Clinical trial NCT04988516: Virtual Reality Distraction for Anxiety (VR-IMAGINE)
Official title: Virtual Reality Distraction for Anxiety in Children During MRIs : A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Magnetic Resonance Imaging
Pediatric
Virtual Reality
Anxiety
Keywords: MRI
Magnetic Resonance Imaging
Pediatric
Virtual Reality
Anxiety
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
Collaborators: name: Maisonneuve-Rosemont Hospital
First posted: 2021-08-03
Enrollment: 98
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background:

Magnetic resonance imaging (MRI) has been known for almost forty years to generate fear and anxiety. Children may become restless during scanning, which results in movement artifacts requiring the MRI to be repeated with sedation. Very few studies seemed to have looked at the effect of virtual reality (VR) on anxiety in children scheduled for an MRI and how to identify which children are more responsive.

Objective:

The aims of this study are three-fold: 1- to develop an algorithm of predictability based on biofeedback; 2- to address feasibility and acceptability of a pre-procedural immersive VR (IVR) game preparation for anxiety management during MRIs and 3- to examine the efficacy of IVR game preparation compared to usual care for the management of procedural anxiety during MRIs.

Methods:

This study will first consist of a field test phase with 10 participants, aged 7 to 17 years old, to develop a predictive algorithm for biofeedback solution and to address the feasibility and acceptability of the research. Following the field test, a RCT will be completed using a parallel design with two groups: 1) experimental group (pre-procedural IVR game preparation), 2) usual care group (standard care as per radiology department's protocol) in an equal ratio of 49 participants per group for a total of 98 participants. Recruitment will be done at CIUSSS de l'Est de l'Île de Montréal, Quebec, Canada. The experimental group will receive a pre-procedural IVR game preparation (IMAGINE) that offers an immersive simulation of the MRI. Participants will complete a questionnaire to assess the acceptability, feasibility and incidence of side effects related to the intervention and the biofeedback device. Data collected will include socio-demographic, clinical characteristics and measures of procedure related-anxiety with the French-Canadian version of the State-Trait Anxiety Inventory for Children (STAIC-F) and the Child Fear Scale (CFS, 0-4). Physiological signs will be noted and include heart rate, skin conductance, hand temperature and muscle tension. Measures of healthcare professionals, parents, and participants' level of satisfaction will also be collected. Analyses will be carried out according to the intention-to-treat principle, with a significance level (α) of 0.05.

Conclusions:

Our study provides an alternative method for anxiety management to better prepare patients for an awake MRI. The biofeedback will help predict which children are more responsive to this type of intervention. This study will guide future medical practice by providing evidence-based knowledge on a non-pharmacological therapeutic modality for anxiety management in children scheduled for an MRI.

Detailed description: BACKGROUND

Magnetic resonance imaging (MRI) is a technique that is considered non-invasive and safe as it does not use any radiation or X-rays unlike PET scans or CT scans. MRI technology, instead, uses a magnetic field to generate images of the tissues and organs. For MRI to work as intended, the patient must remain still while laying down within a confined space for a certain amount of time. The scan environment may be a source of anxiety for some patients. This can be due to the claustrophobic nature of a narrow space. MRIs have been known for almost forty years to generate fear and anxiety caused by claustrophobia \[1\]. In addition, MRI scanners generate loud clicking sounds while running. These loud acoustic noises may be as loud as 100dB, the equivalent of a snowmobile next to the patient \[2\]. Not surprisingly, up to 30% of patients undergoing MRIs had anxiety-related reactions of various degree of intensity \[3\]. Interviews performed with small children and their parents revealed that MRIs caused anxiety in children because of their size, design and sound \[4\]. Hence, this environment is difficult to tolerate, especially for children. Oftentimes, anxious children may become restless during the exam leading to uncontrolled movements resulting in undiagnostic images. As a consequence, this may result in a premature termination of the procedure itself, requiring the exam to be repeated ulteriorly, thus, causing subsequent episodes of anxiety \[4-6\].

As a result, it is becoming common practice in many hospitals' radiology department to require conscious sedation as the frequency of repeated MRI scans are higher within the pediatric population \[5, 7\]. However, sedation is not without any risk or consequences. Emerging evidence suggests that sedation in children might have long-term neurocognitive side effects, in addition to the short-term procedure-related risks \[8\]. As some authors also pointed out, its use is also related to an increase amount of fear in children and their parents and will require extended hospital stays for monitoring, adding to the cost burden \[9\].

