Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Hyperbaric Oxygen Therapy for Ulcerative Colitis Flares (HBO-UC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03494764
Recruitment Status : Recruiting
First Posted : April 11, 2018
Last Update Posted : October 25, 2018
Sponsor:
Collaborators:
Foundation for Clinical Research in IBD
The Eli and Edythe Broad Foundation
University of California, San Diego
Mayo Clinic
University of Pittsburgh
Virginia Mason Memorial Hospital
University of Texas Southwestern Medical Center
Information provided by (Responsible Party):
Corey Siegel, Dartmouth-Hitchcock Medical Center

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.


Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Other: Hyperbaric Oxygen Therapy Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hyperbaric Oxygen Therapy for Moderate to Severe Ulcerative Colitis Flares: A Multi-Center Randomized Trial
Actual Study Start Date : September 7, 2017
Estimated Primary Completion Date : March 1, 2019
Estimated Study Completion Date : March 31, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 5 Days Hyperbaric Therapy
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
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

Active Comparator: 3 Days Hyperbaric Therapy
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
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 Outcome Measures :
  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 Outcome Measures :
  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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03494764


Contacts
Layout table for location contacts
Contact: Kim Thompson, MS 860-287-2714 kimberly.d.thompson@hitchock.org
Contact: Laurie Skinner 603-653-3651

Locations
Layout table for location information
United States, California
UC San Diego Health Systems Recruiting
La Jolla, California, United States, 92093
Contact: Christina Chickering    858-246-2544    cechickering@ucsd.edu   
University of California San Diego Recruiting
San Diego, California, United States, 92103
Contact: Christina Chickering    858-246-2544    cendrigachickering@mail.ucsd.edu   
Principal Investigator: Parambir Dulai, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Jessica Friton    507-538-0678    Friton.jessica@mayo.edu   
Principal Investigator: Laura Raffals, MD         
United States, New Hampshire
Dartmouth-Hitchcock Medical Center Recruiting
Lebanon, New Hampshire, United States, 03766
Contact: Penny Doughty    603-653-6048    Penny.J.Doughty@hitchcock.org   
Principal Investigator: Corey Siegel, MD         
United States, New York
NYU Langone Medical Center Not yet recruiting
New York, New York, United States, 10016
Contact: Christopher Hawryluk       Christopher.Hawryluk@nyulangone.org   
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Cathy McNeil    214-648-9647    Cathy.mcneill@utsouthwestern.edu   
Principal Investigator: Tasneem Ahmed, MD         
United States, Washington
Virginia Mason Memorial Hospital Not yet recruiting
Yakima, Washington, United States, 98902
Contact: Sarah Ackermann    206-341-1295    sarah.ackermann@virginiamason.org   
Principal Investigator: Michael Chiorean, MD         
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Foundation for Clinical Research in IBD
The Eli and Edythe Broad Foundation
University of California, San Diego
Mayo Clinic
University of Pittsburgh
Virginia Mason Memorial Hospital
University of Texas Southwestern Medical Center
Investigators
Layout table for investigator information
Principal Investigator: Parambir Dulai, MD University of California, San Diego

Layout table for additonal information
Responsible Party: Corey Siegel, Section Chief, Section of Gastroenterology, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT03494764     History of Changes
Other Study ID Numbers: Broad-IBD-HBO-UC D12161
First Posted: April 11, 2018    Key Record Dates
Last Update Posted: October 25, 2018
Last Verified: October 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Corey Siegel, Dartmouth-Hitchcock Medical Center:
Hyperbaric Oxygen Therapy

Additional relevant MeSH terms:
Layout table for MeSH terms
Colitis
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases