Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001143516
Ethics application status
Approved
Date submitted
4/09/2024
Date registered
20/09/2024
Date last updated
22/07/2025
Date data sharing statement initially provided
20/09/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Exploring whether home-based neuromodulation can prevent the transition from acute to chronic low back pain
Scientific title
Exploring whether home-based neuromodulation can prevent the transition from acute to chronic low back pain in adults
Secondary ID [1] 312766 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Low back pain 334806 0
Condition category
Condition code
Musculoskeletal 331365 331365 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention group: active transcranial direct current stimulation (tDCS)

A trained investigator will fit the tDCS headpiece and give a detailed demonstration of how to operate the device. A checklist for set-up and operation of the device and an instructional video regarding correct headpiece positioning will be provided for use at home. Participants will then be assessed on their ability to administer and operate the device safely against checklist procedures, and if able to complete all procedures they will be permitted to continue in the trial.

Participants in the intervention group will receive 20 minutes of active tDCS on ten consecutive days. This period of tDCS is consistent with the available literature in chronic pain conditions and laboratory-based studies.

During active tDCS, stimulation with a constant current intensity of 2 mA will be applied over the motor cortex using a Soterix mini-CT Stimulator (Soterix Medical Inc.) with a coded study mode to facilitate randomisation and blinding. The current is delivered via two 5x7cm saline-soaked sponge electrodes, fitted into a custom headpiece, with the anode electrode placed over M1 contralateral to the side of worst LBP using the International 10-20 system at position C3 or C4 (according to side of pain). The reference electrode (cathode) will be placed on the side ipsilateral to pain and positioned over the supraorbital region. These positions will be set up at the initial baseline assessment, and participants will not be required to adjust them. Each day, participants will receive a single-use treatment code, which they input into the device to commence the stimulation. They will not be able to modify the settings. Participants will be instructed to sit comfortably and minimise movement throughout the session, but will be permitted to engage in activities such as reading or watching TV. Participants will keep the headpiece in position for a duration of 20 minutes until the tDCS unit turns off automatically and generates a completion code.

Adherence to the use of home based tDCS will be assessed using a digital platform (ElectraRx, Soterix Medical Inc., 2024, Woodbridge, USA) which is programmed with the treatment schedule for each participant. If a participant does not send their completion code to be entered into ElectraRx by a researcher, the platform will record the session as missed. The tDCS device usage will also be checked by accessing the “Stimulation History” on each tDCS device, which is located within the passcode-protected “Administration” menu, and recording the number of completed sessions for each participant.

The first tDCS session will be administered in the laboratory under supervision of the research team, following the baseline testing and tDCS set up described above. For the first home-based session, participants will be supervised by researchers via secure videoconferencing software (Zoom Video Communications, Inc., CA) to provide support and monitor for adverse events. All subsequent sessions will be self-administered without the research team present, and participants will be monitored throughout the two-week period via daily text messages and online questionnaires, and weekly phone calls. If a participant fails to respond for two days, they will be contacted via email or phone. Previous studies in neuropsychiatric populations have demonstrated that self-administered, home-based tDCS without supervision is well-tolerated and safe.
Intervention code [1] 329296 0
Treatment: Devices
Intervention code [2] 329297 0
Prevention
Comparator / control treatment
Control: sham tDCS

A trained investigator will fit the tDCS headpiece and give a detailed demonstration of how to operate the device. An instructional video regarding correct headpiece positioning for use at home will be provided. Participants will then be assessed on their ability to administer and operate the device safely against checklist procedures, and if able to complete all procedures they will be permitted to continue in the trial.

Participants in the control group will receive 20 minutes of sham tDCS on ten consecutive days. During sham tDCS, stimulation will be applied over the motor cortex using a Soterix mini-CT Stimulator (Soterix Medical Inc.) with a coded study mode to facilitate randomisation and blinding. The current is delivered via two 5x7cm saline-soaked sponge electrodes. The sham condition will involve identical procedures to the active tDCS, but will only deliver a 30s “ramp up” and “ramp down” stimulation that will range between 0 and 2mA. This replicates the initial tingling sensation of active tDCS, improving the likelihood of blinding success, but is unlikely a sufficient duration to induce any appreciable modulatory effects on the brain. The remainder of the 20-minute intervention period will involve delivery of stimulation averaging no more than 0.002mA (leakage current from the stimulator).

