Colitis, UlcerativePhase 2HBO-UCNCT03494764
Hyperbaric Oxygen Therapy for Ulcerative Colitis Flares
A Phase 2 study testing Hyperbaric Oxygen Therapy in people with Colitis, Ulcerative, run by Dartmouth-Hitchcock Medical Center at 8 sites in United States.
Trial summary
Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with recurrent mucosal inflammation. Clinically, the disease is characterized by bloody diarrhea, abdominal pain, and constitutional symptoms such as fever and weight loss. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colitis, Ulcerative
- What is being tested?
- Hyperbaric Oxygen Therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 8 sitesUnited States
- Study dates
- 7 Sep 2017to 31 Mar 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hospitalized patients with known or newly diagnosed moderate to severe ulcerative colitis (as defined by the Mayo score ≥6)
- Consented within the first 48 hours of initiating IV steroids
- Risk score of >3 points (pts)
- Mean stool frequency/24 hrs (<4 = 0 pts, 4-6 = 1 pt, 7-9 = 2 pts, >9 = 4 pts)
- Colonic Dilation = 4pts
- Hypoalbuminemia (< 3mg/dL) = 1 pts
- Mayo endoscopic sub-score >2 (moderate to severe)
- Age >18 and able to make their own medical decisions
Who cannot join
- Complication requiring urgent surgical intervention (in the opinion of the investigators)
- Clinically significant cardiac, renal, neurological, endocrine, respiratory or hepatic impairment in the opinion of the investigator, including but not limited to:
- Pulmonary (COPD with CO2 retention; Previous/current imaging showing hyperinflation/air trapping/bullous disease/blebs (opinion of investigators), Current pneumothorax or previous spontaneous pneumothorax, Bronchogenic cyst(s))
- Cardiac (Uncontrolled HTN (systolic >160 or diastolic >100), Unstable angina or myocardial infarction within the previous 3 months, Ejection fraction < 35%, Current or previous amiodarone use, ICD in place, Pacemaker in place not approved for chamber use)
- Hematological/Oncological (Current chemotherapeutic drug use, and past history of bleomycin use,Hereditary Spherocytosis, Sickle cell anemia)
- Gastrointestinal and Infectious Disease (Known or suspected Crohn's disease, Previous infection with mycobacterium, fungus, HIV, Hepatitis B or C, Severe gastrointestinal or systemic infection (opinion of investigator), Current capsule endoscopy or previously non-retrieved capsule
Show all 11Show fewer
- Endocrinology (Uncontrolled hyperthyroidism)
- Neurological and Psychological (Vagal or other nerve stimulators, Uncontrolled seizure disorder, Medications or medical conditions that lower seizure threshold (opinion of the investigator), Drug or alcohol abuse/dependence,Current treatment for alcohol cessation with disulfiram, Current or recent (within past week) use of baclofen)
- Head and Neck (Previous middle ear damage, surgery or infection(s) which may increase the risk for needing ear tubes (opinion of the investigator),Current or previous retinal detachment or optic neuritis, Retinal or vitreous surgery within the past 3 months)
- Implanted devices not on the approved list for use with HBOT
- Women who are pregnant or nursing. Women with childbearing potential were required to use effective birth control if not surgically sterile or postmenopausal for >2 years.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Maryland
Baltimore, Maryland, 21201
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
UC San Diego Health Systems
La Jolla, California, 92093
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03766
NYU Langone Medical Center
New York, New York, 10016
Mayo Clinic
Rochester, Minnesota, 55905
University of California San Diego
San Diego, California, 92103
Virginia Mason Memorial Hospital
Yakima, Washington, 98902
About this study
Official title: Hyperbaric Oxygen Therapy for Moderate to Severe Ulcerative Colitis Flares: A Multi-Center Randomized Trial
Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with recurrent mucosal inflammation. Clinically, the disease is characterized by bloody diarrhea, abdominal pain, and constitutional symptoms such as fever and weight loss. Treatment strategies vary based on disease activity and target various aspects of the inflammatory cascade. Options include: anti-inflammatory drugs (mesalamine), immunosuppressive or modulatory medications (corticosteroids, thiopurines, cyclosporine) and biologic agents (Anti-TNF). Disease severity can be wide ranging, and nearly 25% of UC patients are hospitalized for acute severe disease. Of these patients, 30% will undergo colectomy after the acute episode, a quarter of which will experience post-operative complications. Although there has been great progress in treatment of UC over the past decade, even with the anti-TNF agent infliximab, the one-year remission rate for patients not responding to conservative management is barely 20%. Furthermore, corticosteroids have significant long-term consequences and immune suppressive drugs such as 6-mercaptopurine, azathioprine and infliximab have been associated with serious adverse events including life-threatening infections and lymphomas. With growing evidence that the pathogenesis of UC is multi-factorial and involves a complex interaction of genetic and environmental factors, newer treatment modalities are being evaluated to target the mucosal immune response and mucosal inflammatory regulatory system.
