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).

Pilot Feasibility Study of Fecal Microbiota Transplant for the Treatment of Small Intestinal Bacterial Overgrowth

Small Intestinal Bacterial Overgrowth

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.

Fecal Microbiota Transplant

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.

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.

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).

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.

Associate Professor, Division of Pediatric Gastroenterology & Nutrition

Recruitment/month. ≥2 participants/month.

Adverse and serious events will be recorded using the Common Terminology Criteria for Adverse Events. <10% participants

Participant provides all required blood, stool, lactulose breath tests, and symptom scores per protocol. >80% participants

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).

Pilot Feasibility Study of Fecal Microbiota Transplant for the Treatment of Small Intestinal Bacterial Overgrowth

About this trial

Study ID

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Type

Phase

Placebo

Accepting

Not accepting

Trial Timing

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