Trial Title:
Visual Telerehabilitation in Children, Adolescents and Young Adults With Hemianopsia Consecutive to a Brain Tumour
NCT ID:
NCT06362434
Condition:
Hemianopsia
Conditions: Official terms:
Brain Neoplasms
Hemianopsia
Conditions: Keywords:
pediatric brain tumor
visual fields
quality of life
reading
MRI
SD-OCT
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Crossover Assignment
Primary purpose:
Supportive Care
Masking:
Single (Outcomes Assessor)
Intervention:
Intervention type:
Device
Intervention name:
Audiovisual stimulation
Description:
The MOT IVR audiovisual stimulation task involves the 3D multiple-object-tracking
paradigm composed of 6-8 high-contrast spheres which features are adapted to the visual
ability of individuals with low-vision (luminosity = 80 nits, size = 1° to 3° visual
angle). The spheres move for 20s. following random linear paths, bouncing on one another
and on the walls of a virtual 3D cube when collisions occur. The participant, comfortably
seated, is asked to track the moving cued target among moving distractors for 20s. A
spatial sound is correlated to the movement of the cued target. After 20s., the movement
stops and the participant is asked to select, using a laser pointer, the cued sphere
among the distractors (mark-all procedure). Speed of the spheres is regulated by a
staircase 1:1 procedure. The stimulation can here be stopped by the participant if
required. After 3 blocks of 15x20s., the system stops and goes on stand-by mode until the
next session. Data are collected in real time.
Arm group label:
Intervention - No Intervention
Summary:
Brain malignancies are the most common cause of death from cancer in the pediatric
population and a major source of morbidity amongst survivors. Many children with a brain
tumour often suffer from visual field defects (hemianopia) dramatically impacting their
daily life with poorer social interaction, difficulties learning, playing sports and
engaging with peers. Practically, they bump into people and objects and have problems in
finding their way in unfamiliar places and in detecting incoming objects in their blind
field. There is growing recognition of the diverse and deep impact of hemianopia on
physical and mental health, quality of life, and social outcomes of the affected
individuals and their family. However, despite the frequent impact of brain tumours on
the visual function and functional vision, ophthalmologic evaluations are not standard of
care for all brain tumour patients and there are no standardized protocols of vision loss
management in the pediatric population with hemianopia. There is an unmet need of
restoring perception in the blind field in individuals with hemianopia consecutive to
pediatric brain tumor.
Our laboratory has developed a visual rehabilitation procedure based on the combination
of adaptative audio and visual target tracking in a 3D environment in virtual reality.
Participants perform audiovisual stimulation at home in a headset, with remote control
from the laboratory. Preliminary on data on paediatric patients with hemianopia
consecutive to a brain tumour indicate feasibility and potential effectiveness of a
6-week Re:Vision program on visual fields, visual perception and quality of life.
Our objective is to evaluate the effectiveness of Re:Vision, an 8-week visual
telerehabilitation program, on visual perception in 50 individuals aged 10-40 years old
with hemianopia consecutive to a pediatric brain tumor in a phase IIa/b multi-centric
clinical study across Canada.
This intervention provides more equitable access to individuals, with the ability to
receive rehabilitation therapy at home without supervision by a healthcare professional,
meaning that Canadians living outside urban centres could take advantage of specialized
therapies with remote supervision. This is the first study that could lead to a major
change in the management of these patients. It could open the door for visual
rehabilitation strategies to other population of visually impaired children,
significantly impacting public health strategies.
Detailed description:
Central nervous system tumors are the second most common malignancies in childhood. A
brain tumor and its treatment can affect the visual system at different levels, from the
optic nerves (through compression or infiltration), to sub-cortical structures such as
the superior colliculus (SC) and lateral geniculate nuclei (LGN) to optic tracts, optic
radiations and visual cortices. Children with brain tumors can present visual impairments
like decreased visual acuity and contrast sensitivity, loss of color vision, and visual
field loss such as hemianopsias. Individuals with hemianopsia present difficulties in
detecting stimuli in the defective visual field and show defective scanning and
exploration. Moreover, they show a rotation and compression of the auditory space leading
to imprecise localization of sound across both hemispaces. Hemianopsia patients naturally
develop oculo-3D-MOTor strategies to compensate for visual field loss, but visual
rehabilitation procedure must still be developed to optimize/improve visual perception in
the blind field. Several studies demonstrated that individuals with hemianopsia could
improve visual perception in the damaged hemifield after a stimulation procedure where
auditory and visual stimuli were temporally and spatially correlated. Such repetitive
audiovisual stimulation programs induce a functional and anatomical reorganization of the
visual connectivity in sub-cortical and cortical structures over time mediated by
perceptual learning and synaptic plasticity.
