<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/NCT02213172</url>
  </required_header>
  <id_info>
    <org_study_id>14PIHL</org_study_id>
    <nct_id>NCT02213172</nct_id>
  </id_info>
  <brief_title>Evaluation of the Efficacy of Two Probiotic Strains for Irritable Bowel Syndrome</brief_title>
  <acronym>14PIHL</acronym>
  <official_title>Evaluation of the Efficacy of Two Probiotic Strains for Irritable Bowel Syndrome: an 8-Week, Randomized, Placebo-Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>KGK Science Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Lallemand Health Solutions</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>KGK Science Inc.</source>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if two different probiotic strains, Lactobacillus&#xD;
      paracasei HA-196 and Bifidobacterium longum R0175, are effective in helping subjects manage&#xD;
      the symptoms of IBS&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 30, 2014</start_date>
  <completion_date type="Actual">March 2018</completion_date>
  <primary_completion_date type="Actual">February 15, 2018</primary_completion_date>
  <phase>Phase 2</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>Other</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>IBS Symptom Severity Score</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Assessed using IBS Severity Scoring System Questionnaire, Part I.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>IBS Symptom Severity Score by IBS Subtype</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assessed using IBS Severity Scoring System Questionnaire, Part I.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Responders</measure>
    <time_frame>8 weeks</time_frame>
    <description>A responder is defined as a participant who has at least a 20% improvement in the IBS-SSS severity score after 8 weeks of supplementation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anxiety and Depression</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assessed by administering the HADS questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abdominal pain frequency</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assessed using IBS Severity Scoring System Questionnaire, Part I(c)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abdominal distension/tightness</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assessed using the IBS-SSS Question 2(b)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abdominal Pain Intensity</measure>
    <time_frame>8 weeks</time_frame>
    <description>Mean weekly score. Assessed using IBS-SSS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of straining</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assessed using IBS daily diary, 5 point ordinal scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health Status</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assessed by administration of the SF-36 questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of IBS symptoms on Quality of Life</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assessed by administration of the IBS-QOL Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of IBS Symptoms</measure>
    <time_frame>4 weeks</time_frame>
    <description>Assessed by administration of the IBS-SSS questionnaire, difference from baseline to week 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bowel Habit Satisfaction</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assessed by question 3 of the IBS-SSS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stool Consistency</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assessed using the Bristol Stool Scale included in the IBS Daily Diary</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stool Frequency</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assessed using the IBS Daily Diary</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Compliance and Recovery of Probiotic strains</measure>
    <time_frame>8 weeks</time_frame>
    <description>Monitored by qPCR of fecal samples</description>
  </other_outcome>
  <other_outcome>
    <measure>Microbiome Composition</measure>
    <time_frame>8 weeks</time_frame>
    <description>Detected in fecal samples</description>
  </other_outcome>
  <other_outcome>
    <measure>Cysteine and serine-protease activity</measure>
    <time_frame>8 weeks</time_frame>
    <description>Measured in stool samples</description>
  </other_outcome>
  <other_outcome>
    <measure>Amount of rescue medication used throughout the trial</measure>
    <time_frame>8 weeks</time_frame>
    <description>Use of rescue medication (Bisacodyl 5mg tablet)</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety Anthropometric Measurements</measure>
    <time_frame>8 weeks</time_frame>
    <description>Blood pressure, Heart rate, Weight and BMI</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety blood parameters</measure>
    <time_frame>8 weeks</time_frame>
    <description>Complete blood count, electrolytes, markers of kidney and liver function</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of Adverse Events occurring throughout the trial</measure>
    <time_frame>8 weeks</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">285</enrollment>
  <condition>Irritable Bowel Syndrome</condition>
  <arm_group>
    <arm_group_label>Bifidobacterium longum R0175</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 x 10^9 CFU per capsule, 1 capsule daily for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lactobacillus paracasei HA-196</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 x 10^9 CFU per capsule, 1 capsule daily for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>1 capsule daily for 8 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Bifidobacterium longum R0175</intervention_name>
    <arm_group_label>Bifidobacterium longum R0175</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Lactobacillus paracasei HA-196</intervention_name>
