Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000841572
Ethics application status
Approved
Date submitted
17/06/2024
Date registered
8/07/2024
Date last updated
8/07/2024
Date data sharing statement initially provided
8/07/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
An Interventional Trial for Persisting Post-Concussive Symptoms after Mild Traumatic Brain Injury
Scientific title
Intervention for Persisting Post-Concussive Symptoms after Mild Traumatic Brain Injury in adults aged 18 - 65 years
Secondary ID [1] 312339 0
Nil known
Universal Trial Number (UTN)
Trial acronym
PPCS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Concussion 334106 0
Mild traumatic brain injury 334107 0
Persistent post-concussion symptoms 334108 0
Condition category
Condition code
Neurological 330781 330781 0 0
Other neurological disorders
Injuries and Accidents 330862 330862 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group 1: Neurofeedback
Neurofeedback sessions will train brain specific brain regions using real-time feedback of the individual’s electrophysiological brain activity. Participants allocated to the neurofeedback group will attend the Sarich Neuroscience Research Institute – Curtin University laboratory for 18 neurofeedback sessions (3 sessions/week for 6 weeks). Each neurofeedback session is expected to take approximately 40 minutes, including time to fit the Electro-Cap, fill the electrodes and achieve good impedance, and perform rounds of neurofeedback. Neurofeedback will be conducted in 7 rounds, with 3 minutes of training and 30-second breaks in between, for a total neurofeedback time of 24.5 minutes.
Participants will sit facing a computer monitor and see an electroencephalography (EEG) map on the screen. A research team member will remain with the participant, directly observing the participant as the complete the intervention. They will be given instruction on what the training will involve (i.e. meeting a target), but as an operant conditioning method will not receive specific instruction on how that is to be achieved. Instead, when the target brain behaviour is achieved, the participant is rewarded with a sound and appearance of a circle on the screen. The participant receives a score for each round which indicates their performance in achieving that target. Over time, the participant learns to regulate their own brain activity, though often they are not consciously aware of the learning mechanism. Target Z scores will be gradually reduced over each session based on improvement in performance. For example, a participant with a Z score of +3 (over-activation) will train to reduce brain activation in that area with a target Z score of 2.5. When this is achieved and maintained, the Z score will be reduced to 2, then 1.5, and so on, until the Z score is returned to a ‘normal’ score of 0.

Group 2: Concentration
This group will be recruited as a comparator to neurofeedback, to allow delineation of neurofeedback effects from effects of repeated focused concentration on a screen, participant-therapist interaction, environment, or other factors which may be associated with neurofeedback (but are not, in themselves, neurofeedback). This group will be informed that they are participating in a trial of concentration as a therapy for persistent post-concussive symptoms (PPCS). Participants allocated to the concentration group will attend the Sarich Neuroscience Research Institute – Curtin University laboratory for 18 concentration sessions (3 sessions/week for 6 weeks). To match the neurofeedback experience, each session is expected to take approximately 40 minutes (including fitting and filling of the Electro-Cap, etc.), with 7 rounds of 3 minute concentration and 30-second breaks in between, for a total time of 24.5 minutes.
Participants will sit facing a computer monitor and see an EEG map on the screen. They will be given instruction to look at the screen and pay particular attention when a sound plays and circle appears on the screen. A research team member will remain with the participant, directly observing the participant as the complete the intervention. For this group, the sound and circle will appear at random.
Intervention code [1] 328826 0
Treatment: Other
Comparator / control treatment
Group 3: Control
This group will be recruited as a separate control comparator to neurofeedback, to allow us to examine whether participants would demonstrate natural improvement relative to baseline assessments over the same period without any specific intervention. In the few neurofeedback studies in traumatic brain injury (TBI) that have included a control group, this is the most common scenario. Participants allocated to the control group will attend the Sarich Neuroscience Research Institute – Curtin University laboratory for baseline and follow-up testing, and are not required to perform any training or attend for other sessions.
Control group
Active

