Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000667819
Ethics application status
Approved
Date submitted
19/04/2021
Date registered
1/06/2021
Date last updated
24/04/2024
Date data sharing statement initially provided
1/06/2021
Date results information initially provided
24/04/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Axon for Pain: A trial of home-based electroencephalogram (EEG) neurofeedback for the management of chronic pain
Scientific title
Axon for Pain: A double blind randomised controlled trial of home-based EEG neurofeedback for the management of chronic pain in adults
Secondary ID [1] 303993 0
None
Universal Trial Number (UTN)
U1111-1265-8341
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic pain
 321606 0
Condition category
Condition code
Anaesthesiology 319345 319345 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment as usual plus 8 weeks of 4-5 x 40-minute sessions (32-40 sessions in total) of self-administered home-based active (real) electroencephalogram (EEG) neurofeedback training using a custom-built EEG headset and a tablet-based app with games designed to train participants to upregulate power in the alpha frequency band of the C4 electrode, with the opportunity to simultaneously downregulate beta and theta frequency band power. For example, participants will aim to keep a hot air balloon afloat by upregulating their alpha band power and receive additional auditory feedback when alpha band power is maintained above the training threshold for more than 5 seconds. Individual training thresholds will be set based on baseline EEG recordings at the start of each session. Adherence (number of sessions completed) will be automatically captured on the app.
Intervention code [1] 320299 0
Treatment: Devices
Comparator / control treatment
Treatment as usual plus 8 weeks of 4-5 x 40-minute sessions (32-40 sessions in total) of home-based sham (fake) electroencephalogram (EEG) neurofeedback training using a custom-built EEG headset and a tablet-based app with games designed to train participants to upregulate power in the alpha frequency band of the C4 electrode, with the opportunity to simultaneously downregulate beta and theta frequency band power. All aspects of the experience will be alike, except the feedback received will not be contingent on the participant’s own EEG signal, but rather, the pre-recorded EEG signal from an individual who participated in a previous neurofeedback study. Adherence (number of sessions completed) will be automatically captured on the app.
Control group
Placebo

Outcomes
Primary outcome [1] 327211 0
Change in the Brief Pain Inventory Average Pain Rating
Timepoint [1] 327211 0
From Baseline to the beginning of Week 9
Secondary outcome [1] 394227 0
Change in Brief Pain Inventory Worst Pain Rating
Timepoint [1] 394227 0
From Baseline to the beginning of Week 9
Secondary outcome [2] 394228 0
Change in Brief Pain Inventory Interference Score
Timepoint [2] 394228 0
From Baseline to the beginning of Week 9
Secondary outcome [3] 394229 0
Change in Depression, Anxiety and Stress-21 (DASS-21) score
Timepoint [3] 394229 0
From Baseline to the beginning of Week 9
Secondary outcome [4] 394230 0
Change in Pain Catastrophising Scale Score
Timepoint [4] 394230 0
From Baseline to the beginning of Week 9
Secondary outcome [5] 394231 0
Change in Pittsburgh Sleep Quality Index Score
Timepoint [5] 394231 0
From Baseline to the beginning of Week 9
Secondary outcome [6] 394232 0
Change in EuroQol-5D quality of life score
Timepoint [6] 394232 0
From Baseline to the beginning of Week 9
Secondary outcome [7] 394233 0
Patient global impression of improvement with respect to their chronic pain condition
Timepoint [7] 394233 0
Beginning of Week 9
Secondary outcome [8] 394234 0
Number of treatment responders as assessed by change in brief pain inventory average pain score
Timepoint [8] 394234 0
Calculated from measurements at Baseline and the beginning of Week 9.
Secondary outcome [9] 394236 0
Change in resting-state EEG alpha frequency band power from the C4 electrode.
Timepoint [9] 394236 0
Calculated using measurements taken during the first vs the last week of the intervention period.
Secondary outcome [10] 394237 0
Change in EEG peak alpha frequency from the C4 electrode
Timepoint [10] 394237 0
Calculated using measurements taken during the first vs the last week of the intervention period.
Secondary outcome [11] 394238 0
Change in sleep onset latency
Timepoint [11] 394238 0
Calculated using measurements taken from an Oura ring during the first vs the last week of the intervention period.
Secondary outcome [12] 394239 0
Change in total sleep time
Timepoint [12] 394239 0
Calculated using measurements taken from an Oura ring during the first vs the last week of the intervention period.
Secondary outcome [13] 394240 0
Change in wake after sleep onset
Timepoint [13] 394240 0
Calculated using measurements taken from an Oura ring during the first vs the last week of the intervention period.
Secondary outcome [14] 394241 0
Change in sleep efficiency
Timepoint [14] 394241 0
Calculated using measurements taken from an Oura ring during the first vs the last week of the intervention period.
Secondary outcome [15] 394242 0
Change in resting heart rate variability
Timepoint [15] 394242 0
Calculated using measurements taken from an Oura ring during the first vs the last week of the intervention period.
Secondary outcome [16] 434416 0
Change in Central Sensitization Symptoms (Central Sensitization Inventory)
Timepoint [16] 434416 0
From Baseline to beginning of week 9 (measured at these time points only).

