Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000561785
Ethics application status
Approved
Date submitted
23/03/2022
Date registered
12/04/2022
Date last updated
31/05/2024
Date data sharing statement initially provided
12/04/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of Immersive Virtual Reality on Touch Perception in People with Discomplete Paraplegia
Scientific title
RESTORE: A Pilot Single-arm Study of the Effect of Immersive Virtual Reality Treatment on Touch Perception in People with Discomplete Paraplegia
Secondary ID [1] 306745 0
Nil known
Universal Trial Number (UTN)
Trial acronym
RESTORE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spinal cord injury 325750 0
discomplete paraplegia 325857 0
Condition category
Condition code
Injuries and Accidents 323088 323088 0 0
Other injuries and accidents
Neurological 323171 323171 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single-arm pilot treatment trial. Participants will not be supervised, but the research team will have access to the virtual reality (VR) software (VRHapticWalk) logs to monitor adherence to the intervention.
Participants will be able to utilize volitional walking elements; specifically, participants will use gait-associated arm motions with hand controllers which are attached to their wrists, to control their virtual legs and walking activity in the virtual environment. Simultaneously they will receive haptic feedback associated with the virtual walking environment via the foot device. An initial 1 min “Orientation” environment will serve to familiarize participants with virtual ambulation and interaction with the virtual environment. Then the subjects will participate in 21 min daily sessions for 20 days at either UNSW or home. Each treatment session will be divided into three 7 minute sections with 3 minutes break in between [(7 min treatment + 3 min break) x 3 repeats]. The interactive virtual walking experience is facilitated by a commercially available head-mounted display (HMD), wearable hand controllers and a foot device with haptic feedback. Participants’ arms and legs are represented from a first-person perspective within a fully immersive 360-degree 3D virtual scene. The individual participant's avatar legs will be the primary modality of interaction with the virtual world. Simple obstacles will call for subject interaction with the VR world, e.g., walking on/touching sand/snow/gravel. Analogous biological body areas will be concurrently stimulated. Haptic stimulation via soft tactile actuators will be applied using a foot device on participants’ actual feet (soles of feet bilaterally) and corresponding visual input provided in the virtual environment.
Participation does not require transfer from personal chair equipment and is compatible with various chair types.
Intervention code [1] 323193 0
Treatment: Devices
Intervention code [2] 323194 0
Rehabilitation
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 330855 0
On physical examination, a change in sensory perception of touch following contact with a cotton swab and weighted needle, in at least one dermatome on either side of the body at or below the level of injury, as determined by the International Standards for Neurological Classification of spinal cord injury
Timepoint [1] 330855 0
At intervention completion (primary endpoint; between 20-28 days after baseline) and 3 months post-intervention completion.
Secondary outcome [1] 407844 0
Sensorimotor function assessed using Quantitative Sensory Testing (QST)
Timepoint [1] 407844 0
Administered at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [2] 407847 0
The sensory levels for the right and left side and the overall neurological level of the injury will be assessed using the impairment scale for sensory examination of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI)
Timepoint [2] 407847 0
Administered at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [3] 407848 0
The characteristics and symptoms of pain will be assessed using the DN4 (Douleur Neuropathique)
Timepoint [3] 407848 0
Administered at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [4] 407849 0
The intensity and specific qualities of neuropathic pain will be measured using a Numeric Rating Scale (NRS)
Timepoint [4] 407849 0
Administered at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [5] 407850 0
Depression will be assessed using the The Patient Health Questionnaire (PHQ)-9
Timepoint [5] 407850 0
Administered at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [6] 407851 0
Sleep quality (time to fall asleep and hours of sleep per night) will be assessed using the PROMIS - Sleep Disturbance module
Timepoint [6] 407851 0
Administered at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [7] 407852 0
The degree of positive affect and well-being will be assessed using the Neuro quality of life (QOL) Positive Affect & Well Being
Timepoint [7] 407852 0
Administered at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [8] 408095 0
The degree of satisfaction with participation in social roles and activities will be assessed using the Neuro-QOL Satisfaction with Social Roles and Activities
