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Trial registered on ANZCTR


Registration number
ACTRN12614001004651
Ethics application status
Approved
Date submitted
29/08/2014
Date registered
17/09/2014
Date last updated
20/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Individualised neuromodulation with transcranial direct current stimulation for motor recovery after stroke
Scientific title
GABA-ergic intracortical function and its modulation by real and sham transcranial direct current stimulation during the sub-acute phase of recovery after ischaemic stroke
Secondary ID [1] 285258 0
Nil
Universal Trial Number (UTN)
Trial acronym
POLARIS: Personalised NeurOmoduLation And Recovery In Stroke
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischaemic stroke 292903 0
Condition category
Condition code
Stroke 293192 293192 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be recruited within 14 days of stroke. Assessments will be made at baseline, 6 weeks, 3 months, and 6 months after stroke. These assessments will measure motor function and intracortical GABA function within primary motor cortex, to observe the evolution of GABA function over the first 6 months after stroke. Motor function will be measured with clinical assessments of upper limb impairment (Fugl-Meyer scale) and function (Action Research Arm Test), at all 4 time points. Primary motor cortex function will be assessed on both sides of the brain using single and paired pulse transcranial magnetic stimulation, to measure the excitability of the corticomotor pathway and intracortical GABAergic inhibitory networks. Transcranial direct current stimulation will be applied at baseline, 6 weeks and 3 months after stroke, to see whether the excitability of the corticomotor pathway and intracortical GABAergic inhibitory networks can be temporarily modulated at these time points. Patients will be randomised to receive either real or sham transcranial direct current stimulation, to control for potential non-specific effects. Each participant will receive the same TDCS protocol (either real or sham) at all three time points. Real transcranial direct current stimulation will be delivered for 20 minutes at an intensity of 1.5 milliamps. Sham stimulation will involve initially ramping up to 1.5 milliamps, then the stimulation will be switched off for the remainder of the 20 minutes. Both real and sham stimulation will be delivered via a pair of saline-soaked sponge electrodes, inside a 'MindCap' worn by the participant. The electrodes will be located over the primary motor cortices. This is not a clinical trial of transcranial direct current stimulation, as it is being used to probe motor cortical function at three time points, rather than to produce clinical benefits over multiple sessions. Motor cortex activation and GABA concentration will also be assessed using magnetic resonance imaging at baseline and 6 weeks after stroke. Participants will receive usual and standard rehabilitation care during the study, delivered by their clinical team. Therapy dose (therapist contact time) will be recorded for each participant.
Intervention code [1] 290139 0
Other interventions
Comparator / control treatment
This study will observe the effects of transcranial direct current stimulation on motor cortex function applied once at each of three different time points after stroke. It is necessary to randomly assign patients to real or sham stimulation. This will control for non-specific effects of the stimulation. Real stimulation will be delivered for 20 minutes at an intensity of 1 milliamp. Sham stimulation will involve initially ramping up the stimulation to 1 milliamp, and then switching the stimulator off for the remainder of the 20 minute period. The temporary effect of transcranial direct current stimulation on the excitability of corticomotor pathways and intracortical GABAergic inhibition networks will be determined by comparing data from patients who received real and sham stimulation. The stimulation will be applied once at each of 3 time points (baseline, 6 weeks, 3 months) and is not expected to have any effects on patients' motor recovery. It is an experimental probe rather than a treatment.
Control group
Placebo

Outcomes
Primary outcome [1] 293061 0
Change in paretic upper limb Action Research Arm Test score between baseline and 6 weeks post-stroke
Timepoint [1] 293061 0
6 weeks post-stroke
Secondary outcome [1] 310271 0
Relationship between the change in motor cortex GABAergic inhibition, measured with transcranial magnetic stimulation at 2 and 6 weeks post-stroke, and the change in paretic upper limb Action Research Arm Test score between 2 and 6 weeks post-stroke
Timepoint [1] 310271 0
Between 2 and 6 weeks post-stroke
Secondary outcome [2] 310272 0
Relationship between the change in motor cortex GABAergic inhibition, measured with magnetic resonance imaging at 2 and 6 weeks post-stroke, and the change in paretic upper limb Action Research Arm Test score between 2 and 6 weeks post-stroke
Timepoint [2] 310272 0
Between 2 and 6 weeks post-stroke
Secondary outcome [3] 310331 0
Change in paretic upper limb function measured with the ARAT between baseline and 3 months post-stroke
Timepoint [3] 310331 0
3 months post-stroke
Secondary outcome [4] 310332 0
Change in paretic upper limb function measured with the ARAT between baseline and 6 months post-stroke
Timepoint [4] 310332 0
6 months post-stroke
Secondary outcome [5] 310333 0
Change in paretic upper limb impairment measured with the Fugl-Meyer (FM) scale between baseline and 6 weeks post-stroke
Timepoint [5] 310333 0
6 weeks post-stroke
Secondary outcome [6] 310334 0
Change in paretic upper limb impairment measured with FM between baseline and 3 months post-stroke
Timepoint [6] 310334 0
3 months post-stroke
Secondary outcome [7] 310335 0
Change in paretic upper limb impairment measured with the FM between baseline and 6 months post-stroke
Timepoint [7] 310335 0
6 months post-stroke
Secondary outcome [8] 310336 0
Relationship between the change in motor cortex GABAergic inhibition, measured with transcranial magnetic stimulation at 2 weeks and 3 months post-stroke, and the change in paretic upper limb Action Research Arm Test score between 2 weeks and 3 months post-stroke
Timepoint [8] 310336 0
Two weeks and 3 months post-stroke

