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Trial registered on ANZCTR


Registration number
ACTRN12620000871943p
Ethics application status
Submitted, not yet approved
Date submitted
10/07/2020
Date registered
31/08/2020
Date last updated
31/08/2020
Date data sharing statement initially provided
31/08/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
ESPRESSo: Enhancing spontaneous recovery of hand and arm movement with high intensity therapy beginning one week after stroke
Scientific title
Enhancing spontaneous recovery after stroke study (ESPRESSo): A single-site, randomised, controlled, Phase IIa, assessor-blind trial to evaluate the effects of a three week programme of high-intensity, high-dose exploratory arm and hand movements initiated within 1 week of stroke on upper limb motor capacity measured with the Action Research Arm Test..
Secondary ID [1] 301742 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 318201 0
Condition category
Condition code
Stroke 316208 316208 0 0
Ischaemic
Stroke 316492 316492 0 0
Haemorrhagic
Physical Medicine / Rehabilitation 316493 316493 0 0
Physiotherapy
Physical Medicine / Rehabilitation 316494 316494 0 0
Occupational therapy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants in the intervention group will complete 90 minutes of upper limb therapy each week day, for three weeks, to complete 15 days of therapy. The therapy can be completed in three 30 minute sessions per day, two 45 minute sessions per day, or one 90 minute session per day, depending on patient preference and the clinical judgement of the treating therapist.

Therapy will be initiated within 7 days of stroke and delivered by a trained and registered therapist (physiotherapy and/or occupational therapy). Therapy will involve the patient interacting with video games provided by the MindPod platform. This is a new therapy approach currently available for research, but not more widely available for routine care. While playing the games participants will control the movement of animals on screen by moving their weaker hand and arm. Patients can play the game either seated or standing, depending on their preference and the clinical judgement of the treating therapist. Sessions will be one-on-one, with one participant interacting with the games under the guidance and supervision of one therapist.

For sessions focused on arm movements, patients will control the movements of a dolphin on screen, to make the dolphin swim, jump, catch fish, and avoid sharks. The movements of the patient's upper limb will be video captured, no markers will be attached to the patient. This video information is used in real-time by the MindPod platform to transform the patients’ arm movements into movements of the dolphin. This video information also allows the measurement of the amount of movement and amount of time spent moving by each patient in each session, ,for subsequent reporting. Patients with initially moderate to severe upper limb weakness may be fitted with a vest that provides weight support for the arms, to enable them to engage with the game. The amount of weight support provided by the vest will be adjusted by the treating therapist according to their clinical judgement. The video game will be progressed as the range, speed, and quality of upper limb movement improves over time, by the treating therapist using an interface to adjust the amount of assistance provided by the game.

For the hand, patients will rest their hands on a table top device that measures the amount of force produced by each of their fingertips. They will engage in a video game that allows them to control birds on screen by moving their fingers individually. Patients will be seated for this part of the programme, and no upper limb weight support will be necessary. The video game will be progressed as the force and individuation of finger movement improves over time, by the treating therapist using an interface to adjust the amount of assistance provided by the game. The game will record the number of movements and amount of time spent moving during each therapy session for subsequent reporting.

For both types of game, the software will record various movement parameters, including distance, time, speed, and accuracy. These characteristics will be subsequently reported. The 90 minutes of therapist time per day can be completed in two 45 minute sessions, or three 30 minute sessions, depending on participant and therapist preferences. The maximum therapist time per week is 450 minutes. The intervention will be considered successfully delivered if the participant completes at least 360 minutes of therapist time in the first week, at least 390 minutes of therapist time in the second week, and at least 420 minutes of therapist time in the third week of the therapy programme.
Intervention code [1] 318039 0
Rehabilitation
Comparator / control treatment
Participants in the control group will complete 90 minutes of upper limb therapy each week day, for three weeks, to complete 15 days of therapy, in one-on-one sessions. The therapy can be completed in three 30 minute sessions per day, two 45 minute sessions per day, or one 90 minute session per day, depending on patient preference and the clinical judgement of the treating therapist.