The investigators have developed an audiovisual stimulation procedure using immersive
virtual reality (IVR) in head-mounted display (HMD) as a delivery platform. IVR is an
emerging and very promising approach for visual and auditory rehabilitation. There are
currently limited practical results whether this technology is suitable for low-vision
patients to use at home and if it can be deployed on a large scale. A few case
report/series studies suggested a potential effectiveness of IVR on visual perception in
teenagers and young adults but more information as to the potential of use and
effectiveness of this technology is necessary.
Real-time measurement of task performance and neurophysiological signals while immersed
in virtual reality can bring many benefits, from monitoring experience-related factors to
the development of bio/neuromarkers. In Multiple Object Tracking in 3D (3D-MOT), visual
tracking and detection is directly influenced by the speed of the spheres and is tailored
to the participants' performance using an adapted design to efficiently reach perceptual
threshold, therefore constantly challenging the patient's perceptual abilities. Progress
made by the participants can be evaluated following real-time measures such as speed of
the spheres, percentage of positive hits and reaction time. These outcomes naturally
increase over sessions as a learning effect (generally around 5-6 sessions in our
settings) but then quickly stabilize. Further progress of performance is related to
improvement in vision as a strong correlation between performance at 3D-MOT and
functional vision outcomes is observed in our pilot studies.
Eye-tracking measures eye position and movement using pupil position to infer fixation,
gaze durations, saccadic velocities and saccadic amplitudes which altogether reveal
strategies that lead to successful detection and tracking. Eye-tracking has been
extensively used during the 3D-MOT task to describe the strategies of attention
allocation during visual tracking. Target/head/eye-tracking measures (positions recorded
every 14 ms - 90Hz) will be used to investigate the visual strategies (head movement,
saccades, fixation, smooth pursuit) developed by the participants to track the targets in
3D-MOT.
Visual field recovery and restoration from hemianopsia has been postulated to occur from
both improved function of perilesional tissue and recruitment of additional cortical
structures to assume the function of the permanently damaged centers. However,
longitudinal studies detailing functional and structural changes in the visual system
before and after treatment are lacking. EEG recordings in individuals with hemianopsia
revealed some residual activity in V1. Here, brain activity in V1 will be measured before
and after treatment and in comparison between control and treated group using visually
evoked potential (VEP). Retinal anatomy changes will be investigated between control and
treated group by measuring the ganglion cell complex (GCC) integrity and the retinal
nerve fiber layer (RNFL) thickness, indicative of retinal ganglion cell atrophy using
spectral domain optic coherence tomography (SD-OCT), a non-invasive imaging technique.
Brain scans (Diffusion MRI, Retinotopy) will be performed using a 3T MRI at the Toronto
site (Advanced MRI, Toronto Western Hospital, University Health Network) to visualize the
integrity (optic radiation) and activity (primary visual cortex) of the visual system
between control and treated group.
Hypothesis: Home-based audiovisual 3D-MOT IVR stimulation program will improve visual
perception (primary outcome Esterman binocular field test, +3 points perceived) in the
blind field of individuals with hemianopsia and increase contrast sensitivity, fixation
stability, reading speed and quality of life (secondary outcomes).
