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Trial registered on ANZCTR


Registration number
ACTRN12623000905662
Ethics application status
Approved
Date submitted
31/07/2023
Date registered
23/08/2023
Date last updated
23/08/2023
Date data sharing statement initially provided
23/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Neurofeedback targeting effective connectivity for chronic low back pain.
Scientific title
Effect of novel effective connectivity neurofeedback training on pain and function in chronic low back pain- A pilot double blinded randomised placebo-controlled trial.
Secondary ID [1] 310243 0
None
Universal Trial Number (UTN)
U1111-1295-9668
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic low back pain 330938 0
Condition category
Condition code
Musculoskeletal 327747 327747 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Electroencephalography based (EEG) infraslow frequency (0.01-0.1 Hz) neurofeedback (NF) will be administered three times a week (30 minutes/session) for a total of 4 weeks (i.e., 12 sessions) by the researcher experienced in delivering neuromodulation techniques, using a 21 channel DC coupled amplifier produced by Brainmaster Inc. During each session, participants will be asked to close their eyes and sit relaxed on a chair with back supported. No form of stimulus will be given. The Comby EEG lead cap with sensors will be placed on the individual’s scalp.

For the active NF treatment group, the Brainmaster Inc. system delivers a sound feedback (reward) each time participant’s effective connectivity between targeted regions in the infraslow band (0.01–0.1 Hz) meets the threshold. The effective connectivity will be trained in the direction of the pregenual anterior cingulate cortex (pgACC) to somatosensory cortex (SSC) in the infraslow frequency (ISF) band.

Adherence to the intervention will be measured using the session attendance checklist.
Intervention code [1] 326637 0
Treatment: Devices
Comparator / control treatment
For placebo-NF treatment group, all conditions will be the same as the active-NF treatment group except that the participants will not receive a sound feedback based on their real-time effective connectivity, but according to someone else’s pre-recorded NF session. The pre-recorded files will be chosen randomly, using an open-access randomization software program, from a database of files of healthy participants who underwent NF training using the concurrent up-train pgACC and down-train dorsal anterior cingulate cortex (dACC) + SSC protocol.
Control group
Placebo

Outcomes
Primary outcome [1] 335548 0
Brief Pain Inventory
Timepoint [1] 335548 0
Baseline, immediately post-completion of NF program, and at follow-up of 10-days and 1 month post-completion of NF program
Primary outcome [2] 335549 0
Low back pain related disability assessed using the Roland–Morris Disability Questionnaire
Timepoint [2] 335549 0
Baseline, immediately post-completion of NF program, and at follow-up of 10-days and 1 month post-completion of NF program
Primary outcome [3] 335550 0
Feasibility measures

