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Trial registered on ANZCTR


Registration number
ACTRN12619001523190
Ethics application status
Approved
Date submitted
21/10/2019
Date registered
4/11/2019
Date last updated
4/11/2019
Date data sharing statement initially provided
4/11/2019
Date results information initially provided
4/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effects of transcranial direct current stimulation for improving attention after traumatic brain injury
Scientific title
transcranial Direct Current Stimulation (tDCS) effects on task-related activation and working memory performance in traumatic brain injury
Secondary ID [1] 299595 0
None
Universal Trial Number (UTN)
U1111-1242-2521
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
traumatic brain injury 314876 0
Condition category
Condition code
Injuries and Accidents 313224 313224 0 0
Other injuries and accidents
Neurological 313225 313225 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. Brief description of intervention:
The intervention for all participants was a 20 minute session of transcranial direct current stimulation (tDCS: 2mA) which was compared to a sham tDCS session delivered to the same participant a week or so apart.
a) Frequency- both active tDCS and sham sessions were delivered once only. Order (sham, active) was randomised across participants. There was approximately one week between the two sessions (M = 8.03, SD = 2.76 days).
b) Parameters- tDCS was administered using a battery driven, constant current stimulator and a pair of conductive rubber electrodes (7 cm×5 cm, 35 cm2) covered in normal saline-soaked, synthetic sponge which were restrained by a latex headband. tDCS was delivered in a 20 minute session (2mA) with a 5 s fade in and 5 s fade out time by an anode placed on the head over the left parietal lobe with the cathode placed over the same area on the right side. Sham stimulation used the same montage for 20 minutes and consisted of 2 mA of tDCS delivered for 30 s with a 5 s fade in and 5 s fade out time.
c) The intervention was administered by a research assistant.
d) Treatment adherence was audited by a second researcher during initial training but not thereafter.
2. Procedure: Prior to the first treatment session (Active or sham as randomly allocated), participants completed a brief neuropsychological battery including the the WAIS-IV Digit Span Test (forward, backward and sequencing) (Wechsler, 2008), animals fluency (Tombaugh, Kozak, & Rees, 1999), Digit Symbol Modality test (Smith, 2007) and the Trail Making Test (TMT) (Reitan, 1992).

Prior to each session (active and sham) of tDCS they completed a measure of mood state (the Profile of Mood State) and a fatigue and alertness scale. In order to examine arousal levels participants were fitted with skin conductance electrodes and were asked to sit relaxed and (1) close their eyes for two minutes (EC1); (2) open their eyes in response to a beep signal and focus their eyes on a fixation cross for two minutes (EO) and (3) close their eyes again for another two minutes (EC2).

During the administration of active (or sham tDCS) participants completed a 1-back and a 2-back working memory task (order counterbalanced across participants).

At the completion of the tDCS (active or sham) and the N-back tasks, participants again had their arousal monitored (using the EC1, EO, EC2 procedure) and completed the POMS and the fatigue and alertness scales.
Intervention code [1] 315848 0
Treatment: Devices
Comparator / control treatment
The comparitor trial (also delivered to all participants) was a 20 minute episode of sham tDCS using the same anode/cathode placement but with 2MA delivered for 30 seconds only.
Control group
Placebo

Outcomes
Primary outcome [1] 321722 0
Accuracy (d prime) of performance on 1-Back working memory task
Timepoint [1] 321722 0
During active/sham tDCS
Primary outcome [2] 321723 0
Reaction time and reaction time SD (variability) on 1-Back working memory task
Timepoint [2] 321723 0
During sham/active tDCS
Primary outcome [3] 321724 0
Task activated arousal (difference in skin conductance levels between rest (eyes closed, eyes open, eyes closed (see procedure) and during 1-back task.