Patients will complete usual care therapies for the hand and arm, selected and progressed by the treating therapist based on their clinical judgement. The number of upper limb movements and the total time spent in active task performance will be recorded during each session by placing a small inertial measurement unit on the wrist of the patient's affected arm.

Therapy will be initiated within 7 days of stroke and delivered by a trained and registered therapist (physiotherapy and/or occupational therapy).
Control group
Active

Outcomes
Primary outcome [1] 324395 0
Action Research Arm Test score (ARAT, maximum 57) will be used to measure upper limb motor capacity.
Timepoint [1] 324395 0
12 weeks post-stroke
Secondary outcome [1] 384538 0
Action Research Arm Test score (ARAT, maximum 57) will be used to measure upper limb motor capacity.
Timepoint [1] 384538 0
Immediately post-intervention
Secondary outcome [2] 384539 0
Action Research Arm Test score (ARAT, maximum 57) will be used to measure upper limb motor capacity.
Timepoint [2] 384539 0
26 weeks post-stroke
Secondary outcome [3] 384540 0
Upper extremity Fugl-Meyer scale score (UE-FM, maximum 66) will be used to measure upper limb motor impairment.
Timepoint [3] 384540 0
Immediately post-intervention
Secondary outcome [4] 384541 0
Upper extremity Fugl-Meyer scale score (UE-FM, maximum 66) will be used to measure upper limb motor impairment.
Timepoint [4] 384541 0
12 weeks post-stroke
Secondary outcome [5] 384542 0
Upper extremity Fugl-Meyer scale score (UE-FM, maximum 66) will be used to measure upper limb motor impairment.
Timepoint [5] 384542 0
26 weeks post-stroke
Secondary outcome [6] 384543 0
Stroke Impact Scale score will be used to evaluate patient-reported quality of life.
Timepoint [6] 384543 0
26 weeks post-stroke
Secondary outcome [7] 384544 0
Modified Rankin scale score will be used to evaluate disability.
Timepoint [7] 384544 0
26 weeks post-stroke

Eligibility
Key inclusion criteria
i. People with monohemispheric ischaemic stroke or intracerebral haemorrhage confirmed by CT or MRI admitted to Auckland City Hospital within the last 7 days
ii. First-ever stroke or previous stroke with no upper limb weakness
iii. At least 18 years old
iv. Received a “Good” or “Excellent” prediction from the Predict Recovery Potential (PREP2) algorithm
v. UE-FM score < 51 at enrolment
vi. Able to give informed consent
vii. Patients treated with intravenous thrombolysis and/or intra-arterial thrombectomy are eligible
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i. UE-FM score > 50 at enrolment
ii. Cognition and/or communication impairment precluding informed consent or engagement with the research procedures, as determined by the patient’s clinical team
iii. Received a “Limited” or “Poor” PREP2 prediction
iv. Inability to sit in a chair and perform upper limb exercises
v. Life expectancy less than 12 months, as determined by the patient’s clinical team
vi. Upper limb motor performance limited by pre-existing conditions, such as musculoskeletal disease
vii. Residing out of region precluding in-person assessment
viii. Social and/or personal circumstances that interfere with the ability to return for therapy sessions and follow up assessments