Following the ORBIT model, a phase IIa/b, single blind (to assessor), prospective,
randomized, controlled, multi-centre, cross-over study involving 5 academic centres in
Canada (St Justine - Montreal, CHUL - Quebec, Alberta Children's Hospital - Calgary, BC
Children's Hospital - Vancouver and Hospital for Sick Children - Toronto) will be
performed. Participants will be randomized into 2 groups: Group 1 receives no treatment
for the first 8 weeks and then start the 3D-MOT IVR program. Group 2 starts with 3D-MOT
IVR and then switches to an observation period for 8 weeks. Using this cross-over design,
outcome measures at week 8 (W8 - Period 1) will assess the effectiveness of 3D-MOT
stimulation between the control non-treated (G 1) and treated (G 2) groups (independent
measures). Primary outcomes assessment at week 16 (W16 - Period 2) will measure the
effectiveness of 3D-MOT IVR within Group 1 (internal control, repeated measures) and the
sustainability of the treatment in Group 2 (repeated measures). Visual assessments will
be performed at baseline, 8 and 16 weeks with follow-ups at 20 and 40 weeks (W21, W42).
Population:
Male and female individuals aged 10 - 40 years old diagnosed with hemianopsia consecutive
to a brain tumour with no prior visual rehabilitation interventions.
Intervention:
3D-MOT in immersive virtual reality:
- 1 session every 2 days (± 1 day) for 8 weeks (28 sessions total)
- 1 session = 3 blocks of 15 audiovisual stimulation tasks (2 min break between each
block).
- 1 task = 20 seconds audiovisual IVR stimulation (3D-MOT + correlated sound). Rest
time is 30 sec. to 2 min. between blocks. 1 session lasts 19 min. The duration of
subject's participation is 8 months, including follow-up. Treatment period: 8 weeks
Follow-up period: 6 months The expected frequency and duration of study visits
(anticipated time commitment) for study participants Screening/inclusion visit: 2-3
hours (visit 1) Period change visit: 1.5 hours (visit 2) Final visit: 2 hours (visit
3) Follow-up visit 1 month: 1.5 hours (visit 4) Follow-up visit 6 months: 1.5 hours
(visit 5)
Primary outcome, the Esterman binocular field testing will be performed at the
ophthalmology clinic of the participating centers at baseline, week 8, week 16 and
follow-up at week 21 and week 42.
There are no risks for participants enrolled in the study. The use of IVR may cause
moderate dizziness, nausea or disorientation for continuous stimulation above 10 minutes.
If nausea, dizziness or disorientation is experienced during IVR stimulation, stopping
the VR stimulation immediately restores normal condition.
Participants will be assessed for IVR sensitivity using the Virtual reality Induced
Symptoms and Effects (VRISE) questionnaire score at inclusion (exclusion criteria: three
(3) consecutive VRISE score <25). At-home continuous VR stimulation will be 5 minutes of
continuous stimulation, below the critical 10 minutes threshold inducing effects and
symptoms.
Bias minimization:
- Selection bias will be addressed by randomly assigning participants to treatment or
reference group using a permuted block randomization approach (block size = 2).
- Attrition bias will be addressed by including all participants who were randomized
into the study (intention-to-treat analysis).
- Performance and detection biases will be partially controlled for as primary outcome
assessors will be blind of the assigned group (single blinding).
- Reporting bias will be minimized by reporting all statistically and clinically
significant and non-significant results in publications.
Procedures for monitoring subject compliance. Compliance will be monitored in real-time
after each block of tasks. Data are sent to dedicated and secured laboratory computer via
Wi-Fi in a .csv file containing the date, time, duration and performance of the 3D-MOT
IVR stimulation performed. If no files received for 72 hours, the research team will
contact the participants by phone and/or email to inquire about the absence of data
received. Action will be taken accordingly. Experience has shown that the main reason for
the absence of data for 72 hours is a lost Wi-Fi connection. As soon as Wi-Fi connection
is restored, all non-sent data will be sent automatically with timestamp.
Safety parameters:
AEs will be the safety endpoints. Known AEs induced by IVR stimulation are nausea,
dizziness and disorientation. The severity of these AEs will be scored using the
validated VRISE questionnaire40. Three (3) consecutive VRISE scores <25 is considered as
an AE.
VRISE questionnaire will be recorded electronically (.csv file) after each home-based
session (every 2 days) and sent via Wi-Fi to a dedicated and secured laboratory computer
in real-time.
