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

Primary Purpose

Colitis, Ulcerative

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Hyperbaric Oxygen Therapy
Sponsored by
Dartmouth-Hitchcock Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colitis, Ulcerative focused on measuring Hyperbaric Oxygen Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UC San Diego Health Systems
  • University of California San Diego
  • University of Maryland
  • Mayo Clinic
  • Dartmouth-Hitchcock Medical Center
  • NYU Langone Medical Center
  • University of Texas Southwestern Medical Center
  • Virginia Mason Memorial Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

5 Days Hyperbaric Therapy

3 Days Hyperbaric Therapy

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

relative and absolute reduction in the Mayo score
Relative and absolute reduction in the Mayo score
Flair duration
time to reduction in mayo score
Hospitalization duration
time in the hospital
proportion of patients requiring other therapy
Proportion who require cyclosporine, infliximab or colectomy during index flare
Relative and absolute change in inflammatory markers
Relative absolute change in inflammatory markers: ESR
Relative and absolute change in inflammatory markers
Relative absolute change in inflammatory markers: CRP
Relative and absolute change in inflammatory markers
Relative absolute change in inflammatory markers: fecal calprotectin
Relative and absolute change in inflammatory markers
Relative absolute change in inflammatory markers: interleukins
Relative and absolute change in gene expression
Relative absolute change in gene expression: VEGF
Relative and absolute change in gene expression
Relative absolute change in gene expression: HIF-1
Relative and absolute change in gene expression
Relative absolute change in gene expression: HO-1
microbiome composition
Describe the HBOT specific changes in the microbiome composition

Full Information

First Posted
April 4, 2018
Last Updated
February 4, 2021
Sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
Foundation for Clinical Research in IBD, The Eli and Edythe Broad Foundation, University of California, San Diego, Mayo Clinic, University of Pittsburgh Medical Center, Virginia Mason Memorial Hospital, University of Texas Southwestern Medical Center, University of Maryland, College Park, NYU Langone Health
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1. Study Identification

Unique Protocol Identification Number
NCT03494764
Brief Title
Hyperbaric Oxygen Therapy for Ulcerative Colitis Flares
Acronym
HBO-UC
Official Title
Hyperbaric Oxygen Therapy for Moderate to Severe Ulcerative Colitis Flares: A Multi-Center Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
September 7, 2017 (Actual)
Primary Completion Date
March 31, 2020 (Actual)
Study Completion Date
March 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
Foundation for Clinical Research in IBD, The Eli and Edythe Broad Foundation, University of California, San Diego, Mayo Clinic, University of Pittsburgh Medical Center, Virginia Mason Memorial Hospital, University of Texas Southwestern Medical Center, University of Maryland, College Park, NYU Langone Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colitis, Ulcerative
Keywords
Hyperbaric Oxygen Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
39 (Actual)

8. Arms, Groups, and Interventions

Arm Title
5 Days Hyperbaric Therapy
Arm Type
Active Comparator
Arm Description
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.
Arm Title
3 Days Hyperbaric Therapy
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Hyperbaric Oxygen Therapy
Intervention Description
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 Measure Information:
Title
Impact of HBOT on clinical response/remission
Description
Impact of HBOT on clinical response/remission to medical therapy as measured by the partial Mayo score at study day 5.
Time Frame
5 Days
Secondary Outcome Measure Information:
Title
relative and absolute reduction in the Mayo score
Description
Relative and absolute reduction in the Mayo score
Time Frame
Day 5, 10
Title
Flair duration
Description
time to reduction in mayo score
Time Frame
day 5, 10
Title
Hospitalization duration
Description
time in the hospital
Time Frame
day5, 10
Title
proportion of patients requiring other therapy
Description
Proportion who require cyclosporine, infliximab or colectomy during index flare
Time Frame
Day 5, 10
Title
Relative and absolute change in inflammatory markers
Description
Relative absolute change in inflammatory markers: ESR
Time Frame
day 10
Title
Relative and absolute change in inflammatory markers
Description
Relative absolute change in inflammatory markers: CRP
Time Frame
day 10
Title
Relative and absolute change in inflammatory markers
Description
Relative absolute change in inflammatory markers: fecal calprotectin
Time Frame
day 10
Title
Relative and absolute change in inflammatory markers
Description
Relative absolute change in inflammatory markers: interleukins
Time Frame
day 10
Title
Relative and absolute change in gene expression
Description
Relative absolute change in gene expression: VEGF
Time Frame
day 10
Title
Relative and absolute change in gene expression
Description
Relative absolute change in gene expression: HIF-1
Time Frame
day 10
Title
Relative and absolute change in gene expression
Description
Relative absolute change in gene expression: HO-1
Time Frame
day 10
Title
microbiome composition
Description
Describe the HBOT specific changes in the microbiome composition
Time Frame
day 10

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Parambir Dulai, MD
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
Facility Information:
Facility Name
UC San Diego Health Systems
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
University of California San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03766
Country
United States
Facility Name
NYU Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Virginia Mason Memorial Hospital
City
Yakima
State/Province
Washington
ZIP/Postal Code
98902
Country
United States

12. IPD Sharing Statement

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Hyperbaric Oxygen Therapy for Ulcerative Colitis Flares

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