Hyperbaric Oxygen Therapy for Ulcerative Colitis Flares

NCT03494764 | Completed Phase 2 DMC

• 1 other identifier: Broad-IBD-HBO-UC D12161
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 8

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.

Conditions

Colitis, Ulcerative

Keywords

Hyperbaric Oxygen Therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• relative and absolute reduction in the Mayo score

  Day 5, 10

• Flair duration

  day 5, 10

• Hospitalization duration

  day5, 10

• proportion of patients requiring other therapy

  Day 5, 10

• Relative and absolute change in inflammatory markers

  day 10

Study Arms (2)

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.

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.

Other: Hyperbaric Oxygen Therapy

Interventions

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

3 Days Hyperbaric Therapy; 5 Days Hyperbaric Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (8)

UC San Diego Health Systems

La Jolla, California, 92093, United States

Location

University of California San Diego

San Diego, California, 92103, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03766, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Virginia Mason Memorial Hospital

Yakima, Washington, 98902, United States

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Hyperbaric Oxygenation

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Oxygen Inhalation Therapy; Respiratory Therapy; Therapeutics

Study Officials

• Parambir Dulai, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Section Chief, Section of Gastroenterology

Study Record Dates

• First Submitted: April 4, 2018
• First Posted: April 11, 2018
• Study Start: September 7, 2017
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: February 8, 2021

Record last verified: 2021-02

Locations

US (8)