Study design

This is a multisite, assessor-blinded randomised controlled trial to be conducted in two Australian centres (Melbourne, Victoria and Launceston, Tasmania). The Consolidated Standards of Reporting Trials (CONSORT) statement (figure 1) has been used to guide trial design.21 The trial will be reported according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines22 and the Template for Intervention Description and Replication.23

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Figure 1

The CONSORT 2010 flow diagram for the study. CONSORT, Consolidated Standards of Reporting Trials.

Participants

Community-dwelling stroke survivors will be recruited to participate from the Melbourne metropolitan area, Victoria, and from Launceston, Tasmania. The study will be advertised on the Australian Stroke Foundation and Heart Foundation websites, through social media (eg, twitter and facebook), in local newspapers and at local community centres.

Potential participants will initiate contact with the research team by responding to the study advertisements by phone or email. The researchers will respond in kind and provide information about the project, and then send an electronic or paper copy of the plain language statement to the participant. All potential participants will then attend an initial screening session at Deakin University, Burwood, Melbourne or the University of Tasmania, Launceston, to determine their eligibility to participate according to the inclusion/exclusion criteria. Participants will be included if they are (1) above the age of 18 years, (2) community-dwelling stroke survivors, (3) with mild-to-moderate UE impairments (Fugl-Meyer Upper Extremity (UE-FM) Score 25–45), (4) no cognitive impairments (Mini Mental State Examination Score >24), (5) at least 3 months poststroke, (6) can demonstrate an observable motor-evoked potential from the resting paretic hand, of at least 0.05 mV, in 5 out 10 trials during transcranial magnetic stimulation and (7) able to read English. Participants will be excluded from the study if they have (1) other neurological conditions (eg, Parkinson’s disease or dementias), (2) no observable movements in shoulders or elbows and (3) upper extremity joint pain that would limit their ability to complete the trial.

If eligible, the principal investigator will provide the individual with a consent form to read and sign. The individual will be given the opportunity to ask the principal investigator any questions about the study and their potential participation in it. On providing signed informed consent, all individuals will be scheduled for baseline and postintervention testing at Deakin University Physical Activity and Nutrition research laboratory (Burwood, Melbourne, Australia) or the University of Tasmania Exercise Physiology Clinic (Launceston, Tasmania, Australia).

Randomisation and blinding

Following study enrolment and completion of the baseline testing, participants will be randomised into a VT intervention or usual care (control; UC) group via a computerised random sequence generator and using a block randomisation design (according to location) and stratified by gender.

Location and setting

The participants randomised to the VT group will undertake training at the High Street Road Uniting Church (for the Melbourne-based participants) or the University of Tasmania Exercise Physiology Clinic, Launceston (for the Tasmanian-based participants). A Microsoft Xbox Kinect V.2 (Microsoft, Redmond, Washington, USA) and a laptop will be placed at each training location. All participants will be instructed to complete a daily physical activity diary throughout the study.

An exercise physiologist with at least 2  years of experience working with people with neurological impairments and/or brain injuries will be located at each training site to provide technical support on the VT system and document any adverse events (AEs) .

Intervention

The participants in the VT group will attend their local exercise training facility twice weekly, with each session separated by at least 24 hours, for eight consecutive weeks to complete the VT training. Each VT session will last approximately 45–60 min, which will equate to approximately 12– 16 hours of total therapy time across the duration of the study. This total amount of therapy is consistent with previous research as necessary to elicit improvements in motor function.9 Figure 2 contains examples of the UE exercises that will be used in this study.

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Figure 2

Examples of VT therapy games that target UE mobility of the shoulders, elbows and wrists. UE, upper extremity; VT, Virtual therapy.

The Jintronix Rehabilitation System (Montreal, Canada) to be used in this study will assess the participants active range of motion (ROM) of the shoulders, elbows and wrists, which will be used to establish the initial ROM of the exercises. The prescription of UE exercises will be determined by the researcher at the initial session. In the initial training session, the participants will be asked to provide feedback on their preference and capacity to perform the prescribed exercises. If the participants report experiencing difficulties with the intensity and type of exercises prescribed, an alternative exercise, that still targets the intended muscle group and action, will be selected. The exercise type and intensity will be selected and tailored to target the individual’s UE impairment, which will be based on the individual’s baseline function and active ROM of the shoulder, elbow and wrist. The Jintronix Rehabilitation System records each participant’s performance (ie, number of task repetitions, time in therapy for each exercise and task performance accuracy) for each session completed, and the training intensity for each participant will be modified according to their performance during the previous week. An advantage of the Jintronix Rehabilitation System is the capability of the system to adjust the training stimulus by changing the number of repetitions performed, and the ROM that the exercises are performed in, as the participant adapts over the duration of the intervention.

