Evaluation of a virtual reality-directed brain-gut behavioural treatment inpatient program for patients with inflammatory bowel disease: protocol for a pilot feasibility trial

Abstract

Introduction

Pain is one of the most bothersome symptoms that affects patients with inflammatory bowel disease (IBD) but is often inadequately treated. Inadequate pain control in the inpatient setting not only impacts patients’ experience but increases opioid use and hospital length of stay. Opioids are often considered first-line treatment for severe pain but are associated with significant morbidity and mortality in IBD. Non-steroidal anti-inflammatory drugs are a non-opioid analgesic option, but concerns regarding their contribution to IBD flares have limited their use. Brain-gut behavioural therapies (BGBT), such as cognitive behavioural therapy, meditation and gut-directed hypnotherapy, are effective for pain management and have a role in the treatment of IBD symptoms. However, the use of BGBT in IBD is challenging, given limited access to behavioural health specialists, especially in the inpatient setting. Virtual reality (VR)-directed BGBT programmes can bridge this gap and enhance pain treatment for inpatients with IBD. Therefore, in this study, we aim to establish feasibility and acceptability for a VR-directed BGBT inpatient programme for patients with IBD.

Methods and analysis

We will recruit 40 patients with IBD who are hospitalised at Michigan Medicine and who endorse IBD-related pain. We will assess patient-reported outcomes (pain rating, IBD-specific symptoms, perceived stress, mood) before and after treatment, cumulative inpatient analgesic requirements and hospital length of stay. Our primary objective will be to establish intervention feasibility defined by the frequency and percentage of enrolled participants that use the VR-directed BGBT inpatient intervention in any capacity. Our secondary objective will be to evaluate intervention acceptability by conducting semistructured interviews with study participants. We will also explore the preliminary effectiveness of VR-directed BGBT on patient-reported outcomes and healthcare utilisation as compared with historic controls.

Ethics and dissemination

The study was approved by the institutional review board of the University of Michigan Medical School on 10 October 2023 (HUM00240999). All human subjects will be required to sign an informed consent document prior to study participation. Study findings will be reported through peer-reviewed publication.

Trial registration number

NCT06188793.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• Access to a large and diverse population of hospitalised patients with inflammatory bowel disease.

• Use of both qualitative and quantitative methods to assess the acceptability of virtual reality-directed brain-gut behavioural treatment.

• Limited power to assess preliminary efficacy, and the primary focus is on feasibility and acceptability.

• This is a single-centre study, which limits the generalisability of the study findings.

Introduction

Inflammatory bowel diseases (IBDs), such as Crohn’s disease and ulcerative colitis, are frequently complicated by pain. Pain affects over 80% of patients with IBD and leads to significant morbidity.1,3 In fact, pain in IBD has been associated with lower health-related quality of life, increased healthcare utilisation and disability.4,8 Patients with IBD experience pain that can be generalised or localised most commonly to the abdomen, pelvis, joints or skin. Acute pain in IBD is multifactorial in aetiology and can be influenced by disease activity, structural factors (eg, strictures, abscesses), dysmotility, psychological factors or central sensitisation from changes in pain processing pathways.⁹ While pain in IBD is common, few feasible pharmacologic treatments are accepted for managing pain in IBD.¹⁰ Opioids are effective at managing acute pain, but have been associated with a higher likelihood of serious morbidity and mortality in patients with IBD.¹¹ In addition, opioid use disorder is becoming more common among patients with IBD.¹² Our group demonstrated that 35% of opioid naïve patients who receive opioids around the time of a flare become persistent opioid users.¹³ Nonetheless, more than one in three hospitalised patients with IBD continue to receive opioids for pain,¹⁴ and one in five hospitalised IBD patients report inadequate pain control, despite opioid use.¹⁴ Non-steroidal anti-inflammatory drugs (NSAIDs) are a non-opioid analgesic option, but concerns regarding their contribution to flares have limited their use in IBD.^{15 16}

Brain-gut behavioural therapies (BGBT), such as cognitive behavioural therapy (CBT), meditation and gut-directed hypnotherapy, are promising options for managing pain in IBD. Evidence suggests a bidirectional relationship between psychological functioning and gastrointestinal (GI) symptoms.¹⁷ Data strongly support the use of BGBT for disorders of gut-brain interaction such as irritable bowel syndrome.¹⁸ However, there is also evidence that BGBT is an important adjunctive treatment to immune-targeted therapies in IBD to address depression, anxiety, cognitive dysfunction, central sensitisation and inflammation.¹⁹ Further, many patients exhibit an overlap between IBD and irritable bowel syndrome and experience significant GI symptoms and pain even when they do not have active inflammation.^{20 21} A recent randomised controlled trial demonstrated that CBT-based treatment improved stress levels and health-related quality of life and reduced flare relapse rates compared with standard of care in IBD.²² Further, a mind-body approach with elements of CBT and mindfulness was associated with significant reductions in emergency department visits (71%), unplanned hospitalisations (94%), opioid use (49%) and corticosteroid use (73%) in IBD.²³ However, poor access to trained behavioural health specialists limits the use of BGBT for patients with IBD, particularly in the inpatient setting.