The first tDCS session will be administered in the laboratory under supervision of the research team, following the baseline testing and tDCS set up described above. For the first home-based session, participants will be supervised by researchers via secure videoconferencing software (Zoom Video Communications, Inc., CA) to provide support and monitor for adverse events. All subsequent sessions will be self-administered without the research team present, and participants will be monitored throughout the two-week period via daily text messages and online questionnaires, and weekly phone calls. If a participant fails to respond for two days, they will be contacted via email or phone. Previous studies in neuropsychiatric populations have demonstrated that self-administered, home-based tDCS without supervision is well-tolerated and safe.
Control group
Placebo

Outcomes
Primary outcome [1] 339127 0
Pain intensity
Timepoint [1] 339127 0
Baseline, daily for ten days during intervention, immediately post-completion of intervention, weekly for weeks 1-12 post-completion of intervention (12 weeks/3 months is the primary timepoint)
Primary outcome [2] 339128 0
Mechanical sensitivity measured via pressure pain threshold (PPT)
Timepoint [2] 339128 0
Pre-intervention baseline, at intervention completion, 4-, 8-, and 12-weeks (primary timepoint) post-completion of intervention
Primary outcome [3] 342261 0
Disability
Timepoint [3] 342261 0
Pre-intervention baseline, at intervention completion, 4-, 8-, and 12-weeks (primary timepoint) post-completion of intervention
Secondary outcome [1] 438650 0
Corticomotor organisation
Timepoint [1] 438650 0
Pre-intervention baseline, at intervention completion, 4-, 8-, and 12-weeks post-completion of intervention
Secondary outcome [2] 438651 0
Left/right judgement
Timepoint [2] 438651 0
Pre-intervention baseline, at intervention completion, 4-, 8-, and 12-weeks post-completion of intervention
Secondary outcome [3] 438652 0
Two point discrimination (TPD)
Timepoint [3] 438652 0
Pre-intervention baseline, at intervention completion, 4-, 8-, and 12-weeks post-completion of intervention
Secondary outcome [4] 438653 0
Tactile localisation
Timepoint [4] 438653 0
Pre-intervention baseline, at intervention completion, 4-, 8-, and 12-weeks post-completion of intervention
Secondary outcome [5] 438654 0
Auditory localisation
Timepoint [5] 438654 0
Pre-intervention baseline, at intervention completion, 4-, 8-, and 12-weeks post-completion of intervention
Secondary outcome [6] 438655 0
Peak alpha frequency (PAF)
Timepoint [6] 438655 0
Pre-intervention baseline, at intervention completion, 4-, 8-, and 12-weeks post-completion of intervention
Secondary outcome [7] 438656 0
Adherence
Timepoint [7] 438656 0
Each day that tDCS is applied (baseline, day 1-10 following treatment commencement)
Secondary outcome [8] 438657 0
Tolerability
Timepoint [8] 438657 0
Each day that tDCS is applied (baseline, day 1-10 following treatment commencement)
Secondary outcome [9] 438658 0
Safety
Timepoint [9] 438658 0
Each day that tDCS is applied (baseline, day 1-10 following treatment commencement)
Secondary outcome [10] 438659 0
Spatial summation
Timepoint [10] 438659 0
Pre-intervention baseline, at intervention completion, 4-, 8-, and 12-weeks post-completion of intervention
Secondary outcome [11] 450184 0
Psychological distress
Timepoint [11] 450184 0
Pre-intervention baseline, at intervention completion, 4-, 8-, and 12-weeks post-completion of intervention
Secondary outcome [12] 450185 0
Temporal summation
Timepoint [12] 450185 0
Pre-intervention baseline, upon intervention completion, 4-, 8-, and 12 weeks post-intervention completion
Secondary outcome [13] 450186 0
Conditioned pain modulation
Timepoint [13] 450186 0
Pre-intervention baseline, upon intervention completion, 4-, 8-, and 12-weeks post-completion of intervention
Secondary outcome [14] 450187 0
Frontal alpha asymmetry [FAA]
Timepoint [14] 450187 0
Pre-intervention baseline, upon intervention completion, 4-, 8-, and 12-weeks post-completion of intervention
Secondary outcome [15] 450188 0
Power spectral density (PSD)
Timepoint [15] 450188 0
Pre-intervention baseline, upon intervention completion, 4-, 8-, and 12-weeks post-completion of intervention

