Transfer of faeces in ulcerative colitis 2: improving efficacy - study protocol for a multicentre randomised...

Area of Science:

• Gastroenterology
• Immunology
• Microbiology

Background:

• Gut microbiota-immune system interactions are key in inflammatory bowel disease (IBD) pathogenesis, including ulcerative colitis (UC).
• Faecal microbiota transplantation (FMT) shows promise for active UC remission, but results vary due to protocol differences.
• Anoxic processing of donor stool may enhance FMT efficacy, as many beneficial microbes, like butyrate producers, are anaerobes.

Purpose of the Study:

• To evaluate the efficacy of strictly anoxic prepared donor FMT versus anoxic prepared autologous FMT in mild to moderate active UC.
• To investigate the impact of anoxic processing, specific donor microbial composition, and dual-route administration on FMT outcomes in UC.
• To explore microbial strains, metabolites, and mechanisms associated with FMT response in UC patients.

Main Methods:

• Randomized, double-blind, placebo-controlled, multicentre trial with 76 evaluable patients.
• Four weekly FMT administrations: two double-route (nasoduodenal + enema) and two enemas.
• Donors selected based on microbial profiles; primary endpoint is steroid-free remission at week 8 (adapted Mayo score).

Main Results:

• Primary endpoint: steroid-free clinical and endoscopic remission at week 8.
• Secondary outcomes: clinical, endoscopic, and histological response.
• Interim analysis by Data Safety Monitoring Board for efficacy and safety monitoring.

Conclusions:

• Strictly anoxic prepared donor FMT with dual-route administration may offer an enhanced therapeutic strategy for ulcerative colitis.
• Understanding microbial and metabolic correlates of response can guide future targeted microbial therapies for UC.
• This trial aims to optimize FMT protocols for improved efficacy and reproducibility in UC treatment.