Skin conductance was recorded from silver-silver chloride (Ag/AgCl) bipolar electrodes filled with electrode paste of 0.05 M NaCl in an inert ointment base, placed on the distal volar surface of digits II and III of the non-dominant hand, with a PowerLab 8/30 Data Acquisition System (AD Instruments, Castle Hill, Australia). SCL was calibrated for each participant at the start of their recording session to detect activity in the range of 0–40 µS and digitized at a sampling rate of 1000 Hz.
Timepoint [3] 321724 0
During active/sham tDCS
Secondary outcome [1] 376010 0
Primary outcome: Accuracy (d prime) of performance on 2-Back working memory task
Timepoint [1] 376010 0
During sham/active tDCS
Secondary outcome [2] 376011 0
Primary outcome: Reaction time and reaction time SD (variability) on 2-Back working memory task
Timepoint [2] 376011 0
During sham/active tDCS
Secondary outcome [3] 376246 0
Primary outcome: Task activated arousal (difference in skin conductance levels between rest (eyes closed, eyes open, eyes closed (see procedure) and during 2-back task.

Skin conductance was recorded from silver-silver chloride (Ag/AgCl) bipolar electrodes filled with electrode paste of 0.05 M NaCl in an inert ointment base, placed on the distal volar surface of digits II and III of the non-dominant hand, with a PowerLab 8/30 Data Acquisition System (AD Instruments, Castle Hill, Australia). SCL was calibrated for each participant at the start of their recording session to detect activity in the range of 0–40 µS and digitized at a sampling rate of 1000 Hz.
Timepoint [3] 376246 0
Immediately prior and immediately after active/sham tDCS
Secondary outcome [4] 376247 0
Mood (as rated using the Profile of Mood states (POMS)
Timepoint [4] 376247 0
Immediately prior to active/sham tDCS and then immediately afterwards.
Secondary outcome [5] 376248 0
Fatigue as rated on an eight-point Likert-scale from 0 (not at all) to 7 (very).
Timepoint [5] 376248 0
Immediately prior to and then immediately after active/sham tDCS
Secondary outcome [6] 376249 0
Alertness as rated on an eight-point Likert-scale from 0 (not at all) to 7 (very).
Timepoint [6] 376249 0
Immediately prior and immediately after active/sham tDCS

Eligibility
Key inclusion criteria
- Definite moderate to severe traumatic brain injury according to the Mayo classification criteria (Malec, Brown, Leibson et al, 2007), i.e.
a period of post-traumatic amnesia (PTA) of 24 hours or greater and/or
loss of consciousness greater than 30 minutes and/or
evidence of intracerebral brain pathology on neuroimaging.
- Aged between 18 – 70 years,
- At least 12 months post-injury,
- Discharged from hospital and living in the community,
- Functional English reading and writing ability.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Uncorrected hearing or vision loss.
-Current diagnosed drug and/or alcohol addiction
- Active psychosis
-Psychiatric condition (other than mild to moderate anxiety or depression).
-Dementia or other neurodegenerative disease
-Aphasia, agnosia, or profound amnesia
- Insertion of a metal shunt.

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 was concealed, i.e. conducted off-site by a person unaware of the study aims.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permutated block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size: Estimates of effect sizes for tDCS in TBI are variable. However, a meta-analysis of the impact of tDCS on cognition in people with Alzheimers and Mild Cognitive Impairment Cruz Gonzalez et al (2018) reported an immediate effect size of .39. Using G*Power, a sample size of 30 was estimated as providing sufficient power to detect a within subject effect of this magnitude (p=.05).

Analyses: Mean scores for questionnaires were assessed in separate repeated-measures MANOVAs. Time (pre, post) and stimulation (Active, Sham) were the within-subjects measures.
N-back task accuracy was quantified as omission errors, i.e. the proportion of targets (button-press responses) that were missed, commission errors, i.e. the proportion of non-targets (non-responses) that mistakenly elicited a response. These variables were used to derive the sensitivity index d’ (calculated as z(hit rate) – z(false alarm rate) as a measure of overall verbal working memory accuracy (Nikolin, Lauf, Loo & Martin, 2018). For correctly responded target trials, RT measures included within-subject mean and intra-individual variability (standard deviation).

