HBOT for Perianal Crohn's Disease (PC-HBOT)
Hyperbaric Oxygen Therapy (HBOT) for Refractory Crohn's Perianal Fistulae: a Prospective Interventional Pilot Study
Background Perianal fistulae are among the most disabling complications of Crohn's disease, causing significant morbidity, impaired quality of life, and substantial healthcare utilisation. Despite advances in biologic and surgical therapies, many patients experience persistent fistula drainage and fail to achieve durable healing.
Tissue hypoxia is a key regulator of intestinal inflammation and impaired wound healing in inflammatory bowel disease. Hyperbaric oxygen therapy (HBOT) increases tissue oxygenation, promotes angiogenesis, modulates inflammatory pathways, and may enhance fistula healing.
Preliminary studies suggest that HBOT is a safe and effective adjunctive treatment for refractory perianal Crohn's fistulae, with reported clinical response rates of 75-87% and remission rates of 50-60%. However, current evidence is limited by small sample sizes and the absence of prospective studies within UK clinical practice.
Aim To evaluate the preliminary efficacy of HBOT in patients with refractory perianal Crohn's fistulae treated in an outpatient setting.
Methods This prospective pilot study will recruit ten adults with refractory perianal Crohn's fistulae from the Inflammatory Bowel Disease service at Barts Health NHS Trust. Refractory disease will be defined as persistent fistula drainage or failure to heal despite optimised medical therapy and appropriate surgical management. Participants will undergo HBOT 100% oxygen at 2.4 ATA for approximately 90 minutes per session, 40 sessions over 8 weeks. The primary outcome will be overall clinical response, defined as either clinical remission (complete cessation of fistula drainage) or partial response (clinically meaningful reduction in drainage and symptoms). Secondary outcomes will include treatment adherence, safety, tolerability, patient acceptability, and feasibility of recruitment and study completion.
Expected Impact This pilot study will generate preliminary efficacy and feasibility data to inform the design, outcome measures, and sample size calculations of a larger clinical trial evaluating HBOT as a novel treatment strategy for refractory perianal Crohn's disease in the United Kingdom.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Hyperbaric Oxygen Therapy for Refractory Perianal Crohn's Disease: A Pilot Feasibility Study Background
Perianal fistulising Crohn's disease (pfCD) affects up to one-third of patients with Crohn's disease and is associated with chronic pain, discharge, recurrent abscess formation, repeated surgery, and impaired quality of life. Despite advances in biologic therapies, long-term fistula healing remains difficult to achieve, particularly in patients with refractory disease.
Hyperbaric oxygen therapy (HBOT) delivers 100% oxygen under increased atmospheric pressure and has demonstrated anti-inflammatory and wound-healing effects through enhanced tissue oxygenation, angiogenesis, and modulation of inflammatory pathways. Previous studies have reported clinical response rates of 75-87% and remission rates of approximately 50-60% in refractory perianal Crohn's disease. The HOT-TOPIC trial demonstrated sustained clinical, biochemical, and radiological improvements at one year, while the AMFIBIO study suggested HBOT may reduce fistula inflammation sufficiently to enable definitive surgical closure.
Despite encouraging results, evidence is limited by small sample sizes, heterogeneous treatment pathways, and lack of UK prospective data. This pilot study aims to evaluate the feasibility, safety, and preliminary efficacy of HBOT in adults with refractory perianal Crohn's disease.
Study Objectives Primary Objective
To evaluate the overall clinical response to HBOT in adults with refractory perianal Crohn's disease.
Overall clinical response is defined as:
Clinical remission (closure of all treated fistula openings with complete absence of drainage), or Partial clinical response (reduction in fistula drainage and improvement in perianal symptoms).
Secondary Objectives Evaluate changes in inflammatory biomarkers (C-reactive protein and faecal calprotectin).
Assess changes in quality of life using the Crohn's Anal Fistula Quality of Life (CAF-QoL) questionnaire.
Assess radiological healing using pelvic MRI and/or transrectal ultrasound. Assess treatment safety and tolerability. Evaluate recruitment, retention, adherence, and feasibility outcomes to inform a future larger trial.
Study Design
This is a prospective, single-centre, open-label pilot interventional study conducted at Barts Health NHS Trust.
Ten adults with refractory perianal Crohn's disease will receive HBOT in addition to standard medical and surgical care.
There is no randomisation or control group owing to the feasibility nature of the study.
Total study duration for each participant will be approximately 34 weeks from enrolment.