Hyperbaric oxygen offers a promising new treatment option since it targets both tissue hypoxia and inflammation. Recent small scales studies evaluating the impact of hyperbaric oxygen treatment in acute ulcerative colitis flares demonstrated improved outcomes. The mechanisms underlying the improvement are not known. In this study, we will treat ulcerative colitis flares with hyperbaric oxygen and measure changes in both markers of tissue hypoxia and inflammation. We hypothesize that hyperbaric oxygen will (a) improve outcomes, and (b) show reductions in markers of both tissue hypoxia and inflammation.
- Conditions
- Colitis, Ulcerative
- Being tested
- Hyperbaric Oxygen Therapy
- Keywords
- Hyperbaric Oxygen Therapy
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperbaric Oxygen TherapyOther
Hyperbaric oxygen (HBO) provides 100% oxygen at a pressure above atmospheric pressure (typically twice to three times standard sea level pressure (2.0-3.0 ATA)). This dramatically increases the amount of oxygen dissolved in blood plasma, which in turn increases oxygen delivery to tissues. This effect of hyperbaric oxygen is used clinically to treat acute hypoxia in crush injuries, severed limbs, and failing skin grafts
| Study group | Role | What they receive |
|---|---|---|
| 5 Days Hyperbaric Therapy | Active comparator | Patients will be enrolled and follow an identical medical treatment algorithm. At day 3 responders (based on partial Mayo score) will be re-randomized in a 1:1 fashion to complete 5 total days of HBOT (1 session per day) or to stop after 3 days of HBOT. Non-responders will be entered into an open label arm to complete 5 total days of HBOT. Receives: Other: Hyperbaric Oxygen Therapy |
| 3 Days Hyperbaric Therapy | Active comparator | Patients will be enrolled and follow an identical medical treatment algorithm. At day 3 responders (based on partial Mayo score) will be re-randomized in a 1:1 fashion to complete 5 total days of HBOT (1 session per day) or to stop after 3 days of HBOT. Non-responders will be entered into an open label arm to complete 5 total days of HBOT. Receives: Other: Hyperbaric Oxygen Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Impact of HBOT on clinical response/remission
Impact of HBOT on clinical response/remission to medical therapy as measured by the partial Mayo score at study day 5.
Measured: 5 Days
Secondary outcomes (12)
relative and absolute reduction in the Mayo score
Relative and absolute reduction in the Mayo score
Measured: Day 5, 10
Flair duration
time to reduction in mayo score
Measured: day 5, 10
Hospitalization duration
time in the hospital
Measured: day5, 10
proportion of patients requiring other therapy
Proportion who require cyclosporine, infliximab or colectomy during index flare
Measured: Day 5, 10
Relative and absolute change in inflammatory markers
Relative absolute change in inflammatory markers: ESR
Measured: day 10
Relative and absolute change in inflammatory markers
Relative absolute change in inflammatory markers: CRP
Measured: day 10
Relative and absolute change in inflammatory markers
Relative absolute change in inflammatory markers: fecal calprotectin
Measured: day 10
Relative and absolute change in inflammatory markers
Relative absolute change in inflammatory markers: interleukins
Measured: day 10
Relative and absolute change in gene expression
Relative absolute change in gene expression: VEGF
Measured: day 10
Relative and absolute change in gene expression
Relative absolute change in gene expression: HIF-1
Measured: day 10
Relative and absolute change in gene expression
Relative absolute change in gene expression: HO-1
Measured: day 10
microbiome composition
Describe the HBOT specific changes in the microbiome composition
Measured: day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2018
- Study start7 Sep 2017
- Primary completion31 Mar 2020
- Study completion31 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colitis, UlcerativeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation for Clinical Research in IBD, The Eli and Edythe Broad Foundation, University of California, San Diego, Mayo Clinic, University of Pittsburgh Medical Center, Virginia Mason Memorial Hospital, University of Texas Southwestern Medical Center, University of Maryland, College Park, NYU Langone Health
- Responsible party
- Principal investigator, Corey Siegel, Dartmouth-Hitchcock Medical Center
- Investigators
- Parambir Dulai, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03494764
- Sponsor's protocol ID
- Broad-IBD-HBO-UC D12161
- Acronym
- HBO-UC
- Status last verified
- Feb 2021
- First submitted
- 4 Apr 2018
- Last updated
- 8 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hyperbaric Oxygen Therapy for Moderate to Severe Ulcerative Colitis Flares: A Multi-Center Randomized Trial
- ClinicalTrials.gov ID
- NCT03494764
- Acronym / sponsor ID
- HBO-UC / Broad-IBD-HBO-UC D12161
- Conditions
- Colitis, Ulcerative
- Keywords
- Hyperbaric Oxygen Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Collaborators
- Foundation for Clinical Research in IBD, The Eli and Edythe Broad Foundation, University of California, San Diego, Mayo Clinic, University of Pittsburgh Medical Center, Virginia Mason Memorial Hospital, University of Texas Southwestern Medical Center, University of Maryland, College Park, NYU Langone Health
- Study start
- 7 Sep 2017 (actual)
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 31 Mar 2020 (actual)
- First posted
- 11 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with recurrent mucosal inflammation. Clinically, the disease is characterized by bloody diarrhea, abdominal pain, and constitutional symptoms such as fever and weight loss. Treatment strategies vary based on disease activity and target various aspects of the inflammatory cascade. Options include: anti-inflammatory drugs (mesalamine), immunosuppressive or modulatory medications (corticosteroids, thiopurines, cyclosporine) and biologic agents (Anti-TNF). Disease severity can be wide ranging, and nearly 25% of UC patients are hospitalized for acute severe disease. Of these patients, 30% will undergo colectomy after the acute episode, a quarter of which will experience post-operative complications. Although there has been great progress in treatment of UC over the past decade, even with the anti-TNF agent infliximab, the one-year remission rate for patients not responding to conservative management is barely 20%. Furthermore, corticosteroids have significant long-term consequences and immune suppressive drugs such as 6-mercaptopurine, azathioprine and infliximab have been associated with serious adverse events including life-threatening infections and lymphomas. With growing evidence that the pathogenesis of UC is multi-factorial and involves a complex interaction of genetic and environmental factors, newer treatment modalities are being evaluated to target the mucosal immune response and mucosal inflammatory regulatory system.