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be carried out by an off-site investigator using customised software.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will minimise between-group differences in age, baseline UE-FM score, baseline NIHSS score, and reperfusion therapy (yes or no).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size calculations are based on existing data from 59 patients in our previous observational studies who match the inclusion criteria for the present study, namely MEP+ and baseline FM-UE < 51. These patients completed usual care rehabilitation, and had a mean 12 week ARAT score of 43/57, with a standard deviation of 11 points. This trial is powered to detect of a difference of 7 points, which reflects an effect size 0.6363 based on our previous data and extends beyond the minimal clinically important difference for the ARAT. The sample size required to detect this effect, with 90% power and two-sided p-values less than 0.05, is 106 patients (53 per group). We therefore plan to recruit 132
patients, to allow for 20% drop out or loss to follow-up. ARAT score will be analysed using mixed models for repeated measures (MMRM) methods. The fixed effects will include group, time, the group x time interaction, baseline ARAT score, total therapy time-ontask and randomisation variables (age, baseline FM-UE and NIHSS scores). The primary outcome of ARAT score at 12 weeks will be assessed by the group main effect and group x time interaction at 12 weeks. The secondary outcome of ARAT score at 26 weeks will be assessed by the group main effect and group x time interaction. Primary analysis will be based on intention to treat. Per protocol analysis will be used for sensitivity analysis. Secondary outcome of FM-UE scores will be analysed using MMRM methods as described for ARAT score. The modified Rankin Scale and Stroke Impact Scale scores at 26 weeks post-stroke will be compared between groups using ordinal logistic regression. Average time-on-task per session, and the average number of upper limb movement repetitions per session, will be compared between groups using
linear regression, unpaired t-tests or Mann-Whitney U tests, depending on the distribution of the data.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 22732 0
New Zealand
State/province [1] 22732 0

Funding & Sponsors
Funding source category [1] 306176 0
Government body
Name [1] 306176 0
Health Research Council of New Zealand
Address [1] 306176 0
Level 3/110 Stanley Street
Grafton
Auckland 1010
New Zealand
Country [1] 306176 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
Private Bag 92019
Auckland 1142
New Zealand
Country
New Zealand
Secondary sponsor category [1] 306649 0
None
Name [1] 306649 0
Address [1] 306649 0
Country [1] 306649 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 306389 0
Health and Disability Ethics Committee
Ethics committee address [1] 306389 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
New Zealand
Ethics committee country [1] 306389 0
New Zealand
Date submitted for ethics approval [1] 306389 0
04/08/2020
Approval date [1] 306389 0
Ethics approval number [1] 306389 0

Summary
Brief summary
The aim is to determine whether a 3-week programme of high-intensity, high-dose spontaneous exploratory arm and hand movements, focused on movement quality and embedded in fun and rewarding game-based virtual environments, will improve upper limb recovery and outcomes early after stroke.

This is a single-site randomised, assessor-blind, controlled Phase IIa clinical trial, that will recruit 140 participants with upper limb impairment within 1 week of stroke. Participants will be randomised to Treatment or Comparison groups (1:1, n = 70 per group), The Treatment group will be given 90 minutes of therapist time per weekday for three weeks to complete high dose arm and hand immersive exploratory therapy. The Comparison group will be given 90 minutes of therapist time per weekday for three weeks to complete conventional upper limb therapy (physiotherapy, occupational therapy).

The main hypothesis is that upper limb motor capacity, measured as mean Action Research Arm Test (ARAT) score at 12 weeks post-stroke, will be better for the treatment group than the comparison group.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103710 0
Prof Winston Byblow
Address 103710 0
Department of Exercise Sciences
University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
Country 103710 0
New Zealand
Phone 103710 0
+64 9 923 6844
Fax 103710 0
Email 103710 0
w.byblow@auckland.ac.nz
Contact person for public queries
Name 103711 0
Prof Cathy Stinear
Address 103711 0
Department of Medicine
University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
Country 103711 0
New Zealand
Phone 103711 0
+64 9 92 33 779
Fax 103711 0
Email 103711 0
c.stinear@auckland.ac.nz
Contact person for scientific queries
Name 103712 0
Prof Winston Byblow
Address 103712 0
Department of Exercise Sciences
University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
Country 103712 0
New Zealand
Phone 103712 0
+64 9 923 6844
Fax 103712 0
Email 103712 0
w.byblow@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Anonymised individual participant data underlying published results.
When will data be available (start and end dates)?
Data will be available for 5 years, beginning 6 months after the publication date of the study's primary report.
Available to whom?
Researchers who provide a methodologically sound analysis plan, at the discretion of the principal investigator.
Available for what types of analyses?
Analyses specified in the approved analysis plan.
How or where can data be obtained?
Data will be shared electronically by the principal investigator to researchers with approved analysis plans. The principal investigator can be contacted by email w.byblow@auckland.ac.nz.
What supporting documents are/will be available?
No other documents available
Summary results
No Results