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Completed

NCT Number: NCT03494764

Hyperbaric Oxygen Therapy for Ulcerative Colitis Flares

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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Key information

Conditions

Colitis, Ulcerative Colitis Colonic Diseases Digestive System Diseases Gastroenteritis Gastrointestinal Diseases Inflammatory Bowel Diseases Intestinal Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

UC San Diego Health Systems, La Jolla, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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

Primary outcomes

  1. 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.

Secondary outcomes

  1. relative and absolute reduction in the Mayo score

    Time frame: Day 5, 10

    Relative and absolute reduction in the Mayo score

  2. Flair duration

    Time frame: day 5, 10

    time to reduction in mayo score

  3. Hospitalization duration

    Time frame: day5, 10

    time in the hospital

  4. proportion of patients requiring other therapy

    Time frame: Day 5, 10

    Proportion who require cyclosporine, infliximab or colectomy during index flare

  5. Relative and absolute change in inflammatory markers

    Time frame: day 10

    Relative absolute change in inflammatory markers: ESR

  6. Relative and absolute change in inflammatory markers

    Time frame: day 10

    Relative absolute change in inflammatory markers: CRP

  7. Relative and absolute change in inflammatory markers

    Time frame: day 10

    Relative absolute change in inflammatory markers: fecal calprotectin

  8. Relative and absolute change in inflammatory markers

    Time frame: day 10

    Relative absolute change in inflammatory markers: interleukins

  9. Relative and absolute change in gene expression

    Time frame: day 10

    Relative absolute change in gene expression: VEGF

  10. Relative and absolute change in gene expression

    Time frame: day 10

    Relative absolute change in gene expression: HIF-1

  11. Relative and absolute change in gene expression

    Time frame: day 10

    Relative absolute change in gene expression: HO-1

  12. microbiome composition

    Time frame: day 10

    Describe the HBOT specific changes in the microbiome composition

Sponsors and collaborators

Lead sponsor

Dartmouth-Hitchcock Medical Center

Other

Collaborators

  • 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

Registry information

Official study title

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

Acronym: HBO-UC

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
Apr 11, 2018
Registry last updated
Feb 8, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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