    <arm_group_label>Lactobacillus paracasei HA-196</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female aged 18 years and older.&#xD;
&#xD;
          -  IBS diagnosis according to Rome III criteria and referral to this study by a&#xD;
             clinician. That is, recurrent abdominal pain or discomfort (i.e., uncomfortable&#xD;
             sensation other than pain) at least 2 days/month in the last 3 months (response to&#xD;
             question 1 of the IBS Rome III module questionnaire &gt; 2) associated with 2 or more of&#xD;
             the following:&#xD;
&#xD;
               -  Improvement with defecation (response to question 4 of the IBS Rome III module&#xD;
                  questionnaire &gt; 0);&#xD;
&#xD;
               -  Onset associated with a change in stool frequency (response to question 5 or 6 of&#xD;
                  the IBS Rome III module questionnaire &gt; 0);&#xD;
&#xD;
               -  Onset associated with a change in stool form (appearance). (response to question&#xD;
                  7 or 8 of the IBS Rome III module questionnaire &gt; 0).&#xD;
&#xD;
          -  For women, the abdominal pain or discomfort should be experienced during days other&#xD;
             than menstrual bleeding (response to question 2 of the IBS Rome III module&#xD;
             questionnaire = 0 or 2)&#xD;
&#xD;
          -  Criterion must be fulfilled for the last 3 months with symptom onset at least 6 months&#xD;
             prior to screening (response to question 3 of the IBS Rome III module questionnaire =&#xD;
             1).&#xD;
&#xD;
          -  A copy of the IBS module is provided in Appendix A: IBS Rome III Module Questionnaire&#xD;
&#xD;
          -  Participants from the general population who have IBS symptoms, without a previous&#xD;
             diagnosis, will be assessed by the Principle Investigator and included in the study if&#xD;
             differential diagnosis confirms IBS. The Principle Investigator will confirm the&#xD;
             diagnosis of IBS in any potential participants who have a previous diagnosis of IBS.&#xD;
&#xD;
          -  Subjects experiencing a pain/discomfort frequency of at least 2 days a week during the&#xD;
             run-in period. At visit 2, subjects will be asked &quot;In the last 2 weeks, how often each&#xD;
             week did you have discomfort or pain anywhere in your abdomen? &quot;. The answer must be&#xD;
             at least 2.&#xD;
&#xD;
          -  Subjects diagnosed with IBS who have depression may be included&#xD;
&#xD;
          -  Absence of black color (melena) or blood in stools.&#xD;
&#xD;
          -  Willingness to complete questionnaires, records, and diaries associated with the study&#xD;
             and to complete all clinic visits.&#xD;
&#xD;
          -  Willingness to discontinue consumption of probiotics (e.g. yogurts, with live, active&#xD;
             cultures or supplements).&#xD;
&#xD;
          -  Able to provide informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a history of suicidal ideation, or current suicidal ideation&#xD;
&#xD;
          -  Previous history of gastrointestinal surgery (except appendectomy, cholecystectomy,&#xD;
             hernia repair, or hemorrhoidectomy).&#xD;
&#xD;
          -  Other gastrointestinal diseases (except hemorrhoids and uncomplicated diverticula), as&#xD;
             assessed by ultrasonography, colonoscopy, or rectoscopy, or history of Clostridium&#xD;
             difficile-associated diarrhea.&#xD;
&#xD;
          -  A family history (immediate family i.e. siblings and parents) of colorectal cancer,&#xD;
             inflammatory bowel disease and/or celiac spruce.&#xD;
&#xD;
          -  Co-existing organic gastrointestinal disease.&#xD;
&#xD;
          -  Presence of rectal bleeding, recent weight loss (greater than 5 kg in the past month)&#xD;
             or iron deficiency anemia.&#xD;
&#xD;
          -  History of, or current diagnosis of, liver disease, kidney disease, pulmonary disease,&#xD;
             cardiovascular disease, pancreatic disease, any cancer.&#xD;
&#xD;
          -  Presence of immune-compromised conditions such as AIDS, lymphoma or undergoing&#xD;
             long-term corticosteroid treatment&#xD;
&#xD;
          -  Presence or history of neurological disorders, or significant psychiatric illness.&#xD;
&#xD;
          -  History of, or current diagnosis of, pelvic floor dyssynergia.&#xD;
&#xD;
          -  Positive drug or alcohol screen or recent history of drug or alcohol abuse (within 3&#xD;
             years of screening).&#xD;
&#xD;
          -  Milk or soy allergy.&#xD;
&#xD;
          -  Use of another investigational product within 3 months of the screening visit. The&#xD;
             screened participant could be eligible to participate after a washout period.&#xD;
&#xD;
          -  Positive pregnancy test in women of child-bearing potential.&#xD;
&#xD;
          -  Pregnant or breast-feeding or planning on becoming pregnant.&#xD;
&#xD;
          -  Women of child-bearing potential not using effective contraception. Acceptable methods&#xD;
             of birth control include:&#xD;
&#xD;
               -  Hormonal contraceptives including oral contraceptives, hormone birth control&#xD;
                  patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable&#xD;
                  contraceptives (Depo-Provera, Lunelle), or hormone implant (Norplant System)&#xD;
&#xD;
               -  Intrauterine devices&#xD;
&#xD;
               -  Vasectomy of partner (shown successful as per appropriate follow-up)&#xD;
&#xD;
               -  Double barrier method (use of physical barrier by both partners)&#xD;
&#xD;
          -  Use of any antibiotic drug (e.g., neomycin, rifaximin) within 1 month of screening.&#xD;
             The screened participant could be eligible to participate after a 1 month washout&#xD;
             period.&#xD;
&#xD;
