IBD ulcerative colitis
Conditions
Interventions
Patients take place in a hyperbaric chamber pressurized to 2.4-2.5 atmosphere
absolute (243-253 kPA), while breathing 100% oxygen through a mask for 80
minutes. Including 5-minute air breaks, the to
Sponsors
Academisch Medisch Centrum
Eligibility
Age
16 Years to 99 Years
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject enrolled in the treatment groups must meet all of the following criteria: All patients in treatment groups: 1. Documented diagnosis of UC >= 4 months prior to entry into the study, confirmed with endoscopy and pathology results available in the source documents 2. Moderately to severely active UC as defined by a total MAYO score of >= 5 and a MAYO ES of >= 2 determined within 7 days of starting HBOT treatment 3. Subjects must have failed or be intolerant (discontinued the medication due to an adverse event as determined by the investigator) of the following treatments: a. Oral corticosteroids b. Azathioprine or 6-mercaptopurine c. Anti-TNF therapy: infliximab, adalimumab or golimumab d. vedolizumab e. Current treatment with ustekinumab (or another p19 inhibitor in a clinical trial) or small-molecule therapy (e.g., tofacitinib) 4. Current treatment with a stable dose of ustekinumab or tofacitinib (>12 weeks of stable dose and interval of ustekinumab and >6 weeks of tofacitinib) 5. Age 16 or older 6. Approved for compassionate use of hyperbaric oxygen therapy by the treating physician and the health insurance company 7. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements. 8. The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 9. Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout week 26. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period]).
Exclusion criteria
Exclusion criteria: A subject will not be eligible for participation in this study if any of the following criteria apply: 1. Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis or clinical findings suggestive of Crohn*s disease 2. Subjects without previous treatment for UC (i.e., treatment-naïve) 3. Subjects at imminent need of surgery as judged by the treating clinician 4. Subjects with evidence of colonic adenomas or dysplasia. However, subjects with prior history of adenomatous polyps will be eligible if the polyps have been completely removed and the subjects are free of polyps at baseline 5. Subjects who have positive stool examinations for enteric pathogens (including Salmonella, Shigella, Yersinia, Campylobacter, C. difficile) detected by stool analysis within 2 weeks prior to enrollment pathogenic ova or parasites, at baseline 6. Patients with an ostomy 7. Unfit for hyperbaric oxygen therapy as assessed by the hyperbaric physician. 8. Contra-indication for endoscopy 9. Patients who received any investigational drug in the past 30 days or 5 half-lives, whichever is longer 10. A history of alcohol or illicit drug use that in the opinion of the principal investigator (PI) would interfere with study procedures 11. Patients with psychiatric problems that in the opinion of the PI would interfere with study procedures 12. Patients unable to attend all study visits 13. Patients with a history of non-compliance with clinical study protocols
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Co-primary outcomes will be assessed within 3 days after the last HBOT session and at week 12 post-treatment in the cohort that reaches predefined response. Changes between baseline and last day of HBOT will be analyzed to assess the mechanistic effects of HBOT. The co-primary outcomes include mucosal immune cell populations, RNA transcription profiles regarding pro- and anti-inflammatory, HIF-dependent and mucosal barrier function cascades, cytokine profiles, changes in microbiome and blood flow assessed by ultrasonography. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Response after completion of HBOT and at week 12 post-treatment defined as a reduction in complete MAYO score of 3 points AND at least 1 point reduction in the MAYO ES WITHOUT escalating therapy such as dose escalations, switching to another drug, adding corticosteroids or colectomy, - Clinical disease activity assessed by the PRO-2 score during treatment at day 2, 4, 6 and the last day of treatment, for the group with 20 and 30 sessions: day 10 and 14 and the group with 30 sessions: day 20, and after treatment at week 2, 4, 6, 9, 12 and 26 - Endoscopic disease activity assessed by Mayo endoscopic score within 3 days of last HBOT session and at week 12 post-treatment, - Histologic disease activity assessed by Robarts* histopathology index within 3 days of last HBOT session and at week 12 post-treatment, - Biochemical disease activity assessed by CRP, albumin and fecal calprotectin at day 0 and 6, for the group with 20 and 30 sessions: day 10 and for the group with 30 sessions: day 20, and for all groups: within 3 days of last HBOT session, week 6, 12 and 26. - Ultrasonographic disease activity assessed by intestinal ultrasound parameters (Bowel wall thickness (mm), color Doppler Signal, presence of inflammatory fat, loss of haustrations, loss of stratification, presence of lymph nodes) at baseline, after HBOT and at week 12. - Quality of life assessed by EQ-5D-5L during treatment at day 0, 6 and the last day of treatment, for the group with 20 and 30 sessions: day 10 and the group with 30 sessions: day 20, and after treatment at week 2, 6, 12 and 26 - Dose-response relationships for 10, 15 or 20 days of HBOT on the co-primary and secondary outcomes above. - Adverse events. All adverse events related or not to study procedures or hyperbaric oxygen therapy will be registered. Side-effects and complications of HBO will be scored by a hyperbaric physician, for the example of barotrauma by the modified TEED score. | — |
Countries
Netherlands
Outcome results
None listed