Study Population Inclusion Criteria
Participants must:
Be aged 18 years or older. Have a confirmed diagnosis of Crohn's disease. Have active draining perianal fistulae classified as TOpClass 2b or 2c, or a non-healing perineal wound following proctectomy (TOpClass 4).
Have persistent disease despite, intolerance to, or loss of response to optimised medical and/or surgical treatment for at least 3-6 months.
Have a loose draining seton in situ for at least 4 weeks prior to treatment. Have stable medical therapy for at least 6 weeks prior to enrolment. Be willing and able to comply with study procedures. Exclusion Criteria
Participants will be excluded if they have:
Undrained perianal abscesses or collections requiring surgical intervention. Rectovaginal fistulae. Fistulae secondary to malignancy, tuberculosis, or non-Crohn's causes. Anal strictures. Severe active proctitis with deep ulceration. Diverting stoma or ileal pouch-anal anastomosis. Untreated pneumothorax. Severe claustrophobia preventing HBOT. Severe chronic obstructive pulmonary disease with carbon dioxide retention. Uncontrolled seizure disorders. Implanted devices incompatible with hyperbaric treatment. Current pregnancy or planned pregnancy during treatment. Intervention
Participants will receive HBOT in a clinically approved multi-place hyperbaric chamber.
Treatment parameters:
100% medical oxygen. 2.4 atmospheres absolute (ATA). Approximately 90 minutes per session. 40 treatment sessions. Five sessions per week over 8 weeks. Scheduled air breaks during treatment to minimise oxygen toxicity.
Participants will continue standard Crohn's disease treatments during the study.
At approximately week 4, and where clinically appropriate, setons may be removed and definitive closure of the external fistula opening performed according to multidisciplinary team recommendations.
Study Assessments Baseline
Participants will undergo:
Medical history and physical examination. Perianal Disease Activity Index (PDAI). Pelvic MRI and/or transrectal ultrasound. Laboratory testing including CRP and faecal calprotectin. CAF-QoL questionnaire. HBOT medical assessment. Follow-Up Schedule
Week 8
End of HBOT treatment assessment.
Week 16
Primary efficacy assessment. PDAI. Clinical drainage assessment. Evaluation of overall clinical response.
Week 24
Durability assessment. PDAI. MRI pelvis and/or transrectal ultrasound. CRP. Faecal calprotectin. CAF-QoL. Safety review.
Outcome Measures Primary Endpoint
Overall clinical response at Week 16.
Clinical remission is defined as complete closure of all treated fistula openings with absence of drainage.
Radiological remission is defined by:
Absence of fluid signal within the fistula tract. Fibrotic replacement of the tract. Absence of contrast enhancement indicating no active inflammation.
Partial response is defined as improvement in fistula drainage and symptoms without complete remission.
Secondary Endpoints Clinical remission rate. Change in PDAI score. MRI evidence of fistula healing. Change in modified Van Assche score and/or PEACE score where applicable. Change in CRP. Change in faecal calprotectin. Change in CAF-QoL score. Treatment completion rate. Participant retention rate. Recruitment rate. Safety and adverse events. Feasibility Outcomes
Pre-specified success criteria include:
Recruitment of at least 8 of 10 planned participants. Completion of at least 75% of scheduled HBOT sessions. Retention at Week 34 of at least 80%. No unexpected serious HBOT-related adverse events.
These outcomes will inform the design of a future larger prospective trial.
Statistical Analysis
As a pilot study, analyses will be exploratory and descriptive.
Baseline characteristics will be summarised using means and standard deviations, or medians and interquartile ranges where appropriate.
Clinical response and remission rates will be reported as proportions with 95% confidence intervals.
Changes in continuous outcomes, including PDAI, CRP, faecal calprotectin, MRI scores, and quality-of-life measures, will be analysed using paired statistical tests according to data distribution.
Effect size estimates and variability measures will be generated to support sample-size calculations for future studies.
Missing data will not be imputed and will be reported descriptively.
Safety Monitoring
HBOT has an established safety profile and is widely used in approved clinical indications.
Potential adverse events include:
Middle-ear barotrauma. Sinus discomfort. Transient myopia. Claustrophobia. Oxygen toxicity (rare). Hypoglycaemia in susceptible individuals.
Participants will undergo standard hyperbaric medicine screening before enrolment and will be monitored throughout treatment by experienced hyperbaric medicine clinicians.
Adverse events will be recorded and reported in accordance with Good Clinical Practice, sponsor requirements, and Health Research Authority guidance.