• Recruitment rate, i.e., number of participants recruited per month, until the proposed sample size is reached. The recruitment rate will be recorded by PI on a weekly basis, since the release of the advertisements, and the number of advertisements will also be recorded. This will be assessed using recruitment logs.
• Proportion of participants recruited from the total number screened (with reasons for exclusion), expressed as a percentage. This will be assessed using recruitment logs.
• Adherence to intervention measured as number of treatment sessions attended by each participant, and expressed as a percentage of the total number of sessions. Adherence rates will be calculated once the treatment phase is completed. This will be assessed using session attendance checklist.
• Drop-out rates, measured as the number of participants who dropped-out in each group, and expressed as a percentage of the total number of participants enrolled in the study. Drop-outs rates will be calculated once the follow-up phase is completed. This will be assessed using session attendance checklist.
• Participant satisfaction levels regarding treatment and the acceptability of the EEG-NF will also be recorded on an 11-point numeric rating scale (0-Not at all satisfied/acceptable to 10-Very satisfied/acceptable).
Timepoint [3] 335550 0
Recruitment rate, Proportion of participants recruited from the total number screened, Adherence to intervention and Drop-out rates will be assessed upon conclusion of the study. Participant satisfaction levels and acceptability of EEG-NF will be assessed at follow up of 10-days and 1 month post-completion of NF program
Secondary outcome [1] 424917 0
Depression, Anxiety, and Stress Scale: this will be assessed as a composite outcome.
Timepoint [1] 424917 0
Baseline, immediately post-completion of NF program, and at follow-up of 10-days and 1 month post-completion of NF program
Secondary outcome [2] 424918 0
Pain Catastrophizing Scale
Timepoint [2] 424918 0
Baseline, immediately post-completion of NF program, and at follow-up of 10-days and 1 month post-completion of NF program
Secondary outcome [3] 424919 0
Pain Vigilance and Awareness Questionnaire
Timepoint [3] 424919 0
Baseline, immediately post-completion of NF program, and at follow-up of 10-days and 1 month post-completion of NF program
Secondary outcome [4] 424920 0
European Quality of Life–5 Dimensions (EQ-5D) scale
Timepoint [4] 424920 0
Baseline, immediately post-completion of NF program, and at follow-up of 10-days and 1 month post-completion of NF program
Secondary outcome [5] 424921 0
World Health Organisation- Five Well-Being Index (WHO-5)
Timepoint [5] 424921 0
Baseline, immediately post-completion of NF program, and at follow-up of 10-days and 1 month post-completion of NF program
Secondary outcome [6] 424922 0
Medical Outcomes Study-Sleep Scale
Timepoint [6] 424922 0
Baseline, immediately post-completion of NF program, and at follow-up of 10-days and 1 month post-completion of NF program
Secondary outcome [7] 424923 0
Mechanical temporal summation (MTS): MTS will be assessed using a nylon monofilament (Semmes monofilament 6.65, 300 g). Brief ten repetitive contacts will be delivered at a rate of 1 Hz, externally cued by auditory stimuli. The participants will be asked to rate the level of pain experienced on the 11 point numeric pain rating scale (NPRS, 0=No pain to 100=Extreme pain) immediately after the first contact, and also to rate their greatest pain intensity after the 10th contact. Three trials will be conducted at the symptomatic low back region.
Timepoint [7] 424923 0
Baseline, immediately post-completion of NF program, and at follow-up of 10-days and 1 month post-completion of NF program
Secondary outcome [8] 424924 0
Pressure pain threshold (PPT): A computerised, handheld digital algometer (AlgoMed; Medoc, Ramat Yishai, Israel) will be used to measure three trials of PPT over the the symptomatic low back region. The 1-cm2 algometer probe will be pressed over the marked test site perpendicularly to the skin at a rate of 30 kPa/s. The participants will be instructed to press the algometer trigger button in the patient control unit when the pressure sensation changes to first pain. Once the patient-controlled unit is activated, the trial is automatically terminated, and the amount of pressure (kPa) will be recorded.
Timepoint [8] 424924 0
Baseline, immediately post-completion of NF program, and at follow-up of 10-days and 1 month post-completion of NF program
Secondary outcome [9] 424925 0
Electroencephalography: will be used to determine the effective connectivity changes between the pgACC and SSC
Timepoint [9] 424925 0
Baseline, immediately post-completion of NF program, and at follow-up of 10-days and 1 month post-completion of NF program
Secondary outcome [10] 425450 0
Safety measures: (This is an additional primary outcome)

Any adverse effects (e.g., headache, pain flare-ups) that likely have a causal relationship with the intervention will be recorded by the treating researcher.
Timepoint [10] 425450 0
Throughout the intervention period and at follow up of 10-days and 1 month post-completion of NF program

Eligibility
Key inclusion criteria
Participants with a diagnosis of chronic low back pain (CLBP) will be eligible to participate.

Participants will need to:
a) have pain in the lumbar back area that occurs every day for greater than or equal to 3 months,
b) have a score of greater than and equal to 4 on the 11-point numeric pain rating scale (NPRS, 0=No pain to 10=Worst pain) in the past 7 days, and
c) have a disability score of greater than and equal to 5 on Roland–Morris Disability Questionnaire
d) be capable of understanding and signing an informed consent form
e) aged between 18 to 70 years on the day of the consent
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants who meet any of the following conditions will be excluded:
• Inflammatory arthritis
• Underwent back surgery in the past 6 months
• Radicular pain and radiculopathy
• Neurological conditions
• Cognitive and psychiatric disorders
• Epilepsy
• Seizures
• Substance abuse
• Pregnant or six-months post-partum

Participants will be permitted to continue their medications for the duration of the trial, with the type and dosage of medication being recorded throughout the duration of the trial. However, participants with the intention of taking new medications in the next three months, will be excluded.

