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Trial registered on ANZCTR


Registration number
ACTRN12618000443291
Ethics application status
Approved
Date submitted
20/03/2018
Date registered
28/03/2018
Date last updated
21/04/2021
Date data sharing statement initially provided
6/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Do brain measures predict improvement of hand or arm function following brain stimulation in people with stroke?
Scientific title
Connectivity of the ipsilesional motor network as a marker of response to anodal transcranial direct current stimulation in people with stroke
Secondary ID [1] 294382 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 307067 0
Condition category
Condition code
Stroke 306177 306177 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will be provided with a home exercise program using the Graded Repetitive Arm Supplementary Program (GRASP). The GRASP level (grade 1-3) will be individualised by a qualified Occupational Therapist based on impairment of the upper limb. GRASP will be performed for 1 hour daily over a two week period (14 sessions). Participants will record exercise compliance using an exercise diary. All participants will be provided with an iPad to video link with the research team to ensure compliance, provide motivation, progress GRASP grade and troubleshoot any issues.

Participants randomised to the 'Active' arm of the study will also receive transcranial direct current stimulation (tDCS) while simultaneously performing the GRASP exercises. TDCS will be delivered for 20 minutes at the start of the 1 hour GRASP program. TDCS involves weak direct current passing between two surface electrodes placed on the scalp. In this study, the electrodes will be positioned with the anode over the ipsilesional M1 and cathode over the contralateral supraorbital region. TDSC will be applied at intensity of 1mA for 20 minutes daily for two weeks (total of 14 sessions) at home. Stimulation will be ramped up from 0mA to 1mA over the first 30 seconds and down from 1mA to 0mA over the final 30 seconds.

Compliance with tDCS use will be monitored using iPad's to video conference with the research team, supportive family members, information sheets and training for tDCS home use from a physiotherapist with extensive experience in brain stimulation.
Intervention code [1] 300651 0
Rehabilitation
Comparator / control treatment
Placebo : Participants randomised to the 'Sham' arm of the study will receive Sham tDCS while undertaking the 1 hour individualised GRASP exercises. Sham tDCS mimics the sensation of stimulation without changing cortical excitability. Sham tDCS will ramp current up from 0mA to 1mA over the first 30 seconds before ceasing for the following 19 minutes. The final 30 seconds will ramp from 1mA down to 0mA.
Control group
Placebo

Outcomes
Primary outcome [1] 305189 0
Change in upper limb impairment as measured by the Fugl-Meyer upper extremity scale
Timepoint [1] 305189 0
Baseline, immediately following the two week intervention, 1 month follow-up and 3 month follow-up.
Secondary outcome [1] 344458 0
A change in cortical excitability as measured with single-pulse Transcranial Magnetic Stimulation
Timepoint [1] 344458 0
Baseline, immediately following the two week intervention, 1 month follow-up and 3 month follow-up.
Secondary outcome [2] 344593 0
A change in sensorimotor network connectivity as measured with electroencephalography
Timepoint [2] 344593 0
Baseline, immediately following the two week intervention, 1 month follow-up and 3 month follow-up.
Secondary outcome [3] 344594 0
A change in sensorimotor connectivity as measured with resting or task functional magnetic resonance imaging
Timepoint [3] 344594 0
Baseline, immediately following the two week intervention
Secondary outcome [4] 380974 0
Change in upper limb activity as measured with the Action Research Arm Test
Timepoint [4] 380974 0
Baseline, immediately following the two week intervention, 1 month follow-up and 3 month follow-up.
Secondary outcome [5] 380975 0
Change in grip strength as measured with a hand dynamometer
Timepoint [5] 380975 0
Baseline, immediately following the two week intervention, 1 month follow-up and 3 month follow-up.

Eligibility
Key inclusion criteria
At least three months post first ischemic stroke with motor impairment
Mild to moderate impairment of the upper limb
Supportive family, friends or carers willing to actively assist and motivate across the two week intervention
Active wrist extension of at least 5 degrees
Active index finger flexion of at least 10 degrees
Modified Ashworth score of <4
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
TMS and tDCS safety exclusion criteria
MRI safety exclusion criteria
Neglect, apraxia, shoulder pain (>4 out of 10 on pain VAS) that would affect the ability to undertake a 1 hour upper limb exercise program
Language of cognitive impairment that would limit ability to communicate with the research team via video conference
Participation in a concurrent research study or clinical program for upper limb rehabilitation

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)
We will use a central randomisation process. Experimental allocation will be randomised between participants by an external researcher not involved in participant recruitment, neurophysiological or behavioural outcome assessment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation was performed using a computerised sequence generation with an allocation of 2:1 for active:sham.
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
Sample size calculation:
Our primary aim is to determine characteristics of the sensorimotor network at baseline that predict response to anodal tDCS in people with stroke. Therefore our sample size calculation was based on pilot data of 10 people with stroke where we observed an effect size of r = 0.59 for a correlation between baseline high beta frequency connectivity and change in cortical excitability following anodal tDCS. Using this effect size with alpha = 0.05 and power of 95% we determined a sample of n=31 would be required in the Active treatment group. However, given the nature of this home based treatment and longer follow-up study period, we are allowing for a 30% drop-out rate and will aim to recruit n=40 into the Active treatment group.