Virtual reality (VR) provides a platform for increasing access to BGBT for inpatients with IBD. Immersive, education-focused and psychological interventions delivered via VR have been used extensively to treat anxiety, depression and pain across conditions.²⁴ For example, meta-analysis data confirm the effectiveness of VR-delivered exposure therapy, relaxation treatment and psychoeducation in reducing anxiety and depression symptoms.²⁴ Users of VR wear a head-mounted display that creates a vivid perception of being transported into immersive and emotionally evocative worlds. VR acts as a distraction to limit the user’s processing of painful stimuli for both somatic and visceral pain. Functional MRI reveals that VR has similar effects on the sensory and insular cortices of the brain as opioids. Data suggest that VR-delivered immersive treatment achieves similar or greater analgesia as hydromorphone in acute pain, through distraction.²⁵ In gastroenterology, VR lowers endoscopic analgesia requirements and reduces pain from dyspepsia and sphincter of Oddi dysfunction.²⁶ However, it is not known whether BGBT-directed VR is effective in treating pain in hospitalised patients with IBD. Further, the underlying mechanisms of action are not well established but are related to the impact of VR on central sensitisation, perceived stress, depression, cognitive dysfunction and inflammation (figure 1). Therefore, there is a critical need for evaluating VR-directed BGBT for patients with IBD in the hospital setting where pain is inadequately treated. We aim to establish the feasibility and acceptability of VR-directed BGBT for pain treatment in patients with IBD receiving standard inpatient care. We will also explore the effectiveness of VR-directed BGBT as compared with historical controls on patient-reported outcomes and healthcare utilisation measures. The study findings will inform a large-scale randomised controlled trial of VR-directed BGBT for hospitalised patients with IBD and will help to identify barriers to the adoption of VR-directed BGBT for IBD in preparation for implementation into clinical practice.

Figure 1. Conceptual model illustrating the potential pathways through which VR-directed brain-gut behavioural treatments may impact pain, gastrointestinal symptoms and inpatient healthcare utilisation. VR, virtual reality.

Methods and analysis

Study design

We propose a prospective single-centre pilot feasibility study with a single treatment arm of participants receiving VR-directed BGBT in the inpatient setting over 3 days. The study protocol will include self-assessments at study entry (day 1) and study completion (day 3), as well as qualitative semistructured postintervention interviews (table 1). We will plan to conduct study recruitment and activities in waves to allow for interim analysis and refinement of study procedures.

Table 1. Virtual reality-directed brain-gut behavioural therapy study event schedule.

Event	Day 1	Day 2	Day 3	Postintervention
Prescreening	X
Screening module and consent	X
Headset and study log	X
Baseline assessment	X
Daily check-in	X	X	X
Postintervention assessment			X
Postintervention interview				X

Setting

Study participants will be recruited from the University of Michigan Hospital. The University Hospital is a 1010-bed hospital that serves patients from Ann Arbor, communities outside the Ann Arbor area and patients referred from regional community hospitals. Patients hospitalised for IBD are primarily admitted to a dedicated gastroenterology and hepatology house staff inpatient service or are followed by a dedicated IBD inpatient consultation service. Potentially eligible patients will be identified through a review of the electronic health record for inpatients admitted with IBD and regular outreach visits with the primary medical teams covering the inpatient gastroenterology and hepatology service. All study activities will take place at the University Hospital, except for postintervention interviews, which may be conducted virtually post discharge.