Outcomes
Primary outcome [1] 338539 0
Change in Persistent Post-concussive Symptoms (PPCS) as determined by overall score on the Post-concussion symptom scale (PCSS)
Timepoint [1] 338539 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)
Secondary outcome [1] 436343 0
Change in quality of life as determined by overall score on Quality of Life After Brain Injury (QOLIBRI)
Timepoint [1] 436343 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)
Secondary outcome [2] 436344 0
Change in coping strategies as determined by overall score on Utrecht Coping Test
Timepoint [2] 436344 0
Baseline (pre-treatment), (week 7 post-treatment)
Secondary outcome [3] 436345 0
Change in resilience as determined by overall score on Brief Resilience Scale
Timepoint [3] 436345 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)
Secondary outcome [4] 436346 0
Change in the impact of headaches as determined by overall score on the Headache Disability Index
Timepoint [4] 436346 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)
Secondary outcome [5] 436347 0
Change in the impact of dizziness as determined by overall score on the Dizziness Handicap Inventory
Timepoint [5] 436347 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)
Secondary outcome [6] 436348 0
Change in depression as determined by overall score on the Depression Anxiety Stress Scales – Short From (DASS-21)
Timepoint [6] 436348 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)
Secondary outcome [7] 436349 0
Change in cognitive functioning as assessed using the Repeatable Battery for Neuropsychological Status (RBANS)
Timepoint [7] 436349 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)
Secondary outcome [8] 436350 0
Exploratory outcome: Abnormal biomarkers in blood and saliva samples
Timepoint [8] 436350 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)
Secondary outcome [9] 436351 0
Exploratory outcome: Changes in MRI structure
Timepoint [9] 436351 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)
Secondary outcome [10] 436352 0
Exploratory outcome: Changes in EEG brain network dysfunction
Timepoint [10] 436352 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)
Secondary outcome [11] 436708 0
Change in anxiety as determined by overall score on the Depression Anxiety Stress Scales – Short From (DASS-21)
Timepoint [11] 436708 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)
Secondary outcome [12] 436709 0
Change in stress as determined by overall score on the Depression Anxiety Stress Scales – Short From (DASS-21)
Timepoint [12] 436709 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)
Secondary outcome [13] 436710 0
Exploratory outcome: Changes in MRI function
Timepoint [13] 436710 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)
Secondary outcome [14] 436711 0
Exploratory outcome: Changes in MRI brain metabolites
Timepoint [14] 436711 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)
Secondary outcome [15] 436713 0
Exploratory outcome: Changes in trauma index scores
Timepoint [15] 436713 0
Baseline (pre-treatment), follow-up (week 7 post-treatment)

Eligibility
Key inclusion criteria
i) Clinical diagnosis of concussion made by a medical practitioner
ii) Concussion experienced 6 months to 4 years ago
iii) Experiencing persistent post-concussion symptoms (PPCS)
iv) Aged 18 – 65 years
v) Willing and able to attend Sarich Neuroscience Research Institute – Curtin University precinct for the required time commitment (3x40 minute sessions per week for 6 weeks, baseline and follow up testing)
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i) Significant history of pre-existing conditions that would interfere with assessment, intervention and follow-up (e.g. Substance abuse/alcohol abuse, homelessness, terminal illness)
ii) Significant debilitating pre-concussion diagnosed mental health disorder (e.g. schizophrenia, bipolar disorder)
iii) Significant pre-existing neurological condition which may interfere with ability to complete outcome measures, intervention or follow up (e.g. stroke, dementia)
iv) Pre-existing cognitive impairment (e.g. intellectual disability) which may interfere with ability to undertake assessment, intervention and follow up
v) Non-English speakers or poor English language skills which may interfere with ability to undertake assessment, intervention and follow up
vi) Pregnant women
vii) Prisoners in custody or people known to be involved in illegal activity
viii) Epilepsy or history of seizure
ix) Presence of surgical or other materials which may interfere with EEG signal e.g. aneurism clips, plates or screws, electronic inner ear implants, shrapnel or other foreign body.
x) Meets exclusion criteria to undertake MRI, which can be any of the following:
Has cardiac pacemaker or pacing wire in situ
Has metal surgical clips or staples of any kind (particularly aneurysm clips) in situ
Has had lap band surgery
Has electronic inner ear implants (bionic ears)
Has metal fragments in your eyes (past or present)
Has electronic stimulators
Has implanted pumps
Has metal pins or rods in bones
Has an IUCD (intrauterine contraceptive device) fitted
Has shrapnel, bullets or foreign bodies .

