Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001038482
Ethics application status
Approved
Date submitted
27/07/2016
Date registered
4/08/2016
Date last updated
8/02/2021
Date data sharing statement initially provided
8/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The relationship between cortical activity and cognitive function after traumatic brain injury
Scientific title
The relationship between cortical activity and cognitive function in patients with traumatic brain injury and healthy controls.
Secondary ID [1] 289175 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Traumatic Brain Injury (TBI) 298709 0
Condition category
Condition code
Injuries and Accidents 298762 298762 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Traumatic brain injuries are common, estimated to affect 107 in 100,000 Australians per year. Of these 80% sustain a mild-moderate traumatic brain injury (mTBI). A wide range of cognitive, behavioural and affective symptoms occur as a result of the biomechanical forces to the brain. The acute and long lasting impact of mTBI on brain activity is not well characterized.

Combined transcranial magnetic stimulation (TMS) with electroencephalography (EEG) can be used as a tool to identify the neurophysiological mechanisms associated with mTBI symptoms. Furthermore, it allows the association between cognitive impairments and the functional integrity of the neural areas underlying these symptoms to be investigated.

An EEG is a recording of the brain’s electrical activity and is a commonly used tool to investigate aspects of brain functioning. After recording some EEG whilst the participant sits still with their eyes open or closed we will use a transcranial magnetic stimulation (TMS) device to assess brain activity. This is done by placing a handheld magnetic coil over the participants scalp while they are seated in a chair. The magnetic field generated by the coil is able to painlessly stimulate nerve cells in the brain. The TMS protocol is 75 single pulses at 0.2Hz with an interstimulus interval of 5 seconds. Single pulse duration is approximately 6.5 minutes.

Thirty mTBI participants and 30 age and gender matched controls will attend three testing sessions across a 6 month period to capture acute, sub-acute and chronic symptoms post injury. A neuropsychological assessment and TMS/EEG recording will be conducted at each time point. Total testing session will take approximately 3 hours and will be conducted by a trained PhD student under the supervision of a Clinical Neuropsychologist. Analyses will be conducted between groups to assess for differences in brain activity and within groups to investigate recovery in mTBI and test-retest reliability in controls. By improving our understanding of how changes in brain activity relate to impairments and recovery of function, targeted therapeutic strategies to modulate these may be developed.
Intervention code [1] 294698 0
Diagnosis / Prognosis
Comparator / control treatment
Control group participants will be age, gender and education level matched and have no history of head injury.
Control group
Active

Outcomes
Primary outcome [1] 298238 0
TMS-EEG data.
TMS-EEG is performed by stimulating the scalp over the DLPFC while simultaneously recording brain activity via surrounding EEG electrodes. The TMS pulse produces a neurophysiological response in the underlying cortex, referred to as the TMS evoked potential (TEP), which is recorded on EEG and the TEP amplitude gives an index of cortical excitability.
Timepoint [1] 298238 0
Baseline, 3 months and 6 months post head injury.
Secondary outcome [1] 323626 0
Neuropsychological Assessment Battery assessing the domains of speed of processing, attention, verbal learning, working memory, visual learning, reasoning, and problem solving.

This is a composite outcome measure.
Timepoint [1] 323626 0
Baseline, 3 months and 6 months post head injury.
Secondary outcome [2] 326341 0
Working memory performance: computerised n-back memory task (accuracy and reaction time)
Timepoint [2] 326341 0
Baseline, 3 months and 6 months post head injury.

Eligibility
Key inclusion criteria
Inclusion Criteria for mTBI
1. Are voluntary and competent to consent,
2. Are right handed,
3. Are between the ages of 18 and 55 years,
4. Sustained a traumatic brain injury (mild to moderate: Glasgow Coma Scale 9>15)

Inclusion Criteria for controls
1. Are voluntary and competent to consent,
2. Are right handed,
3. Are between the ages of 18 and 55 years,
4. No history of head injury
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
General Exclusion Criteria
1. Are pregnant or lactating
2. History of neurological or mental illness
3. Have a DSM-IV history of substance abuse or dependence in the last 6 months
4. Taking medication known to alter brain excitability, plasticity
5. History of seizures
6. Have metal anywhere in the head, except the mouth. This includes metallic objects such as screws, plates and clips from surgical procedures.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
The primary outcome measures will be neurophysiological, i.e. the differences in cortical activity between mTBI participants and controls. A linear mixed-effect model will be used to analyse the group x time interaction. If a significant interaction between group and time is observed, post hoc between group analyses will be conducted to see where the difference lies. The dependent variables will be TEPs, EEG coherence at rest and during the n-back task.
Secondary outcome measures will be neuropsychological. Separate repeated measures ANOVAs will be used to compare neuropsychological measures across time in both groups. Pairwise comparisons will be conducted as follow up for any significant results of the analysis of variance. The dependent variables will be the individual neuropsychological tests (include assessments of working memory, attention, processing speed etc.). Bivariate correlations will be used to examine the relationship between neuropsychology measures and cortical activity in both groups.
Finally, to investigate whether mTBI alters the brains response to TBS, EEG coherence will be compared within group and between groups. Furthermore, the effect of TBS on neurobehavioral performance will be assessed by comparing n-back performance (measures of accuracy and reaction time) pre and post TBS.

All statistical analysis will be conducted using SPSS Version 20 and p-values <0.05 will be considered significant.

30 participants will be included in each group. This sample size has been determined based on previous research within a traumatic brain injury population group. No sample size power calculations have currently been performed.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
8/08/2016
Actual
11/10/2016
Date of last participant enrolment
Anticipated
6/05/2019
Actual
7/03/2019
Date of last data collection
Anticipated
Actual
26/08/2019
Sample size
Target
60
Accrual to date
Final
58
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 293560 0
Government body
Name [1] 293560 0
Australian Post Graduate Award (APA)
Country [1] 293560 0
Australia
Primary sponsor type
Individual
Name
A/Prof Kate Hoy
Address
Monash Alfred Psychiatry Research Centre (MAPrc)
Level 4,
607 St Kilda Road,
Melbourne,
3004,
VIC
Country
Australia
Secondary sponsor category [1] 292978 0
None
Name [1] 292978 0
Address [1] 292978 0
Country [1] 292978 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294997 0
Alfred Health Ethics Committee
Ethics committee address [1] 294997 0
Ethics committee country [1] 294997 0
Australia
Date submitted for ethics approval [1] 294997 0
23/05/2016
Approval date [1] 294997 0
19/07/2016
Ethics approval number [1] 294997 0
260/16

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65738 0
A/Prof Kate Hoy
Address 65738 0
Monash Alfred Psychiatry Research Centre (MAPrc)
Level 4,
607 St Kilda Road,
Melbourne,
3004,
VIC
Country 65738 0
Australia
Phone 65738 0
+61 3 9076 5034
Fax 65738 0
Email 65738 0
[email protected]
Contact person for public queries
Name 65739 0
Hannah Coyle
Address 65739 0
Monash Alfred Psychiatry Research Centre
Level 4,
607 St Kilda Road,
Melbourne,
3004,
VIC
Country 65739 0
Australia
Phone 65739 0
+61 3 9076 8649
Fax 65739 0
Email 65739 0
[email protected]
Contact person for scientific queries
Name 65740 0
Hannah Coyle
Address 65740 0
Monash Alfred Psychiatry Research Centre (MAPrc)
Level 4,
607 St Kilda Road,
Melbourne,
3004,
VIC
Country 65740 0
Australia
Phone 65740 0
+61 3 9076 8649
Fax 65740 0
Email 65740 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
10497Analytic code https://github.com/hcoyle999 



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.