Secondary Prevention of Pouchitis With Rifaximin

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.

Grant Number: 1R03DK140415-01A1
NIH Institute/Center: NIH
Principal Investigator: Edward Barnes