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 be randomised to study groups prior to baseline assessment using the sealed envelope system, in which randomly generated treatment allocations will be placed within sealed opaque envelopes. To further minimise potential bias or tampering, a member of the study team who will not interact with participants in recruitment, consent, training or assessments will select and open one envelope on the day of each participant's baseline testing. The participant will then be offered the allocated treatment or control.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised to study groups prior to baseline assessment using the sealed envelope system, in which treatment allocations will be placed within sealed opaque envelopes that will then be selected at random by a researcher who is not involved with the participant or their treatment.
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
All statistical analyses will be carried-out using SPSS Statistics (version 24). Groups will be initially compared for baseline PPCS symptom, demographic information, cognitive and questionnaire scores and MRI findings, with subsequent within-group comparisons between baseline and follow-up testing. Analysis of EEG values within individual brain regions will be by change in Z score at that location. Nonparametric Monte-Carlo permutation inference will be performed to investigate regional alterations in power using FBRIB software library (FSL) “randomise” tool. These will be entered into a multivariate general linear model in order to control for demographic variables and tested for association with MRI, cognitive, questionnaire and biomarker scores in a linear regression model.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
22/07/2024
Actual
Date of last participant enrolment
Anticipated
21/07/2025
Actual
Date of last data collection
Anticipated
1/09/2025
Actual
Sample size
Target
84
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 316736 0
Charities/Societies/Foundations
Name [1] 316736 0
Bryant Stokes Neurological Research Foundation
Country [1] 316736 0
Australia
Funding source category [2] 316756 0
Government body
Name [2] 316756 0
Western Australian Future Health Research and Innovation Fund
Country [2] 316756 0
Australia
Primary sponsor type
University
Name
Curtin University
Address
Country
Australia
Secondary sponsor category [1] 318946 0
Charities/Societies/Foundations
Name [1] 318946 0
Perron Institute for Neurological Research and Translation
Address [1] 318946 0
Country [1] 318946 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315510 0
Curtin University Human Research Ethics Committee
Ethics committee address [1] 315510 0
Ethics committee country [1] 315510 0
Australia
Date submitted for ethics approval [1] 315510 0
20/04/2021
Approval date [1] 315510 0
30/07/2021
Ethics approval number [1] 315510 0
HRE2021-0451

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

Contacts
Principal investigator
Name 134926 0
Dr Sarah Hellewell
Address 134926 0
Curtin University Level 3, Sarich Neuroscience Institute 8 Verdun st, Nedlands WA 6009
Country 134926 0
Australia
Phone 134926 0
+61434053674
Fax 134926 0
Email 134926 0
[email protected]
Contact person for public queries
Name 134927 0
Dr Sarah Hellewell
Address 134927 0
Curtin University Level 3, Sarich Neuroscience Institute 8 Verdun st, Nedlands WA 6009
Country 134927 0
Australia
Phone 134927 0
+61434053674
Fax 134927 0
Email 134927 0
[email protected]
Contact person for scientific queries
Name 134928 0
Dr Sarah Hellewell
Address 134928 0
Curtin University Level 3, Sarich Neuroscience Institute 8 Verdun st, Nedlands WA 6009
Country 134928 0
Australia
Phone 134928 0
+61434053674
Fax 134928 0
Email 134928 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?

No Supporting Document Provided



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.