Hyperbaric Oxygen Shows Promise for Severe Ulcerative Colitis Flares

Ulcerative colitis (UC) hospitalizations represent critical moments in disease progression, with patients facing high risks of complications, repeat hospitalizations, and emergency surgery for years afterward. Current treatment relies heavily on high-dose intravenous steroids, but over half of patients don't respond and require risky rescue therapies with biologics or small molecules that increase infection and cancer risks.

This multicenter trial will test whether hyperbaric oxygen therapy (HBOT) can improve outcomes for 126 hospitalized UC patients experiencing moderate to severe flares. Participants will be randomized 1:1 to receive either HBOT plus steroids or sham air plus steroids over 5 days, followed by 12 months of observation.

HBOT involves breathing 100% oxygen under increased atmospheric pressure, creating tissue oxygen levels that persist well after treatment. This triggers multiple beneficial effects: reduced inflammation and cytokine production, decreased neutrophil trafficking to inflamed tissues, favorable changes in gut microbiome composition, stabilization of hypoxia response pathways, and enhanced wound healing through increased growth factors and stem cell migration.

Preliminary evidence supports HBOT's potential. A meta-analysis of 17 studies showed 86% overall response rates in inflammatory bowel disease patients, with 100% response rates in UC studies that included endoscopic follow-up. Phase 2 trials demonstrated that HBOT's benefits emerge within the first 3 days, with maximum effect by day 5 - achieving 50% clinical remission versus 0% with sham treatment.

The primary endpoint is clinical response defined as complete resolution of rectal bleeding and improved stool frequency without requiring in-hospital biologics, small molecules, or surgery by day 5. Secondary measures include patient-reported outcomes and tissue-level disease markers. Success could transform UC hospitalization management by providing a safer alternative to current rescue therapies while targeting the fundamental mechanisms driving intestinal inflammation and tissue damage.