Study population

We propose to enrol 40 adult patients, 18 years or older, who carry a diagnosis of IBD and who are admitted to the University Hospital for management of their IBD. Eligible patients will self-report IBD-related pain (eg, abdominal, rectal or joint pain) with a severity of 2 or greater on a 0–10 pain scale within 24 hours of study enrolment. Patients who do not report IBD-related pain (ie, those who score <2 on the pain scale), and those whose anticipated length of hospital stay is less than 72 hours will be excluded from the study, as they are less likely to benefit from a VR-directed BGBT inpatient programme. We will also evaluate several factors that are relative contraindications to the use of VR (table 2). We will exclude patients who have previously had a seizure, loss of awareness or other symptoms linked to an epileptic condition; those with binocular vision loss; who are currently pregnant or with an uncontrolled cardiac condition such as an arrhythmia, coronary artery disease or neurological/cerebrovascular disease. Eligible patients will be sent a recruitment letter by email, followed by two follow-up emails at 2-week intervals for patients who do not respond nor opt out of participation. To maximise recruitment, we will follow up these emails with a phone call for patients who do not opt out, and up to two follow-up calls at 2-week intervals. We will need to recruit at least five participants per month for 8 months to achieve recruitment goals. Patients who enrol in the study and go on to develop conditions identified as study exclusions (eg, a serious medical conditions such as haemodynamic instability or a need for urgent surgery) will be withdrawn from the study given limitations to participating in study activities and confounding of their new serious medical condition.

Table 2. Virtual reality-directed brain-gut behavioural therapy inclusion and exclusion criteria.

Inclusion criteria	Exclusion criteria
Age ≥18 years old	Age <18 years old
Diagnosis of IBD	No IBD diagnosis
Admitted to inpatient service	Pain <2 of 10 over the last 24 hours
Self-reported pain ≥2 of 10 within 24 hours	Anticipated length of hospital stay <72 hours
Anticipated length of hospital stay ≥72 hours	History of seizure, loss of awareness, epileptic conditions
	History of binocular vision loss
	Current pregnancy
	Current uncontrolled cardiac conditions
	Current uncontrolled neurologic/cerebrovascular disease
	Current uncontrolled mental health disorder

IBD, inflammatory bowel disease.

Procedures and assessments

Potential eligibility for study participation will be determined by review of the electronic health record for patients followed by the gastroenterology and hepatology inpatient and consultation services and meeting the above inclusion and exclusion criteria. A study team member will approach potential participants to complete a screening module comprised of two questions related to self-reported pain: (1) a rating of average pain in the prior 24 hours and (2) a rating of the worst pain experienced in the prior 24 hours. Pain will be rated on a 0–10 numerical rating scale where 0 represents no pain and 10 represents the worst possible pain. The screening module will also include questions to identify any study exclusions. A study team member will obtain informed consent from eligible patients for study participation (online supplemental file 1). Study assessments will be completed at baseline (Day 1) and treatment completion (Day 3), and a postintervention interview will be scheduled and conducted within seven business days of study enrolment (table 3). The Day 1 baseline and Day 3 post-treatment self-assessments will include two pain intensity items, a single perceived stress assessment item, a 20-item measure of positive and negative affect, a 6-item daily pain catastrophising scale and the 40-item ulcerative colitis patient-reported outcome (UC-PRO) or Crohn’s disease patient-reported outcome (CD-PRO) measure. Day 1 assessments will also include the primary care post-traumatic stress disorder screen.

Table 3. Patient screening and data collection.

Event	Prescreening	Screening module	Baseline assessment	Postintervention assessment	Postintervention interview
Screening and recruitment
Medical history	X
Anticipated length of hospital stay	X
Provider pain assessment	X
Contact information		X
Screening inclusion and exclusion criteria		X
Agreement to participate and consent		X
Data collection
Patient demographics			X
Subjective pain score			X	X
Perceived stress			X	X
Pain Catastrophising Scale			X	X
IBD-specific patient reported outcomes			X	X
Primary care PTSD screen			X
Treatment Acceptability/Adherence Scale				X
System Usability Scale				X
Qualitative interview					X

PTSD, post-traumatic stress disorder.

