Last updated on February 2018

Pediatric FEcal Microbial Transplant for Ulcerative Colitis


Brief description of study

The PediFETCh study is a pilot trial designed to assess the feasibility of fecal microbial transplants for the therapy of pediatric ulcerative colitis (UC) and pediatric inflammatory bowel disease-unclassified (IBD-U). Investigators will test the hypothesis that a protocol of twice-weekly retention enemas delivered over six weeks, using fecal transplant material from a healthy donor, will improve clinical and biological disease markers in patients with pediatric UC or IBD-U.

Detailed Study Description

BACKGROUND

Approximately 104,000 Canadians are affected by ulcerative colitis (UC), an inflammatory bowel disease characterized by immune dysregulation. Ontario, Canada has some of the highest rates of childhood-onset UC in the world and this disease can be particularly debilitating in childhood. Effects on growth and development are profound in pediatric onset disease, and existing treatments, which include long-term immunosuppression, carry short and long-term risks of infection, malignancy, and toxicity.

The intestinal bacteria has a critical role in the regulation of the immune system. Fecal microbiota transplantation (FMT), the transfer of intestinal bacteria from a healthy donor to a recipient, has been shown to treat recurrent Clostridium difficile intestinal infections. The therapeutic potential of FMT for UC has been demonstrated in a recent adult UC trial at our institution (primary investigator: Dr. Paul Moayyedi; collaborator on the PediFETCh trial). Randomized, placebo-controlled trials of FMT in pediatric inflammatory bowel disease are nonexistent. FMT may present a valuable, safer therapeutic option for pediatric UC and a randomized-controlled trial is needed.

OBJECTIVES

Our objective is to determine whether FMT can improve clinical, biological, and mucosal disease status in pediatric UC and IBD-U. This pilot study will provide access to FMT treatment and demonstrate the feasibility of our study design in order to establish a framework for future studies for assessing the effectiveness of FMT intervention.

HYPOTHESES

Based on previously published case series in pediatrics, and a recent randomized controlled trial in adults, we hypothesize that participants receiving fecal microbial enemas containing healthy donor bacteria will experience clinical remission, improvement in inflammatory markers, and a longer duration of remission compared to participants receiving the placebo.

STUDY DESIGN:

The proposed study is a multicenter, randomized, controlled, single-blind trial. Pediatric patients with a diagnosis of UC, or IBD-U will be enrolled and randomized to receive 6 weeks of bi-weekly fecal microbial enemas or normal saline enemas (placebo). Fecal enemas will contain healthy donor stool that has been extensively safety-screened and provided by Rebiotix(R) (RBX-2660). Participants may continue existing UC medical treatments (probiotics, 5-ASAs, immunomodulators, anti-TNF), but no changes in dosing or new therapies will be permitted over the study period. All fecal enemas will be delivered in the study site by investigators to ensure consistency in technique and viability of fecal transplant material. Participants will have clinical disease activity scores measured at each enema administration (6 weeks), and at weeks 18 and 30. Stool samples will be collected at time points throughout the trial for microbiome analyses, and fecal calprotectin measurements, with support from the Farncombe Family Digestive Health Research Institute. Bloodwork will be collected throughout the trial to further measure change in biological disease activity.

SAMPLE SIZE:

50 patients will be recruited for the trial. Participants will be single-blinded, and randomized to placebo or treatment arms.

SAFETY MONITORING:

Study risks include complications of fecal microbial transplants (infection, fever). Based on results of previous studies, and existing safety data of the fecal enema preparation (RBX2660) from previously conducted trials, the risks of infection, adverse gastrointestinal symptoms, or other adverse events are extremely low. The fecal enema preparation used in this trial (RBX2660) by Rebiotix(R) has received FDA IND and Health Canada approvals for clinical trials in recurrent C. difficile. Donors are initially prescreened, and donor blood and stool are extensively screened at two discrete time points prior to administration. We will be providing close follow-up of participants throughout the trial at our center, and in partnership with the referring physician up to bi-weekly throughout the trial.

OUTCOMES
  1. Primary outcomes for this pilot trial are measures of feasibility.
  2. Secondary outcomes are measures of clinical response. These include: clinical response (Pediatric Ulcerative Colitis Activity Index [PUCAI] scores), biological response (serum bloodwork measures), mucosal healing (fecal calprotectin levels), and change in fecal microbiome (change in 16s rRNA, inferred metagenome, metabolome). We will not be assessing other indices of mucosal healing in this trial.

Clinical Study Identifier: NCT02487238

Contact Investigators or Research Sites near you

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Nikhil Pai, MD FRCPC

McMaster Children's Hospital
Hamilton, ON Canada
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Dhandapani Ashok, MD FRCPCH

Children's Hospital London Health Science Centre
London, ON Canada
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Kelly Grzywacz, BSc, MD

CHU Sainte-Justine
Montreal, QC Canada
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