Pilot UC Study Shows Recruitment is a Major Challenge in Pediatric FMT Trials

Investigators discussed their findings and lessons to be learned from the first pilot trial of FMT in pediatric patients with ulcerative colitis.

Recruitment of children with ulcerative colitis (UC) into controlled trials of fecal microbiota transplants (FMT) remains a significant challenge, as many of these patients and their parents decline participation due to complexities associated with the study interventions, according to a commentary by investigators from the Pediatric FEcal microbiota Transplant in ulcerative Colitis (PediFETCh) trial published in Gastroenterology.

The 36-month PediFETCh trial enrolled 48 patients with UC between 4 and 17 years of age. These patients were recruited from 3 pediatric Canadian inflammatory bowel disease centers. Study investigators excluded 23 patients, leaving a final cohort of 25 patients who were randomly assigned to either FMT (n=13) or placebo (n=12). A total of 7 patients in the placebo group ultimately crossed over to the open-label FMT arm.

According to the researchers, they did not reach the primary feasibility outcome of recruiting 50 patients over a 2-year period. Despite recruitment challenges, the study did reach the composite clinical endpoint (improvement in the pediatric UC activity index, C-reactive protein, or fecal calprotectin) in 92% of patients in the FMT arm vs 50% of patients in the placebo group by week 6 (risk ratio, 1.8; 95% CI, 1.1–3.7). Approximately 75% of patients had maintained a clinical response at 1 year.

Roughly 35% of patients who were originally recruited for the trial declined to participate because they were required to attend 12 biweekly in-hospital visits for rectal enema therapy. Another roughly 22% of patients declined participation after learning more about the trial protocol; however, these patients did not specify their reasons for not enrolling.

Intensive administration protocols were cited as an enrollment barrier in qualitative follow-up interviews with study participants. As such, the investigators suggest future trials could possibly rely on home-based interventions, such as self-administered FMT enemas or lyophilized, oral FMT capsules, to improve recruitment in pediatric FMT trials. Future studies could also simply reduce the number of required in-hospital visits for rectal enema infusions.

Eligibility criteria also tend to limit recruitment, which was particularly true in the PediFETCh trial, as this study required patients to have active disease while also being clinically stable. Additionally, placebo-controlled randomized controlled trials (RCTs) involving children create additional ethical challenges that may prevent clinicians from referring patients to these studies.

“Despite the many challenges underlying this work, our trial offers the first pilot RCT evidence that FMT may have an important role in improving symptoms and inflammatory indices in pediatric UC,” wrote the researchers.

The researchers added that future trials assessing FMT in children with UC should focus on selecting age-appropriate donors, incorporating endoscopic assessment to improve mucosal healing identification, assessing microbiome functional data, and performing follow-up on “mechanistic studies to develop further understanding of the role of FMT in UC management.”

Reference

Pai N, Popov J, Hill L, et al. Results of the first pilot randomized controlled trial of fecal microbiota transplant in pediatric ulcerative colitis: lessons, limitations, and future prospects. Gastroenterol. 2021;161(2):388-393. doi:10.1053/j.gastro.2021.04.067