Hyperbaric Oxygen Therapy for Ulcerative Colitis (HBOT-UC)

Northwestern University126 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

126

Conditions

Ulcerative Colitis

Interventions

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.

Sham Hyperbaric AirOTHER

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

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

Locations (13)

University of Alabama Medicine

Birmingham, Alabama, United States

RECRUITING

University of Los Angeles Health

Los Angeles, California, United States

RECRUITING

University of Miami Health

Miami, Florida, United States

RECRUITING

Orlando Health

Orlando, Florida, United States

RECRUITING

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, United States

RECRUITING

University of Louisville

Louisville, Kentucky, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

RECRUITING

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

RECRUITING

Cornell University Medical Center

New York, New York, United States

ACTIVE_NOT_RECRUITING

...and 3 more locations

Outcomes

Primary Outcomes

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.

Time frame: Day 5

Secondary Outcomes

Clinical Response

Sum of Mayo rectal bleeding and stool frequency sub-scores (Key secondary endpoint)

Time frame: Day 3

Change in inflammation, as measured by C-reactive protein

Change in inflammation, as measured by C-reactive protein (Key secondary endpoint)

Time frame: Day 3

Endoscopic response

Ulcerative Colitis Endoscopic Index of Severity (UCEIS) (Key secondary endpoint)

Time frame: Day 5

Steroid-free, colectomy-free, clinical remission

Proportion of participants steroid-free, colectomy-free, and with clinical remission (Full Mayo ≤ 2, with no sub-score \> 1)

Time frame: Day 90

Endoscopic Improvement

Proportion of participants achieving endoscopic improvement (Mayo endoscopic sub-score of 0 or 1)

Time frame: Day 90

Endoscopic Remission

Proportion of participants achieving Endoscopic remission (Mayo endoscopic sub-score of 0)

Time frame: Day 90

Mucosal Healing

Proportion of participants achieving Mucosal Healing (Endoscopic sub-score 0 or 1 + Geboes histology score ≤ 2)

Time frame: Day 90

Clinical Remission

Proportion of participants achieving clinical remission (Full Mayo ≤ 2, with no sub-score \> 1)

Time frame: Day 5

Colectomy

Proportion of participants requiring colectomy

Time frame: Day 90; 12 month

Re-hospitalization for ulcerative colitis flare

Proportion of participants with re-hospitalization during the follow-up period for ulcerative colitis flare

Time frame: 12 months

Numeric Urgency Rating Score

Score ranges from 0-10 ; higher scores are worse

Time frame: Day 3

Serious Infections or Serious Adverse Events

Proportion of participants experiencing any serious infections or serious adverse events during intervention period

Time frame: Day 5

Hyperbaric Oxygen Therapy for Ulcerative Colitis (HBOT-UC)

Overview

Conditions

Interventions

Eligibility

Locations (13)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts