PARADOX study

Trial details

Who runs it

Stichting Amsterdam UMC

Trial code

EU 2024-515278-28-00

Record updated

2024. november 15.

Original description

The main objective of this study is to evaluate molecular effects in patients with moderate-to-severe ulcerative colitis refractory to medical therapy, more specifically: - Clinical, endoscopic, histological and ultrasonographic disease activity - Mucosal blood flow, oedema and oxygen delivery - Mucosal immune cell populations - Mucosal transcriptional profiles, mainly hypoxia inducible factor (HIF) dependent cascades - Mucosal cytokine profiles - Drug penetration - Mucosal stem cell populations important to mucosal healingRead full original descriptionShow less

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

The main objective of this study is to evaluate molecular effects in patients with moderate-to-severe ulcerative colitis refractory to medical therapy, more specifically: - Clinical, endoscopic, histological and ultrasonographic disease activity - Mucosal blood flow, oedema and oxygen delivery - Mucosal immune cell populations - Mucosal transcriptional profiles, mainly hypoxia inducible factor (HIF) dependent cascades - Mucosal cytokine profiles - Drug penetration - Mucosal stem cell populations important to mucosal healing

Inclusion: 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: 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.

EU CTIS 2024-515278-28-00