Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000556943
Ethics application status
Approved
Date submitted
14/04/2020
Date registered
11/05/2020
Date last updated
7/09/2023
Date data sharing statement initially provided
11/05/2020
Date results information initially provided
7/09/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Neuromodulation of Brain Rhythms to Reduce Pain after Spinal Cord Injury
Scientific title
Evaluation of the effectiveness of a novel brain-computer interface neuromodulative intervention to relieve neuropathic pain following spinal cord injury: single-case experimental design with multiple baselines
Secondary ID [1] 301008 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neuropathic Pain after Spinal Cord Injury 317044 0
Condition category
Condition code
Neurological 315209 315209 0 0
Other neurological disorders
Injuries and Accidents 315210 315210 0 0
Other injuries and accidents
Anaesthesiology 315211 315211 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will be conducted based on a single-case experimental design (SCED) with multiple baselines across participants. The SCED method is based on assessing the dependent variables (e.g. pain intensity) repeatedly for each of the participants across phases. The design of this study will be AB + follow-ups, where A refers to the baseline phase, B is the intervention phase, and they will be followed by two follow-up phases. Three participants will be randomly assigned to different baseline durations of the SCED. In this study, a stable baseline will be considered to be one week (i.e., 7 days of observation). The baseline for the first participant will be 7 days, the second participant will have a 10-day baseline, and the third participant will have a 14-day baseline. All participants will start the baseline phase on the same day. Each baseline phase will be followed by 20 days of 30-minute BCI-N intervention over a 4-week period. Subsequently, there will be a 1-week follow-up for each participant immediately after completion of the intervention. In addition, a further 1-week follow-up will take place 3 months after completion of the intervention. During the baseline phase, participants will administer the self-report questionnaires for the primary and secondary outcomes, and will continue reporting them during intervention and follow-up phases in order to monitor possible changes in pain intensity and pain interference. The participants will be contacted everyday to ensure they are completing their pain diaries and pain interference questionnaires in the required times.

The BCI-N intervention procedure will be administered by a researcher. Each participant will receive 30-minute daily sessions of the BCI-N intervention for 20 days over a 4-week period. Each session will involve two 15-minute BCI-N intervention divided by a 5-minute break, and each session will start and finish with measurement of the resting-state EEG levels. EEG acquisition will be performed using the EEG system “SMARTING” device (mBrainTrain, Serbia). The BCI-N treatment incorporates an interactive gaming interface (i.e. “NeuroGame”), and a neuromodulation protocol targeted to suppress theta and low alpha (4-8 Hz) and high beta (20-30 Hz) band powers, and to enhance high alpha (9-12 Hz) band power. During the BCI-N intervention, neurofeedback will be performed on SCI neuropathic pain-related regions of the brain, e.g., C3 and C4. In particular, the EEG signals will be processed in real-time using custom-scripts in MATLAB (MathWorks Inc, USA) utilizing EEGLAB functions. The neuromodulation procedure during the real-time EEG processing will include extracting the power from the frequency of interest (selected frequency bands, i.e., 4-8 Hz, 9-12 Hz and 20-30 Hz) and transferring the information to the NeuroGame interface. The NeuroGame interface was developed using the Unity3D game engine (Unity Technologies, USA). Our game scenario is based on a online game called “A Waffles Fate”. We modified the concept from a navigating “ghost” to a “jellyfish”. Our scenario, called “Floating Jellyfish”, provides neurofeedback in an interactive, goal-directed gaming environment. The visual feedback of the “Floating Jellyfish” game scenario is as follows: When only one EEG frequency band power is suppressed or reinforced as desired, the jellyfish changes colour; when two frequency band powers are activated correctly, the jellyfish starts to move; and when all three band powers are activated, the ocean background changes colour, and a seconds timer begins. Points accumulate only for those seconds that the participant keeps all three bands activated. The aim of the game is to receive as many points as possible.
Intervention code [1] 317325 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323469 0
The Visual Analogue Scale (VAS) will serve as the primary outcome measure of SCI neuropathic pain. The VAS assesses pain intensity on a 0-10 scale (0 = “no pain” and 10 = “maximum pain imaginable”).
Timepoint [1] 323469 0
The study participants will be asked to rate the average intensity of pain during three specific epochs each day, using a VAS. At 12 noon, they will be asked to rate the average intensity of the pain they experienced from the time they woke up that day until noon. At 6 pm they will be asked to rate their average pain between noon and 6 pm. Finally, they will be asked to rate the average of the pain intensity they experienced between 6 pm and the time they went to bed at the time they go to bed. The mathematical average of the three ratings will then be computed to represent that participant’s average daily pain intensity. If any ratings are missing, the score will be the average of the ratings obtained. This daily paper-and-pencil pain diary will be completed by the participants during all phases: baseline (7, 10, or 14 days), intervention (20 days), and two follow-up (7 days) phases.
Secondary outcome [1] 382014 0
Degree of pain interference will be assessed by 6 items from the Brief Pain Inventory. These items will assess general activity, normal work, relations with other people, enjoyment of life, mood, and sleep on a 0-10 scale (0 = “does not interfere” and 10 = “completely interferes”).
Timepoint [1] 382014 0
Degree of pain interference will be measured on every day of the baseline, intervention, and two follow-up phases.

Eligibility
Key inclusion criteria
Three individuals with a spinal cord injury (SCI) will be recruited for this study. Participants need to meet the following inclusion criteria: (1) aged 18-80 years, (2) persistent neuropathic pain for more than 3 months, (3) pain severity of greater than or equal to 2 (out of 10) on the Visual Analogue Scale (VAS, 0 cm reflecting no pain to 10 cm reflecting maximum pain imaginable), (3) medically stable and (4) demonstrating an ability to use the Visual Analogue Scale (VAS).
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Regarding the neuroimaging component of the study, individuals who have metal objects inside their body (e.g., stents, metal clips, implants and shrapnel) may be excluded.

