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Trial registered on ANZCTR


Registration number
ACTRN12620000414910p
Ethics application status
Submitted, not yet approved
Date submitted
16/03/2020
Date registered
27/03/2020
Date last updated
27/03/2020
Date data sharing statement initially provided
27/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Neurofeedback for chronic low back pain.
Scientific title
Effect of electroencephalography based infraslow neurofeedback on pain and function in individuals with chronic low back pain: A pilot double-blind randomised controlled study.
Secondary ID [1] 300807 0
None
Universal Trial Number (UTN)
U1111-1249-5597
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic low back pain 316680 0
Condition category
Condition code
Musculoskeletal 314924 314924 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Electroencephalography based infraslow frequency (o.o1-0.1 Hz) neurofeedback (ISF-NF) will be administered three times a week (30 minutes/ session) for a total of 4 weeks, by an experienced researcher. 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. The targeted brain regions will include the pregenual anterior cingulate cortex (pgACC), dorsal anterior cingulate cortex (dACC), and primary somatosensory cortex (SSC). For the active ISF-NF treatment groups, the Brainmaster Inc. system delivers a sound feedback (reward) each time the participant’s real-time brain activity at the targeted regions meets the desired infraslow threshold (0.0–0.1 Hz). The infraslow activity will be down-trained at the pgACC (Group 1), up-trained at the dACC+SSC (Group 2), and simultaneously up-trained at pgACC and down-trained at dACC+SSC (Group 3). For all the active ISF-NF treatment groups, the reward threshold will be adjusted in real-time between 60-80%, i.e., for 60-80% of the time, a sound feedback (reward) will be delivered by the system when the participant's real-time brain activity at the targeted regions meets the desired infraslow magnitude (threshold). For placebo ISF-NF treatment group, a pre-recorded sound feedback will be played to create an identical auditory feedback to the active treatment groups.
Intervention code [1] 317127 0
Treatment: Devices
Comparator / control treatment
A placebo ISF-NF treatment group: A pre-recorded sound feedback will be played to create an identical auditory feedback to the active treatment groups.
Control group
Placebo

Outcomes
Primary outcome [1] 323236 0
Brief Pain Inventory
Timepoint [1] 323236 0
Baseline, immediately post-intervention, and at follow-up of 1 week and 1 month post-intervention
Primary outcome [2] 323237 0
Roland–Morris Disability Questionnaire
Timepoint [2] 323237 0
Baseline, immediately post-intervention, and at follow-up of 1 week and 1 month post-intervention
Primary outcome [3] 323276 0
Feasibility and safety 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.
• Proportion of participants recruited from the total number screened (with reasons for exclusion), expressed as a percentage.
• 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.
• 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.
• Participant satisfaction levels regarding treatment and the acceptability of the ISF-NF will also be recorded on an 11-point numeric rating scale (0-Not at all satisfied/acceptable to 10-Very satisfied/acceptable).

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 [3] 323276 0
Throughout the intervention period and at follow up of 1 week and 1 month post-intervention
Secondary outcome [1] 381248 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 three regions (i.e., symptomatic low back region, non-symptomatic low back region, and the distant non-dominant wrist).
Timepoint [1] 381248 0
Baseline, immediately post-intervention, and at follow-up of 1 week and 1 month post-intervention
Secondary outcome [2] 381252 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 three regions (i.e., symptomatic low back region, non-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] 381252 0
Baseline, immediately post-intervention, and at follow-up of 1 week and 1 month post-intervention
Secondary outcome [3] 381261 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 most painful low back region (nominated by the participant). 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] 381261 0
Baseline, immediately post-intervention, and at follow-up of 1 week and 1 month post-intervention

Eligibility
Key inclusion criteria
Participants with a diagnosis of 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 35 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 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
30 Years
Maximum age
75 Years
Gender
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
• 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
• Sleep Apnoe
• Hearing problems (hearing loss or tinnitus)
• Alcohol or substance abuse
• Dyslipidaemia
• Cognitive impairments (dementia, post-traumatic stress disorders, Alzheimer’s disease): A total score of 24 or below on Mini-Mental State Examination
• 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
• Participants who, in the opinion of the investigators, do not understand the information and procedures of the study, or would not be compliant with them.
• Participants with current intake of any centrally acting medications (e.g. antidepressants, anticonvulsants, neuropathic pain drugs) or intention of taking new medications in the next 3 months.

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 four intervention arms:
• Group 1: ISF-NF Up-train pgACC,
• Group 2: ISF-NF Down-train dACC+SSC,
• Group 3: ISF-NF Concurrent Up-train pgACC and Down-train dACC+SSC, and
• Group 4: Placebo ISF-NF
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 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
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 22439 0
New Zealand
State/province [1] 22439 0
Otago

Funding & Sponsors
Funding source category [1] 305263 0
University
Name [1] 305263 0
University of Otago, Dunedin School of Medicine Dean's Bequest funding
Address [1] 305263 0
University of Otago,
PO Box 54.
Dunedin 9054.
Country [1] 305263 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] 305624 0
None
Name [1] 305624 0
Address [1] 305624 0
Country [1] 305624 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305606 0
Health and Disability Ethics Committee
Ethics committee address [1] 305606 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 305606 0
New Zealand
Date submitted for ethics approval [1] 305606 0
12/03/2020
Approval date [1] 305606 0
Ethics approval number [1] 305606 0

Summary
Brief summary
The purpose of this study is to evaluate the feasibility and safety of the targeted EEG based infraslow frequency neurofeedback (ISF-NF) technique in individuals with chronic low back pain (CLBP), and to explore its effects on pain, function and psychological measures in individuals with CLBP. Neurofeedback is a non-invasive technique for
augmenting or inhibiting brain activity patterns associated with pain by modifying one’s brain signal through feedback induced learning. The activity in the brain regions [pregenual anterior cingulate cortex (pgACC), dorsal anterior cingulate cortex (dACC) and primary somatosensory cortex (SSC)] targeted in the current study have been demonstrated to be altered in individuals with CLBP. We propose to explore a novel EEG based infraslow frequency neurofeedback (ISF-NF)technique targeting the pgACC, dACC, and SSC individually as well as simultaneously. The ISF-NF technique has been specifically developed to modulate the infraslow electrical activity (0-0.1 Hz) in the brain.
The infraslow electrical activity, a fundamental frequency range of the brain, re-organises neurons, regulate oscillatory patterns in the brain during awake and sleep cycles, and improves the electrical connectivity of the brainwide functional networks; thereby improve clinical outcomes. The evidence obtained from this study will thus help us to develop novel interventions to improve the health outcomes (pain and function) in individuals with CLBP.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100938 0
Dr Divya Adhia
Address 100938 0
Department of Surgical Sciences,
Dunedin School of Medicine,
University of Otago,
PO Box 54.
Dunedin 9054.
Country 100938 0
New Zealand
Phone 100938 0
+64 34709337
Fax 100938 0
Email 100938 0
divya.adhia@otago.ac.nz
Contact person for public queries
Name 100939 0
Dr Divya Adhia
Address 100939 0
Department of Surgical Sciences,
Dunedin School of Medicine,
University of Otago,
PO Box 54.
Dunedin 9054.
Country 100939 0
New Zealand
Phone 100939 0
+64 34709337
Fax 100939 0
Email 100939 0
divya.adhia@otago.ac.nz
Contact person for scientific queries
Name 100940 0
Dr Divya Adhia
Address 100940 0
Department of Surgical Sciences,
Dunedin School of Medicine,
University of Otago,
PO Box 54.
Dunedin 9054.
Country 100940 0
New Zealand
Phone 100940 0
+64 34709337
Fax 100940 0
Email 100940 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 other documents available
Summary results
No Results