xml: <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/NCT05993247</url>
    </required_header>
    <id_info>
      <org_study_id>KC23MISI0269</org_study_id>
      <nct_id>NCT05993247</nct_id>
    </id_info>
    <brief_title>Efficacy of Probiotics for NSAID-induced Enteropathy in Arthritis Patients</brief_title>
    <acronym>NSAID</acronym>
    <official_title>Efficacy of Probiotics for Non-steroidal Anti-inflammatory Drug-induced Enteropathy in Arthritis Patients: A Double-blinded Pilot Randomized Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Jae Myung Park</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Daewoong Pharmaceutical Co. LTD.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Seoul St. Mary's Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study aimed to investigate the efficacy of probiotics as a preventive agent for&#xD;
        NSAID-induced enteropathy. Arthritis patients are randomly divided into probiotic and placebo&#xD;
        groups, and the drug is administered for eight weeks. Before and after drug administration,&#xD;
        the patient's symptoms/degree of small bowel injuries on capsule endoscopy/microbiome&#xD;
        composition and diversity were investigated.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background:&#xD;
  &#xD;
        Due to aging, there are many long-term users of NSAIDs, increasing enteropathy. The&#xD;
        prophylactic effect of misoprostol, which is currently used, has not been proven, and&#xD;
        misoprostol's long-term compliance and safety remain questionable. Rebamipide shows&#xD;
        insignificant effects in both treatment and prophylaxis.&#xD;
  &#xD;
        Probiotics have been reported to affect enteropathy in animal and human studies. However,&#xD;
        there needs to be more verification studies, and there needs to be confirmatory studies on&#xD;
        the importance of the microbiome in the small bowel. However, it is expected that there will&#xD;
        be fewer complications and less patient resistance, resulting in higher drug compliance.&#xD;
  &#xD;
        Purpose: To identify the efficacy of probiotics on NSAID-induced enteropathy in arthritis&#xD;
        patients by capsule endoscopy and questionnaire, and to analysis the composition and&#xD;
        diversity of the microbiome&#xD;
  &#xD;
        Design: Double-blinded randomized controlled, pilot study&#xD;
  &#xD;
        Participant: Patients diagnosed with osteoarthritis and starting NSAIDs&#xD;
  &#xD;
        Methods: Randomly administering Probiotics or Placebo for eight weeks and comparing &quot;before&#xD;
        and after administration&quot; in arthritis patients&#xD;
  &#xD;
          1. Survey of patient symptoms for enteropathy&#xD;
  &#xD;
          2. Recovery of small bowel mucosal injuries in capsule endoscopy&#xD;
  &#xD;
          3. Analysis of the composition and diversity of the microbiome&#xD;
  &#xD;
          4. Adverse events&#xD;
  &#xD;
        Outcome&#xD;
  &#xD;
          -  Primary outcome: To assess whether probiotics can reduce small bowel injuries caused by&#xD;
             NSAIDs&#xD;
  &#xD;
          -  Secondary outcome:&#xD;
  &#xD;
               1. To investigate whether probiotics can reduce gastrointestinal symptoms caused by&#xD;
                  NSAIDs&#xD;
  &#xD;
               2. To identify the improvement of arthritis symptoms&#xD;
  &#xD;
               3. To examine whether the distribution of the microbiome can be converted into&#xD;
                  beneficial bacteria by administering probiotics&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 20, 2023</start_date>
    <completion_date type="Anticipated">August 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">August 31, 2025</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>
      <intervention_model_description>Probiotics group vs. Placebo group</intervention_model_description>
      <primary_purpose>Prevention</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Changes in the small bowel injuries on capsule endoscopy</measure>
      <time_frame>From enrollment to the end of treatment at 8 weeks</time_frame>
      <description>Changes in the number of ulcers/erosions in the small bowel mucosa on capsule endoscopy before and after taking the NSAIDs and Probiotics/Placebo</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Questionnaire Scores</measure>
      <time_frame>From enrollment to the end of treatment at 8 weeks</time_frame>
      <description>Change from Baseline in Gastrointestinal Symptom Rating Scale Questionnaire Scores at 8 Weeks&#xD;
  Symptoms: Pain or discomfort in upper abdomen, Heartburn, Acid reflux, Hunger pangs, Nausea, Rumbling, Bloating, Passing gas, Constipation, Diarrhea, Loose stool, Hard stool, Urgent bowel movement, Sensation of not completely emptying bowel&#xD;
  Scoring: Each of the 15 items is scored from 0 to 6 points, with the highest score being 45 points and the lowest being 0 points. A score of 0 means no gastrointestinal symptoms, and a higher score indicates a more frequent occurrence of the corresponding symptoms.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change From Baseline in Symptom Scores on the Western Ontario and McMaster Universities (WOMAC) Arthritis Index</measure>
      <time_frame>From enrollment to the end of treatment at 8 weeks</time_frame>