Eligibility
Key inclusion criteria
Eligible participants must be 18 years of age or older and experiencing acute or subacute LBP – defined as pain in the region between the 12th thoracic vertebra and the gluteal fold, present for at least 7 days and no more than 8 weeks at the time of enrolment. Participants with referred pain beyond this region may be included provided there are no clinical signs of radicular pain from neural tissue involvement, as assessed by an experienced physiotherapist. For participants with a previous history of LBP to be eligible, they must have experienced a period of at least one month pain-free prior to the current episode. As part of the screening process, pain intensity will be recorded for all prospective participants using a 10cm visual analogue scale (VAS) and only those reporting a minimum average weekly pain intensity of 4/10 during screening will be included. Participants must provide written informed consent to participate, be able to speak, read and understand instructions in English, and be able to attend laboratory appointments at Western Sydney University in Campbelltown, Australia.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded if they are suspected to have radiculopathy or lumbosacral radicular pain, as determined by an experienced physiotherapist using previously employed diagnostic criteria. All potential participants will be screened for red flags in accordance with the NSW Agency for Clinical Innovation guidelines. Those identified with red flags will be advised to attend the nearest Emergency Department and will be excluded from the study unless subsequently medically cleared of serious spinal pathology (e.g. fracture, tumour, cauda equina syndrome). Participants with a history of lumbar spinal surgery, comorbid acute or chronic pain conditions, a history of a chronic pain condition in the past 12 months, current or past history of a significant neurological disorder, or other comorbidities affecting sensorimotor processes will also be excluded. All potential participants will be screened for contraindications to TMS and home-based tDCS (e.g. epilepsy, electronic or metal implants in the head, cognitive impairment) using the TMS/tDCS Adult Safety Screen questionnaire and excluded if any are present. Participants will also be asked to provide a log of any medications they take currently and within the month preceding the trial, including medication type, frequency and dosage. Participants will be excluded if they take any medications thought to interfere with tDCS (e.g. benzodiazepines) or with cognitive or sensory function (e.g. opioid intake greater than daily morphine equivalent 40mg). Participants will be excluded if they are unable to understand instructions and complete questionnaires provided 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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An investigator with no involvement in assessment or intervention delivery will create a randomisation schedule using a random number generator.
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
Information collected will be used for analysis purposes only, and will be reported as group data. No individual participant will be identified.