Like any medication, there is always a risk for adverse reactions. For this reason, many efforts have been put into the development of non-pharmacological methods to reduce fear and anxiety in children requiring MRI scans. Many interventions ranging from music and artwork to videogames have been used and deemed useful to relieve anxiety in children during an MRI exam \[10, 11\]. Interventions done prior to the scan have also been investigated. Among these, preprocedural patient education has been shown to decrease anxiety and enhance comprehension of MRI exams, which in turn, can serve to increase patient collaboration \[12\]. However, different education material can have different effects on reducing anxiety levels \[13\]. Mock MRI scanners, which involve using a full-size replica scanner for a 5-minute training session to lie still, have been used to help explain to children what the procedure involves and what to expect in an age appropriate manner. This preparation has been reported to reduce MRI-related procedural anxiety, rate of motion artifacts, need for sedation, overall duration of the study, as well as a decrease in heart rate during the procedure \[14, 15\]. However, a shortcoming of mock replica is that there is limited availability in hospitals, since the mock MRI machine would require a room to store, as well as additional resources, including staff and time, to organize these sessions.

Since physical mock sessions prior to MRI scans have shown promising results, virtual reality (VR) used to replicate an MRI environment can also be used as patient preparation \[16\]. Preprocedural virtual reality education has been studied in different medical procedures, including chest radiography, dental procedures, anesthesia and surgeries \[5, 17, 18\]. These studies show that VR preparation helps improve procedural experience among pediatric patients by reducing anxiety, distress and procedure time while increasing parents' satisfaction. VR is a novel technology gaining in popularity in pediatric hospitals across the world for a variety of reasons. It is a distraction method that has been proven effective in reducing pain and anxiety in children in different settings, such as phlebotomy, wound care, chemotherapy, dental procedure and bone pins removal \[19-23\].

To the best of our knowledge, very few studies seemed to have looked at the effect of virtual reality (VR) on anxiety of children scheduled for an MRI scan specifically and how this intervention could help identify which children are more responsive to VR. Since VR technology is becoming progressively more accessible, we believe that incorporating a virtual reality preparation tool ahead of time to familiarize children prior to the MRI procedure would help decrease anxiety, increase patient collaboration, decrease the need for sedation and improve patient, family, and health care professional's satisfaction.

Aims of the study

The aims of this study are three-fold:

1. To develop an algorithm of predictability based on biofeedback;
2. To address feasibility and acceptability of a pre-procedural immersive VR (IVR) game preparation before an MRI for children's anxiety (field test phase) and;
3. To examine the efficacy of a pre-procedural IVR game preparation compared to usual care for the management of procedural anxiety in children undergoing an MRI (RCT).

Hypothesis (For the scientific validation)

We believe that an IVR intervention in the format of an interactive video game to prepare participants prior to an MRI exam is easy to use and could help decrease MRI-related procedural anxiety in children from 7 to 17 years old. We believe that a patient who can follow the instructions well, without any signs of anxiety detected by physiological parameters, will have better results in the MRI than a patient who has difficulty following the instructions and/or who shows signs of anxiety through his physiological parameters.

Objectives

The primary research question is: for children undergoing magnetic resonance imaging, will a preprocedural interactive IVR game preparation decrease their MRI-related procedural anxiety?

Moreover, the secondary objectives of the scientific clinical validation phases are:

1. To determine if pre-procedural IVR game preparation is a feasible and acceptable nonpharmacological method to decrease MRI-related procedural anxiety.
2. To determine if children experiencing pre-procedural IVR game preparation will have a slower heart rate prior to and during the MRI than children not exposed to the IVR game preparation.
3. To determine if children experiencing pre-procedural IVR game preparation will require less need for sedation than children not exposed to the IVR game preparation prior to an MRI exam.
4. To determine if children experiencing pre-procedural IVR game preparation will require less rescheduling of exam than children not exposed to the IVR game preparation prior to an MRI exam.
5. To evaluate the occurrence of side effects with pre-procedural IVR game preparation in comparison to children not exposed to the IVR game preparation prior to an MRI exam.
6. To compare healthcare professionals' satisfaction levels between pre-procedural IVR game preparation and usual care groups.
7. To compare children's and parents' satisfaction levels between pre-procedural IVR game preparation and usual care groups.
8. To compare overall procedure time required for MRI exam between pre-procedural IVR game preparation and usual care groups.
9. To develop a predictability algorithm that will help identify which children will have better results in the MRI following the IVR game preparation.