AE reporting will begin at the time of signing of the informed consent (screening) and
will continue until discharge from the study. AEs will be elicited by:
- spontaneous report by participants, partner/caregiver and/or healthcare staff,
- by 3 consecutive VRISE scores < 25,
- by observation (by the investigators and/or healthcare staff). AEs due to IVR
stimulation resolve as soon as the stimulation stops. Investigators will follow-up
the participant at 24 hours by phone or email assessing the severity of the AEs
using the VRISE questionnaire.
Statistical methods:
Analysis will be performed following an Intention-To-Treat (ITT) approach. Results will
be reported using descriptive statistics (including frequency distributions, a measure of
central tendency and a measure of dispersion) of the primary outcome, average VRISE
scores and secondary outcomes. Data will be analyzed using the statistical software JASP.
Statistical comparison between the 2 groups and strata for the primary outcome will be
made using Bayesian and frequentist two-way ANOVA with repeated measures.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Diagnosed hemianopsia (> 18 months).
- History of a diagnosis of brain tumour
- Being stable for the tumour for >18 months (either on therapy or not)
- Male and female
- 10 - 40 years old
- Ability to follow the visual and auditory stimuli and training instructions.
- Online auditory test positive (-5dbHL to 60dbHL range) at 125 Hz (for research
purposes only)
- Home Wi-Fi access.
Exclusion Criteria:
- < 10 years old.
- > 40 years old.
- Ocular disease
- Both eyes with media opacity that impairs microperimetry testing.
- Inability to perform during testing and training.
- Recreational or medicinal consumption of psychoactive drugs.
- 3 consecutive VRISE (cybersickness) scores < 25 at inclusion.
- History of vertigo or dizziness.
- Prior vision rehabilitation interventions.
Gender:
All
Minimum age:
10 Years
Maximum age:
40 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Alberta Children's Hospital
Address:
City:
Calgary
Zip:
T3B 6A8
Country:
Canada
Contact:
Last name:
Lucie Lafay-Cousin, MD
Phone:
403-955-7272
Email:
llafayco@ucalgary.ca
Investigator:
Last name:
Lucie Lafay-Cousin, MD
Email:
Principal Investigator
Facility:
Name:
British Columbia Children's Hospital
Address:
City:
Vancouver
Zip:
V6H 3N1
Country:
Canada
Contact:
Last name:
Sylvia Cheng, MD
Phone:
604-875-2406
Email:
sylvia.cheng@cw.bc.ca
Investigator:
Last name:
Sylvia Cheng, MD
Email:
Principal Investigator
Facility:
Name:
The Hospital for Sick Children
Address:
City:
Toronto
Zip:
M5G 1E8
Country:
Canada
Contact:
Last name:
Eric Bouffet, MD
Phone:
416-813-7500
Email:
eric.bouffet@sickkids.ca
Investigator:
Last name:
Eric Bouffet, MD
Email:
Principal Investigator
Investigator:
Last name:
Uri Tabori, MD
Email:
Sub-Investigator
Investigator:
Last name:
Inci Yaman Bajin, MD
Email:
Sub-Investigator
Facility:
Name:
Centre Hospitalier Universitaire Sainte-Justine
Address:
City:
Montreal
Zip:
H3T 1C5
Country:
Canada
Contact:
Last name:
Sebastien Perreault, MD
Phone:
514-345-2372
Email:
s.perreault@umontreal.ca
Investigator:
Last name:
Sebastien Perreault, MD
Email:
Principal Investigator
Facility:
Name:
CHU de Québec
Address:
City:
Québec
Zip:
G1J 1Z4
Country:
Canada
Contact:
Last name:
Valerie Larouche, MD
Phone:
418-654-2282
Email:
valerie.larouche@fmed.ulaval.ca
Investigator:
Last name:
Valerie Larouche, MD
Email:
Principal Investigator
Start date:
June 1, 2024
Completion date:
June 1, 2027
Lead sponsor:
Agency:
University Health Network, Toronto
Agency class:
Other
Collaborator:
Agency:
Alberta Children's Hospital
Agency class:
Other
Collaborator:
Agency:
St. Justine's Hospital
Agency class:
Other
Collaborator:
Agency:
The Hospital for Sick Children
Agency class:
Other
Collaborator:
Agency:
British Columbia Children's Hospital
Agency class:
Other
Source:
University Health Network, Toronto
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06362434