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)
Sealed opaque envelopes: A research administrator, not involved in treatment or assessment procedures, will randomise eligible volunteers using an open-access computerised randomization software program, to one of the two intervention arms (Active treatment or Placebo). The randomisation schedule will be concealed in a number sealed and opaque envelopes and provided to the participants at their baseline measurements.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving 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
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
4/09/2023
Actual
Date of last participant enrolment
Anticipated
29/02/2024
Actual
Date of last data collection
Anticipated
7/05/2024
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment outside Australia
Country [1] 25681 0
New Zealand
State/province [1] 25681 0
Otago

Funding & Sponsors
Funding source category [1] 314451 0
University
Name [1] 314451 0
University of Otago
Country [1] 314451 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
University of Otago,
PO Box 54.
Dunedin 9054.
Country
New Zealand
Secondary sponsor category [1] 316397 0
None
Name [1] 316397 0
Address [1] 316397 0
Country [1] 316397 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313502 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 313502 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 313502 0
New Zealand
Date submitted for ethics approval [1] 313502 0
Approval date [1] 313502 0
27/07/2023
Ethics approval number [1] 313502 0
2023 EXP 17953

Summary
Brief summary
Chronic low back pain (CLBP) is a disabling condition worldwide, associated with huge economic costs. Currently available treatments have a small effect, warranting new targeted treatment approaches. Several studies have demonstrated altered functional connectivity between pain processing brain regions in individuals with CLBP. Neurofeedback is a novel technique that can enable an individual to normalize the brain's electrical activity and functional connectivity through learning, thereby improve pain, function, and associated disability. The proposed double-blinded randomised placebo-controlled pilot study will explore the effect of a novel neurofeedback technique to improve the directional functional connectivity (i.e., effective connectivity) between pain processing brain regions in a specific frequency band in people with CLBP. This pilot study will provide benchmark data and assist in development of a larger trial investigating long-term impact (trajectory profiles) of the proposed intervention on pain and associated disability.

The objectives of the proposed pilot study are:
• To evaluate the feasibility and safety of the targeted EEG-NF technique training effective connectivity from pgACC to SSC region in individuals with CLBP.
• To determine the estimates [central tendency, variability, and confidence intervals] of change in the pain, function, and psychological outcomes following targeted NF training in people with CLBP.
• To explore the effect of NF on the effective connectivity from pgACC to SSC region, and
• To explore the association between changes in effective connectivity to changes in clinical outcomes (pain, function, and psychological measures).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128354 0
Dr Divya Adhia
Address 128354 0
Department of Surgical Sciences,
Dunedin School of Medicine,
University of Otago,
PO Box 54.
Dunedin 9054.
Country 128354 0
New Zealand
Phone 128354 0
+64 34709337
Fax 128354 0
Email 128354 0
divya.adhia@otago.ac.nz
Contact person for public queries
Name 128355 0
Dr Divya Adhia
Address 128355 0
Department of Surgical Sciences,
Dunedin School of Medicine,
University of Otago,
PO Box 54.
Dunedin 9054.
Country 128355 0
New Zealand
Phone 128355 0
+64 34709337
Fax 128355 0
Email 128355 0
divya.adhia@otago.ac.nz
Contact person for scientific queries
Name 128356 0
Dr Divya Adhia
Address 128356 0
Department of Surgical Sciences,
Dunedin School of Medicine,
University of Otago,
PO Box 54.
Dunedin 9054.
Country 128356 0
New Zealand
Phone 128356 0
+64 34709337
Fax 128356 0
Email 128356 0
divya.adhia@otago.ac.nz

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.