Study design
Purpose of the study
Treatment
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
Efficacy
Statistical methods / analysis
Primary and secondary outcomes will be analysed separately based on the SCED analysis. The SCED analysis mainly relies on visual inspection, however, the outcome measures from this study will be inspected and analysed using both visual analysis and supplementary statistical analysis. In visual analysis, the baseline phase establishes a benchmark against the intervention phase to investigate any natural change in the outcome of interest. A structured analysis will be used to investigate whether the treatment-induced changes in the primary and secondary outcomes are reliable and consistent across participants.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/11/2022
Actual
11/01/2023
Date of last participant enrolment
Anticipated
Actual
13/01/2023
Date of last data collection
Anticipated
Actual
11/06/2023
Sample size
Target
3
Accrual to date
Final
2
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 305452 0
Charities/Societies/Foundations
Name [1] 305452 0
Rebecca L. Cooper Medical Research Foundation
Country [1] 305452 0
Australia
Funding source category [2] 305454 0
University
Name [2] 305454 0
Cross-faculty collaboration scheme from University of Technology Sydney (UTS)
Country [2] 305454 0
Australia
Funding source category [3] 305455 0
Other Collaborative groups
Name [3] 305455 0
SPHERE Frontiers Technology Clinical Academic Group
Country [3] 305455 0
Australia
Primary sponsor type
Other
Name
Neuroscience Research Australia
Address
139 Barker Street, Randwick NSW 2031
Country
Australia
Secondary sponsor category [1] 305851 0
University
Name [1] 305851 0
University of Technology Sydney
Address [1] 305851 0
15 Broadway, Ultimo NSW 2007
Country [1] 305851 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305769 0
UNSW Human Research Ethics Committee A
Ethics committee address [1] 305769 0
UNSW Research Ethics & Compliance Support
The University of New South Wales
Sydney NSW 2052 Australia
Ethics committee country [1] 305769 0
Australia
Date submitted for ethics approval [1] 305769 0
27/05/2019
Approval date [1] 305769 0
22/07/2019
Ethics approval number [1] 305769 0
HC190411
Ethics committee name [2] 305771 0
UTS Human Ethics Committee
Ethics committee address [2] 305771 0
University of Technology Sydney
123 Broadway NSW 2007 Australia
Ethics committee country [2] 305771 0
Australia
Date submitted for ethics approval [2] 305771 0
23/08/2019
Approval date [2] 305771 0
15/01/2020
Ethics approval number [2] 305771 0
ETH19-4090

Summary
Brief summary
Neuropathic pain is a debilitating secondary condition for many individuals with spinal cord injury (SCI). SCI neuropathic pain remains minimally responsive to existing pharmacological and non-pharmacological treatments. A growing body of evidence supports the potential for brain-computer interface (BCI) systems to reduce SCI neuropathic pain via electroencephalography (EEG) neurofeedback. However, further studies are needed to provide more definitive findings regarding the effectiveness of this intervention.
We have developed a novel BCI-based neuromodulative (BCI-N) intervention for SCI neuropathic pain. Our BCI-N treatment includes an interactive gaming interface, and a neuromodulation protocol targeted to suppress theta (4-8 Hz) and high beta (20-30 Hz) frequency powers, and enhance alpha (9-12 Hz) frequency power. A single-case experimental design (SCED) with multiple baselines will be used to examine the effectiveness of our self-developed BCI-N intervention for the treatment of SCI neuropathic pain. Three participants with SCI neuropathic pain will be recruited. Each participant will be randomly assigned to a different baseline phase (i.e., 7, 10 or 14 days), which will then be followed by 20 sessions of 30-min BCI-N intervention over a 4-week period. The visual analogue scale assessing average pain intensity will serve as the primary outcome measure. Pain interference will also be assessed as a secondary outcome domain. Generalisation measures will assess quality of life, sleep quality, anxiety and depressive symptoms as well as resting-state EEG and thalamic gamma-aminobutyric acid (GABA) concentration. SCEDs are considered a viable alternative approach to randomised clinical trials to identify evidence-based practices in the field of technology-based health interventions when recruitment of large samples is not feasible.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101534 0
A/Prof Sylvia Gustin
Address 101534 0
Neuroscience Research Australia
139 Barker Street, Randwick NSW 2031
Country 101534 0
Australia
Phone 101534 0
+61 2 9399 1894
Fax 101534 0
Email 101534 0
s.gustin@unsw.edu.au
Contact person for public queries
Name 101535 0
Sylvia Gustin
Address 101535 0
Neuroscience Research Australia
139 Barker Street, Randwick NSW 2031
Country 101535 0
Australia
Phone 101535 0
+61 2 9399 1894
Fax 101535 0
Email 101535 0
s.gustin@unsw.edu.au
Contact person for scientific queries
Name 101536 0
Sylvia Gustin
Address 101536 0
Neuroscience Research Australia
139 Barker Street, Randwick NSW 2031
Country 101536 0
Australia
Phone 101536 0
+61 2 9399 1894
Fax 101536 0
Email 101536 0
s.gustin@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
We do not have Ethics Approval to share the trial data.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
14232Study protocol https://www.researchprotocols.org/2020/9/e20979 



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Plain language summaryNo While there was a significant decrease in pain int... [More Details]

Documents added automatically
No additional documents have been identified.