          -  Use of PPI or H2R antagonist within 1 month of screening. The screened participant&#xD;
             could be eligible to participate after a 1 month washout period.&#xD;
&#xD;
          -  Daily use of non-steroidal anti-inflammatory drugs, cortisone, or other&#xD;
             anti-inflammatory drugs 1 month prior to screening. The screened participant could be&#xD;
             eligible to participate after a 1 month washout period.&#xD;
&#xD;
          -  Current use, or use within the past 1 month, of narcotics or other medications for IBS&#xD;
             symptom management (e.g. alosetron, tegaserod, lubiprostone, antispasmodics,&#xD;
             antidiarrheals, laxatives, antipsychotics, tricyclic anti-depressants, selective&#xD;
             serotonin reuptake inhibitors (SSRIs)). Subjects taking a stable dose of&#xD;
             anti-depressants for at least 30 days with no plan to change dosage during the trial&#xD;
             will be eligible for inclusion in the study.&#xD;
&#xD;
          -  Regular use of anti-diarrhea medications and laxatives. Occasional use is permitted&#xD;
             prior to screening (≤ than once a month); if current use is &gt;once per month a one&#xD;
             month wash out period is needed prior to screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tetyana Pelipyagina, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>KGK Science Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>KGK Synergize Inc.</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5R8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 11, 2014</study_first_posted>
  <last_update_submitted>March 11, 2020</last_update_submitted>
  <last_update_submitted_qc>March 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>IBS</keyword>
  <keyword>Probiotic</keyword>
  <keyword>Constipation</keyword>
  <keyword>Bifidobacterium longum</keyword>
  <keyword>Lactobacillus paracasei</keyword>
  <keyword>Lallemand Health Solutions</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irritable Bowel Syndrome</mesh_term>
    <mesh_term>Syndrome</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/NCT02213172
org study id: 14PIHL
nct id: NCT02213172
lead sponsor: 
collaborator: 
The purpose of this study is to determine if two different probiotic strains, Lactobacillus
      paracasei HA-196 and Bifidobacterium longum R0175, are effective in helping subjects manage
      the symptoms of IBS
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: IBS Symptom Severity Score
time frame: 8 Weeks
description: Assessed using IBS Severity Scoring System Questionnaire, Part I.
measure: IBS Symptom Severity Score by IBS Subtype
time frame: 8 weeks
description: Assessed using IBS Severity Scoring System Questionnaire, Part I.
measure: Number of Responders
time frame: 8 weeks
description: A responder is defined as a participant who has at least a 20% improvement in the IBS-SSS severity score after 8 weeks of supplementation
measure: Anxiety and Depression
time frame: 8 weeks
description: Assessed by administering the HADS questionnaire
measure: Abdominal pain frequency
time frame: 8 weeks
description: Assessed using IBS Severity Scoring System Questionnaire, Part I(c)
measure: Abdominal distension/tightness
time frame: 8 weeks
description: Assessed using the IBS-SSS Question 2(b)
measure: Abdominal Pain Intensity
time frame: 8 weeks
description: Mean weekly score. Assessed using IBS-SSS
measure: Severity of straining
time frame: 8 weeks
description: Assessed using IBS daily diary, 5 point ordinal scale
measure: Health Status
time frame: 8 weeks
description: Assessed by administration of the SF-36 questionnaire
measure: Impact of IBS symptoms on Quality of Life
time frame: 8 weeks
description: Assessed by administration of the IBS-QOL Questionnaire
measure: Severity of IBS Symptoms
time frame: 4 weeks
description: Assessed by administration of the IBS-SSS questionnaire, difference from baseline to week 4
measure: Bowel Habit Satisfaction
time frame: 8 weeks
description: Assessed by question 3 of the IBS-SSS
measure: Stool Consistency
time frame: 8 weeks
description: Assessed using the Bristol Stool Scale included in the IBS Daily Diary
measure: Stool Frequency
time frame: 8 weeks
description: Assessed using the IBS Daily Diary
measure: Compliance and Recovery of Probiotic strains
time frame: 8 weeks
description: Monitored by qPCR of fecal samples
measure: Microbiome Composition
time frame: 8 weeks
description: Detected in fecal samples
measure: Cysteine and serine-protease activity
time frame: 8 weeks
description: Measured in stool samples
measure: Amount of rescue medication used throughout the trial
time frame: 8 weeks
description: Use of rescue medication (Bisacodyl 5mg tablet)
measure: Safety Anthropometric Measurements
time frame: 8 weeks
description: Blood pressure, Heart rate, Weight and BMI
measure: Safety blood parameters
time frame: 8 weeks
description: Complete blood count, electrolytes, markers of kidney and liver function
measure: Number of Adverse Events occurring throughout the trial
time frame: 8 weeks
arm group label: Bifidobacterium longum R0175
arm group type: Experimental
description: 10 x 10^9 CFU per capsule, 1 capsule daily for 8 weeks
arm group label: Lactobacillus paracasei HA-196
arm group type: Experimental
description: 10 x 10^9 CFU per capsule, 1 capsule daily for 8 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: 1 capsule daily for 8 weeks
intervention type: Dietary Supplement
intervention name: Bifidobacterium longum R0175
arm group label: Bifidobacterium longum R0175
intervention type: Dietary Supplement
intervention name: Lactobacillus paracasei HA-196
arm group label: Lactobacillus paracasei HA-196
intervention type: Other
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tetyana Pelipyagina, MD
role: Principal Investigator
affiliation: KGK Science Inc.
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Irritable Bowel Syndrome
mesh term: Syndrome