Clinical trial NCT06182436: Virtual Reality for Pain Management During Dupilumab Injection
Official title: Use of Virtual Reality to Improve Pain and Anxiety Management of Children During Dupilumab Injection for Atopic Dermatitis (VR-DERMA)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Atopic Dermatitis
Pain
Anxiety
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
First posted: 2023-12-27
Enrollment: 98
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Every patient (98) will be their own control (98+98=196). Allocation to either intervention or control will be randomized at first then switched at the crossover period.
Primary purpose: TREATMENT

Brief summary: The aim of this within-subject randomized study is to examine the efficacy of a VR immersive game for pain and anxiety management of children during the subcutaneous injection of dupilumab for moderate to severe atopic dermatitis. We will recruit children from 6 to 17 years.

The main research question is:

1. Does VR immersive game will generate less anxiety and pain than standard procedures, for children receiving dupilumab injection for moderate to severe atopic dermatitis?
2. Does the occurence of side effects is similar between both study groups?

Participants will be randomized according to either sequences: VR-Standard care or Standard care-VR. During the VR sequence, participants will be playing the VR immersive game during the injection. During the Standard care sequence participants will not benefit from any pain management but passive distraction tools will be offered (and documented) to children.

The investigators will take measures of pain and anxiety, using validated scales, before and after the procedures at each sequence.

Detailed description: Background :

Atopic dermatitis is one of the most common inflammatory diseases of the skin and usually starts in early childhood.The prevalence of atopic dermatitis ranges from 15 to 20% among children and up to 10% in adults. Atopic dermatitis treatment has been revolutionized in the past years with the approval of dupilumab (Dupixent®, Sanofi) in recent years for children. Dupilumab subcutaneous injections are highly effective in our real-world setting. However, pain at the site of injection is often reported by the parents and the patients. Regardless of the site of injection or the injection device being used, the injection remains difficult mainly because of the anxiety generated before the procedure and the anticipated pain, even if the injection only lasts five seconds.

In addition, many strategies have been unsuccessfully attempted to improve the injection experience, for example numbing cream or anxiolytic administration prior to the injection. A few authors have studied the effect of Virtual Reality (VR) on procedural pain and anxiety management. Indeed, a review of the literature has yielded only three studies who used VR with burn children. One study has verified the efficacy of VR compared to standard pharmacological care in an RCT on 54 children (6 to 19 years) suffering from burn-related injuries with TBSA (Total Body Surface Area) varying from 1 to 50%. Results showed better pain control and maximum Range of Motion (ROM) of children in the VR group.

Finally, considering the lack of optimal pain and anxiety management during dupilumab subcutaneous injections for a subset of pediatric patients, and the positive effect of an immersive distraction method such as VR for painful procedures, using VR for dupilumab injections may show promising results. To our knowledge, no other studies have tested the effect of an immersive distraction such as VR for procedural pain and anxiety management in children suffering from atopic dermatitis receiving subcutaneous injections of dupilumab.

Aim of the study

The aim of this within-subject randomized clinical trial is to verify the efficacy of an immersive distraction (virtual reality) compared to the standard of care, for pain and anxiety management of children undergoing an injection of dupilumab for moderate to severe atopic dermatitis.

Hypothesis

The use of Virtual Reality (VR) as a distraction technique during dupilumab subcutaneous injections will provide better pain and anxiety management than the standard intervention alone.

Objectives

The primary objectives are as follows:

1. To determine if VR distraction is more effective than standard care to manage procedural pain of children during dupilumab subcutaneous injections.
2. To compare if VR distraction is more effective than standard care to manage procedural anxiety of children during dupilumab subcutaneous injections.

The secondary objectives are as follows:

1. To compare if, in children with atopic dermatitis receiving subcutaneous injections of dupilumab, VR distraction generates less distressing recall of procedural pain and anxiety than the standard subcutaneous injections without distraction strategies.
2. To compare the occurrence of side effects between VR distraction and no distraction strategy in the context of dupilumab subcutaneous injections.
3. To compare healthcare professionals' satisfaction levels between VR distraction and no distraction strategy in the context of dupilumab subcutaneous injections.
4. To compare children's satisfaction levels between VR distraction and no distraction strategy in the context of dupilumab subcutaneous injections.
5. To compare parents' satisfaction levels between VR distraction and no distraction strategy in the context of dupilumab subcutaneous injections.

Methods

Design

A within-subject randomized clinical trial design with randomized sequences. Given the difficulty of ensuring any blinding conditions with the nature of the experimentation, and in order to limit the interpersonal variability between participants, each child will serve as their own control, hence receiving both standard (control) and experimental treatments (VR) during two consecutive treatment visits through a randomized order.

Sample and setting

This study will consist of 98 patients with an attrition rate of 20% where each child will serve as their own control, hence receiving both standard (control) and experimental treatments during two consecutive treatment visits through a randomized order. Thus, making a total of 196 participants. Recruitment will be done through convenience sampling of patients in the dermatology department of CHU Ste-Justine, Montreal (Qc), Canada, receiving dupilumab for moderate to severe atopic dermatitis.

Study proceedings

Every participant will be randomized to either receive the control treatment or the experimental treatment in a successive order in two different visits. Each participant will receive the two treatments and act as their own control. For the control treatment, the research nurse will administrate the subcutaneous injection as prescribed without any distractive measure, as usually performed. For the experimental treatment, the child will play with the VR device for five minutes prior to the subcutaneous injection. The participant will not be aware that the purpose of the visit is to receive the subcutaneous dupilumab injection. The child will not be informed of the exact moment of the injection and will not receive notification prior to the injection to keep the maximal effect of the immersive distraction provided by the VR experience. On the next visit, the participant will receive the other treatment, in a randomized order.

