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/NCT05967871</url>
    </required_header>
    <id_info>
      <org_study_id>16581</org_study_id>
      <nct_id>NCT05967871</nct_id>
    </id_info>
    <brief_title>Pilot Feasibility Study of Fecal Microbiota Transplant for the Treatment of Small Intestinal Bacterial Overgrowth</brief_title>
    <official_title>Pilot Feasibility Study of Fecal Microbiota Transplant for the Treatment of Small Intestinal Bacterial Overgrowth</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>McMaster Children's Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>The Hospital for Sick Children</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>McMaster Children'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>
        The objective of the study is to assess feasibility, and clinical efficacy of a novel Fecal&#xD;
        Microbiota Transplantation protocol for the treatment of pediatric small intestinal bacterial&#xD;
        overgrowth (SIBO).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        BACKGROUND AND RATIONALE Fecal microbiota transplant (FMT) is an established treatment for&#xD;
        the management of recurrent Clostridioides difficile (CDI) infection in children and adults,&#xD;
        including children with underlying immunodeficiency syndromes and extensive surgical&#xD;
        resection. While CDI is the most common indication for FMT, this intervention has also been&#xD;
        studied for Crohn's disease, ulcerative colitis, autism, and small intestinal bacterial&#xD;
        overgrowth (SIBO). SIBO is a disorder in which the small bowel is colonized by excessive&#xD;
        aerobic and anaerobic microbes normally present in the colon. This condition may cause&#xD;
        malabsorption, bloating, bloodstream infections (BSI), and D-lactic acidosis (DLA). Treatment&#xD;
        traditionally involves broad-spectrum antibiotic use yet this approach may promote persistent&#xD;
        dysbiosis, multidrug resistant organisms (MDROs), and often lacks clinical efficacy. Patients&#xD;
        with short bowel syndrome (SBS), which involves intestinal resection, dysmotility, and&#xD;
        altered enteral feeding are at highest risk for SIBO. Pediatric SBS SIBO patients face&#xD;
        significant impacts on quality of life, and higher rates of bacteremia and liver disease.&#xD;
  &#xD;
        Specific Aims i. To determine the feasibility, and safety of administering an FMT based&#xD;
        treatment to pediatric SBS patients with SIBO. This aim will include measures of adverse&#xD;
        events, acceptability to children and parents, ease of administration and sample collection.&#xD;
  &#xD;
        ii. To determine short-term clinical efficacy of FMT for the treatment of SIBO. This aim will&#xD;
        include measures of time to symptom resolution, completeness of symptom resolution, change in&#xD;
        enteral feeding tolerance, and development of any new clinical gastrointestinal symptoms&#xD;
        after FMT. Weeks 1-4 after FMT.&#xD;
  &#xD;
        iii. To determine long-term clinical efficacy of FMT for the treatment of SIBO. This aim will&#xD;
        include measures of durability of remission, including time to recurrence of symptom&#xD;
        resolution, severity of clinical symptoms if recurrence, sustained changes in feeding&#xD;
        tolerance, and efficacy of repeat FMT administration (second treatment). Week 8 after FMT.&#xD;
  &#xD;
        iv. To assess changes in intestinal microbial composition and function before and after FMT.&#xD;
        This aim will attempt to identify functional changes in the intestinal microbiome that&#xD;
        correlate with symptom resolution. These data will support future translational and clinical&#xD;
        studies with our collaborators and support the development of new therapeutic innovations.&#xD;
  &#xD;
        D. TRIAL OBJECTIVES Our objectives are to assess feasibility, and clinical efficacy of this&#xD;
        intervention in children (Table 2).&#xD;
  &#xD;
        Feasibility Objectives:&#xD;
  &#xD;
        Acceptability of this intervention for patients and families, ability of patients and&#xD;
        families to conduct the required screening to monitor efficacy and recruitment rate of&#xD;
        patients to the study.&#xD;
  &#xD;
        Clinical Objectives:&#xD;
  &#xD;
        Clinical efficacy of treating SIBO in our patient population using FMT. These outcomes will&#xD;
        be collected at the following timepoints: baseline (pre-FMT), one-, four-, and eight-weeks&#xD;
        post-FMT administration&#xD;
  &#xD;
        E. STUDY DESIGN AND DURATION We will recruit 5-17-year-old patients with intestinal resection&#xD;
        (any length), experiencing an active episode of SIBO (diagnosed through lactose breath&#xD;
        testing and gastrointestinal symptom scores). Patients will discontinue antibiotics for &gt;1&#xD;
        week prior to FMT. FMT infusions will be administered through patients' enteral tubes&#xD;
        (nasogastric, gastrostomy, jejunostomy), or via endoscopy (duodenal infusion).&#xD;
  &#xD;
        Patients will receive a single FMT (Week 0). They will then have outcomes (including a&#xD;
        combination of clinical symptom scores, blood, stool and urine testing) measured one week&#xD;
        after FMT, four weeks after FMT, and eight weeks after FMT.&#xD;
  &#xD;
        As this is an open-label trial, there will be no randomization or blinding required. A&#xD;
        placebo / comparative treatment will not be assessed.&#xD;
  &#xD;
        All FMT treatments will be conducted at MCH, using local pediatric stool bank materials.&#xD;
        Patients will have follow-up monitoring, per protocol through their local institution&#xD;
        (MCH/HSC). Serial measurements of biological, clinical and microbial outcomes will occur, per&#xD;
        protocol.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">August 2026</completion_date>
    <primary_completion_date type="Anticipated">August 2026</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in Clinical Symptoms (pre/post fecal microbiota transplant)</measure>
      <time_frame>Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.</time_frame>
      <description>SIBO Clinical Symptom Scores will be measured using the PedsQL Gastrointestinal Symptoms Scale. This validated instrument has strong age-specific test-retest properties and has been used for functional GI disorders, which have symptoms that strongly overlap with SIBO. Participants will also report symptoms using a Likert scale (Izumo scale). Results of both will be compared.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Rate of Clinical Remission (post fecal microbiota transplant)</measure>
      <time_frame>Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.</time_frame>
      <description>Absence of SIBO symptoms</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Urine Metabolomics Analysis</measure>
      <time_frame>Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.</time_frame>