Any participants who are wheelchair users or have difficulty standing for long periods may perform their exercises while seated, with the Jintronix system capable of detecting UE movement in either a standing or seated position. Monitoring of the training programme and modification in exercise prescription will be performed remotely by an exercise physiologist at Deakin University at the end of each week via the clinician’s interface module of the Jintronix software. They will not have any direct contact with the participants, but will tailor each participant’s VT training in response to their adaptation to the programme. Progression of each exercise will be based on achievement of at least 80% success (ie, the participant is able to hit at least 8 out of 10 targets in a game) in exercise performance over two consecutive training sessions. The difficulty of the exercise will be progressed by 10%, which may consist of, but not limited to, more targets to hit, need for greater active ROM to successfully perform the task or quicker movement time to target. If a participant achieves a score of <50% in two consecutive exercise sessions for a particular exercise, the level of difficulty for that particular exercise will be reduced by 10%.

Control

UC, in the context of this study, is defined as maintaining the level of physical activity similar to that prior to enrolment into the trial. All participants allocated to the UC control group will be requested to maintain their daily routine and any existing therapy, and to report any change in the dose of their therapy. The UC group participants will only be required to attend the testing sessions (outlined below) at baseline and after 8 weeks.

Outcome measures

Table 1 shows the standard protocol items and outcome measures as recommended by the SPIRIT guidelines for interventional trials. A change in the Action Research Arm Test (ARAT) score and the UE-FM scale from preintervention to postintervention will be joint primary outcomes in this study.

The ARAT is a measure of arm motor function that consists of 19 items grouped into four subscales: grasp, grip, pinch and gross movement.24 It uses ordinal scoring, with each item scored as either a 0 (‘cannot perform any part of the test’), 1 (‘performs the test partially’), 2 (‘completes the test, but takes abnormally long time’) or 3 (‘performs the test normally’), with a lower score indicating reduced UE function.24 The ARAT has established reliability25 26 and validity, is responsive to change27 and has good concurrent validity compared with other measures used to assess arm motor function.28

The UE-FM assessment is a stroke-specific functional performance measure that includes 33 questions (maximum score of 66) designed to assess muscle strength, reflexive activity and motor control.29 Each item is scored as either a 0 (‘unable to perform’), 1 (‘able to perform in part’) or 2 (‘able to perform’), with a lower score indicating reduced UE function.29 30 The UE-FM is a reliable and valid assessment of UE motor function,31 that is sensitive to change.32

Secondary outcome measures include the box and block test (BBT), which provides a measure of arm and hand function, and the Modified Ashworth Scale (MAS) score, which measures upper and lower limb spasticity. The Motor Activity Log-28 (MAL-28) and Euro-Quality of Life-5 Dimension-5 Level (EQ-5D-5L) Scale will be used to document the daily use of the stroke-affected arm and how VT may impact on quality of life (QoL), respectively. fNIRS will be used to measure task-related changes in haemodynamic responses of the bilateral primary sensorimotor cortices (SMCs).

The BBT is commonly used to measure unilateral gross motor dexterity of the arm and hand poststroke.33 During the BBT, participants will be seated at a table, facing a rectangular box that is partitioned into two square compartments of equal dimension. One hundred and fifty, 2.5 cm, coloured, wooden blocks are placed in one compartment, and the participant will be instructed to move as many blocks as possible, one at a time, to the other compartment in 60 s. The BBT is scored by counting the number of blocks carried over the partition from one compartment to the other during the 60 s trial period. In order to score a point, the participant’s hand must cross over the partition, and blocks that drop or bounce out of the second compartment onto the table or floor are still recorded as a point. Should multiple blocks be carried over at the same time, only a single point will be recorded. Higher scores on the test indicate better gross motor dexterity. Previous studies using the BBT in people with stroke have shown excellent test-retest reliability (ICC=0.96) and inter-rater reliability (ICC=0.99).34

