<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/NCT01699191</url>
  </required_header>
  <id_info>
    <org_study_id>ProCeDo</org_study_id>
    <nct_id>NCT01699191</nct_id>
  </id_info>
  <brief_title>Probiotics for the Treatment of Irritable Bowel Syndrome in Celiac Patients</brief_title>
  <acronym>ProCel</acronym>
  <sponsors>
    <lead_sponsor>
      <agency>University of Bari</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Bari</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Probiotics play an important role in preventing overgrowth of potentially pathogenic bacteria&#xD;
      and maintaining the integrity of the gut mucosal barrier. The beneficial effects of&#xD;
      probiotics have been previously studied in adult patients with IBS. Clinical studies show&#xD;
      that patients meeting the criteria for diagnosis for IBS have greater probability for being&#xD;
      affected by celiac desease if compared to controls without IBS. Since one of the causes&#xD;
      attributed to the onset of IBS is the modified flora gut, it is interesting to determine the&#xD;
      beneficial effects that probiotics may have on gastrointestinal symptoms in celiac disease&#xD;
      patients. The goal of the present study is to determine whether oral administration of a&#xD;
      probiotic mixture of Lactobacillus plantarum 14D-CECT 4528, Lactobacillus casei,&#xD;
      Bifidobacterium breve Bbr8 LMG P-17501, Bifidobacterium breve Bl10 LMG P-17500 and&#xD;
      Bifidobacterium animalis under randomized, double-blind, placebo-controlled conditions would&#xD;
      improve symptoms of adult celiac patients with IBS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double blind study, placebo-controlled, carried out in three&#xD;
      departments of gastroenterology in Southern Italy (Bari, Taranto e Castellana Grotte).&#xD;
&#xD;
      Celiac patients with Irritable Bowel Syndrome will considered eligible for inclusion. They&#xD;
      will be between 18 and 65 years old and they will be in GFD for at least 2 year.&#xD;
&#xD;
      Will be excluded from the study patients with previous abdominal surgery, chronic disease,&#xD;
      alarm signs of organic conditions, treatment with probiotics, prebiotics, antibiotics and&#xD;
      antispasmodics in the previous month, immunodeficiency, pregnancy.&#xD;
&#xD;
      The size of the sample, which must show a benefit greater than 25% compared to placebo&#xD;
      (untreated group that usually able to respond positive in 20% of cases), will require 58&#xD;
      patients per arm to ensure a power of 90% with an alpha error of 0.5.&#xD;
&#xD;
      Patient will be assigned consecutive numbers, starting with the lowest number available, and&#xD;
      randomly assigned, with the use of a computer generated randomisation list using permuted&#xD;
      block design, to receive orally either a probiotic mixture of Lactobacillus plantarum&#xD;
      14D-CECT 4528, Lactobacillus casei, Bifidobacterium breve Bbr8 LMG P-17501, Bifidobacterium&#xD;
      breve Bl10 LMG P-17500 and Bifidobacterium animalis or placebo (sachets identical in taste&#xD;
      and appearance to the active study product except for the absence of probiotic mixture) once&#xD;
      a day.&#xD;
&#xD;
      The study consists of three phases:&#xD;
&#xD;
        1. phase of &quot;running-in&quot; of two weeks to reduce the possibility of a next significant&#xD;
           placebo effect in which the patient should not take no product;&#xD;
&#xD;
        2. supplementation for 6 weeks in which the patient will take one packet per day of placebo&#xD;
           or active product;&#xD;
&#xD;
        3. follow-up of 6 weeks.&#xD;
&#xD;
      Enrolled patients will be entered sequentially to receive the assigned treatment. Boxes&#xD;
      containing placebo will have the same shape, dimension, indication and appearance as those&#xD;
      containing the viable probiotic mixture and will be provided by the probiotic producer&#xD;
      (Moviscom Srl, Rome, Italy) which ensure that the study is blinded for investigators and&#xD;
      patients. Group assignment will be concealed from participants and investigators.&#xD;
&#xD;
      During the duration of the trial (w1- w14) patients will record gastrointestinal symptoms on&#xD;
      weekly diary. During the same time will compiled, every two week, the Gastrointestinal&#xD;
      symptom rating score (GSRS), that consists of a 15-point questionnaire to assess severity and&#xD;
      frequency of symptoms validated by Svedlund et al.. For all patients will be collected, at T&#xD;
      = 0 and T = 42 days, stool samples on which will be performed the extraction of DNA and RNA&#xD;
      for a possible assessment of the intestinal microflora. Bacteria DNA in stools will be&#xD;
      extracted and stored at -80°C for future analysis. At the end of the study, for patients who&#xD;
      have achieved the primary objective will be made specific identification of the intestinal&#xD;
      microflora for verify any amendments.&#xD;
&#xD;
      The compliance to the study will be demonstrated according to the number of sachets consumed&#xD;
      by the patient during the 6 weeks of administration, and on the basis of the compilation of&#xD;
      the questionnaires provided by the protocol.&#xD;
&#xD;
      Outcome Measures Primary outcome will be the incidence in IBS in celiac patients receiving&#xD;
      probiotics as compared to those receiving placebo. We have chosen pain as the primary outcome&#xD;
      measure, in line with the proposed points-to-consider for IBS trials.&#xD;
&#xD;