      <description>Collected urine will be assessed by multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS), using previously described protocols. This technique will offer additional data on microbiome functional changes. Samples will be measured centrally through the Britz-McKibbin laboratory (PBM). Urine metabolomics outcomes are exploratory.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Microbiome Composition, Function (pre/post fecal microbiota transplant)</measure>
      <time_frame>Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.</time_frame>
      <description>Stool will be collected for microbiome 16S rRNA and shotgun metagenomic sequencing. Samples will be obtained from either stool (per rectum), or distal ostomy outputs (ostomy in continuity with proximal bowel). All samples will be sequenced centrally through the McMaster Genomics Centre (MGC). Samples will be stored in -80 freezers. Participants unable to bring stool samples to MCH or HSC will receive funding support for temperature-controlled courier services from home. Costs of microbiome analyses will be partially subsidized by collaborators (MS).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Breath Test Results (pre/post fecal microbiota transplant)</measure>
      <time_frame>Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.</time_frame>
      <description>Lactulose breath test</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Bloodwork</measure>
      <time_frame>Baseline and Week 8 (post-FMT)</time_frame>
      <description>Bloodwork will include complete blood count (CBC), C-reactive protein (CRP), ferritin, folic acid, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), serum cytokine profiles (including IL-2, IL-6, IL10, IL-18, TNF) and serum bile acids. Routine institutional testing protocols will be followed at MCH and HSC. Bloodwork outcomes are exploratory. Data will support the development of primary and secondary objectives for future studies.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Monthly Rate of Recruitment</measure>
      <time_frame>30 weeks</time_frame>
      <description>Recruitment/month. ≥2 participants/month.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse Events</measure>
      <time_frame>30 Weeks</time_frame>
      <description>Adverse and serious events will be recorded using the Common Terminology Criteria for Adverse Events. &lt;10% participants</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood, stool specimens, breath tests, clinical symptom scores</measure>
      <time_frame>30 Weeks</time_frame>
      <description>Participant provides all required blood, stool, lactulose breath tests, and symptom scores per protocol. &gt;80% participants</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Small Intestinal Bacterial Overgrowth</condition>
    <arm_group>
      <arm_group_label>Fecal Microbiota Transpant</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive a Fecal Microbiota transplant Infusion via participants' existing enteral feeding tubes or via elective upper endoscopy (with infusion into the duodenum). Most patients with SBS at MCH and HSC have an existing enteral feeding tube (gastrostomy or jejunostomy tube).</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Fecal Microbiota Transplant</intervention_name>
      <description>Participants will receive approximately 50 grams of human stool/150mL (approximately 107 microbes/mL of suspension) in saline, prepared as per standard collection, preparation, and screening protocols for FMT infusion developed by our institutional stool bank in accordance with recognized standards. Fecal microbiota transplant infused via existing enteral feeding tube or upper elective endoscopy (with infusion into the duodenum) x1.</description>
      <arm_group_label>Fecal Microbiota Transpant</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients 3-18 years old&#xD;
  &#xD;
            -  Patients will discontinue antibiotics for at least 1 week prior to FMT&#xD;
  &#xD;
            -  A diagnosis of SIBO established through lactose breath test (LBT), and showing of&#xD;
               symptoms of SIBO&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Participants will not be permitted to start any new treatments (including antibiotics,&#xD;
               probiotics, antacid treatments, or antimotility treatments) until Week 8, unless&#xD;
               clinically indicated&#xD;
  &#xD;
            -  We will exclude participants &lt;3yo to avoid potential concerns of microbial&#xD;
               transmission in young children, and to ensure participants are developmentally able to&#xD;
               perform LBT&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>3 Years</minimum_age>
      <maximum_age>18 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <link>
      <url>https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm</url>
      <description>US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE). Published 2017.</description>
    </link>
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    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 13, 2023</study_first_submitted>
    <study_first_submitted_qc>July 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 22, 2023</last_update_submitted>
    <last_update_submitted_qc>July 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>McMaster Children's Hospital</investigator_affiliation>
      <investigator_full_name>Nikhil Pai</investigator_full_name>
      <investigator_title>Associate Professor, Division of Pediatric Gastroenterology &amp; Nutrition</investigator_title>
    </responsible_party>
    <!-- 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/NCT05967871
  org study id: 16581
  nct id: NCT05967871
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  The objective of the study is to assess feasibility, and clinical efficacy of a novel Fecal
        Microbiota Transplantation protocol for the treatment of pediatric small intestinal bacterial
        overgrowth (SIBO).
  BACKGROUND AND RATIONALE Fecal microbiota transplant (FMT) is an established treatment for
        the management of recurrent Clostridioides difficile (CDI) infection in children and adults,
        including children with underlying immunodeficiency syndromes and extensive surgical
        resection. While CDI is the most common indication for FMT, this intervention has also been
        studied for Crohn's disease, ulcerative colitis, autism, and small intestinal bacterial
        overgrowth (SIBO). SIBO is a disorder in which the small bowel is colonized by excessive
        aerobic and anaerobic microbes normally present in the colon. This condition may cause
        malabsorption, bloating, bloodstream infections (BSI), and D-lactic acidosis (DLA). Treatment
        traditionally involves broad-spectrum antibiotic use yet this approach may promote persistent
        dysbiosis, multidrug resistant organisms (MDROs), and often lacks clinical efficacy. Patients
        with short bowel syndrome (SBS), which involves intestinal resection, dysmotility, and
        altered enteral feeding are at highest risk for SIBO. Pediatric SBS SIBO patients face
        significant impacts on quality of life, and higher rates of bacteremia and liver disease.
  