The following analyses will be performed. Significance level will be p = 0.05.
1. To identify changes in neurophysiological and functional measures following tDCS, a 2 group (Active, Sham) x 4 session (Baseline, Post Intervention, 1 Month, 3 Months) factorial mixed ANOVA will be performed.
2. Regression models will determine the relationship between baseline measures of connectivity of the sensorimotor network and neurophysiological and functional measures following the tDCS.

*Covariates will control for clinical characteristics known to affect stroke function.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
2/04/2018
Date of last participant enrolment
Anticipated
21/12/2018
Actual
20/09/2019
Date of last data collection
Anticipated
4/04/2019
Actual
20/12/2019
Sample size
Target
60
Accrual to date
Final
51
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 298990 0
University
Name [1] 298990 0
Sansom Institute, University of South Australia (UNISA)
Country [1] 298990 0
Australia
Funding source category [2] 298995 0
Charities/Societies/Foundations
Name [2] 298995 0
Sylvia & Charles Viertel Charitable Foundation
Country [2] 298995 0
Australia
Funding source category [3] 299022 0
Government body
Name [3] 299022 0
National Health & Medical Research Council
Country [3] 299022 0
Australia
Primary sponsor type
University
Name
University of South Australia (UNISA)
Address
108 North Terrace, Adelaide, SA 5001
Country
Australia
Secondary sponsor category [1] 298245 0
None
Name [1] 298245 0
Address [1] 298245 0
Country [1] 298245 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299918 0
The University of South Australia Human Research Ethics Committee
Ethics committee address [1] 299918 0
108 North Terrace, Adelaide, SA, 5001
Ethics committee country [1] 299918 0
Australia
Date submitted for ethics approval [1] 299918 0
26/04/2017
Approval date [1] 299918 0
19/05/2017
Ethics approval number [1] 299918 0
0000036781

Summary
Brief summary
Stroke is a leading cause of long term disability with around 60,000 people experiencing a stroke each year in Australia. In the acute post-stroke period over two thirds of patients experience some level of reduced upper limb function, while 15-30% of stroke survivors suffer permanent motor impairments despite extensive rehabilitation. Although extensive research has been devoted to establishing novel treatment modalities, few have made significant and reliable improvements to stroke rehabilitation and recovery. Brain based interventions which target affected brain networks are likely to be highly effective. Transcranial direct current stimulation (TDCS), a form of non-invasive brain stimulation, has demonstrated some promise for improving upper limb function post stroke. TDCS can facilitate motor learning by increasing network excitability. This raises the possibility that combining TDCS with therapy may lead to functional recovery beyond that normally achieved by therapy alone. However inconsistencies of both physiological and behavioural responses to TDCS suggests a ‘one-size-fits-all’ treatment might not be optimal. The neural sequelae arising from stroke are highly heterogeneous with the extent of subsequent impairment dependent upon lesion location and disruption of brain networks. Therefore individual differences in residual integrity of the lesioned motor network may contribute, at least in part, to variable TDCS responses. Motor network connectivity may be a valuable predictor of those who will benefit from TDCS application in general, or alternatively, benefit for different stimulation approaches (e.g. facilitatory vs inhibitory TDCS or ipsilesional vs contralesional stimulation). Biomarkers predictive of TDCS response would be beneficial to improve clinical translation of this ‘state-of-the-art’ intervention capable of substantially transforming stroke therapy and improving recovery.

We hypothesise connectivity of the lesioned motor network will be greater in stroke patients who demonstrate a strong response to TDCS combined with upper limb exercise therapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81986 0
Dr Brenton Hordacre
Address 81986 0
University of South Australia, City East Campus, Centenary Building, Level 7, 108 North Terrace, Adelaide, SA, 5001
Country 81986 0
Australia
Phone 81986 0
+61 8 8302 1286
Fax 81986 0
Email 81986 0
[email protected]
Contact person for public queries
Name 81987 0
Brenton Hordacre
Address 81987 0
University of South Australia, City East Campus, Centenary Building, Level 7, 108 North Terrace, Adelaide, SA, 5001
Country 81987 0
Australia
Phone 81987 0
+61 8 8302 1286
Fax 81987 0
Email 81987 0
[email protected]
Contact person for scientific queries
Name 81988 0
Brenton Hordacre
Address 81988 0
University of South Australia, City East Campus, Centenary Building, Level 7, 108 North Terrace, Adelaide, SA, 5001
Country 81988 0
Australia
Phone 81988 0
+61 8 8302 1286
Fax 81988 0
Email 81988 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


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
7264Study protocol http://www.researchprotocols.org/2018/10/e10848 
7265Ethical approval  [email protected]



Results publications and other study-related documents

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