      IBS will be diagnosed and categorised according to ROME III criteria. Secondary outcomes are:&#xD;
      1) evaluation of frequency/severity of symptoms according to treatment arm; 2) modification&#xD;
      of intestinal microbiota.&#xD;
&#xD;
      The analysis of the intestinal microbiota of these informative cases will help to assess&#xD;
      whether there is a intestinal microbiota suggestive of future inset of IBS and ability of our&#xD;
      probiotic mixture to stabilize the intestinal microbiota.&#xD;
&#xD;
      Adverse Events and Disallowed Medication Adverse events will be monitored throughout the&#xD;
      study. Patients will not allowed to consume any probiotic other than those provided and they&#xD;
      will be invited to continue their eating and physical exercise habits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>October 2012</start_date>
  <completion_date type="Anticipated">January 2014</completion_date>
  <primary_completion_date type="Anticipated">October 2013</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, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Treatment of abdominal pain in celiac patients</measure>
    <time_frame>14 weeks</time_frame>
    <description>Primary outcome will be the incidence in IBS in celiac patients receiving probiotics mixture as compared to those receiving placebo.&#xD;
IBS will be diagnosed and categorised according to ROME III criteria.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>IBS in Celiac Desease</condition>
  <arm_group>
    <arm_group_label>Probiotic Mixture</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Probiotic mixture</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Probiotic</intervention_name>
    <arm_group_label>Probiotic Mixture</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Celiac patients aged between 18 and 65 years&#xD;
&#xD;
          -  Diagnosis of IBS on the basis of Rome III criteria&#xD;
&#xD;
          -  GFD&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous sigmoidoscopy or colonoscopy in the past 5 years&#xD;
&#xD;
          -  Known concomitant organic diseases, including inflammatory bowel disease and other&#xD;
             systemic diseases significant&#xD;
&#xD;
          -  Treatment with antispasmodic drugs within the previous month&#xD;
&#xD;
          -  Are pregnant&#xD;
&#xD;
          -  Immunodeficiency&#xD;
&#xD;
          -  Previous abdominal surgery, with the exception of the hernia repair or appendectomy&#xD;
&#xD;
          -  Treatment with antibiotics within the previous month&#xD;
&#xD;
          -  Treatment with probiotics and / or prebiotics within the previous month&#xD;
&#xD;
          -  Participation in other clinical trials&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ruggiero Francavilla</last_name>
    <role>Principal Investigator</role>
    <affiliation>DEPARTMENT OF BIOMEDICINA ETA' EVOLUTIVA</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ruggiero Francavilla</last_name>
    <phone>0805592963</phone>
    <email>rfrancavilla@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Clinica Pediatrica</name>
      <address>
        <city>Bari</city>
        <state>Puglia</state>
        <zip>70125</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 1, 2012</study_first_submitted>
  <study_first_submitted_qc>October 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2012</study_first_posted>
  <last_update_submitted>October 2, 2012</last_update_submitted>
  <last_update_submitted_qc>October 2, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 3, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Bari</investigator_affiliation>
    <investigator_full_name>Ruggiero Francavilla</investigator_full_name>
    <investigator_title>Consultant in Gastroenterology</investigator_title>
  </responsible_party>
  <keyword>Irritable Bowel Syndrome</keyword>
  <keyword>Celiac Desease</keyword>
  <keyword>Probiotic</keyword>
  <keyword>Lactobacillus plantarum</keyword>
  <keyword>Bifidobacterium breve</keyword>
  <keyword>Lactobacillus casei</keyword>
  <keyword>Bifidobacterium animalis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irritable Bowel Syndrome</mesh_term>
    <mesh_term>Celiac Disease</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/NCT01699191
org study id: ProCeDo
nct id: NCT01699191
lead sponsor: 
has dmc: No
Probiotics play an important role in preventing overgrowth of potentially pathogenic bacteria
      and maintaining the integrity of the gut mucosal barrier. The beneficial effects of
      probiotics have been previously studied in adult patients with IBS. Clinical studies show
      that patients meeting the criteria for diagnosis for IBS have greater probability for being
      affected by celiac desease if compared to controls without IBS. Since one of the causes
      attributed to the onset of IBS is the modified flora gut, it is interesting to determine the
      beneficial effects that probiotics may have on gastrointestinal symptoms in celiac disease
      patients. The goal of the present study is to determine whether oral administration of a
      probiotic mixture of Lactobacillus plantarum 14D-CECT 4528, Lactobacillus casei,
      Bifidobacterium breve Bbr8 LMG P-17501, Bifidobacterium breve Bl10 LMG P-17500 and
      Bifidobacterium animalis under randomized, double-blind, placebo-controlled conditions would
      improve symptoms of adult celiac patients with IBS.
This is a randomized, double blind study, placebo-controlled, carried out in three
      departments of gastroenterology in Southern Italy (Bari, Taranto e Castellana Grotte).