        Specific Aims i. To determine the feasibility, and safety of administering an FMT based
        treatment to pediatric SBS patients with SIBO. This aim will include measures of adverse
        events, acceptability to children and parents, ease of administration and sample collection.
  
        ii. To determine short-term clinical efficacy of FMT for the treatment of SIBO. This aim will
        include measures of time to symptom resolution, completeness of symptom resolution, change in
        enteral feeding tolerance, and development of any new clinical gastrointestinal symptoms
        after FMT. Weeks 1-4 after FMT.
  
        iii. To determine long-term clinical efficacy of FMT for the treatment of SIBO. This aim will
        include measures of durability of remission, including time to recurrence of symptom
        resolution, severity of clinical symptoms if recurrence, sustained changes in feeding
        tolerance, and efficacy of repeat FMT administration (second treatment). Week 8 after FMT.
  
        iv. To assess changes in intestinal microbial composition and function before and after FMT.
        This aim will attempt to identify functional changes in the intestinal microbiome that
        correlate with symptom resolution. These data will support future translational and clinical
        studies with our collaborators and support the development of new therapeutic innovations.
  
        D. TRIAL OBJECTIVES Our objectives are to assess feasibility, and clinical efficacy of this
        intervention in children (Table 2).
  
        Feasibility Objectives:
  
        Acceptability of this intervention for patients and families, ability of patients and
        families to conduct the required screening to monitor efficacy and recruitment rate of
        patients to the study.
  
        Clinical Objectives:
  
        Clinical efficacy of treating SIBO in our patient population using FMT. These outcomes will
        be collected at the following timepoints: baseline (pre-FMT), one-, four-, and eight-weeks
        post-FMT administration
  
        E. STUDY DESIGN AND DURATION We will recruit 5-17-year-old patients with intestinal resection
        (any length), experiencing an active episode of SIBO (diagnosed through lactose breath
        testing and gastrointestinal symptom scores). Patients will discontinue antibiotics for >1
        week prior to FMT. FMT infusions will be administered through patients' enteral tubes
        (nasogastric, gastrostomy, jejunostomy), or via endoscopy (duodenal infusion).
  