Game specifications

The VR game Dream and the Pico Neo 4 VR headset were designed by Paperplane Therapeutics for the pediatric population. In the game, participants will be able to direct laser beams at magical elements such as trolls and crystals. Since it is a no-success game, participants can enjoy it regardless of their past video game experience. The game was made to minimize cybersickness and was approved by a team of healthcare professionals in pediatric care.

Study time-points and Secondary outcomes

Measures of pain with the Verbal Numerical Rating Scale (VNRS 0-10) and anxiety with the Child Fear Scale (CFS, 0-4) will be taken before the first treatment session at (T1), after the first treatment session (T2), before the second treatment session (T3), and after the second treatment session (T4). After T2 and T4, a measure of healthcare professionals' level of satisfaction via a questionnaire developed and pretested by the team will beadministered as well. Data will also be collected on the occurrence of side effects. Clinical monitoring will be performed by an independent nurse from the research team.

Measures of the primary outcomes

Pain intensity will be assessed using the Numerical Rating Scale (NRS) for children 6 years and older immediately after the procedure during each visit (T2 and T4). The NRS is an 11-item scale for pain intensity ranging from 0 to 10; 0=no pain to 10= worst pain ever felt. This scale has an established validity (Convergent validity with Faces Pain Scale-R: r = 0.75-0.93) and reliability (Test-retest using Bland-Altman agreement: -0.9 to 1.2, 95%CI) for self-reported pain intensity in children and adolescents (6 to 17 years old). Pain intensity will also be measured at T1 and T3 to establish baseline.

The level of anxiety will be assessed using the Child Fear Scale (CFS) immediately after the procedure at each visit (T2 and T4). The CFS is a self-reported measure of anxiety adapted from the adult Faces Anxiety Scale for specific use in children undergoing painful experiences. It consists of five faces ranging from 0 (no fear/anxiety) through 4 (extremely fearful/anxious). The child is asked to indicate which face shows best how he/she felt during the procedure. Test-retest reliability has been established with children aged 5 to 10 years during painful procedure (rs = 0.76) and concurrent validity with the Children Anxiety and Pain Scale (CAPS) (rs = 0.73). The CFS was chosen because of its psychometric qualities and it is a one-item self-measure of anxiety/fear. Moreover, "although fear tends to decrease with age in general, medical fears may be an exception". Also, "age-related differences in fear ratings have not been found". Further, this scale has been used with children ranging from 5 to 18 years old for procedural fear related to venipuncture and children from 11 to 13 years for fear/anxiety of vaccine.

Sample size and statistical analysis

Recruiting 98 patients being their own control will provide a total of 196 patients which is necessary to achieve 90% power to detect a mean of paired differences of 0,40 (medium effect) with an estimated standard deviation of differences of 1,00 and with a significance level (alpha) of 0,025 using a two-sided paired t-test considering a mean difference for pain of 2.0 with a standard deviation of 1.0, a mean difference for anxiety of 1.0 with a standard deviation of 1.0 and a significance level (alpha) of 0.05/2 for both components. This sample size considers an attrition rate of 20%. Comparisons will be conducted within and between subjects for the dependent variables for repeated measures. For all variables except adverse events, an analysis of variance with one within factor condition (distraction or standard care) and one between factor order will be used. The 95% confidence interval of the difference between treatment condition will be reported. All analysis will be done in intention-to-treat using a significance level of 0,05. For primary outcomes, the Bonferroni correction will be used for the multiplicity of tests. All adverse events will be described separately by treatment condition. Statistics will be performed by an independent biostatistician.

Discussion

The investigators believe that the results of this study will provide evidence-based knowledge on a non-pharmacological method for anxiety and pain management for patients with a chronic condition undergoing a long term recurrent painful and stressful treatment through innovative interventions.

Eligibility criteria: Inclusion Criteria:

1. between the ages of 6 to 17 years old,
2. suffering from moderate to severe atopic dermatitis and receiving or about to start subcutaneous injections of dupilumab,
3. in the presence of a consenting parent who can understand, read, and write either French or English.

Exclusion Criteria:

1. have a diagnosed cognitive impairment precluding them from playing a virtual reality game,
2. suffer from epilepsy considering the nature of the intervention,
3. cannot be in a sitting position during the procedure as the virtual reality game requires an angle of at least 30 degrees for head-tracking.

Primary outcomes:
measure: mean difference in pain intensity score between sequences
timeFrame: Immediately after the procedure on day 1 and a week later on day 2 (T2 and T4) (self-report of pain levels during the procedure).
measure: mean difference in anxiety between sequences
timeFrame: Immediately after the procedure on day 1 and a week later on day 2 (T2 and T4) (self-report of anxiety levels during the procedure).
Secondary outcomes:
measure: Mean difference in cognitive, affective and sensory components of pain as well as sense of presence in VR and engagement into the game between groups
timeFrame: Reported immediately after the procedure on day 1 and a week later on day 2 (T2 and T4)
measure: children's satisfaction levels
timeFrame: Reported immediately after the procedure on day 1 and a week later on day 2 (T2 and T4)
measure: healthcare professionals' satisfaction levels
timeFrame: Reported immediately after the sequence, a week later on day 2 (T4)
measure: Occurrence of adverse events
timeFrame: Reported immediately after the procedure on day 1 and a week later on day 2 (T2 and T4)
measure: parents' satisfaction levels
timeFrame: Reported immediately after the sequence a week later on day 2 (T4)
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: St. Justine's Hospital
state: Quebec
Study officials:
affiliation: St. Justine's Hospital
name: Sylvie Le May, PhD
role: PRINCIPAL_INVESTIGATOR
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