A Prospective, Open-label Pilot Study to Evaluate Effector mechanisms of Hyperbaric Oxygen Therapy in Patients with Moderate-to-Severe Ulcerative Colitis: The PARADOX study

Phase 3

Recruiting

Conditions: IBD
ulcerative colitis
10017969

Registration Number: NL-OMON52110

Lead Sponsor: Academisch Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 24

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

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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Co-primary outcomes will be assessed within 3 days after the last HBOT session<br /><br>and at week 12 post-treatment in the cohort that reaches predefined response.<br /><br>Changes between baseline and last day of HBOT will be analyzed to assess the<br /><br>mechanistic effects of HBOT. The co-primary outcomes include mucosal immune<br /><br>cell populations, RNA transcription profiles regarding pro- and<br /><br>anti-inflammatory, HIF-dependent and mucosal barrier function cascades,<br /><br>cytokine profiles, changes in microbiome and blood flow assessed by<br /><br>ultrasonography. </p><br>

Secondary Outcome Measures