Hyperbaric oxygen therapy for ulcerative colitis patients hospitalized for moderate to severe flares (HBOT-UC): study protocol for a multi-center, randomized, double-blind, sham-controlled trial

Background: Chronic intestinal hypoxia and accompanying mucosal inflammation is a hallmark of ulcerative colitis. Hyperbaric oxygen therapy involves breathing 100% oxygen under increased atmospheric pressure to increase tissue oxygenation. It reduces systemic and local inflammation and up-regulates hypoxia response pathways, making it an attractive therapeutic option. In this trial we aim to confirm the treatment benefits of hyperbaric oxygen therapy for hospitalized ulcerative colitis patients and assess the long-term durability of treatment effect. Methods: This prospective, double-masked, multicenter, 1:1 randomized, sham-controlled trial will enroll 126 participants with known or newly diagnosed ulcerative colitis hospitalized for an acute moderate to severe flare. Participants will be randomized to either hyperbaric oxygen therapy with steroids or sham air with steroids. The trial will involve a 5-day intervention period followed by a 12-month observational period with a 90-day standard of care visit and 12-month telephone visit. The primary outcome measure is clinical response defined as complete resolution of rectal bleeding and improvement in stool frequency, without need for in-hospital biologics, small molecules, or colectomy by study day 5. Secondary endpoints include additional key patient-reported outcomes and histo-endoscopic measures of disease activity. Discussion: Novel and effective treatments are needed for this population to optimize disease outcomes while minimizing treatment-related risks. Demonstrating the ability of hyperbaric oxygen therapy to improve clinical response to steroids and avoid in-hospital rescue therapy has the potential to change the management of hospitalized ulcerative colitis flares. Trial registration: ClinicalTrials.gov NCT05987852. Registered on August 14, 2023.