Eligibility
Key inclusion criteria
Males and females 18 years of age or older who have had ongoing pain for 3 months or more; have an average pain rating in the last week of at least 4/10 at the time of initial screening and a head circumference of 520-620mm will be included.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria will be as follows: Previous neurofeedback training; Contraindication for neurofeedback training including: serious head injury, history of seizures, cognitive impairment, neurological disorder or major psychiatric disorder; Dreadlocks, braids, beads or any other hairstyle or head covering that cannot be removed and is incompatible with EEG neurofeedback training; Any physical impairment that prevents home-based EEG neurofeedback training; Implanted electronic neuromodulation device, pacemaker or loop recorder; Any change in medication or treatment planned in the 4 weeks prior to or during the initial intervention period; Not fluent in English.

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)
The study personnel conducting the recruitment and screening procedures will be unaware of the allocation schedule, which will be password protected and kept "off site" with a central study administrator.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised in a 1:1 ratio using a computer generated randomisation schedule with permuted blocks of random size.
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
To detect a minimal clinically important difference of 1.5 points in the change in BPI average pain between groups (assuming a standard deviation of 2.5) with power of 80% and a two-sided alpha level of 0.05, 92 participants are required. To account for a dropout rate of up to 20%, 116 participants will be recruited.

Linear or generalised linear mixed effects models will be used to assess the treatment effects of Real EEG neurofeedback and Sham EEG neurofeedback on the primary outcome measure (BPI average pain).Two levels of analysis will be performed 1) intention-to-treat and 2) according to treatment received. Secondary outcomes will be also analysed and compared between groups using linear or generalised linear mixed effects models. Analysis of differential versus non-differential occurrence of missing observations will be carried out to assure that any missing data are not systematic and further, to account for potential bias in the intention-to-treat analyses. We will report our imputation methods, and we will perform a sensitivity analysis, examining effects on the outcomes reported, with explicit reporting of missing observations and withdrawals.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
7/06/2021
Actual
14/09/2021
Date of last participant enrolment
Anticipated
1/11/2022
Actual
1/08/2022
Date of last data collection
Anticipated
4/01/2023
Actual
5/10/2022
Sample size
Target
116
Accrual to date
Final
116
Recruitment outside Australia
Country [1] 23605 0
New Zealand
State/province [1] 23605 0
Auckland

Funding & Sponsors
Funding source category [1] 308375 0
Commercial sector/Industry
Name [1] 308375 0
Exsurgo Ltd.
Country [1] 308375 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Exsurgo Ltd.
Address
Unit i, 45 William Pickering Drive, Albany, Auckland, 0632, New Zealand
Country
New Zealand
Secondary sponsor category [1] 309194 0
None
Name [1] 309194 0
Address [1] 309194 0
Country [1] 309194 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308340 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 308340 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 308340 0
New Zealand
Date submitted for ethics approval [1] 308340 0
26/03/2021
Approval date [1] 308340 0
17/05/2021
Ethics approval number [1] 308340 0
21/CEN/98

Summary
Brief summary
Chronic pain is a pervasive condition, affecting an estimated 20-40% of all people worldwide. There is now extensive evidence of structural and functional changes in the brain of people with chronic pain. Knowledge of functional changes in the pattern of brain activity in people with chronic pain has been used to develop EEG neurofeedback interventions, which non-invasively record brain signals with a wireless headset and then use game-based software applications to progressively train people with chronic pain to increase or decrease their brain (EEG) activity in the direction associated with pain-relief. This randomised controlled trial will compare the effects of 8 weeks of active (real) home-based EEG neurofeedback vs sham (fake) neurofeedback training in people with chronic pain. We hypothesize that, compared to the sham condition, active EEG neurofeedback training will lead to significantly larger improvements in pain intensity and a range of secondary outcomes including pain interference, psychological distress, sleep quality and quality of life.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110366 0
Dr David Rice
Address 110366 0
School of Clinical Sciences, Auckland University of Technology, 90 Akoranga Drive, Northcote, Auckland, 0620

Waitemata Pain Services, Level 10, North Shore Hospital, 124 Shakespeare Road, Takapuna, Auckland 0622
Country 110366 0
New Zealand
Phone 110366 0
+64 9 921 7032
Fax 110366 0
Email 110366 0
[email protected]
Contact person for public queries
Name 110367 0
Dr David Rice
Address 110367 0
School of Clinical Sciences, Auckland University of Technology, 90 Akoranga Drive, Northcote, Auckland, 0620

Waitemata Pain Services, Level 10, North Shore Hospital, 124 Shakespeare Road, Takapuna, Auckland 0622
Country 110367 0
New Zealand
Phone 110367 0
+64 9 921 7032
Fax 110367 0
Email 110367 0
[email protected]
Contact person for scientific queries
Name 110368 0
Dr David Rice
Address 110368 0
School of Clinical Sciences, Auckland University of Technology, 90 Akoranga Drive, Northcote, Auckland, 0620

Waitemata Pain Services, Level 10, North Shore Hospital, 124 Shakespeare Road, Takapuna, Auckland 0622
Country 110368 0
New Zealand
Phone 110368 0
+64 9 921 7032
Fax 110368 0
Email 110368 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
Participant consent has not been given. Some of the data may be commercially sensitive.


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
SourceTitleYear of PublicationDOI
EmbaseEP069 / #94 HOME-BASED EEG NEUROFEEDBACK FOR THE TREATMENT OF CHRONIC MIGRAINE: A MIXED METHODS CASE REPORT: EPOSTER VIEWING: AS09 - HEADACHE.2023https://dx.doi.org/10.1016/j.neurom.2023.10.077
N.B. These documents automatically identified may not have been verified by the study sponsor.