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Trial registered on ANZCTR


Registration number
ACTRN12616000254493
Ethics application status
Approved
Date submitted
19/02/2016
Date registered
24/02/2016
Date last updated
26/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
TOPS: Transcranial direct-current stimulation (tDCS) to optimise participation in stroke rehabilitation – a sham controlled cross over study
Scientific title
TOPS: tDCS to optimise participation in stroke rehabilitation – a sham controlled cross over study (TOPS)
Secondary ID [1] 288563 0
NONE
Universal Trial Number (UTN)
U1111-1180-3226
Trial acronym
TOPS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 297684 0
Fatigue following stroke 297685 0
Lack of concentration following stroke
297753 0
Condition category
Condition code
Stroke 297864 297864 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a double blind sham controlled randomised cross-over pilot study.

Transcranial direct current stimulation (tDCS) will be applied to the left dorsolateral prefrontal cortex (DLPFC) (with the reference electrode over the right supra-orbital area). tDCS is a type of non-invasive brain stimulation (NIBS) delivering a weak electrical current via small pads taped onto the scalp. The voltage levels do not exceed those from a normal household 9V battery (i.e. it is NOT a form of electroconvulsive [“shock”] therapy).

*The active group will receive a 30-sec stimulation followed by 19 minutes of constant current stimulation (1.5mA) and a 30-sec decline to zero current = total 20 mins.
*The sham (or ‘dummy/placebo’ group) will receive a brief 30 sec stimulation, after which the current declines to zero and stays at zero for 19.5mins) = total 20mins.

Consenting individuals will be randomly allocated to receive 2mA anodal (excitatory) tDCS or sham tDCS to the left DLPFC for a 20 minute session within one hour prior to their first session of normal rehabilitation. This will happen for 10 normal rehabilitation sessions (Block 1) - spread over 12 days (that is, Mon-Fri wk 1, Mon-Fri wk 2). After Block 1, they will cross over to the other group for matched duration and number of sessions for 10 x 20min sessions (Block 2). This will also be spread over 12 days (Mon-Fri wk 3, Mon-Fri wk 4).

The time between cross-over of Block 1 and Block 2 is 2 days (ie the Sat-Sun following wk 2).

ALL participants will receive a block of active, and a block of sham tDCS.
Intervention code [1] 293948 0
Rehabilitation
Intervention code [2] 294002 0
Treatment: Other
Comparator / control treatment
The sham (or ‘dummy/placebo’ group) will receive a brief 30 sec stimulation, after which the current declines to zero and stays at zero for 19.5mins) = total 20mins.

This sham protocol is routinely used in tDCS studies, as perception of current normally occurs only during periods of changing current strength rather than constant current. At amplitudes less than 2mA most participants are unable to detect whether they are receiving sham or active tDCS.

Consenting individuals will be randomly allocated to receive 2mA anodal (excitatory) tDCS or sham tDCS to the left DLPFC for 10x 20 minute sessions within one hour prior to their first session of normal post-stroke rehabilitation therapy of the day (Block 1). After Block 1, they will cross over to the other group for matched duration and number of sessions for 10 x 20min sessions (Block 2).

ALL participants will receive a block of active, and a block of sham tDCS.
Control group
Placebo

Outcomes
Primary outcome [1] 297392 0
The primary aim of this pilot is to determine the effects of anodal (excitatory) tDCS on engagement in rehabilitation (physiotherapy and occupational therapy) sessions in this cohort.

The primary measure will be whether the first therapy session of the day is completed as intended (binary yes/no, analysed as a proportion) and the duration of this therapy session (analysed as a continuous variable).