      Celiac patients with Irritable Bowel Syndrome will considered eligible for inclusion. They
      will be between 18 and 65 years old and they will be in GFD for at least 2 year.

      Will be excluded from the study patients with previous abdominal surgery, chronic disease,
      alarm signs of organic conditions, treatment with probiotics, prebiotics, antibiotics and
      antispasmodics in the previous month, immunodeficiency, pregnancy.

      The size of the sample, which must show a benefit greater than 25% compared to placebo
      (untreated group that usually able to respond positive in 20% of cases), will require 58
      patients per arm to ensure a power of 90% with an alpha error of 0.5.

      Patient will be assigned consecutive numbers, starting with the lowest number available, and
      randomly assigned, with the use of a computer generated randomisation list using permuted
      block design, to receive orally either a probiotic mixture of Lactobacillus plantarum
      14D-CECT 4528, Lactobacillus casei, Bifidobacterium breve Bbr8 LMG P-17501, Bifidobacterium
      breve Bl10 LMG P-17500 and Bifidobacterium animalis or placebo (sachets identical in taste
      and appearance to the active study product except for the absence of probiotic mixture) once
      a day.

      The study consists of three phases:

        1. phase of "running-in" of two weeks to reduce the possibility of a next significant
           placebo effect in which the patient should not take no product;

        2. supplementation for 6 weeks in which the patient will take one packet per day of placebo
           or active product;

        3. follow-up of 6 weeks.

      Enrolled patients will be entered sequentially to receive the assigned treatment. Boxes
      containing placebo will have the same shape, dimension, indication and appearance as those
      containing the viable probiotic mixture and will be provided by the probiotic producer
      (Moviscom Srl, Rome, Italy) which ensure that the study is blinded for investigators and
      patients. Group assignment will be concealed from participants and investigators.

      During the duration of the trial (w1- w14) patients will record gastrointestinal symptoms on
      weekly diary. During the same time will compiled, every two week, the Gastrointestinal
      symptom rating score (GSRS), that consists of a 15-point questionnaire to assess severity and
      frequency of symptoms validated by Svedlund et al.. For all patients will be collected, at T
      = 0 and T = 42 days, stool samples on which will be performed the extraction of DNA and RNA
      for a possible assessment of the intestinal microflora. Bacteria DNA in stools will be
      extracted and stored at -80°C for future analysis. At the end of the study, for patients who
      have achieved the primary objective will be made specific identification of the intestinal
      microflora for verify any amendments.

      The compliance to the study will be demonstrated according to the number of sachets consumed
      by the patient during the 6 weeks of administration, and on the basis of the compilation of
      the questionnaires provided by the protocol.

      Outcome Measures Primary outcome will be the incidence in IBS in celiac patients receiving
      probiotics as compared to those receiving placebo. We have chosen pain as the primary outcome
      measure, in line with the proposed points-to-consider for IBS trials.

      IBS will be diagnosed and categorised according to ROME III criteria. Secondary outcomes are:
      1) evaluation of frequency/severity of symptoms according to treatment arm; 2) modification
      of intestinal microbiota.

      The analysis of the intestinal microbiota of these informative cases will help to assess
      whether there is a intestinal microbiota suggestive of future inset of IBS and ability of our
      probiotic mixture to stabilize the intestinal microbiota.

      Adverse Events and Disallowed Medication Adverse events will be monitored throughout the
      study. Patients will not allowed to consume any probiotic other than those provided and they
      will be invited to continue their eating and physical exercise habits.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Treatment of abdominal pain in celiac patients
time frame: 14 weeks
description: Primary outcome will be the incidence in IBS in celiac patients receiving probiotics mixture as compared to those receiving placebo.
IBS will be diagnosed and categorised according to ROME III criteria.
arm group label: Probiotic Mixture
arm group type: Active Comparator
description: Probiotic mixture
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Dietary Supplement
intervention name: Probiotic
arm group label: Probiotic Mixture
intervention type: Dietary Supplement
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Ruggiero Francavilla
role: Principal Investigator
affiliation: DEPARTMENT OF BIOMEDICINA ETA' EVOLUTIVA
last name: Ruggiero Francavilla
phone: 0805592963
email: rfrancavilla@gmail.com
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: University of Bari
investigator full name: Ruggiero Francavilla
investigator title: Consultant in Gastroenterology
mesh term: Irritable Bowel Syndrome
mesh term: Celiac Disease