Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001835235
Ethics application status
Approved
Date submitted
21/10/2018
Date registered
12/11/2018
Date last updated
5/11/2019
Date data sharing statement initially provided
12/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Robot-assisted arm therapy and brain stimulation to enhance recovery after stroke
Scientific title
Enhancing recovery of function after stroke – combined use of physical training (robot-assisted arm therapy) with non-invasive brain stimulation
Secondary ID [1] 295910 0
None
Universal Trial Number (UTN)
U1111-1219-4596
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 309385 0
Condition category
Condition code
Stroke 308245 308245 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each participant will receive 18 sessions of treatment over 6-9 weeks (3days a week for 6 weeks or 2 days a week for 9 weeks depending on patients convenience) supervised one on one by a neuro-physiotherapist.
Each treatment will comprise brain stimulation (real or sham tDCS) for 20 minutes followed by about 1 hour of robotic therapy.
Transcranial direct current stimulation (tDCS) is a non-invasive technique that changes the excitability of brain cells by applying a weak direct current (1-2mA) to the brain. The method of applying tDCS involves placing saline-soaked sponge electrodes onto the skin of the scalp. These electrodes are connected to a battery driven direct current stimulator. tDCS is painless, inexpensive, has no major adverse effects and is easy to apply clinically. tDCS has been shown to improve arm function after stroke, with different montages of electrode placement over the affected and unaffected hemispheres (Kim et al. 2010; Hesse et al. 2011). In this study 2mA of anodal tDCS will be applied over the affected hemisphere for 20 minutes prior to arm therapy using the robot.
The MITManus InMotion Shoulder-Elbow Robot will be used to provide shoulder and elbow movement training in the horizontal plane. The affected arm will be placed in an arm support trough and strapped in, with the hand grasped around a cone-shaped handle. This robot-arm is connected to a computer. All subjects will perform the same goal-directed activities to improve shoulder and elbow movements in different directions. The robot-arm detects the amount of movement that the subject can perform, and assists when they cannot reach the targets independently. The amount of assistance the robot-arm gives is constantly altered depending on the degree of movement from the subject.
Intervention code [1] 312236 0
Treatment: Devices
Intervention code [2] 312855 0
Rehabilitation
Comparator / control treatment
This is a double blind placebo controlled study where half the participants will be treated with sham tDCS for 20 minutes followed by ~ 1 hour of robotic therapy. The therapist supervising the robotic training will be blinded to the form of TDCS (anodal or sham), as will the stroke patients .For sham stimulation current will ramp up to 2mA and then
back to zero at the beginning and end of the 20-minute sham, but there will be no current
flow between these periods.
Control group
Placebo

Outcomes
Primary outcome [1] 307845 0
Fugl-Meyer Upper Extremity Scale (FM UE)
Timepoint [1] 307845 0
single time point 1-2 weeks (primary time point) and 6 months after treatment
Secondary outcome [1] 353126 0
Motor assessments using Chedoke Arm and Hand Activity Inventory-7 (CAHAI-7)
Timepoint [1] 353126 0
single time point 1-2 weeks and 6 months after treatment
Secondary outcome [2] 353127 0
Arm Activity Measure (ARMA)
Timepoint [2] 353127 0
single time point 1-2 weeks and 6 months after treatment
Secondary outcome [3] 353128 0
Stroke Specific Quality of Life Scale (SS-QOL)
Timepoint [3] 353128 0
single time point 1-2 weeks and 6 months after treatment
Secondary outcome [4] 353129 0
modified Barthel Index
Timepoint [4] 353129 0
single time point 1-2 weeks and 6 months after treatment
Secondary outcome [5] 353130 0
Neurophysiological assessments using TMS (resting motor threshold)
Timepoint [5] 353130 0
single time point 1-2 weeks and 6 months after treatment
Secondary outcome [6] 353732 0
Neurophysiological assessments using TMS (stimulus response curve)
Timepoint [6] 353732 0
single time point 1-2 weeks and 6 months after treatment
Secondary outcome [7] 353733 0
Neurophysiological assessments using TMS (intra-cortical inhibition)
Timepoint [7] 353733 0
single time point 1-2 weeks and 6 months after treatment
Secondary outcome [8] 353734 0
Neurophysiological assessments using TMS (intra-cortical facilitation)
Timepoint [8] 353734 0
single time point 1-2 weeks and 6 months after treatment
Secondary outcome [9] 376588 0
Stroke Impact Scale Questionnaire
Timepoint [9] 376588 0
single time point 1-2 weeks and 6 months after treatment
Secondary outcome [10] 376589 0
Montreal Cognitive Assessment (MoCA)
Timepoint [10] 376589 0
single time point 1-2 weeks and 6 months after treatment
Secondary outcome [11] 376590 0
Patient Health Questionnaire - 9 (PHQ9) mood questionnaire
Timepoint [11] 376590 0
single time point 1-2 weeks and 6 months after treatment
Secondary outcome [12] 376591 0
General Anxiety Disorder Questionnaire (GAD7)
Timepoint [12] 376591 0
single time point 1-2 weeks and 6 months after treatment