No independent Data Monitoring Committee has been established for this pilot study. Safety oversight will be provided through the study investigators, sponsor processes, and routine adverse event reporting procedures.
Expected Outcomes
This study aims to provide preliminary estimates of treatment effect, feasibility, and safety for HBOT in refractory perianal Crohn's disease within UK clinical practice.
Findings will support:
Development of a future multicentre prospective trial. Improved understanding of clinical and radiological healing following HBOT. Generation of UK feasibility and safety data. Future peer-reviewed publications and conference presentations.
This pilot study will contribute important evidence regarding the role of HBOT as an adjunctive treatment for refractory perianal Crohn's disease.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Cinzia Papadia, MBBS, MD, FRCP
- Phone Number: 24458 0044(0)20 8539 5522
- Email: cinzia.papadia@nhs.net
Study Contact Backup
- Name: Vivek Srivastava, MBBS, MD, FRCP
- Phone Number: 02071885848
- Email: vivek.srivastava@nhs.net
Study Locations
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London, United Kingdom, E11 1NR
- Whipps Cross University Hospital
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Contact:
- Cinzia Papadia, MBBS, MD
- Phone Number: 02071885848
- Email: cinzia.papadia@nhs.net
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Contact:
- Vivek Srivastava, MBBS, MD
- Phone Number: 01733673900
- Email: vivek.srivastava@nhs.net
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Principal Investigator:
- Cinzia Papadia, MBBS, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Aged 18 years or older. Confirmed diagnosis of Crohn's disease. Presence of at least one draining perianal fistula of cryptoglandular origin secondary to Crohn's disease.
Refractory perianal fistulising disease despite conventional and/or advanced medical therapy, as determined by the treating clinician.
Stable Crohn's disease medical therapy for at least 4 weeks prior to enrolment. Able and willing to undergo hyperbaric oxygen therapy. Able to provide written informed consent.
Exclusion Criteria:
Age <18 years. Inability or unwillingness to provide informed consent. Contraindication to hyperbaric oxygen therapy, including untreated pneumothorax.
Severe claustrophobia not manageable within the hyperbaric chamber. Pregnancy or breastfeeding. Active malignancy requiring treatment. Requirement for major surgery during the HBOT treatment period. Inability to comply with the study procedures or complete the HBOT treatment course.
Any medical condition that, in the opinion of the investigator, would make participation unsafe or interfere with study assessments
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Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: HBOT Treatment Arm
Single experimental arm including patients with refractory Crohn's disease fistulae. Patients will receive hyperbaric oxygen therapy (HBOT) in addition to standard medical care. HBOT consists of 40 treatment sessions delivered over approximately 8 weeks, with participants breathing 100% oxygen at 2.4 atmospheres absolute (ATA) for approximately 90 minutes per session in a multiplace hyperbaric chamber |
Participants with refractory perianal Crohn's disease fistulae will receive hyperbaric oxygen therapy (HBOT) in addition to standard medical care. HBOT consists of 40 treatment sessions delivered over approximately 8 weeks, with participants breathing 100% oxygen at 2.4 atmospheres absolute (ATA) for approximately 90 minutes per session in a multiplace hyperbaric chamber |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Clinical Response of Perianal Crohn's Disease Fistulae
Time Frame: 16 weeks
|
Clinical response defined as a ≥50% reduction from baseline in the number of draining perianal fistulae, assessed by gentle finger compression. |
16 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Sami Hoque, MBBS,pHD, FRCP, Barts Health Trust
Publications and helpful links
General Publications
- Lansdorp CA, Gecse KB, Buskens CJ, Land Wenberg M, Stoker J, Bemelman WA, D'Haens GRAM, van Hulst RA. Hyperbaric oxygen therapy for the treatment of perianal fistulas in Crohn's disease (HOT-TOPIC): study protocol of a prospective interventional cohort study with one-year follow-up. Undersea Hyperb Med. 2019 Jan-Feb;46(1):45-53.
- Dokmak A, Sweigart B, Orekondy NS, Jangi S, Weinstock JV, Hamdeh S, Kochar GS, Shen B, Levy AN. Efficacy and Safety of Hyperbaric Oxygen Therapy in Fistulizing Crohn's Disease: A Systematic Review and Meta-analysis. J Clin Gastroenterol. 2024 Feb 1;58(2):120-130. doi: 10.1097/MCG.0000000000001905.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 377106
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
De-identified individual participant data may be made available upon reasonable request to the study sponsor, subject to approval, data protection requirements, and appropriate data sharing agreements.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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