      <description>WOMAC index: Descending stairs, Ascending stairs, Rising from sitting, Standing, Bending to floor, Walking on flat surface, Getting in/out of car, Going shopping, Putting on socks, Lying in bed, Talking off socks, Rising from bed, Getting in/out of bath, Sitting, Getting on/off toilet, Heavy domestic duties, Light domestic duties&#xD;
  Each of the 24 items is scored from 0 to 4 points, with the highest score being 96 points and the lowest being 0 points. A score of 0 means no symptoms and a higher score indicates more severe symptoms of the corresponding symptoms.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change From Baseline in Symptom Scores on the Knee Injury and Osteoarthritis Outcome Scores (KOOS) Questionnaire at 8 Weeks</measure>
      <time_frame>From enrollment to the end of treatment at 8 weeks</time_frame>
      <description>Assessment of KOOS: Daily living, Sports and recreational activities, Pain, Quality of life, Symptoms and stiffness&#xD;
  Each of the 42 items is scored from 0 to 4 points, with the highest score being 168 points and the lowest being 0 points. A score of 0 means no symptoms, and a higher score indicates more severe and frequent symptoms of the corresponding symptoms.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in the gut microbiome through Next Generation Sequencing</measure>
      <time_frame>From enrollment to the end of treatment at 8 weeks</time_frame>
      <description>Changes in composition and diversity of gut microbiota through stool samples&#xD;
  Changes in microbial genome composition</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">36</enrollment>
    <condition>Osteoarthritis</condition>
    <arm_group>
      <arm_group_label>Probiotics arm</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Probiotics combination capsule (Bacillus Subtilis 150 mg /Clostridium Burtyricum Toa 150 mg /Saccharomyces Boulardii 113 mg) per oral, three times a day, for 8 weeks</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo arm</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Placebo capsule in the same form as probiotics, per oral, three times a day, for 8 weeks</description>
    </arm_group>
    <intervention>
      <intervention_type>Combination Product</intervention_type>
      <intervention_name>Probiotics capsule</intervention_name>
      <description>Subjects will take a probiotics combination capsule (Bacillus Subtilis 150 mg /Clostridium Burtyricum Toa 150 mg /Saccharomyces Boulardii 113 mg) three times a day for 8 weeks in combination with NSAIDs</description>
      <arm_group_label>Probiotics arm</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Combination Product</intervention_type>
      <intervention_name>Placebo capsule</intervention_name>
      <description>Subjects will take a placebo capsule identical in shape and size to probiotics capsule three times a day for 8 weeks in combination with NSAIDs</description>
      <arm_group_label>Placebo arm</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients with axial SpA who meet the 2009 ASAS criteria or osteoarthritis diagnosed by&#xD;
               hand or foot x-rays&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of taking NSAIDs or antibiotics within the last month&#xD;
  &#xD;
            -  Those who have been taking probiotics, steroids, or immunosuppressants for a long time&#xD;
  &#xD;
            -  Abdominal surgical history (exception: appendectomy, cholecystectomy)&#xD;
  &#xD;
            -  History of gastrointestinal malignant disease&#xD;
  &#xD;
            -  Abnormal findings requiring drug treatment or surgery in upper gastrointestinal&#xD;
               endoscopy (e.g., digestive cancer, acute peptic ulcer, etc.)&#xD;
  &#xD;
            -  Hemorrhagic disease&#xD;
  &#xD;
            -  Anemia with hemoglobin less than 10 g/dL&#xD;
  &#xD;
            -  Past NSAIDs drug side effects (allergy)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>19 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jae Myung Park, MD</last_name>
      <role>Study Chair</role>
      <affiliation>The Catholic University of Korea</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jae Myung Park, MD</last_name>
      <phone>+82222586023</phone>
      <email>parkjerry@catholic.ac.kr</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 20, 2023</study_first_submitted>
    <study_first_submitted_qc>August 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 11, 2023</last_update_submitted>
    <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Seoul St. Mary's Hospital</investigator_affiliation>
      <investigator_full_name>Jae Myung Park</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Arthritis</mesh_term>
      <mesh_term>Osteoarthritis</mesh_term>
      <mesh_term>Intestinal Diseases</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05993247
  org study id: KC23MISI0269
  nct id: NCT05993247
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  This study aimed to investigate the efficacy of probiotics as a preventive agent for
        NSAID-induced enteropathy. Arthritis patients are randomly divided into probiotic and placebo
        groups, and the drug is administered for eight weeks. Before and after drug administration,
        the patient's symptoms/degree of small bowel injuries on capsule endoscopy/microbiome
        composition and diversity were investigated.
  Background:
  
