Clinical trial NCT03494764: Hyperbaric Oxygen Therapy for Ulcerative Colitis Flares
Official title: Hyperbaric Oxygen Therapy for Moderate to Severe Ulcerative Colitis Flares: A Multi-Center Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colitis, Ulcerative
Keywords: Hyperbaric Oxygen Therapy
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: Foundation for Clinical Research in IBD
name: The Eli and Edythe Broad Foundation
name: University of California, San Diego
name: Mayo Clinic
name: University of Pittsburgh Medical Center
name: Virginia Mason Memorial Hospital
name: University of Texas Southwestern Medical Center
name: University of Maryland, College Park
name: NYU Langone Health
First posted: 2018-04-11
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Impact of HBOT on clinical response/remission
timeFrame: 5 Days
Secondary outcomes:
measure: relative and absolute reduction in the Mayo score
timeFrame: Day 5, 10
measure: Flair duration
timeFrame: day 5, 10
measure: Hospitalization duration
timeFrame: day5, 10
measure: proportion of patients requiring other therapy
timeFrame: Day 5, 10
measure: Relative and absolute change in inflammatory markers
timeFrame: day 10
measure: Relative and absolute change in inflammatory markers
timeFrame: day 10
measure: Relative and absolute change in inflammatory markers
timeFrame: day 10
measure: Relative and absolute change in inflammatory markers
timeFrame: day 10
measure: Relative and absolute change in gene expression
timeFrame: day 10
measure: Relative and absolute change in gene expression
timeFrame: day 10
measure: Relative and absolute change in gene expression
timeFrame: day 10
measure: microbiome composition
timeFrame: day 10
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Health Systems
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Yakima
country: United States
facility: Virginia Mason Memorial Hospital
state: Washington
Study officials:
affiliation: University of California, San Diego
name: Parambir Dulai, MD
role: PRINCIPAL_INVESTIGATOR
References: