Secondary Prevention of Pouchitis With Rifaximin

About This Grant

PROJECT SUMMARY/ABSTRACT There is a significant lack of evidence to guide care for patients with UC following a restorative proctocolectomy with IPAA. Specific evidence gaps include 1) an absence of reliable risk factors for recurrent or chronic pouchitis and 2) a lack of evidence-based approaches for the primary or secondary prevention of pouchitis and pouch-related disorders. The overarching hypothesis underlying this proposal is that rifaximin will be a safe, tolerable, and ultimately effective method of secondary prevention of pouchitis. In this proposal, we aim to 1) demonstrate the feasibility of recruitment, retention, and protocol fidelity of rifaximin as a method of secondary prevention of recurrence after an initial episode of acute pouchitis in a single-arm, open-label pilot study, 2) determine the safety and tolerability of rifaximin as a method of secondary prevention of recurrence after an initial episode of acute pouchitis in a single-arm, open-label pilot study, and 3) explore differences in microbiome profiles from whole genome sequencing of patients at specific time points during 12 months of rifaximin treatment following an acute episode of pouchitis and microbiota profiles from samples collected at the same time points from patients not treated with rifaximin following an episode of acute pouchitis collected in an ongoing study funded by my K23 award (external control population). We will carry out these objectives in a single-arm, open-label, pilot study, where patients will receive rifaximin for 365 days after an initial episode of pouchitis and appropriate treatment with 14 days of antibiotic therapy via a standard protocol. Patients will complete patient reported outcomes (PROs) and submit stool samples at pre-specified, serial time points to allow for both assessments of feasibility of rifaximin as a method of secondary prevention as well as tolerability of this therapy. Additionally, serial stool samples will allow for exploration of differences in the microbial profiles via whole genome shotgun sequencing among patients treated with rifaximin and stool samples submitted at serial time points in a separate prospective cohort funded by Aim 3 of my K23 award. Completion of these aims will demonstrate the safety and tolerability of rifaximin as a method of secondary prevention of pouchitis, explore the mechanisms underlying the potential role, and demonstrate the feasibility of a future multicenter randomized controlled trial. Furthermore, these proposed aims and their associated pilot data will allow me to pursue my ultimate goal of developing tailored interventions for those patients at the highest risk for developing chronic inflammatory conditions of the pouch and crafting strategies for the potential early prevention of these conditions.