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' existing enteral tubes (gastrostomy, jejunostomy), or potentially 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.