        Due to aging, there are many long-term users of NSAIDs, increasing enteropathy. The
        prophylactic effect of misoprostol, which is currently used, has not been proven, and
        misoprostol's long-term compliance and safety remain questionable. Rebamipide shows
        insignificant effects in both treatment and prophylaxis.
  
        Probiotics have been reported to affect enteropathy in animal and human studies. However,
        there needs to be more verification studies, and there needs to be confirmatory studies on
        the importance of the microbiome in the small bowel. However, it is expected that there will
        be fewer complications and less patient resistance, resulting in higher drug compliance.
  
        Purpose: To identify the efficacy of probiotics on NSAID-induced enteropathy in arthritis
        patients by capsule endoscopy and questionnaire, and to analysis the composition and
        diversity of the microbiome
  
        Design: Double-blinded randomized controlled, pilot study
  
        Participant: Patients diagnosed with osteoarthritis and starting NSAIDs
  
        Methods: Randomly administering Probiotics or Placebo for eight weeks and comparing "before
        and after administration" in arthritis patients
  
          1. Survey of patient symptoms for enteropathy
  
          2. Recovery of small bowel mucosal injuries in capsule endoscopy
  
          3. Analysis of the composition and diversity of the microbiome
  
          4. Adverse events
  
        Outcome
  
          -  Primary outcome: To assess whether probiotics can reduce small bowel injuries caused by
             NSAIDs
  
          -  Secondary outcome:
  
               1. To investigate whether probiotics can reduce gastrointestinal symptoms caused by
                  NSAIDs
  
               2. To identify the improvement of arthritis symptoms
  
               3. To examine whether the distribution of the microbiome can be converted into
                  beneficial bacteria by administering probiotics
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Probiotics group vs. Placebo group
  primary purpose: Prevention
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Changes in the small bowel injuries on capsule endoscopy
  time frame: From enrollment to the end of treatment at 8 weeks
  description: Changes in the number of ulcers/erosions in the small bowel mucosa on capsule endoscopy before and after taking the NSAIDs and Probiotics/Placebo
  measure: Change from Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Questionnaire Scores
  time frame: From enrollment to the end of treatment at 8 weeks
  description: Change from Baseline in Gastrointestinal Symptom Rating Scale Questionnaire Scores at 8 Weeks
  Symptoms: Pain or discomfort in upper abdomen, Heartburn, Acid reflux, Hunger pangs, Nausea, Rumbling, Bloating, Passing gas, Constipation, Diarrhea, Loose stool, Hard stool, Urgent bowel movement, Sensation of not completely emptying bowel
  Scoring: Each of the 15 items is scored from 0 to 6 points, with the highest score being 45 points and the lowest being 0 points. A score of 0 means no gastrointestinal symptoms, and a higher score indicates a more frequent occurrence of the corresponding symptoms.
  measure: Change From Baseline in Symptom Scores on the Western Ontario and McMaster Universities (WOMAC) Arthritis Index
  time frame: From enrollment to the end of treatment at 8 weeks
  description: WOMAC index: Descending stairs, Ascending stairs, Rising from sitting, Standing, Bending to floor, Walking on flat surface, Getting in/out of car, Going shopping, Putting on socks, Lying in bed, Talking off socks, Rising from bed, Getting in/out of bath, Sitting, Getting on/off toilet, Heavy domestic duties, Light domestic duties
  Each of the 24 items is scored from 0 to 4 points, with the highest score being 96 points and the lowest being 0 points. A score of 0 means no symptoms and a higher score indicates more severe symptoms of the corresponding symptoms.
  measure: Change From Baseline in Symptom Scores on the Knee Injury and Osteoarthritis Outcome Scores (KOOS) Questionnaire at 8 Weeks
  time frame: From enrollment to the end of treatment at 8 weeks
  description: Assessment of KOOS: Daily living, Sports and recreational activities, Pain, Quality of life, Symptoms and stiffness
  Each of the 42 items is scored from 0 to 4 points, with the highest score being 168 points and the lowest being 0 points. A score of 0 means no symptoms, and a higher score indicates more severe and frequent symptoms of the corresponding symptoms.
  measure: Changes in the gut microbiome through Next Generation Sequencing
  time frame: From enrollment to the end of treatment at 8 weeks
  description: Changes in composition and diversity of gut microbiota through stool samples
  Changes in microbial genome composition
  arm group label: Probiotics arm
  arm group type: Active Comparator
  description: Probiotics combination capsule (Bacillus Subtilis 150 mg /Clostridium Burtyricum Toa 150 mg /Saccharomyces Boulardii 113 mg) per oral, three times a day, for 8 weeks
  arm group label: Placebo arm
  arm group type: Placebo Comparator
  description: Placebo capsule in the same form as probiotics, per oral, three times a day, for 8 weeks
  intervention type: Combination Product
  intervention name: Probiotics capsule
  description: Subjects will take a probiotics combination capsule (Bacillus Subtilis 150 mg /Clostridium Burtyricum Toa 150 mg /Saccharomyces Boulardii 113 mg) three times a day for 8 weeks in combination with NSAIDs
  arm group label: Probiotics arm
  intervention type: Combination Product
  intervention name: Placebo capsule
  description: Subjects will take a placebo capsule identical in shape and size to probiotics capsule three times a day for 8 weeks in combination with NSAIDs
  arm group label: Placebo arm
  criteria: 
  gender: All
  minimum age: 19 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Jae Myung Park, MD
  role: Study Chair
  affiliation: The Catholic University of Korea
  last name: Jae Myung Park, MD
  phone: +82222586023
  email: parkjerry@catholic.ac.kr
  responsible party type: Sponsor-Investigator
  investigator affiliation: Seoul St. Mary's Hospital
  investigator full name: Jae Myung Park
  investigator title: Professor
  mesh term: Arthritis
  mesh term: Osteoarthritis
  mesh term: Intestinal Diseases