The MAS is commonly used to measure the intensity of muscle spasticity experienced poststroke in the upper and lower extremities.35 Relevant muscle groups are passively moved about a joint and scored on a 0 (‘no increase in tone’) to 4 (‘affected part(s) rigid in flexion or extension’) scale, with a lower score indicating a lower resistance to movement (ie, reduced spasticity). The MAS has excellent inter-rater and intrarater reliability36 and convergent validity with motor performance37 38 and neurophysiological measures.37

The MAL-28 is a stroke-specific self-report questionnaire that quantifies UE performance in real world activities.39 The participant will be asked to rate their arm function each week according to two subscales: the Quality of Movement (QOM) scale and the Amount of Use (AOU) scale. Each scale is rated on a scale of 0 (‘the weaker arm was not used at all for that activity’ on the QOM scale, and ‘did not use my weaker arm’ on the AOU scale) to 5 (‘the ability to use the weaker arm for that activity was as good as before the stroke’ on the QOM and ‘used my weaker arm as often as before the stroke’ on the AOU scale).39 Scores on each scale are calculated as the mean of the scored items attempted with the affected arm, with a higher average score indicative of better QOM and more use of the weaker arm.

The EQ-5D-5L provides an assessment of health-related QoL after stroke across five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.40 Each dimension is divided into 5 levels of perceived problems: no problems (level 1), slight problems (level 2), moderate problems (level 3), severe problems (level 4) and extreme problems (level 5). The participant will be asked to indicate their health state by ticking the box corresponding to the most appropriate statement in each of the five dimensions. Once all five dimensions have been scored, the digits for the five dimensions are combined into a 5-digit number that describes the patient’s health state. Lower scores indicate a higher QoL. The EQ-5D-5L is a valid measure of health-related QoL after stroke,40 with acceptable responsiveness.41

fNIRS is a non-invasive and portable optical neuroimaging technique that can measure task-related changes in cortical haemodynamics (ie, an indirect measure of cortical activation) in stroke survivors,42 but without the large costs and non-portability of fMRI assessments. fNIRS has previously been used to measure changes in prefrontal cortical activation during a virtual reality movement task in healthy individuals.43 In this study, fNIRS will be used to measure bilateral SMC activation during functional seated hand reaching and wrist extension movement tasks of the paretic and non-paretic arm. The assessment of these motor task-related bilateral SMC activation changes after the STRIVE intervention will provide a cortical correlate of the change in motor function,44 as quantified using the Kinect V.2 with the Macoki software (NaturalPad, Montpellier, France).45

Compliance and safety monitoring

The VT system provides information on usage time during each training session, which will be remotely monitored as a measure of exercise compliance. In addition, the attending exercise physiologist will record the participant’s attendance. Should a participant miss a training session, they will be contacted by the attending exercise physiologist and the reason for their absence will be documented. If more than one training session is missed, a make-up session will be scheduled. The attending exercise physiologist will also document and handle any AEs (ie, muscle or joint pain, syncope, falls and injuries) or serious adverse events (SAEs, ie, any incident requiring hospitalisation).46 The study is voluntary and participants can discontinue the study on request at any time, or if there is a change in health status (ie, worsening of function or overall health) or in the event of an AE or SAE. All AEs and SAEs experienced by the study participants during the trial will be reported immediately to the principal investigator and the Deakin University Human Research Ethics Committee. Should any participant suffer from any AE or SAE because of this trial, ancillary support and/or post-trial care will be provided.

Sample size estimation

To successfully detect a minimal clinically important difference in the UE-FM score of 6.4%–11% (an increase of 4.25–7.25 points out of 66),47 30 participants in each group (VT and UC) will be sufficient to provide 80% power (95% CI) and account for a 30% dropout rate.

Statistical analysis plan

Mixed factorial analysis of variance will be used to determine the difference in clinical and neurophysiological measures across GROUP (VT vs Control) and TIME (PREINTERVENTION vs POSTINTERVENTION). Bonferroni post hoc t-tests for multiple comparisons will be used to determine where significance has occurred. Significance will be set at P<0.05.