Clinical trial NCT05967871: Pilot Feasibility Study of Fecal Microbiota Transplant for the Treatment of Small Intestinal Bacterial Overgrowth
Official title: Pilot Feasibility Study of Fecal Microbiota Transplant for the Treatment of Small Intestinal Bacterial Overgrowth
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Small Intestinal Bacterial Overgrowth
Lead sponsor: McMaster Children's Hospital
Sponsor class: OTHER
Collaborators: name: The Hospital for Sick Children
First posted: 2023-08-01
Enrollment: 20
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Patients 3-18 years old
* Patients will discontinue antibiotics for at least 1 week prior to FMT
* A diagnosis of SIBO established through lactose breath test (LBT), and showing of symptoms of SIBO

Exclusion Criteria:

* Participants will not be permitted to start any new treatments (including antibiotics, probiotics, antacid treatments, or antimotility treatments) until Week 8, unless clinically indicated
* We will exclude participants \<3yo to avoid potential concerns of microbial transmission in young children, and to ensure participants are developmentally able to perform LBT

Primary outcomes:
measure: Change in Clinical Symptoms (pre/post fecal microbiota transplant)
timeFrame: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
measure: Rate of Clinical Remission (post fecal microbiota transplant)
timeFrame: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
measure: Urine Metabolomics Analysis
timeFrame: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
measure: Change in Microbiome Composition, Function (pre/post fecal microbiota transplant)
timeFrame: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
measure: Change in Breath Test Results (pre/post fecal microbiota transplant)
timeFrame: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
measure: Bloodwork
timeFrame: Baseline and Week 8 (post-FMT)
Secondary outcomes:
measure: Monthly Rate of Recruitment
timeFrame: 30 weeks
measure: Adverse Events
timeFrame: 30 Weeks
measure: Blood, stool specimens, breath tests, clinical symptom scores
timeFrame: 30 Weeks
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
Study officials:
affiliation: McMaster University | McMaster Children's Hospital
name: Nikhil Pai, MD
role: PRINCIPAL_INVESTIGATOR
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