Reason(s) for failure to complete the session will be recorded. The primary outcome has been chosen as it is unambiguous, addresses the identified clinical problem, is an important surrogate of fatigue and is linked to rehabilitation outcomes.
Timepoint [1] 297392 0
At the end of each normal rehabilitation therapy session, staff will record whether the session was completed as intended (ie per usual Stroke Rehabilitation Unit protocol). There will be collection timepoints at each of the 10 sessions for block 1 & each of the 10 for block 2 - a total of 20 collection points.
Secondary outcome [1] 320953 0
Participant self-reported fatigue using the Fatigue Assessment Scale (FAS) which is the most commonly used measure of post-stroke fatigue, It has a Minimal Clinically Important Difference (MCID) of 4 points.
Timepoint [1] 320953 0
There will be a total of 3 x FAS assessments for each participant, collected at:
Timepoint 1. - at baseline
Timepoint 2. - at the mid-point of the treatment series (ie after Block 1 (10 sessions) completed and before crossover to Block 2 (10 sessions) started)
Timepoint 3. - at the completion of all 20 sessions.

Secondary outcome [2] 320954 0
Alertness/vigilance measured using the Go/NoGo test; which provides a sensitive measure of attention with high test–retest reliability. It has been shown to be sensitive to change in alertness following tDCS. (Completed by participant)
Timepoint [2] 320954 0
There will be a total of 3 x Go/No assessments for each participant, collected at:
Timepoint 1. - at baseline
Timepoint 2. - at the mid-point of the treatment series (ie after Block 1 (10 sessions) completed and before crossover to Block 2 (10 sessions) started)
Timepoint 3. - at the completion of all 20 sessions.
Secondary outcome [3] 320955 0
Alertness (visual analogue scale – based on Maldonado et al 2004) self-rated by participant and reported during subsequent therapy sessions (therapy staff) and at set times during the day (nursing staff).
Timepoint [3] 320955 0
There will be a total of 15 x Alertness (VAS) assessments completed by each participant, collected at:
Timepoint 1 - at baseline. 3 collections a) between 7-10am, b) between 12-3pm and c) between 5-8pm
Timepoint 2 - at the mid-point of Block 1 (ie after 5 sessions). 3 collections a) between 7-10am, b) between 12-3pm and c) between 5-8pm
Timepoint 3 - at the completion of the Block 1 session (ie after 10 sessions) before crossover to Block 2. 3 collections a) between 7-10am, b) between 12-3pm and c) between 5-8pm.
Timepoint 4 - at the mid-point of Block 2 (ie after 5 sessions). 3 collections a) between 7-10am, b) between 12-3pm and c) between 5-8pm
Timepoint 5 - at the completion of the Block 2 sessions (ie after 10 sessions). 3 collections a) between 7-10am, b) between 12-3pm and c) between 5-8pm

Therapy and nursing staff will each complete this VAS at the same timepoints and collection rates. This will mean there will also be 15 x VAS assessments completed by the therapy staff and 15 x VAS assessments completed by the nursing staff.

While this might seem onerous, each VAS takes less than 2 minutes to complete.

Eligibility
Key inclusion criteria
All individuals admitted with Bentley Health Service with stroke will be approached to consent to screening for participation in this study. Inclusion criteria: greater than or equal to 60 years, diagnosis of ischaemic stroke, likely to be inpatient for at least one month.
Minimum age
60 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria: pre stroke history of fatigue related syndromes, unstable co-morbid medical or psychiatric disease; history of seizures or metallic foreign body implant; concurrent use of NMDA receptor antagonists or calcium channel blockers.

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)
Sealed opaque envelopes will be used for randomisation. In case of a medical emergency where the treatment requires knowledge of the intervention type (anodal tDCS or sham stimulation) the principal investigator may break the randomization code for that participant. Any such event will be treated as a serious adverse event.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated by independent bio-statistician.
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
Crossover
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary measures will be whether the first therapy session of the day is completed as intended (binary yes/no, analysed as a proportion) and the duration of this therapy session (analysed as a continuous variable). Reason(s) for failure to complete the session will be recorded. The primary outcome has been chosen as it is unambiguous, addresses the identified clinical problem, is an important surrogate of fatigue and is linked to rehabilitation outcomes.