After obtaining informed consent and completing a day 1 baseline assessment, study team members will offer study participants a head-mounted display through which the VR-directed BGBT will be delivered. Patients will be trained on the basics of using the VR headset, accessing the VR-directed BGBT programme on the headset and troubleshooting common head-mounted display issues (eg, losing Wi-Fi connectivity). Throughout the intervention period, a study member will complete a daily in-person or remote (phone or text) check-in with participants, pending their preferences, to assess for and troubleshoot any technological issues. Participants will be counselled that they should use the VR-directed BGBT at their discretion over the 3-day study period alongside standard inpatient care. On day 3, study participants will complete the VR-BGBT intervention regardless of the anticipated length of hospital stay. Participants will complete a post-treatment questionnaire that includes the same items as the day 1 baseline assessment, in addition to the validated 10-item Treatment Acceptability/Adherence Scale, which quantifies intervention acceptability, and the validated 10-item System Usability Scale, which quantifies intervention usability.^{27 28} The scores on the Treatment Acceptability/Adherence Scale range from 10 to 70 with higher scores indicating greater acceptability. The scores on the System Usability Scale range from 0 to 100 with a higher score indicating great usability. We will also collect information on patients’ daily pain scores collected with vital signs and cumulative inpatient opioid, NSAID, acetaminophen and other analgesic requirements via the electronic health record. Study team members will conduct a semistructured interview with study participants to better understand their acceptability, satisfaction and experiences (including adverse events) with the VR-directed BGBT inpatient programme. Interviews will be conducted with the help of an interview guide with open-ended questions focused on participants’ experience with the programme, perceived impact of the programme and suggested improvements for programme refinement. Interview questions will also elicit information on any components of the VR-directed BGBT that were perceived to be most or least helpful, tolerable and acceptable. Interviews will be completed by telephone or video conferencing (eg, Zoom), audiorecorded and transcribed. All study data will be stored on a secure REDCap server.

Intervention: VR-directed BGBT

The VR-directed BGBT will be delivered through the SynerGI software developed at Cedars-Sinai Medical Center in Los Angeles, California using a human-centred design approach. The SynerGI programme was originally developed for the treatment of irritable bowel syndrome and includes three specific virtual environments or modules that will be included in the VR-directed BGBT inpatient programme for IBD: (1) two interactive games designed to distract from acute pain; (2) a gut-directed meditative environment (‘chill room’) and (3) a gastroenterology-specific CBT module (‘coaching’).²⁹

Outcome measures

Primary and secondary outcomes

The primary outcome measure will be intervention feasibility defined by the frequency and percentage of enrolled participants that use the VR-directed BGBT inpatient intervention in any capacity. We will also collect data on study recruitment (the number of eligible patients who enrol in the study) and the frequency (percentage) of enrolled participants that specifically use each of the three individual virtual environments/modules. Intervention adherence will be determined using VR log data to assess the time spent interacting with the VR-directed BGBT programme and the specific modules accessed. The secondary outcome will be intervention acceptability, which will be defined based on both quantitative and qualitative data. Qualitative data on acceptability, satisfaction and any perceived benefit or harm of the VR-directed BGBT inpatient programme for IBD will be collected from audiorecordings of semistructured interviews. We will quantitatively evaluate acceptability and usability using the Treatment Acceptability/Adherence Scale and the System Usability Scale.

Exploratory outcomes

We will explore preliminary effectiveness based on patient-reported outcome measures from self-report questionnaires and healthcare utilisation measures from the electronic health record. Patient-reported outcomes will be measured as a mean change by participant from the Day 1 baseline to Day 3 postintervention assessments of pain intensity, perceived stress, feelings and emotions, catastrophising and IBD-specific burden. The perceived stress questionnaire rates current stress on a 0–10 scale if 10 is the worst stress possible.³⁰ The Positive and Negative Affect Schedule is a validated measure that rates twenty current feelings and emotions.³¹ The validated daily pain catastrophising scale measures pain catastrophising in the last 24 hours.³² Finally, the validated UC-PRO and CD-PRO measures were developed as IBD-specific instruments for measuring IBD burden through six domains representing bowel symptoms, abdominal symptoms, systemic symptoms, daily life impact, emotional impact and coping strategies.^{33 34} Using electronic health record data, we will capture opioid, NSAID, acetaminophen and other analgesic administration and dosing during the study period and length of hospital stay.

Statistical analysis and sample size considerations

The primary outcome of intervention feasibility will be reported as the frequency and percentage of enrolled participants who use the VR-directed BGBT inpatient programme. The secondary outcome of intervention acceptability will be determined using qualitative content analysis and quantitatively using mean (SD) scores on the Treatment Acceptability/Adherence Scale and System Usability Scale. Exploratory outcome measures will be reported as means (SD) and participant-level changes in patient-reported outcomes and healthcare utilisation outcomes from day 1 to day 3 will be compared using paired-sample T-tests and Pearson chi-square tests for continuous and categorical variables, respectively. Bivariate differences in the exploratory outcomes will be further examined using linear regression for continuous endpoints and logistic regression for categorical endpoints. We will also compare exploratory healthcare utilisation outcomes to historic controls (ie, any patient with IBD hospitalised during the study period who was not approached for study enrolment) who did not receive VR-directed BGBT and whose data is available in the electronic health record during the study period. A two-tailed alpha <0.05 will be considered significant. As the primary endpoint of this study is intervention feasibility and the study is not powered to evaluate differences in effectiveness endpoints, a sample size calculation is not strictly necessary, based on NIH guidance on pilot studies.^{35 36} However, we plan to enrol 40 patients, which will be more than sufficient to determine intervention feasibility and acceptability.^{37 38}

