Ulcerative Colitis
Conditions
Keywords
hyperbaric oxygen therapy, HBOT, ulcerative colitis, hyperbaric oxygen
Brief summary
Chronic intestinal hypoxia and accompanying mucosal inflammation is a hallmark of ulcerative colitis (UC). Hyperbaric oxygen therapy (HBOT) involves breathing 100% oxygen under increased atmospheric pressure to increase tissue oxygenation. Two small prospective randomized controlled trials have demonstrated that the delivery of HBOT to UC patients hospitalized for acute moderate to severe flares results in improved remission rates and avoidance of in-hospital progression to biologics, small molecules, or colectomy. In this larger trial the study aims to confirm the treatment benefits of HBOT for hospitalized UC patients and study the immune-microbe mechanisms underpinning treatment response.
Interventions
DEVICEHyperbaric Oxygen Therapy
Participants enrolled in the active intervention group receiving HBOT will undergo compression to 2.4 Atmospheres Absolute (ATA; 100% O2) for 90 minutes with two 5-10 minute air breaks (breathing room air at the 2.4 ATA) during the session. This is done once a day for 5 days.
OTHERSham Hyperbaric Air
This control arm will undergo compression to 1.34 ATA for monoplace chambers and 2.4 ATA for multiplace chambers for the full 90-minute session but 21% oxygen instead of 100% oxygen being administered. These participants will also have two 5-10 minute air breaks to mimic the treatment protocol. Multiplace sham sessions will have modified air breaks to avoid decompression sickness. This will happen once a day for 5 days.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
5-day intervention period; 12 months observational period through standard of care visits and follow-up
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Participants with known or newly diagnosed UC who require hospitalization for an acute moderate to severe flare * Age 18-85 * Able to fully participate in all aspects of the trial * Consented and able to receive first HBOT session within first 48 hours of initiation of intravenous steroids * Agreement to not participate in another trial for the duration of the active intervention period
Exclusion criteria
* Received hyperbaric oxygen therapy either as part of standard of care or through a clinical trial prior to enrollment * Complication requiring urgent surgical intervention * Requirement for new start of a biologic or small molecule during the hospitalization prior to randomization and/or anticipated requirement for rescue medical or surgical therapy within 48 hours of randomization * Toxic megacolon * Inability to receive intravenous steroids * Historically failed or been exposed to 4 or more classes of advanced therapeutic options * Known or suspected diagnosis of Crohn's colitis, indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, microscopic colitis or infectious colitis * Received any investigational drug within 30 days * Clinically significant cardiac, renal, neurological, endocrine, respiratory or hepatic impairment that increases the risk for HBOT toxicity * Women who are pregnant or nursing * Unwillingness to complete course of HBOT
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Day 5 | Proportion of participants achieving clinical response as measured by complete resolution of rectal bleeding (Mayo rectal bleeding sub-score of 0) and improvement in stool frequency (at least 1 point reduction in Mayo stool frequency sub-score), without the need for in-hospital biologics, small molecules, or colectomy, by study day 5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Steroid-free, colectomy-free, clinical remission | Day 90 | Proportion of participants steroid-free, colectomy-free, and with clinical remission (Full Mayo ≤ 2, with no sub-score \> 1) |
| Change in inflammation, as measured by C-reactive protein | Day 3 | Change in inflammation, as measured by C-reactive protein (Key secondary endpoint) |
| Endoscopic response | Day 5 | Ulcerative Colitis Endoscopic Index of Severity (UCEIS) (Key secondary endpoint) |
| Endoscopic Improvement | Day 90 | Proportion of participants achieving endoscopic improvement (Mayo endoscopic sub-score of 0 or 1) |
| Endoscopic Remission | Day 90 | Proportion of participants achieving Endoscopic remission (Mayo endoscopic sub-score of 0) |
| Clinical Response | Day 3 | Sum of Mayo rectal bleeding and stool frequency sub-scores (Key secondary endpoint) |
| Clinical Remission | Day 5 | Proportion of participants achieving clinical remission (Full Mayo ≤ 2, with no sub-score \> 1) |
| Colectomy | Day 90; 12 month | Proportion of participants requiring colectomy |
| Re-hospitalization for ulcerative colitis flare | 12 months | Proportion of participants with re-hospitalization during the follow-up period for ulcerative colitis flare |
| Numeric Urgency Rating Score | Day 3 | Score ranges from 0-10 ; higher scores are worse |
| Serious Infections or Serious Adverse Events | Day 5 | Proportion of participants experiencing any serious infections or serious adverse events during intervention period |
| Mucosal Healing | Day 90 | Proportion of participants achieving Mucosal Healing (Endoscopic sub-score 0 or 1 + Geboes histology score ≤ 2) |
Countries
United States
Contacts
Primary ContactYasmin Pina, BS
Backup ContactMary Beth Tull, MS
Outcome results
None listed