METHODS

Design

This study will be two-fold A) consisting of a field test phase with 10 participants (10% of the total sample size calculated) to initiate the development of a predictive algorithm for biofeedback solution requiring actual participants and to address the feasibility and acceptability of the VR intervention and research process. The field test phase will follow the steps indicated in this protocol. Any changes needed will be made between the end of the field test and the start of the RCT. No changes will be made once the RCT starts. Following the field test, B) we will proceed to a scientific clinical validation based on a randomized clinical trial design using a parallel design with two groups: 1) experimental group (pre-procedural IVR game preparation), 2) usual care group (standard care as per radiology department's protocol) in an equal ratio of 49 participants per group for a total of 98 participants including a correction for an attrition rate of 24%, established according to the 2020 radiology records at the study setting.

Sample and setting

Recruitment will be done at CIUSSS de l'Est de l'Île de Montréal, a general care hospital with a pediatric unit and services. Participants will be identified through the radiology information system as having an appointment for an upcoming MRI. A research nurse will be notified by the radiology technologist and will proceed to contact the parents for recruitment ahead of time before their arrival to the radiology department. On the day of the appointment, parents will be approached to sign the consent if they still agree to the study. Child assent will also be obtained on the same day. Unfortunately, due to the COVID sanitary crisis, recruiting personnel availability and the difficulty of movement between units and departments, recruitment will be limited to the radiology department. According to the statistics in year 2020, 145 MRI procedures were prescribed for children between the age of 7 to 17 years at this setting, but actually 193 procedures were done because of delays and repeating procedures. Thus, an attrition rate of 24% was considered in the calculation of the sample size.

Study time-points

Socio-demographic and clinical characteristics will be assessed in the waiting room to establish baseline at T0. Measures of procedure related-anxiety with the French-Canadian version of the StateTrait Anxiety Inventory for Children (STAIC-F) and also the Child Fear Scale (CFS, 0-4) will be taken before the intervention (T0), immediately after the intervention (T1) and after the MRI procedure (T2). A measure of healthcare professionals, parents, and participants' level of satisfaction via a questionnaire developed and pretested by the team will also be collected at T2. Physiological signs such as heart rate, skin conductance, hand temperature and muscle tension via an EMG will be collected throughout the simulation. Data will be collected on the occurrence of side effects throughout the study. Clinical monitoring will be performed by an independent nurse from the research team.

Sample size and statistical analysis

Sample Size consideration. Primary analysis will involve the comparison of two group means. In addition, no interim analysis will be conducted. Therefore, group sample sizes of 37 (i.e. 74 in total) are necessary to achieve 80% power to reject the null hypothesis of equal means when the population mean difference for State anxiety score is 5 with a standard deviation for both groups of 7.47 \[27\] and a significance level (alpha) of 5% using a two-sided t-test. Standard deviation for both groups was varying from 4.61 to 7.47 \[27\]. In order to be conservative, we chose 7.47. Based on data from the medical imaging registry, the attrition rate was approximately 24%. Assuming a similar attrition rate, a total of 98 participants (49 per group) will be required. The sample size calculation was performed using PASS Software (version 12). Statistical analysis. Analyses will be conducted using the statistical analysis software SAS (version 9.4). Descriptive statistics will be conducted for socio-demographic and clinical variables and presented by treatment group.

A. Primary outcomes analyses: An analysis of covariance (ANCOVA) adjusted for age, sex, baseline (T0) Trait anxiety score measurement and baseline State anxiety score measurement will be used to assess the mean difference in State anxiety scores on the STAIC-S, between the experimental and the control groups at T2. Analyses will be carried out according to the intention-to-treat principle, with a significance level (α) of 0.05.