Qualitative analysis

We will identify key concepts in the qualitative interview data related to IBD and experience with the VR-directed BGBT using a rapid qualitative analysis approach.³⁹ This approach will generate a broad understanding of participants’ experiences, perceived impact and suggested improvements to aid intervention refinement and implementation. Two study team members will independently analyse transcripts. We will first create a summary of each interview transcript using a structured template and then transfer interview summaries into a matrix by each of the key domains. Next, we will write detailed descriptions of experiences with the intervention, including illustrative quotes from participants. All members of the research team will meet to review and discuss the interview summaries to establish rigour and validity.

Quantitative and qualitative data integration

Separately, we will stratify study participants by Treatment Acceptability/Adherence Scale scores (ie, participants who report scores in the top 50th percentile vs the bottom 50th percentile). We will compare interview summaries and key domains in these two subgroups to evaluate any factors that may vary between participants who find the inpatient VR-BGBT intervention more or less acceptable.

Patient and public involvement

The overarching objective of this study is to conduct a pilot feasibility trial of an inpatient VR-directed BGBT programme for pain among hospitalised patients with IBD. This work was informed by a prior survey study in which patients identified gaps in pain management during hospitalisation. This study involves patients in the development and refinement of the VR-directed BGBT intervention through interviews. This will inform the refined intervention to be further tested in future work.

Ethics and dissemination

The study protocol follows the Recommendations for Interventional Trials (SPIRIT) 2013 (see online supplemental file 2) and was approved by the institutional review board of the University of Michigan Medical School on 10 October 2023 (HUM00240999). The study was registered on ClinicalTrials.gov (NCT06188793) on 3 January 2024, before recruitment began on 13 February 2024. All human subjects will be required to sign an informed consent document prior to study participation. Study completion is expected by February 2026. Study findings will be reported through peer-reviewed publication.

Discussion

The study protocol describes a single-centre single-arm pilot study to evaluate the feasibility and acceptability of a VR-directed BGBT programme for hospitalised patients with IBD. Pain in IBD is challenging to control and plays a substantial role in impairing health-related quality of life for patients with IBD. 4,8Current pain management strategies in IBD that leverage opioid and NSAID analgesics have considerable downsides, most notably the increase in long-term opioid use and contribution to negative health outcomes.^{15 16} Although BGBT has been shown to be effective in managing perceived pain and stress in IBD, its implementation is limited as the demand for qualified behavioural health specialists is high. VR-directed BGBT is a promising strategy for managing pain among patients with IBD in the inpatient setting. With the rapid technological advancement and increasing accessibility of VR-directed programmes for individuals in the community, the interest in VR applications for healthcare will continue to grow. This pilot study will establish the feasibility and acceptability of VR-directed BGBT among inpatients with IBD and begin to inform the preliminary effectiveness of VR-directed BGBT on patient-reported outcomes and healthcare utilisation in IBD, as well as to increase our understanding of the mechanisms by which VR-directed BGBT may improve these outcomes.

The strengths of the study include access to a large population of hospitalised patients with IBD to facilitate study recruitment, few study exclusions to capture a broad range of patients with IBD and use of mixed methods to better understand study endpoints from both a qualitative and quantitative angle. This study also has its limitations. First, as a pilot feasibility study, we lack power to test the effectiveness of VR-directed BGBT on patient-reported outcomes or healthcare utilisation. Second, as a single-centre study, the generalisability of study findings to other settings may be limited. However, study findings will inform future multisite studies to evaluate the effectiveness of VR-directed BGBT for hospitalised patients with IBD in diverse inpatient settings.

This is the first pilot study of VR-directed BGBT for hospitalised patients with IBD. This study will guide us in understanding the feasibility and acceptability of VR-directed BGBT in the inpatient setting to treat IBD-related pain. Since there are few acceptable pharmacological options for treating IBD-related pain in the inpatient setting and hospitalised IBD patients continue to report inadequate pain control, this study fills a need for evaluating and implementing novel pain management strategies for inpatients with IBD.

Data availability statement

Data are available upon reasonable request.