The effect of home-based tDCS on pain intensity, disability (ODI), mechanical sensitivity (PPTs), temporal summation, and CPM will be analysed using mixed-model analyses of variance (ANOVAs) with factors “Group” (active versus sham) and “Time” (pre-intervention baseline, at intervention completion, 4-, 8-, and 12-weeks post-completion of intervention). The effect of the intervention on spatial summation will be analysed using mixed-model ANOVAs with “Group” (active versus sham) as a between-subject factor, and both “Time” (pre-intervention baseline, at intervention completion, 4-, 8-, and 12-weeks post-completion of intervention) and “Probe Size” (0.5, 1 and 2cm2) as within-subject factors. Where appropriate, post-hoc analyses will be performed using Sidak-adjusted multiple comparison tests.
Pain persistence will be evaluated using a chi-square test to compare between groups the number of participants who present with persistent pain (average weekly VAS score >0) at 6 weeks and 12 weeks post-completion of the intervention, reported descriptively. Adverse effects and adherence (completed sessions) will also be compared descriptively. The proportion of people who were successfully blinded (incorrect guess or unsure) will be calculated for each group and compared using Fisher’s exact tests. The Bang Blinding Index (percentage of blinding beyond chance) will also be calculated for each group, whereby a 95% confidence interval that covers 0 will indicate unblinding, and a Blinding Index >0.20 will indicate unblinding beyond chance.
For the intervention group only, the difference between the individualised MCID reported by each participant prior to their first tDCS session, and the actual change in pain intensity they report at each subsequent assessment session (completion of intervention, 4-, 8-, and 12-weeks post-completion of intervention) will be calculated. The number of participants who do or do not meet their individualised MCID following the intervention will then be compared and reported descriptively.
All analyses will be conducted in consultation with an experienced biostatistician. All ANOVAs will be performed using the Statistical Package for the Social Sciences software (version 23; IBM Corp, Armonk, NY, USA). Statistical significance will be set at p < 0.05.
We intend to also investigate the mechanisms underlying any observed effects of tDCS compared to sham on pain intensity, mechanical sensitivity and disability using causal mediation analysis. The hypothesised potential mediators are described in the previous section under the heading Mechanistic factors (potential mediators) based on theory and experimental evidence of tDCS targets. The statistical analysis plan will be prospectively registered and follow the counterfactual-based framework using a regression-based approach. Results will be reported as indirect and direct effect estimates with corresponding 95% confidence intervals and follow the AGReMA (A Guideline for Reporting Mediation Analyses) statement.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
4/12/2024
Actual
5/06/2025
Date of last participant enrolment
Anticipated
19/03/2027
Actual
Date of last data collection
Anticipated
18/06/2027
Actual
Sample size
Target
40
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 317198 0
Commercial sector/Industry
Name [1] 317198 0
HCF Research Foundation
Country [1] 317198 0
Australia
Primary sponsor type
Individual
Name
Dr Rocco Cavaleri - Western Sydney University
Address
Country
Australia
Secondary sponsor category [1] 319465 0
University
Name [1] 319465 0
Western Sydney University
Address [1] 319465 0
Country [1] 319465 0
Australia
Other collaborator category [1] 283141 0
Individual
Name [1] 283141 0
Dr Simon Summers
Address [1] 283141 0
Country [1] 283141 0
Australia
Other collaborator category [2] 283142 0
Individual
Name [2] 283142 0
Associate Professor Tasha Stanton
Address [2] 283142 0
Country [2] 283142 0
Australia
Other collaborator category [3] 283143 0
Individual
Name [3] 283143 0
Dr Daniel Thomson
Address [3] 283143 0
Country [3] 283143 0
Australia
Other collaborator category [4] 283144 0
Individual
Name [4] 283144 0
Ariane Suhood
Address [4] 283144 0
Country [4] 283144 0
Australia
Other collaborator category [5] 283175 0
Individual
Name [5] 283175 0
Dr Luke Jenkins
Address [5] 283175 0
Country [5] 283175 0
Australia
Other collaborator category [6] 283176 0
Individual
Name [6] 283176 0
Dr Amitabh Gupta
Address [6] 283176 0
Country [6] 283176 0
Australia
Other collaborator category [7] 283177 0
Individual
Name [7] 283177 0
Dr Ghufran Alhassani
Address [7] 283177 0
Country [7] 283177 0
Australia
Other collaborator category [8] 283180 0
Individual
Name [8] 283180 0
Prof James McAuley
Address [8] 283180 0
Country [8] 283180 0
Australia
Other collaborator category [9] 283596 0
Individual
Name [9] 283596 0
Dr Aidan Cashin
Address [9] 283596 0
Country [9] 283596 0
Australia
Other collaborator category [10] 283597 0
Individual
Name [10] 283597 0
Keeley McNally
Address [10] 283597 0
Country [10] 283597 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315937 0
University of Western Sydney Human Research Ethics Committee
Ethics committee address [1] 315937 0
Ethics committee country [1] 315937 0
Australia
Date submitted for ethics approval [1] 315937 0
14/10/2024
Approval date [1] 315937 0
19/02/2025
Ethics approval number [1] 315937 0
H16334

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

Contacts
Principal investigator
Name 136274 0
Dr Rocco Cavaleri
Address 136274 0
Western Sydney University, School of Health Sciences, Locked Bag 1797, Penrith, NSW 2751
Country 136274 0
Australia
Phone 136274 0
+61 2 4620 3994
Fax 136274 0
Email 136274 0
[email protected]
Contact person for public queries
Name 136275 0
Rocco Cavaleri
Address 136275 0
Western Sydney University, School of Health Sciences, Locked Bag 1797, Penrith, NSW 2751
Country 136275 0
Australia
Phone 136275 0
+61 2 4620 3994
Fax 136275 0
Email 136275 0
[email protected]
Contact person for scientific queries
Name 136276 0
Rocco Cavaleri
Address 136276 0
Western Sydney University, School of Health Sciences, Locked Bag 1797, Penrith, NSW 2751
Country 136276 0
Australia
Phone 136276 0
+61 2 4620 3994
Fax 136276 0
Email 136276 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Available on a case-by-case basis at the discretion of the lead investigator

Conditions for requesting access:
• -

What individual participant data might be shared?
• All individual participant data collected throughout the trial, after de-identification. This includes baseline participant characteristics and data relating to all outcome measures listed in Step 4: Outcomes.

What types of analyses could be done with individual participant data?
• Grant applications and any future studies including systematic reviews

When can requests for individual participant data be made (start and end dates)?
From:
Immediately following publication, up until 5 years following main results publication

To:
-

Where can requests to access individual participant data be made, or data be obtained directly?
• Access subject to approvals by Principal Investigator ([email protected])

Are there extra considerations when requesting access to individual participant data?
No


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.