Hyperbaric Oxygen Therapy for Perianal Fistulizing Crohn's Disease Not Responsive or Intolerant to Conventional Care: HYPNOTIC Pilot Study

Trial Title: Hyperbaric Oxygen Therapy for Perianal Fistulizing Crohn's Disease Not Responsive or Intolerant to Conventional Care: HYPNOTIC Pilot Study

NCT ID: NCT06109961

Condition: Inflammatory Bowel Disease (IBD)

Conditions: Official terms:
Crohn Disease
Inflammatory Bowel Diseases

Conditions: Keywords:
Perianal Crohn's disease (PCD)
Hyperbaric oxygen therapy (HBOT)
Tumor necrosis factor (TNF)

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: A prospective, multicenter, randomized open-label clinical trial and parallel registry.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Oxygen Gas for Inhalation
Description: The active Hyperbaric Oxygen Therapy (HBOT) arm will receive 100% oxygen at 2.0-2.5 atmospheres (ATM).
Arm group label: Active Hyperbaric Oxygen Therapy

Intervention type: Other
Intervention name: Standard of care
Description: The accepted standard of care for perianal Crohn's disease (PCD) involves conventional therapies such as immunosuppressive agents and biologics, which can be used to induce and maintain fistula remission.
Arm group label: Standard of care treatment

Other name: Conventional therapies

Summary: This study aims to test a new treatment called hyperbaric oxygen therapy (HBOT) for a severe type of inflammatory bowel disease called perianal Crohn's disease (PCD). PCD causes painful perianal infections and chronic drainage from fistula tracts, and current treatments are only moderately effective and may not be suitable for all patients. HBOT is a safe and commonly used treatment for chronic non-healing wounds and other conditions. Previous studies have suggested that HBOT may help heal fistulas in PCD patients, but these studies were small and lacked controls.

Detailed description: Hyperbaric oxygen therapy (HBOT) is an effective intervention for improving healing of chronic wounds. HBOT involves the delivery of 100% oxygen in a pressurized environment, typically two to three times standard atmospheric pressure at sea level (2.0-2.5 ATA). This results in increased oxygen tension in plasma and promotes the diffusion of oxygen into tissue, which stimulates tissue restorative pathways that are essential for wound healing16. Hyperoxia also modulates the immune system by suppressing proinflammatory cytokines and promoting the production of anti-inflammatory cytokines. It also enhances the production of growth factors, mobilize stem cells, and stimulates anti-microbial pathways, all of which are believed to be central mechanisms involved in the repair of damaged tissue in IBD. The safety profile of HBOT is also excellent, with a reported adverse event incidence of 10 per 10,000. The most reported adverse event is middle ear barotrauma, which is minor and not life threatening. There is emerging evidence that HBOT may be an effective treatment option for perianal Crohn's disease (PCD). To date, 10 observational studies with a total of 118 patients with PCD refractory to conventional therapy have assessed the effectiveness and safety of HBOT (McCurdy et al., IBDJ 2021). In this small number of patients, HBOT resulted in high rates of clinical response (75% [95% CI, 66%-83%; I2, 0]) and clinical remission (55% [95% CI, 44%-65%; I2, 61]) (Figure 1). Additionally, the HOT-TOPICs study, an open-label observational study demonstrated that HBOT was associated with radiologic improvement of fistula tracts as shown by a reduction in the modified Van Assche MRI score from 9.2 (95% CI, 7.3-11.2) to 7.3 (95% CI, 6.9-9.7). Despite these encouraging results, formal controlled clinical trials have not yet been conducted in patients with PCD to determine the true clinical impact of HBOT in this disease.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Adults (>17 years old) - Diagnosis of Crohn's disease based on standard endoscopic, radiologic and/or histologic criteria. - One or more perianal fistula tract connecting the rectum and the perianal skin. Patients must have active fistula drainage and/or a recurrent perianal abscess within the past month. - Failure or intolerance of conventional therapy (imuran, methotrexate, anti-TNF therapies, vedolizumab and/or ustekinumab). Failure is defined as persistent perianal drainage or recurrent abscesses after a minimum of 3 months of therapy. - Standard or care treatment has been stable (dose and treatment interval) for at least 3 months. - Able to provide written consent to participate Exclusion Criteria: - Fistulas not believed to be due to Crohn's disease (examples include, obstetrical complications, tuberculosis, anorectal cancer or diverticular fistula). - Rectovaginal fistulas. - Undrained perianal abscesses on pelvic MRI exams (abscesses will require successful drainage by an exam under anaesthesia with or without seton prior to study inclusion). - Surgical procedure such as an advancement flap, fistula plug, fistula glue or ligation of intersphincteric fistula tract (LIFT) procedure within the past 6 months. - Diverting ostomies or ileal pouch anal anastomosis. - Current or planned pregnancy or lactation during the study treatment period. - Contraindications to HBOT (claustrophobia, incompatible implanted medical device, and other conditions) based on the discretion of our HBOT clinicians.

Gender: All

Minimum age: 17 Years

Maximum age: N/A

Healthy volunteers: No

Start date: January 2024

Completion date: March 2026

Lead sponsor:
Agency: Ottawa Hospital Research Institute
Agency class: Other

Source: Ottawa Hospital Research Institute

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06109961