Hyperbaric Oxygen Therapy for Ulcerative Colitis

Study Overview
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Brief Summary
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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.

Official Title
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Hyperbaric Oxygen Therapy for Ulcerative Colitis Patients Hospitalized for Moderate to Severe Flares: A Multi-Center, Randomized, Double-Blind, Sham-Controlled Trial

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Device: Hyperbaric Oxygen Therapy
* Other: Sham Hyperbaric Air


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with known or newly diagnosed UC who require hospitalization for an acute moderate to severe flare Age 18-85 Consented and able to receive first HBOT session within first 48 hours of initiation of intravenous steroids Exclusion Criteria: Complication requiring urgent surgical intervention Toxic megacolon Inability to receive intravenous steroids Historically failed 3 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 Active SARS CoV 2 infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 5-day intervention period; 12 months observational period through standard of care visits and follow-up
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyperbaric Oxygen Therapy<br>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. | Device: Hyperbaric Oxygen Therapy<br>* 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.<br>|
| Sham Comparator: Sham Hyperbaric Air<br>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. | Other: Sham Hyperbaric Air<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endoscopic Improvement | Proportion of participants achieving endoscopic improvement (Mayo endoscopic sub-score of 0 or 1) | Day 5; Day 90 | 
| Endoscopic Remission | Proportion of participants achieving Endoscopic remission (Mayo endoscopic sub-score of 0) | Day 5; Day 90 | 
| Histologic Remission | Proportion of participants achieving Histologic Remission (Geboes histology score ≤ 2) | Day 5; Day 90 | 
| Mucosal Healing | Proportion of participants achieving Mucosal Healing (Endoscopic sub-score 0 or 1 + Geboes histology score ≤ 2) | Day 5; Day 90 | 
| Clinical Remission | Proportion of participants achieving clinical remission (Full Mayo ≤ 2, with no sub-score > 1) | Day 3; Day 5; 12 months | 
| Initiation and/or adjustment of biologics or small molecule inhibitors | Proportion of participants who require initiation and/or adjustment in biologics or small molecule inhibitors, and number of biologics or small molecule inhibitors and/or adjustments required over 12 months | 12 months | 
| Colectomy | Proportion of participants requiring colectomy | Day 5; 12 months | 
| Re-hospitalization | Proportion of participants with any re-hospitalization during the follow-up period | 12 months | 
| Serious Infections or Serious Adverse Events | Proportion of participants experiencing any serious infections or serious adverse events during intervention period | Day 5 | 
| Number of new initiations and/or adjustments in biologics or small molecule inhibitors | Number of new initiations and/or adjustments in biologics or small molecule inhibitors | 12 months | 
| Duration of index hospitalization | Duration of index hospitalization | From date of hospitalization to time of discharge, assessed up to 30 days | 
| Number of re-hospitalizations | Number of re-hospitalizations | 12 months | 
| Change in inflammation, as measured by C-reactive protein | Change in inflammation, as measured by C-reactive protein | Day 3; Day 5 | 
| Change in inflammation, as measured by fecal calprotectin | Change in inflammation, as measured by fecal calprotectin | Day 5 | 
| Full Mayo Score | Score ranges from 0-12 ; higher scores are worse | Day 5; Day 90 | 
| Ulcerative Colitis Endoscopic Index of Severity (UCEIS) | Score ranges from 0-8 ; higher scores are worse | Day 5; Day 90 | 
| Numeric Urgency Rating Score | Score ranges from 0-10 ; higher scores are worse | Day 3; Day 5 | 
| Improvement in individual Mayo sub-score for stool frequency | Score ranges from 0-3 ; higher scores are worse ; improvement defined as decrease in score from baseline | Day 3; Day 5 | 
| Improvement in individual Mayo sub-score for rectal bleeding | Scores range from 0-3 ; higher scores are worse ; improvement defined as decrease in score from baseline | Day 3; Day 5 | 
| Improvement in individual Mayo Endoscopic sub-score for mucosal appearance at endoscopy | Scores range from 0-3 ; higher scores are worse ; improvement defined as decrease in score from baseline | Day 5 | 
| Improvement in individual Mayo sub-score for physician rating of disease activity | Scores range from 0-3 ; higher scores are worse ; improvement defined as decrease in score from baseline | Day 3; Day 5 | 
| Improvement in urgency Simple Clinical Colitis Activity Index (SCCAI) sub-score | Scores range from 0-3 ; higher scores are worse ; improvement defined as decrease in score from baseline | Day 3; Day 5 | 
| Improvement in nocturnal bowel movement frequency Simple Clinical Colitis Activity Index (SCCAI) sub-score | Scores range from 0-2 ; higher scores are worse ; improvement defined as decrease in score from baseline | Day 3; Day 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperbaric oxygen therapy, HBOT, ulcerative colitis, hyperbaric oxygen