        Patients will receive a single FMT (Week 0). They will then have outcomes (including a
        combination of clinical symptom scores, blood, stool and urine testing) measured one week
        after FMT, four weeks after FMT, and eight weeks after FMT.
  
        As this is an open-label trial, there will be no randomization or blinding required. A
        placebo / comparative treatment will not be assessed.
  
        All FMT treatments will be conducted at MCH, using local pediatric stool bank materials.
        Patients will have follow-up monitoring, per protocol through their local institution
        (MCH/HSC). Serial measurements of biological, clinical and microbial outcomes will occur, per
        protocol.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Change in Clinical Symptoms (pre/post fecal microbiota transplant)
  time frame: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
  description: SIBO Clinical Symptom Scores will be measured using the PedsQL Gastrointestinal Symptoms Scale. This validated instrument has strong age-specific test-retest properties and has been used for functional GI disorders, which have symptoms that strongly overlap with SIBO. Participants will also report symptoms using a Likert scale (Izumo scale). Results of both will be compared.
  measure: Rate of Clinical Remission (post fecal microbiota transplant)
  time frame: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
  description: Absence of SIBO symptoms
  measure: Urine Metabolomics Analysis
  time frame: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
  description: Collected urine will be assessed by multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS), using previously described protocols. This technique will offer additional data on microbiome functional changes. Samples will be measured centrally through the Britz-McKibbin laboratory (PBM). Urine metabolomics outcomes are exploratory.
  measure: Change in Microbiome Composition, Function (pre/post fecal microbiota transplant)
  time frame: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
  description: Stool will be collected for microbiome 16S rRNA and shotgun metagenomic sequencing. Samples will be obtained from either stool (per rectum), or distal ostomy outputs (ostomy in continuity with proximal bowel). All samples will be sequenced centrally through the McMaster Genomics Centre (MGC). Samples will be stored in -80 freezers. Participants unable to bring stool samples to MCH or HSC will receive funding support for temperature-controlled courier services from home. Costs of microbiome analyses will be partially subsidized by collaborators (MS).
  measure: Change in Breath Test Results (pre/post fecal microbiota transplant)
  time frame: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
  description: Lactulose breath test
  measure: Bloodwork
  time frame: Baseline and Week 8 (post-FMT)
  description: Bloodwork will include complete blood count (CBC), C-reactive protein (CRP), ferritin, folic acid, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), serum cytokine profiles (including IL-2, IL-6, IL10, IL-18, TNF) and serum bile acids. Routine institutional testing protocols will be followed at MCH and HSC. Bloodwork outcomes are exploratory. Data will support the development of primary and secondary objectives for future studies.
  measure: Monthly Rate of Recruitment
  time frame: 30 weeks
  description: Recruitment/month. ≥2 participants/month.
  measure: Adverse Events
  time frame: 30 Weeks
  description: Adverse and serious events will be recorded using the Common Terminology Criteria for Adverse Events. <10% participants
  measure: Blood, stool specimens, breath tests, clinical symptom scores
  time frame: 30 Weeks
  description: Participant provides all required blood, stool, lactulose breath tests, and symptom scores per protocol. >80% participants
  arm group label: Fecal Microbiota Transpant
  arm group type: Experimental
  description: Participants will receive a Fecal Microbiota transplant Infusion via participants' existing enteral feeding tubes or via elective upper endoscopy (with infusion into the duodenum). Most patients with SBS at MCH and HSC have an existing enteral feeding tube (gastrostomy or jejunostomy tube).
  intervention type: Biological
  intervention name: Fecal Microbiota Transplant
  description: Participants will receive approximately 50 grams of human stool/150mL (approximately 107 microbes/mL of suspension) in saline, prepared as per standard collection, preparation, and screening protocols for FMT infusion developed by our institutional stool bank in accordance with recognized standards. Fecal microbiota transplant infused via existing enteral feeding tube or upper elective endoscopy (with infusion into the duodenum) x1.
  arm group label: Fecal Microbiota Transpant
  criteria: 
  gender: All
  minimum age: 3 Years
  maximum age: 18 Years
  healthy volunteers: No
  url: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm
  description: US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE). Published 2017.
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  responsible party type: Principal Investigator
  investigator affiliation: McMaster Children's Hospital
  investigator full name: Nikhil Pai
  investigator title: Associate Professor, Division of Pediatric Gastroenterology & Nutrition