Hyperbaric Oxygen Therapy for Ulcerative Colitis (HBOT-UC)

• ClinicalTrials.gov Identifier: NCT05987852
• Recruitment Status: Recruiting
• First Posted: August 14, 2023
• Last Update Posted: April 15, 2024
• Sponsor: Northwestern University
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Lauren C Balmert, Northwestern University

Tracking Information

• First Submitted Date: August 1, 2023
• First Posted Date: August 14, 2023
• Last Update Posted Date: April 15, 2024
• Actual Study Start Date: January 9, 2024
• Estimated Primary Completion Date: September 1, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 9, 2023)

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 [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 28, 2023)

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

Original Secondary Outcome Measures (submitted: August 9, 2023)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Hyperbaric Oxygen Therapy for Ulcerative Colitis
• Official Title: Hyperbaric Oxygen Therapy for Ulcerative Colitis Patients Hospitalized for Moderate to Severe Flares: A Multi-Center, Randomized, Double-Blind, Sham-Controlled Trial
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

5-day intervention period; 12 months observational period through standard of care visits and follow-up

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Ulcerative Colitis

Intervention

• Device: Hyperbaric 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.
• Other: Sham 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.

Study Arms

• Experimental: Hyperbaric 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.
  Intervention: Device: Hyperbaric Oxygen Therapy
• Sham Comparator: Sham 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.
  Intervention: Other: Sham Hyperbaric Air

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 9, 2023): 126
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 1, 2027
• Estimated Primary Completion Date: September 1, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Yasmin Pina, BS; 312-503-6459; yasmin.pina@northwestern.edu

Contact: Mary Beth Tull, MS; 312-503-4746; mary.tull@northwestern.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05987852
• Other Study ID Numbers: HBOT-UC; 1U01DK134321 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Dataset with National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Repository.
• Supporting Materials: Study Protocol
• Supporting Materials: Informed Consent Form (ICF)

• Current Responsible Party: Lauren C Balmert, Northwestern University
• Original Responsible Party: Lauren C Balmert, Northwestern University, Associate Professor
• Current Study Sponsor: Northwestern University
• Original Study Sponsor: Same as current
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Lauren Balmert Bonner, PhD; Northwestern University

• PRS Account: Northwestern University
• Verification Date: April 2024