Timepoint [8] 408095 0
Administered at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [9] 408096 0
Self-rated level of health in multiple domains and then generates a single score that integrates all domains will be measured using the PROMIS Global Health
Timepoint [9] 408096 0
Administered at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [10] 408097 0
Participant's sexual concerns will be assessed using the International spinal cord injury sexual function basic data sets—version 2.0
Timepoint [10] 408097 0
Administered at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [11] 408175 0
The efficacy of the intervention (the VR HapticWalk game) will be assessed using the Treatment Evaluation Inventory (TEI)
Timepoint [11] 408175 0
Administered at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [12] 408176 0
Participants’ perceived change in sensation intensity following the intervention will be assessed using the Patient Global Impression of Change (PGIC) Scale
Timepoint [12] 408176 0
Administered at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [13] 408177 0
The degree to which the participants experience embodiment will be assessed using the Avatar Embodiment Questionnaire
Timepoint [13] 408177 0
Administered at intervention completion (between 20-28 days after baseline) only
Secondary outcome [14] 408178 0
Participant agreement/disagreement with a series of statements about their experience during and after the intervention (VRHapticWalk) will be assessed using the VR Experience (VRE) questionnaire
Timepoint [14] 408178 0
Administered at intervention completion (between 20-28 days after baseline) only
Secondary outcome [15] 408179 0
Discomfort during the VR gaming sessions will be assessed using the Simulator Sickness Questionnaire (SSQ)
Timepoint [15] 408179 0
Administered at intervention completion (between 20-28 days after baseline) only
Secondary outcome [16] 408189 0
Changes in brain grey matter volume (structural magnetic resonance imaging)
Timepoint [16] 408189 0
Measured at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [17] 408191 0
Changes in brain function (functional magnetic resonance imaging)
Timepoint [17] 408191 0
Measured at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [18] 408192 0
Changes in brain neurochemistry (magnetic resonance spectroscopy)
Timepoint [18] 408192 0
Measured at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [19] 408193 0
Changes in brain structural connectivity (diffusion-weighted magnetic resonance imaging)
Timepoint [19] 408193 0
Measured at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [20] 408194 0
Changes in cerebral blood flow (magnetic resonance arterial spin labelling)
Timepoint [20] 408194 0
Measured at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [21] 408418 0
Changes in spine grey matter volume (structural magnetic resonance imaging)
Timepoint [21] 408418 0
Measured at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [22] 408419 0
Changes in spine function (functional magnetic resonance imaging)
Timepoint [22] 408419 0
Measured at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [23] 408420 0
Changes in spine structural connectivity (diffusion-weighted magnetic resonance imaging)
Timepoint [23] 408420 0
Measured at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion
Secondary outcome [24] 408421 0
Changes in spine blood flow (magnetic resonance arterial spin labelling)
Timepoint [24] 408421 0
Measured at baseline, at intervention completion (between 20-28 days after baseline), and at 3-month following intervention completion

Eligibility
Key inclusion criteria
The study will recruit individuals with complete (according to the American Spinal Injury Association [ASIA] classification A) thoracic injury. Additional criteria will include:
a) age of 18 or more
b) more than 3 months post-injury
c) on MRI scanning evidence of signal in brain areas in response to touch below the injury level
d) ability to fully participate in the VRHapticWalk intervention (must be able to move both arms at least a little)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a) incompatible for MRI
b) on MRI scanning, no evidence of signal in brain areas in response to touch below the injury level
c) have been diagnosed with an inner ear/balance disorder and commonly suffer motion sickness or vertigo
d) have vascular or other major disease
e) have a significant visual impairment
f) have an active pressure injury
g) have an unhealed foot fracture
h) inability to comprehend spoken English

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
All continuous outcomes (MRI, ISNCSCI, NRS, PHQ-9 etc.) and demographic measures (age, time since injury) will be tabulated over time (baseline, post intervention and follow up). The data will be normalized to the baseline and will be summarized using measures of central tendency (sample mean, sample medians) and dispersion (sample variance, sample range). The data will be further analysed for statistical significance using repeated measures analysis of variance (ANOVA) to determine the effect of the intervention at different time points. The significance level will be set at 0.05.