D-prime, RT and RT variability were analysed separately for the 1-back and 2-back conditions using MANOVA with stimulation (Active, Sham) as the within subject condition.

Resting-arousal was quantified as the mean SCL across the 10 to 120 s period of the lowest eyes-closed resting baseline recording, and activated-arousal was the mean SCL for the duration of each n-back task. Task-activation was the difference between these arousal measures: activated minus resting arousal. Task-activation was assessed in separate repeated-measures MANOVAs for 1-back and 2-back tasks with stimulation (Active, Sham) as the within-subjects measure.

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)
NSW
Recruitment hospital [1] 15005 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 15006 0
Royal Rehabilitation Hospital - Coorabel/Moorong - Ryde
Recruitment postcode(s) [1] 28290 0
2170 - Liverpool
Recruitment postcode(s) [2] 28291 0
2112 - Ryde

Funding & Sponsors
Funding source category [1] 304075 0
Government body
Name [1] 304075 0
National Health and Medical Research Council
Address [1] 304075 0
16 Marcus Clarke St, Canberra ACT 2601.
Country [1] 304075 0
Australia
Primary sponsor type
University
Name
UNSW
Address
School of Psychology, UNSW, Sydney, 2052
Country
Australia
Secondary sponsor category [1] 304272 0
None
Name [1] 304272 0
Address [1] 304272 0
Country [1] 304272 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304567 0
South Western Sydney Local Health District Ethics Committee
Ethics committee address [1] 304567 0
Administrative Officer | Research and Ethics Office
South Western Sydney Local Health District (SWSLHD)
Locked Bag 7103 Liverpool BC NSW 1871
Ethics committee country [1] 304567 0
Australia
Date submitted for ethics approval [1] 304567 0
03/06/2016
Approval date [1] 304567 0
12/09/2016
Ethics approval number [1] 304567 0
NEAF (AU/1/E6D6214) Protocol No X16-079 & HREC 08/RPAH/141

Summary
Brief summary
This study evaluates the efficacy of brain stimulation, i.e. Transcranial Direct Current Stimulation (tDCS) to improve attention skills and working memory in people with traumatic brain injury. The study involves placing electrodes on the scalp and passing a weak direct electrical current through the brain that can increase neuronal excitability. The stimulation is non-invasive and painless with few reported side effects such as skin irritation or a mild headache. Individuals received one active/actual tDCS sessions and one sham or placebo session. During both sessions they also completed two computer-based task in which they responded to symbols appearing on the computer monitor. Participants were fully awake and alert during these sessions. Test sessions were approximately an hour in duration and took place approximately 1 week apart. The order of session (active or sham) was unknown to participants and, indeed, people find it very difficult to guess.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 97410 0
Prof Skye McDonald
Address 97410 0
School of Psychology, University of NSW, Sydney, 2052, NSW, AUSTRALIA
Country 97410 0
Australia
Phone 97410 0
+61 2 93853029
Fax 97410 0
Email 97410 0
s.mcdonald@unsw.edu.au
Contact person for public queries
Name 97411 0
Prof Skye McDonald
Address 97411 0
School of Psychology, University of NSW, Sydney, 2052, NSW, AUSTRALIA
Country 97411 0
Australia
Phone 97411 0
+61 2 93853029
Fax 97411 0
Email 97411 0
s.mcdonald@unsw.edu.au
Contact person for scientific queries
Name 97412 0
Prof Skye McDonald
Address 97412 0
School of Psychology, University of NSW, Sydney, 2052, NSW, AUSTRALIA
Country 97412 0
Australia
Phone 97412 0
+61 2 93853029
Fax 97412 0
Email 97412 0
s.mcdonald@unsw.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Confidentiality of participants with brain injury could be compromised by sharing individual participant data
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary