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| Name | Class |
|---|---|
| Foundation for Clinical Research in IBD | UNKNOWN |
| The Eli and Edythe Broad Foundation | UNKNOWN |
| University of California, San Diego | OTHER |
| Mayo Clinic |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hyperbaric Oxygen Therapy | Other | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 5 Days |
| Measure | Description | Time Frame |
|---|---|---|
| relative and absolute reduction in the Mayo score | Relative and absolute reduction in the Mayo score | Day 5, 10 |
| Flair duration | time to reduction in mayo score |
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Inclusion Criteria:
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
Exclusion Criteria:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Parambir Dulai, MD | University of California, San Diego | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC San Diego Health Systems | La Jolla | California | 92093 | United States | ||
| University of California San Diego |
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| ID | Term |
|---|---|
| D003093 | Colitis, Ulcerative |
| ID | Term |
|---|---|
| D003092 | Colitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D006931 | Hyperbaric Oxygenation |
| ID | Term |
|---|---|
| D010102 | Oxygen Inhalation Therapy |
| D012138 | Respiratory Therapy |
| D013812 | Therapeutics |
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| OTHER |
| University of Pittsburgh Medical Center | OTHER |
| Virginia Mason Memorial Hospital | UNKNOWN |
| University of Texas Southwestern Medical Center | OTHER |
| University of Maryland, College Park | OTHER |
| NYU Langone Health | OTHER |
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| day 5, 10 |
| Hospitalization duration | time in the hospital | day5, 10 |
| proportion of patients requiring other therapy | Proportion who require cyclosporine, infliximab or colectomy during index flare | Day 5, 10 |
| Relative and absolute change in inflammatory markers | Relative absolute change in inflammatory markers: ESR | day 10 |
| Relative and absolute change in inflammatory markers | Relative absolute change in inflammatory markers: CRP | day 10 |
| Relative and absolute change in inflammatory markers | Relative absolute change in inflammatory markers: fecal calprotectin | day 10 |
| Relative and absolute change in inflammatory markers | Relative absolute change in inflammatory markers: interleukins | day 10 |
| Relative and absolute change in gene expression | Relative absolute change in gene expression: VEGF | day 10 |
| Relative and absolute change in gene expression | Relative absolute change in gene expression: HIF-1 | day 10 |
| Relative and absolute change in gene expression | Relative absolute change in gene expression: HO-1 | day 10 |
| microbiome composition | Describe the HBOT specific changes in the microbiome composition | day 10 |
| San Diego |
| California |
| 92103 |
| United States |
| University of Maryland | Baltimore | Maryland | 21201 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| Dartmouth-Hitchcock Medical Center | Lebanon | New Hampshire | 03766 | United States |
| NYU Langone Medical Center | New York | New York | 10016 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| Virginia Mason Memorial Hospital | Yakima | Washington | 98902 | United States |
| D015212 |
| Inflammatory Bowel Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |