Hyperbaric Oxygen Therapy for Ulcerative Colitis Flares

Colitis, Ulcerative Clinical Trial

— HBO-UC  

Official title:

Hyperbaric Oxygen Therapy for Moderate to Severe Ulcerative Colitis Flares: A Multi-Center Randomized Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03494764
• Other study ID #: Broad-IBD-HBO-UC D12161
• Status: Completed
• Phase: Phase 2
• Start date: September 7, 2017
• Est. completion date: March 31, 2020

Study information

• Verified date: February 2021
• Source: Dartmouth-Hitchcock Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: March 31, 2020
• Est. primary completion date: March 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

• 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

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:

• 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

• 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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer

Intervention

Other:
• Hyperbaric Oxygen Therapy
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

Locations

Country	Name	City	State
United States	University of Maryland	Baltimore	Maryland
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	UC San Diego Health Systems	La Jolla	California
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	NYU Langone Medical Center	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California San Diego	San Diego	California
United States	Virginia Mason Memorial Hospital	Yakima	Washington

Sponsors (10)

Lead Sponsor	Collaborator
Dartmouth-Hitchcock Medical Center	Foundation for Clinical Research in IBD, Mayo Clinic, NYU Langone Health, The Eli and Edythe Broad Foundation, University of California, San Diego, University of Maryland, College Park, University of Pittsburgh Medical Center, University of Texas Southwestern Medical Center, Virginia Mason Memorial Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	relative and absolute reduction in the Mayo score	Relative and absolute reduction in the Mayo score	Day 5, 10
Secondary	Flair duration	time to reduction in mayo score	day 5, 10
Secondary	Hospitalization duration	time in the hospital	day5, 10
Secondary	proportion of patients requiring other therapy	Proportion who require cyclosporine, infliximab or colectomy during index flare	Day 5, 10
Secondary	Relative and absolute change in inflammatory markers	Relative absolute change in inflammatory markers: ESR	day 10
Secondary	Relative and absolute change in inflammatory markers	Relative absolute change in inflammatory markers: CRP	day 10
Secondary	Relative and absolute change in inflammatory markers	Relative absolute change in inflammatory markers: fecal calprotectin	day 10
Secondary	Relative and absolute change in inflammatory markers	Relative absolute change in inflammatory markers: interleukins	day 10
Secondary	Relative and absolute change in gene expression	Relative absolute change in gene expression: VEGF	day 10
Secondary	Relative and absolute change in gene expression	Relative absolute change in gene expression: HIF-1	day 10
Secondary	Relative and absolute change in gene expression	Relative absolute change in gene expression: HO-1	day 10
Secondary	microbiome composition	Describe the HBOT specific changes in the microbiome composition	day 10