Eligibility
Key inclusion criteria
First-ever mono-hemispheric ischaemic stroke within the previous 14 days.
Upper limb symptoms requiring rehabilitation.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Not requiring upper limb rehabilitation
Contraindications to transcranial magnetic and direct current stimulation, including: epilepsy, history of seizures, cardiac pacemaker, metal implanted in the head or brain, pregnancy, medications that lower seizure threshold.
Contraindications to magnetic resonance imaging, including: cardiac pacemaker, metallic fragments in the eyes, ferromagnetic metals in the head or body.
Cognitive or communication impairment precluding informed consent or compliance with study 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)
Participants will provide written informed consent and will then be randomised to receive either real or sham transcranial direct current stimulation, using custom software to minimise between-group differences in age, gender, initial stroke severity, and potential for upper limb recovery using the PREP algorithm. The PREP algorithm combines clinical measures, transcranial magnetic stimulation, and magnetic resonance imaging, to evaluate the extent of damage to descending motor pathways in the stroke side of the brain. This information is then used to stratify patients into one of four predictions for recovery of upper limb function.
By using custom software to randomise (and minimise), allocation will be concealed, and known only to the researchers. Participants and clinical assessors will remain blinded to allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving 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
Linear regression will be used to determine associations between variables such as motor cortex GABA concentration and GABAergic inhibition, rate of recovery (change in clinical scores between 2 and 6 weeks, and between 2 weeks and 3 months post-stroke), and therapy dose. The temporary effects of transcranial direct current stimulation on corticomotor excitability and inhibition with RM-ANOVA with factors stimulation (real, sham) and time (baseline, 6 weeks, 3 months, 6 months).
Stastical power calculations have been based on our previous research using similar measures of GABAergic inhibition with patients at the sub-acute stage of recovery. With an alpha = 0.05 and beta = 0.08, 96 participants will be required to detect an effect of transcranial direct current stimulation on GABAergic inhibition, with 24 patients in each PREP stratification. 120 patients will be recruited to allow for potential drop-out.

Recruitment
Recruitment status
Completed
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] 6325 0
New Zealand
State/province [1] 6325 0

Funding & Sponsors
Funding source category [1] 289877 0
Government body
Name [1] 289877 0
Health Research Council of New Zealand
Address [1] 289877 0
PO Box 5541
Wellesley Street
Auckland 1141
Country [1] 289877 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
Private Bag 92019
Auckland Mail Centre
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 288558 0
Hospital
Name [1] 288558 0
Auckland District Health Board
Address [1] 288558 0
Private Bag 92024
Auckland Mail Centre
Auckland 1142
Country [1] 288558 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291599 0
Health and Disability Ethics Committees
Ethics committee address [1] 291599 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington 6145
Ethics committee country [1] 291599 0
New Zealand
Date submitted for ethics approval [1] 291599 0
19/09/2014
Approval date [1] 291599 0
06/10/2014
Ethics approval number [1] 291599 0

Summary
Brief summary
Stroke is the leading cause of adult disability worldwide. Inhibitory tone in the brain is altered by
stroke and dictates how plasticity and recovery of function occur after stroke, but this varies from one
individual to the next. Our objective is to identify factors that predict how best to apply noninvasive
brain stimulation to modulate inhibitory tone and facilitate motor recovery in the initial days and weeks
after stroke. To fuflill this objective advanced neuroimaging and neurophysiological assessments will
be undertaken to establish links between inhibitory function, effects of brain stimulation on recovery,
and patient outcomes. This project will increase the understanding of the molecular, cellular and
neurophysiological mechanisms of recovery of motor function in human patients after stroke, and
reduce inequalities in stroke outcomes for people who are more likely to suffer stroke earlier and live
with disability longer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 51102 0
Prof Winston Byblow
Address 51102 0
Movement Neuroscience Laboratory
Dept of Sport & Exercise Science
University of Auckland
Private Bag 92019
Auckland 1142
Country 51102 0
New Zealand
Phone 51102 0
+64 9 3737 599 ext 86844
Fax 51102 0
Email 51102 0
w.byblow@auckland.ac.nz
Contact person for public queries
Name 51103 0
A/Prof Cathy Stinear
Address 51103 0
Department of Medicine
University of Auckland
Private Bag 92019
Auckland 1142
Country 51103 0
New Zealand
Phone 51103 0
64 9 923 3779
Fax 51103 0
Email 51103 0
c.stinear@auckland.ac.nz
Contact person for scientific queries
Name 51104 0
Prof Winston Byblow
Address 51104 0
Movement Neuroscience Laboratory
Dept of Sport & Exercise Science
University of Auckland
Private Bag 92019
Auckland 1142
Country 51104 0
New Zealand
Phone 51104 0
+64 9 3737 599 ext 86844
Fax 51104 0
Email 51104 0
w.byblow@auckland.ac.nz

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary