Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000505909
Ethics application status
Approved
Date submitted
28/03/2020
Date registered
23/04/2020
Date last updated
4/03/2022
Date data sharing statement initially provided
23/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Non-invasive brain stimulation for chronic low back pain.
Scientific title
Safety and feasibility of transcranial electrical stimulation for chronic low back pain.
Secondary ID [1] 300878 0
None
Universal Trial Number (UTN)
U1111-1250-1177
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic low back pain 316809 0
Condition category
Condition code
Musculoskeletal 315019 315019 0 0
Other muscular and skeletal disorders
Neurological 315141 315141 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Transcranial electrical stimulation will be administered five times a week (30 minutes/session, once daily on weekdays) for a total of 4 weeks (i.e. 20 sessions in total) using a 32 channel transcranial current stimulator (Starstim-Home TES®, Neuroelectrics, Spain), by a researcher with health professional background and considerable experience in administering non-invasive neuromodulation techniques. The participants will be positioned comfortably and quietly in a seated/half lying position on a bed, and will wear a neoprene head cap with circular stimulation electrodes placed on it. For the active treatment group, the high definition transcranial infraslow pink noise stimulation will be delivered at a current strength of maximum of 2mA for 30min, with 60s ramp up and ramp down at the beginning and end of each stimulation session, with continuous stimulation in between. For sham stimulation, to create an identical skin sensation to the active stimulation, the actisham protocol created by neuroelectrics will be used. The current will be applied for a 60s ramp up (0-2mA) and 60s ramp down (2-0mA) at the beginning and the end of each stimulation session, without any current for the remainder of the stimulation period.

Adherence to intervention will be measured by the principal investigator as the 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. Treatment fidelity will be assessed by the principal investigator at each session, who will supervise that the treatment is delivered in a standardized manner as planned. The treatment delivered for each participant for each session will be saved on the NIC2 computer software.

Intervention code [1] 317205 0
Treatment: Devices
Comparator / control treatment
Sham stimulation: To create an identical skin sensation to the active stimulation, the current will be applied for a 60s ramp up (0-2mA) and 60s ramp down (2-0mA) at the beginning and the end of each stimulation session, without any current for the remainder of the stimulation period.
Control group
Placebo

Outcomes
Primary outcome [1] 323319 0
Brief Pain Inventory
Timepoint [1] 323319 0
Baseline, immediately post-intervention, and at follow-up of 1 week, 1 month and 3 months post-intervention
Primary outcome [2] 323320 0
Roland–Morris Disability Questionnaire
Timepoint [2] 323320 0
Baseline, immediately post-intervention, and at follow-up of 1 week, 1 month and 3 months post-intervention
Primary outcome [3] 323410 0
The following variables will be recorded:
• Qualitative description and intensity of each symptom on a Likert scale (0=none to 10=extreme)
• Relation of symptom to treatment, measured on a scale ranging from 1=unrelated to 5=strongly related.
• Duration and time taken for resolution of each symptom expressed in minutes.
• Worsening or improvement of symptoms: The Discontinuation-Emergent Sign and Symptom (DESS), will be used to record worsening or improving side effects compared to status prior to previous session.
• Any drop-outs due to adverse effects and how the adverse effects were managed.

These will be described qualitatively as a composite measure for safety of HD-tIPNS technique.
Timepoint [3] 323410 0
Throughout the study period and at follow up of 1 week, 1 month and 3 months post-intervention.
Secondary outcome [1] 381547 0
Experimental pain measures: 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 for each of the two regions (i.e., symptomatic low back region, and the distant non-dominant wrist)
Timepoint [1] 381547 0
Baseline, immediately post-intervention, and at follow-up of 1 week, 1 month and 3 months post-intervention
Secondary outcome [2] 381548 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 two regions (i.e., symptomatic low back region and the distant non-dominant wrist). 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 [2] 381548 0
Baseline, immediately post-intervention, and at follow-up of 1 week, 1 month and 3 months post-intervention
Secondary outcome [3] 381549 0
Condition pain modulation (CPM): Conditioning stimulus will consist of a cold pressor task, where the participants will be asked to immerse their hand (until mid-forearm), in a thermos containing circulating cold water (~5 degree C) for a maximum period of 2 minutes. Test stimulus: A computerised, handheld digital algometer (AlgoMed; Medoc, Ramat Yishai, Israel) will be used to measure suprathreshold pressure pain threshold (pain40) at the non-dominant leg region (tibialis anterior). Two PPT (pain40) trials will be recorded before the conditioning stimulus and will be averaged (pre average score) to obtain a baseline score for each participant. Three PPT (pain40) trials will be recorded in the same region at 30, 60, and 90 seconds immediately after the conditioning stimulus. A percent change score will be calculated for each time point.
Timepoint [3] 381549 0
Baseline, immediately post-intervention, and at follow-up of 1 week, 1 month and 3 months post-intervention
Secondary outcome [4] 381550 0
Depression, Anxiety and Stress Scale (DASS-21)
Timepoint [4] 381550 0
Baseline, immediately post-intervention, and at follow-up of 1 week, 1 month and 3 months post-intervention
Secondary outcome [5] 381854 0
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. (Primary outcome measures)
Timepoint [5] 381854 0
Throughout the study period and at follow up of 1 week, 1 month and 3 months post-intervention.
Secondary outcome [6] 381855 0
Participant satisfaction levels regarding treatment and the acceptability of the transcranial stimulation treatment will also be recorded on an 11-point numeric rating scale (0-Not at all satisfied/acceptable to 10-Very satisfied/acceptable) and through qualitative semi-structured interview. (Primary outcome measures)
Timepoint [6] 381855 0
Immediately post-intervention,
Secondary outcome [7] 381856 0
Recruitment rate, i.e., number of participants recruited per month, until the proposed sample size is reached. The recruitment rate will be recorded every week, since the release of the advertisements, and the number of advertisements will also be recorded. Proportion of participants recruited from the total number screened (with reasons for exclusion), expressed as a percentage. (Primary outcome measure)
Timepoint [7] 381856 0
Throughout the study period and at follow up of 1 week, 1 month and 3 months post-intervention.
Secondary outcome [8] 382243 0
Pain Catastrophising Scale
Timepoint [8] 382243 0
Baseline, immediately post-intervention, and at follow-up of 1 week, 1 month and 3 months post-intervention
Secondary outcome [9] 382244 0
Pain Vigilance and Awareness Questionnaire
Timepoint [9] 382244 0
Baseline, immediately post-intervention, and at follow-up of 1 week, 1 month and 3 months post-intervention
Secondary outcome [10] 407114 0
Pain unpleasantness (affective component) measured using an 11-point unpleasantness NRS (0=not at all unpleasant to 10=most unpleasant imaginable).
Timepoint [10] 407114 0
Baseline, immediately post-intervention, and at 1-week, 1 month and 3 months follow up.
Secondary outcome [11] 407115 0
Pain bothersomeness: measured using an 11-point bothersomeness NRS (0=not at all bothering to 10=most bothering). A categorical question will also be used “In the last one week, how bothersome has your low back pain been?’’ with five choices: “not at all”, “slightly”, “moderately”, “very much”, and “extremely”.
Timepoint [11] 407115 0
Baseline, immediately post-intervention, and at 1-week, 1 month and 3 months follow up.
Secondary outcome [12] 407116 0
The global rate of change: assessed using the question “Compared to the beginning of treatment, how would you describe your back at this moment?” Participants will rate their perceived change on an 11-point scale (-5=much worse, through 0=unchanged, to +5=completely, recovered).
Timepoint [12] 407116 0
Immediately post-intervention, and at 1-week, 1 month and 3 months follow up.
Secondary outcome [13] 407117 0
Quality of life: will be assessed using European Quality of Life–5 Dimensions scale.
Timepoint [13] 407117 0
Baseline, Immediately post-intervention, and at 1-week, 1 month and 3 months follow up.
Secondary outcome [14] 407118 0
Resting-state electroencephalogram (EEG): Whole brain analysis, Current density at targeted region of interest (pgACC, dACC, and SSC), and functional connectivity between the targeted region of interest.
Timepoint [14] 407118 0
Baseline, Immediately post-intervention, and at 1-week, 1 month and 3 months follow up.
Secondary outcome [15] 407119 0
World Health Organisation- Five Well-Being Index
Timepoint [15] 407119 0
Baseline, Immediately post-intervention, and at 1-week, 1 month and 3 months follow up.

Eligibility
Key inclusion criteria
Participants with a diagnosis of chronic low back pain (CLBP) will be eligible to participate. To be included in the study, participants must meet all of the following inclusion criteria:
• Capable of understanding and signing an informed consent form
• Age between 18 to 75 years on the day of the consent
• Pain in the lower back area (region between the 12th rib and the gluteal fold) that occurs every day for more than or equal to 3 months
• A score of more than or equal to 4 on the 11-point numeric pain rating scale (NPRS, 0 is No pain to 10 is Worst pain) in the past 4 weeks
• A disability score of more than or equal to 5 on Roland–Morris Disability Questionnaire
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
•Inflammatory arthritis
•Undergoing any therapy from a health professional (e.g. physiotherapists or chiropractor)
•Recent soft tissue injuries of the back in the last 3 months
•History of surgery to the back region or waiting/scheduled for any procedures within the next six months
•Current intake of any centrally-acting medications or intention of taking new medications in the next 3 months.
•Recent steroid injections to the back (in the past 6 months)
•Radicular pain and radiculopathy
•History of neurological diseases
•Unstable medical or psychiatric conditions
•History of epilepsy or seizures
•Presence of any peripheral neuropathy or vascular pathology
•Alcohol or substance abuse
•Dyslipidaemia
•Cognitive impairments (dementia, post-traumatic stress disorders, Alzheimer’s disease)
•History of uncontrolled/untreated hypertension
•Presence of any pacemaker or defibrillator
•Presence of any electronic implants or metal implant in the body (particularly head and neck)
•Recent or current pregnancy

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)
A research administrator, not involved in treatment or assessment procedures, will randomise eligible volunteers using an open-access randomization software program, to one of the two intervention arms:
• Group 1: Transcranial electrical stimulation
• Group 2: Sham stimulation
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)
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
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/07/2020
Actual
1/06/2021
Date of last participant enrolment
Anticipated
31/05/2022
Actual
Date of last data collection
Anticipated
30/09/2022
Actual
Sample size
Target
40
Accrual to date
14
Final
Recruitment outside Australia
Country [1] 22456 0
New Zealand
State/province [1] 22456 0
Otago

Funding & Sponsors
Funding source category [1] 305327 0
Charities/Societies/Foundations
Name [1] 305327 0
Healthcare Otago Charitable trust (part funding)
Country [1] 305327 0
New Zealand
Funding source category [2] 310454 0
Government body
Name [2] 310454 0
Health Research Council New Zealand
Country [2] 310454 0
New Zealand
Funding source category [3] 310455 0
Government body
Name [3] 310455 0
Lottery Health Research
Country [3] 310455 0
New Zealand
Primary sponsor type
Individual
Name
Dr Divya Adhia
Address
University of Otago,
PO Box 54.
Dunedin 9054.
Country
New Zealand
Secondary sponsor category [1] 305696 0
None
Name [1] 305696 0
Address [1] 305696 0
Country [1] 305696 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305665 0
Health and Disability Ethics Committee
Ethics committee address [1] 305665 0
Ethics committee country [1] 305665 0
New Zealand
Date submitted for ethics approval [1] 305665 0
26/03/2020
Approval date [1] 305665 0
28/07/2020
Ethics approval number [1] 305665 0

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

Contacts
Principal investigator
Name 101146 0
Dr Divya Adhia
Address 101146 0
Department of Surgical Sciences,
Dunedin School of Medicine,
University of Otago.
PO Box 56.
Dunedin 9054, New Zealand
Country 101146 0
New Zealand
Phone 101146 0
+64 211167594
Fax 101146 0
Email 101146 0
[email protected]
Contact person for public queries
Name 101147 0
Divya Adhia
Address 101147 0
Department of Surgical Sciences,
Dunedin School of Medicine,
University of Otago.
PO Box 56.
Dunedin 9054, New Zealand
Country 101147 0
New Zealand
Phone 101147 0
+64 211167594
Fax 101147 0
Email 101147 0
[email protected]
Contact person for scientific queries
Name 101148 0
Divya Adhia
Address 101148 0
Department of Surgical Sciences,
Dunedin School of Medicine,
University of Otago.
PO Box 56.
Dunedin 9054, New Zealand
Country 101148 0
New Zealand
Phone 101148 0
+64 211167594
Fax 101148 0
Email 101148 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
SourceTitleYear of PublicationDOI
EmbaseHigh-definition transcranial infraslow pink noise stimulation for chronic low back pain: Protocol for a pilot, safety and feasibility randomised placebo-controlled trial.2022https://dx.doi.org/10.1136/bmjopen-2021-056842
N.B. These documents automatically identified may not have been verified by the study sponsor.