoulou, Hon. Prof. Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Athens Interconnected Children's Hospitals &quot;AGIA SOPHIA&quot; and &quot;P &amp; A KYRIAKOU&quot;</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hania Szajewska, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Warsaw University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rok Orel, Ass. Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ljubljana University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Athens Children's Hospital &quot;AGIA SOPHIA&quot;</name>
      <address>
        <city>Athens</city>
        <state>Attica</state>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Warsaw, Department of Pediatrics</name>
      <address>
        <city>Warsaw</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Ljubljana, Children's Hospital, Department of Gastroenterology</name>
      <address>
        <city>Ljubljana</city>
        <country>Slovenia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
    <country>Poland</country>
    <country>Slovenia</country>
  </location_countries>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>October 28, 2012</study_first_submitted>
  <study_first_submitted_qc>October 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 1, 2012</study_first_posted>
  <last_update_submitted>February 20, 2016</last_update_submitted>
  <last_update_submitted_qc>February 20, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 23, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Aghia Sophia Children's Hospital of Athens</investigator_affiliation>
    <investigator_full_name>Alexandra Papadopoulou</investigator_full_name>
    <investigator_title>Consultant in Pediatrics, Honorary Professor Dr. med.</investigator_title>
  </responsible_party>
  <keyword>Functional abdominal pain</keyword>
  <keyword>Probiotics</keyword>
  <keyword>Lactobacilus reuteri</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Abdominal Pain</mesh_term>
  </condition_browse>
  <!-- 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/NCT01719107
org study id: CSUB0003
nct id: NCT01719107
lead sponsor: 
collaborator: 
has dmc: Yes
The aim of the study is to investigate the effect of L. reuteri DSM 17938 on pain frequency
      and severity in children of 5-16 years old and with diagnosis of FAP.
This is a randomized, double-blind, placebo-controlled study. Subjects between of 5-16 years
      of age with FAP as defined in the Rome III criteria and with pain severity of at least 40 mm
      on a 100 mm VAS scale and pain frequency of at least 1 episode per week over the preceding 8
      weeks will be recruited. In accordance to the specific Rome III criteria for inclusion, FAP
      is defined as a variable combination of chronic or recurrent gastrointestinal symptoms not
      explained by structural or biochemical abnormalities.

      A study questionnaire to record pain and other gastrointestinal symptoms will be used.

      One-hundred and six (106) Subjects will be randomized to receive either dietary
      supplementation with L. reuteri DSM 17938 (2 chewable tablets with breakfast), or the same
      number of comparable placebo tablets, for 4 weeks. Supplementation will be stopped after 4
      weeks, and the subjects will be followed up for an additional 4 weeks. The subjects will
      complete a diary to record frequency and intensity of pain, use of medication, deviation from
      the usual diet, physical activities, and absence from school and other activities.
      Gastrointestinal symptoms are assessed by the GSRS (Gastrointestinal Symptom Rating Score).

      Subjects/caregivers will be instructed to maintain the usual diet throughout the study, but
      not to consume other probiotics (foods or supplements) during the entire study period.

      The symptoms diary will be completed daily by the parents and will report information on the
      frequency of pain episodes, location of pain, presence or absence of associated symptoms,
      need to take medication for pain and interference with normal activities. The intensity of
      the symptoms will be assessed by using the Wong-Baker Faces scale.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Abdominal pain frequency and severity over the 4-week treatment period.
time frame: 4 weeks
description: Reduction in pain frequency measured by a subject diary, in the L. reuteri DSM 17938 group and the placebo group, expressed as area under the pain-frequency curve and comparing L. reuteri DSM 17938 vs placebo over the treatment period.
Reduction in pain severity is assessed using the face score system of Wong-Baker at day 14 and at the end of treatment (day 28)vs. baseline. Area under the pain-intensity curve will be assessed for Weeks 1-4 and Weeks 1-2
measure: Reduction in pain frequency and intensity over the 8-week study period
time frame: 8 weeks
description: Reduction in pain frequency measured by a subject diary in the L. reuteri group expressed as area under the L. reuteri pain-frequency curve compared to placebo over the initial 2 weeks of the treatment period as well as over the whole study period.
Reduction in pain intensity, measured by the face score system of Wong-Baker at day 14, end of treatment (day 28), and end of follow-up period (day 56) vs baseline. Area under the pain-intensity curve for Weeks 1-4 and Weeks 1-2 will be compared.
measure: Reduction in other GI symptoms over the whole study period
time frame: 8 weeks
description: Reduction in other GI symptoms as measured by Gastrointestinal Symptom Rating Scoring system. Time points: baseline, day 14, end of treatment and end of follow-up, in the L. reuteri group vs. placebo.
measure: Days of absence from school and other activities due to abdominal pain over the whole study period
time frame: 8 weeks
description: The number of days of absence from school and other activities due to abdominal pain will be compared between the L. reuteri group vs placebo.
measure: Reduction in absence from work by parents over the whole study period
time frame: 8 weeks
description: he number of days of absence from work by parents due to abdominal pain of the child will be compared between the L. reuteri group vs placebo.
measure: Safety outcome over the whole study period
time frame: 8 weeks
description: The number of adverse events will be observed and recorded during the entire study period
arm group label: L. reuteri DSM 17938 chewable tablets
arm group type: Active Comparator
description: The active study product consists of a citrus flavored 450 mg chewable tablet containing freeze-dried L. reuteri DSM 17938. The study product is a convex tablet 10.3 mm in diameter, plain on both sides and with faint spots. It is composed of freeze-dried L. reuteri, isomalt, xylitol, sucrose distearate, hydrogenated palm oil, lemon-lime flavoring and anhydrous citric acid. The total viable count of L. reuteri DSM 17938 is 1x108 live bacteria (CFU)/tablet.
arm group label: Placebo chewable tablets
arm group type: Placebo Comparator
description: The placebo study product consists of an identical formulation in all respects except that the live bacteria are excluded.
intervention type: Dietary Supplement
intervention name: L. reuteri DSM 17938 chewable tablets
description: 2 chewable tablets with breakfast for 4 weeks
arm group label: L. reuteri DSM 17938 chewable tablets
intervention type: Dietary Supplement
intervention name: Placebo chewable tablets
description: 2 chewable tablets with breakfast for 4 weeks
arm group label: Placebo chewable tablets
criteria: 
gender: All
minimum age: 5 Years
maximum age: 16 Years
healthy volunteers: No
last name: Alexandra Papadopoulou, Hon. Prof. Dr. med.
role: Principal Investigator
affiliation: Athens Interconnected Children's Hospitals "AGIA SOPHIA" and "P & A KYRIAKOU"
last name: Hania Szajewska, Prof
role: Principal Investigator
affiliation: Warsaw University
last name: Rok Orel, Ass. Prof.
role: Principal Investigator
affiliation: Ljubljana University
facility: 
facility: 
facility: 
country: Greece
country: Poland
country: Slovenia
responsible party type: Principal Investigator
investigator affiliation: Aghia Sophia Children's Hospital of Athens
investigator full name: Alexandra Papadopoulou
investigator title: Consultant in Pediatrics, Honorary Professor Dr. med.
mesh term: Abdominal Pain