Eligibility
Key inclusion criteria
1. Adults (>18 years old) with single first ever hemispheric ischaemic stroke verified by brain imaging, within the last 12 months
2. Moderate upper limb weakness and/or reduced function
Fugl-Meyer upper limb score 25-52/66
3. Discharged from inpatient physiotherapy program
4. Previously independent (prior to stroke)
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Significant medical co-morbidities that would reduce exercise tolerance and rehabilitation potential such as heart failure, unstable angina, etc
2. Significant psychiatric co-morbidities, such as depression or anxiety
3. History of seizures, epilepsy or unexplained syncopal episodes
4. Cognitive impairment or receptive dysphasia (except if minimal)
5. Significant shoulder pain or arthritis, injury or fixed deformity of the affected limb
6. Presence of magnetically or electrically sensitive implants such as cardiac pacemakers, stimulators, pumps, cochlear implants, etc
7. To minimise potential risks, all participants will be thoroughly screened for tDCS/TMS risk factors twice: prior to enrolment and immediately prior to the experimental session

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)
Neurologist assessing eligibility for recruitment will be blinded to subsequent real or sham tDCS.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomization using computer sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
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
Statistical analysis: The primary outcome (FM UE score) at 1-2 weeks and 6 months after treatment will be compared between the two groups using t-tests. ANOVA and t-tests will also be performed to compare primary and secondary outcomes before and after intervention, as well as scores between the 2 groups. Corrections will be used for multiple comparisons.
Subgroup analysis will be performed to examine the consistency of the effects among participants with cortical and subcortical stroke, dominant and non-dominant hand, and with additional focal neurological deficits (dysphasia and spatial neglect).
Sample size: The primary outcome of this study is the change in Fugl-Meyer Upper extremity (FM) scores with the addition of tDCS (anodal or sham) to robot-assisted arm therapy, immediately after and 6 months after the treatment block. The anticipated mean FM UE score in the control group (sham tDCS) 6 months after randomisation is 35-40. The smallest additional treatment effect of adding tDCS to robot-assisted therapy that would be clinically important is a true difference between the means that is about 0.8 times the standard deviation (SD). Thus, as in Lo et al (2010) a SD of 5 points on the FM would allow us to detect a difference of 4 points between the groups with a probability of 90% at a 0.05 two-sided significance level, if we enrol 75 patients in total to the present study. Assuming a drop out of 10% for any reason, we plan to recruit 85 patients for the trial.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
15/04/2014
Date of last participant enrolment
Anticipated
3/10/2020
Actual
Date of last data collection
Anticipated
3/06/2021
Actual
Sample size
Target
85
Accrual to date
13
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 12219 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [2] 12220 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [3] 12221 0
Osborne Park Hospital - Stirling
Recruitment hospital [4] 12222 0
Fremantle Hospital and Health Service - Fremantle
Recruitment postcode(s) [1] 24398 0
6009 - Nedlands
Recruitment postcode(s) [2] 24399 0
6150 - Murdoch
Recruitment postcode(s) [3] 24400 0
6021 - Stirling
Recruitment postcode(s) [4] 24401 0
6160 - Fremantle

Funding & Sponsors
Funding source category [1] 300506 0
Other
Name [1] 300506 0
Perron Institute for Neurological and Translational Science
Country [1] 300506 0
Australia
Primary sponsor type
Individual
Name
Clinical Professor Soumya Ghosh
Address
Perron Institute for Neurological and Translational Science
QEII Medical Centre RR Block
Verdun Street, Nedlands
WA 6009
Country
Australia
Secondary sponsor category [1] 299982 0
None
Name [1] 299982 0
Address [1] 299982 0
Country [1] 299982 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301299 0
Sir Charles Gairdner Osborne Park Health Care Group Human Research Ethics Commitee
Ethics committee address [1] 301299 0
Sir Charles Gairdner Hospital
Department of Research
Hospital Avenue
Nedlands WA 6009
Ethics committee country [1] 301299 0
Australia
Date submitted for ethics approval [1] 301299 0
18/07/2013
Approval date [1] 301299 0
03/10/2013
Ethics approval number [1] 301299 0
2013-128

Summary
Brief summary
This randomised, double blind, sham-controlled trial aims to investigate whether non-invasive brain stimulation in the form of transcranial direct current stimulation (tDCS) can alter cortical neuro-excitability and thus enhance the effects of physical therapies in people with stroke. We hope to recruit 75 subjects who have had their first-ever ischemic stroke within the previous 12 months who have mild to moderate upper limb impairments. Subjects undergo 20 minutes of tDCS followed by 1 hour of robot-assisted arm therapy 2-3 times/week for 6-9 weeks (total 18 interventions). Outcome measures include neurophysiological, impairment, functional, psychological and subjective measures.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 86546 0
Prof Soumya Ghosh
Address 86546 0
Perron Institute for Neurological and Translational Science
QEII Medical Centre RR Block
Verdun Street, Nedlands WA 6009
Country 86546 0
Australia
Phone 86546 0
+61 8 64570200
Fax 86546 0
+61 8 6457 0281
Email 86546 0
[email protected]
Contact person for public queries
Name 86547 0
Mr Jesse Dixon
Address 86547 0
Perron Institute for Neurological and Translational Science
QEII Medical Centre RR Block
Verdun Street, Nedlands WA 6009
Country 86547 0
Australia
Phone 86547 0
+61 8 6457 0207
Fax 86547 0
+61 8 6457 0281
Email 86547 0
[email protected]
Contact person for scientific queries
Name 86548 0
Prof Soumya Ghosh
Address 86548 0
Perron Institute for Neurological and Translational Science
QEII Medical Centre RR Block
Verdun Street, Nedlands WA 6009
Country 86548 0
Australia
Phone 86548 0
+61 8 64570200
Fax 86548 0
+61 8 6457 0281
Email 86548 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No funding available


What supporting documents are/will be available?

No Supporting Document Provided



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.