B. Secondary outcomes analyses: An ANCOVA adjusted for age, sex and baseline anxiety score measurement will be used to assess the mean difference in anxiety scores on the CFS, between the experimental and the control groups at T2. To assess the mean difference in the sense of presence in VR and engagement into the game (GRS), between the experimental and the control groups at T1, an ANCOVA adjusted for age and sex will also be conducted. We will use a linear mixed model to estimate the effect of the treatment on the changes in heart rate over all assessment timepoints. This analysis will be adjusted for age, sex and baseline heart rate. Differences between arms for Parents, children and healthcare professionals' levels of satisfaction (T2) as well as the overall procedure time will be assessed using Student's t-tests or nonparametric Mann Whitney U Test if data are non-normal. Chi-squared Test or Fisher's Exact Test will be conducted to compare dichotomous variables including the occurrence of side effects, the number of rescheduled MRI and use of sedation in each group.

Adverse events and serious adverse events (if any) will be reported using the MedDRA terminology and their proportions will be compared between the groups.

To help develop the predictability algorithm, the head deviations and other physiological data will be analysed. An algorithm based on those deviations will be developed prospectively as the study is ongoing to evaluate the success of the MRI in the intervention context and offer useful predictability inputs in preparation for the real MRI exam. No existing algorithm specific to the study were found. The physiological data will also help create a time sequence that could be matched with the information will be extracted from the intervention. At the end of the session, it will be possible to see if, for example, a movement of the patient is generally triggered by an increase in stress as captured by the sensors. The result of the examination will then be compared to the data obtained during the intervention. The team will attempt to determine which variables correlate with the real-life outcome. Our hypothesis is that a patient who can follow the instructions well without any signs of anxiety captured by physiological parameters will have better results in the MRI than a patient who has difficulty following the instructions and/or who shows signs of anxiety expressed through his physiological parameters.

Eligibility criteria: Inclusion Criteria:

* aged from 7 to 17 years old
* required to undergo MRI
* accompanied by a consenting parent or legal guardian who can understand, read and write either French or English

Exclusion Criteria:

* have a diagnosis of epilepsy or any other condition preventing them from playing a virtual reality game
* cannot stand a sitting or semi-upright sitting position (Fowler's position) during the preparation as the VR gear requires an angle of at least 30 degrees for head-tracking

Primary outcomes:
measure: Level of state-trait anxiety in children
timeFrame: Change from Baseline (T0) at 15 minutes (T1) and at 30 minutes (T2)
measure: Level of anxiety
timeFrame: Change from Baseline (T0) at 15 minutes (T1) and at 45 minutes (T2)
Secondary outcomes:
measure: Sense of presence/engagement
timeFrame: Measured after intervention - 15 minutes (T1)
measure: Head deviation in space
timeFrame: Measured for the duration of the VR simulation for an approximate duration of 15 minutes (From T0 to T1)
measure: Heart Rate
timeFrame: Measured at baseline (T0), immediately after the VR intervention at 15 minutes (T1), and measured after the MRI at 45 minutes (T2)
measure: Oxygen saturation
timeFrame: Measured at baseline (T0), immediately after the VR intervention at 15 minutes (T1), and measured after the MRI at 45 minutes (T2)
measure: Parent's satisfaction
timeFrame: Measured at 45 minutes (T2)
measure: Children's satisfaction
timeFrame: Measured at 45 minutes (T2)
measure: Healthcare professional's satisfaction
timeFrame: Measured at 45 minutes (T2)
measure: Occurrence of side effects
timeFrame: Change from Baseline (T0) to 45 minutes (T2)
measure: Procedural time
timeFrame: Measured at 45 minutes (T2)
measure: Number of rescheduled MRI
timeFrame: Measured at 45 minutes (T2)
measure: Level of State-trait anxiety in parents
timeFrame: Measured at Baseline (T0) and Measured at 45 minutes (T2)
measure: Physiological measurement of anxiety (Alpha-Amylase)
timeFrame: Measured at Baseline (T0) and Measured at 45 minutes (T2)
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
Study officials:
affiliation: Research Centre CHU Sainte-Justine
name: Sylvie Le May, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Research Centre IUSMM
name: Christine Genest, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Le May S, Genest C, Hung N, Francoeur M, Guingo E, Paquette J, Fortin O, Guay S. The Efficacy of Virtual Reality Game Preparation for Children Scheduled for Magnetic Resonance Imaging Procedures (IMAGINE): Protocol for a Randomized Controlled Trial. JMIR Res Protoc. 2022 Jun 13;11(6):e30616. doi: 10.2196/30616.