Hyperbaric oxygen offers a promising new treatment option since it targets both tissue hypoxia and inflammation. Recent small scales studies evaluating the impact of hyperbaric oxygen treatment in acute ulcerative colitis flares demonstrated improved outcomes. The mechanisms underlying the improvement are not known. In this study, we will treat ulcerative colitis flares with hyperbaric oxygen and measure changes in both markers of tissue hypoxia and inflammation. We hypothesize that hyperbaric oxygen will (a) improve outcomes, and (b) show reductions in markers of both tissue hypoxia and inflammation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 5 Days Hyperbaric Therapy | Active comparator | Other: Hyperbaric Oxygen TherapyPatients will be enrolled and follow an identical medical treatment algorithm. At day 3 responders (based on partial Mayo score) will be re-randomized in a 1:1 fashion to complete 5 total days of HBOT (1 session per day) or to stop after 3 days of HBOT. Non-responders will be entered into an open label arm to complete 5 total days of HBOT. |
| 3 Days Hyperbaric Therapy | Active comparator | Other: Hyperbaric Oxygen TherapyPatients will be enrolled and follow an identical medical treatment algorithm. At day 3 responders (based on partial Mayo score) will be re-randomized in a 1:1 fashion to complete 5 total days of HBOT (1 session per day) or to stop after 3 days of HBOT. Non-responders will be entered into an open label arm to complete 5 total days of HBOT. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Hospitalized patients with known or newly diagnosed moderate to severe ulcerative colitis (as defined by the Mayo score ≥6)
- Consented within the first 48 hours of initiating IV steroids
- Risk score of >3 points (pts)
- Mayo endoscopic sub-score >2 (moderate to severe)
- Age >18 and able to make their own medical decisions
Key exclusion criteria (11 listed)
- Complication requiring urgent surgical intervention (in the opinion of the investigators)
- Clinically significant cardiac, renal, neurological, endocrine, respiratory or hepatic impairment in the opinion of the investigator, including but not limited to:
- Implanted devices not on the approved list for use with HBOT
- Women who are pregnant or nursing. Women with childbearing potential were required to use effective birth control if not surgically sterile or postmenopausal for >2 years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyperbaric Oxygen TherapyHyperbaric oxygen (HBO) provides 100% oxygen at a pressure above atmospheric pressure (typically twice to three times standard sea level pressure (2.0-3.0 ATA)). This dramatically increases the amount of oxygen dissolved in blood plasma, which in turn increases oxygen delivery to tissues. This effect of hyperbaric oxygen is used clinically to treat acute hypoxia in crush injuries, severed limbs, and failing skin grafts | Other | 3 Days Hyperbaric Therapy, 5 Days Hyperbaric Therapy |
Primary outcome
Impact of HBOT on clinical response/remission
Time frame: 5 Days
Impact of HBOT on clinical response/remission to medical therapy as measured by the partial Mayo score at study day 5.
12 secondary outcomes
relative and absolute reduction in the Mayo score
Time frame: Day 5, 10
Flair duration
Time frame: day 5, 10
Hospitalization duration
Time frame: day5, 10
proportion of patients requiring other therapy
Time frame: Day 5, 10
Relative and absolute change in inflammatory markers
Time frame: day 10
Relative and absolute change in inflammatory markers
Time frame: day 10
Relative and absolute change in inflammatory markers
Time frame: day 10
Relative and absolute change in inflammatory markers
Time frame: day 10
Relative and absolute change in gene expression
Time frame: day 10
Relative and absolute change in gene expression
Time frame: day 10
Relative and absolute change in gene expression
Time frame: day 10
microbiome composition
Time frame: day 10
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Parambir Dulai, MD principal investigator
University of California, San Diego
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hyperbaric Oxygen Therapy in people with Colitis, Ulcerative, run by Dartmouth-Hitchcock Medical Center at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Impact of HBOT on clinical response/remission (time frame: 5 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2021.