Brain imaging data processing will be performed using standard procedures for each imaging modality. Structural (T1-weighted) and functional MRI (fMRI and ASL) data will be processed using Matlab-based toolboxes such as Statistical Parametric Mapping (SPM12), voxel-based morphometry (VBM) or the ASL toolbox. DTI data will be processed using the FSL package tract-based spatial statistics (TBSS). Similar to the clinical data, statistical analyses will include repeated measures ANOVAs, either on whole-brain statistical maps (fMRI, VBM, ASL, DTI) within each of their specific package, or on specific metabolite levels (MR spectroscopy) exported to SPSS/Prism. Statistical significance will be set at a threshold of p<0.05. Whole-brain analyses will also be corrected for multiple testing, using standard family-wise error correction.
The primary analysis will focus on change in outcomes from baseline to follow-up assessment. To test the primary hypothesis that VRHapticWalk intervention restores sensation, we will be using multiple linear regression and analysis of covariance. Specifically, each individual will be treated as independent observations (N = 36) with the outcome variable being post-treatment sensory measure and covariates from baseline measure. The outcome will be regressed upon the standardized baseline sensory measure.
To examine the longitudinal trends within individuals, mixed linear models and generalized estimating equations will be used. Specifically, piece-wise regression and test of interactions will focus on whether the treatment effects remain constant at 3 months. The mixed linear models and generalized estimating equations allow for missing data over time without case-wise deletion and account for variance inflation due to repeated observations. To account for potential missing data, multiple imputation approaches will be employed. Comparisons will be made between imputed results and the results based upon complete data. If the results differ with regard to interpretation, this fact will be reported, and publications will indicate the findings are sensitive to missing data. All analyses will be conducted in SAS 9.4 or R3.3.3 utilizing a Type I error rate of 0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 311081 0
Government body
Name [1] 311081 0
NSW Health
Country [1] 311081 0
Australia
Primary sponsor type
University
Name
UNSW Sydney
Address
UNSW Sydney, Kensington NSW 2052
Country
Australia
Secondary sponsor category [1] 312411 0
None
Name [1] 312411 0
Address [1] 312411 0
Country [1] 312411 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310619 0
UNSW Human Research Ethics Committee
Ethics committee address [1] 310619 0
Ethics committee country [1] 310619 0
Australia
Date submitted for ethics approval [1] 310619 0
19/04/2022
Approval date [1] 310619 0
29/06/2022
Ethics approval number [1] 310619 0
HC220223

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 118282 0
A/Prof Sylvia Gustin
Address 118282 0
NeuroRecovery Research Hub
School of Psychology
Biomedical Sciences Building, Level 1
UNSW Sydney
Kensington NSW 2052
Country 118282 0
Australia
Phone 118282 0
+61 0413278336
Fax 118282 0
Email 118282 0
[email protected]
Contact person for public queries
Name 118283 0
Sylvia Gustin
Address 118283 0
NeuroRecovery Research Hub
School of Psychology
Biomedical Sciences Building, Level 1
UNSW Sydney
Kensington NSW 2052
Country 118283 0
Australia
Phone 118283 0
+61 0413278336
Fax 118283 0
Email 118283 0
[email protected]
Contact person for scientific queries
Name 118284 0
Sylvia Gustin
Address 118284 0
NeuroRecovery Research Hub
School of Psychology
Biomedical Sciences Building, Level 1
UNSW Sydney
Kensington NSW 2052
Country 118284 0
Australia
Phone 118284 0
+61 0413278336
Fax 118284 0
Email 118284 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data of published results will be made available upon reasonable request.
When will data be available (start and end dates)?
Data will be made available after the publication of study reports. There is no end date for the availability of study data.
Available to whom?
Only upon reasonable request, researchers who wish to access the data will need to provide a copy of their ethics approval to do so before the data is shared for secondary research purposes. A copy of the researchers’ ethics approval will be kept for records, and for monitoring with UNSW Sydney HREC.
Available for what types of analyses?
Data will be available for secondary analyses, including meta-analyses
How or where can data be obtained?
Request to the data custodian, the Principal Investigator ([email protected]). Data transfer to other researchers will be organised by sharing a link to a secure UNSW OneDrive folder.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15518Study protocol  [email protected]
15519Ethical approval  [email protected]
15520Informed consent form  [email protected]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.