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 in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 5291 0
Bentley Health Service - Bentley
Recruitment postcode(s) [1] 12758 0
6102 - Bentley

Funding & Sponsors
Funding source category [1] 292911 0
Charities/Societies/Foundations
Name [1] 292911 0
National Stroke Foundation (NSF)
Address [1] 292911 0
Level 7
461 Bourke St
Melbourne
VIC 3000
Country [1] 292911 0
Australia
Primary sponsor type
University
Name
University of Western Australia
Address
UWA
Office of Research Enterprise
M459, 35 Stirling Highway
CRAWLEY
WA 6009

Country
Australia
Secondary sponsor category [1] 291667 0
None
Name [1] 291667 0
Address [1] 291667 0
Country [1] 291667 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294418 0
WA Health Southern Metropolitan Health Service (SMHS)
Ethics committee address [1] 294418 0
Level 2, Southern Research Facility (Perkins Building) Fiona Stanley Hospital,11 Robin Warren Drive, MURDOCH WA 6150, Western Australia
Ethics committee country [1] 294418 0
Australia
Date submitted for ethics approval [1] 294418 0
09/02/2016
Approval date [1] 294418 0
25/05/2016
Ethics approval number [1] 294418 0
RPH : EC00270. Reg number: 2016-027.

Summary
Brief summary
This pilot study will explore the effect of a type of non-invasive brain stimulation on the ability of older adult stroke survivors to participate in inpatient rehabilitation therapy. Clinicians in the stroke unit at Bentley Health Service (BHS) have identified that after a stroke, many people complain of feeling fatigued and being unable to concentrate during their therapy sessions. This is a problem since rehabilitation is typically offered only in the initial months post stroke, and therefore it is essential that patients are able to take best advantage of the available therapy during their inpatient stay.

Fatigue is common post stroke, and is a complex impairment which may be partly due to reduced excitability of parts of the brain. Research has suggested that a type of non-invasive brain stimulation called ‘transcranial direct current stimulation’ (tDCS), in combination with therapy, can increase brain activity which may facilitate recovery after a stroke.

All stroke admissions to BHS would be screened for eligibility, and consenting individuals will be randomly allocated to receive tDCS or sham tDCS for 10 days (20 minutes immediately prior to 10 therapy sessions), then cross over to the other group for a matched duration and number of sessions. Only the person applying tDCS will be aware of group allocation.

The primary measures will be whether the first therapy session of the day is completed as intended. The duration of this session will be recorded, along with reason(s) for failure to complete the session. This outcome has been chosen as it is unambiguous, addresses the identified clinical problem and is an important surrogate of rehabilitation outcomes. Secondary measures will be patient reported fatigue using the Fatigue Assessment Scale, alertness/vigilance measured using the Go/NoGo test and alertness (numerical rating scale) reported by staff at set times during the day.

It is hypothesized that patients receiving tDCS will be more likely, at the end of the series of ten tDCS sessions, to remain alert and engaged for the planned duration of the therapy session immediately following tDCS, perform better on a test of alertness, report feeling less fatigued and be observed by staff to be more alert during the day, than those receiving an equal number of sham tDCS sessions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63622 0
A/Prof Christopher Etherton-Beer
Address 63622 0
University of Western Australia/WA Centre for Health and Ageing
L5 Ainslie House, GPO Box X2213
Perth WA 6847

Country 63622 0
Australia
Phone 63622 0
+61 8 9224 2750
Fax 63622 0
+61 8 9224 8009
Email 63622 0
christopher.etherton-beer@uwa.edu.au
Contact person for public queries
Name 63623 0
A/Prof Christopher Etherton-Beer
Address 63623 0
University of Western Australia/WA Centre for Health and Ageing
L5 Ainslie House, GPO Box X2213
Perth WA 6847
Country 63623 0
Australia
Phone 63623 0
+61 8 9224 2750
Fax 63623 0
+61 8 9224 8009
Email 63623 0
christopher.etherton-beer@uwa.edu.au
Contact person for scientific queries
Name 63624 0
A/Prof Christopher Etherton-Beer
Address 63624 0
University of Western Australia/WA Centre for Health and Ageing
L5 Ainslie House, GPO Box X2213
Perth WA 6847
Country 63624 0
Australia
Phone 63624 0
+61 8 9224 2750
Fax 63624 0
+61 8 9224 8009
Email 63624 0
christopher.etherton-beer@uwa.edu.au

No information has been provided regarding IPD availability
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