Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613001320741
Ethics application status
Approved
Date submitted
25/11/2013
Date registered
28/11/2013
Date last updated
28/11/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Combined exercise and non-invasive brain
stimulation for the treatment of pain and disability in knee osteoarthritis: a pilot randomised, double-blind sham-controlled trial.
Scientific title
An investigation of exercise in conjunction with non-invasive brain stimulation versus exercise with sham brain stimulation in people with knee osteoarthritis to evaluate i) the feasibility, safety, and perceived participant response to a combined exercise and brain stimulation treatment and ii) effects on pain/disability and pain system function.
Secondary ID [1] 283607 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Knee Osteoarthritis 290528 0
Condition category
Condition code
Musculoskeletal 290926 290926 0 0
Osteoarthritis
Physical Medicine / Rehabilitation 290997 290997 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive 20 minutes of active transcranial direct current stimulation (tDCS) immediately prior to exercise therapy 2 x per week for 8 weeks. The intervention will be delivered by a qualified physiotherapist trained in the use of tDCS. Participants will also complete home exercises 2 x per week to mimic typical clinical practice. Adherence to the home exercise program will be monitored using a log book.

Transcranial direct current stimulation (tDCS): will be delivered using a direct current stimulator via two 35 cm2 surface sponge electrodes. The active electrode (anode) will be placed over the primary motor cortex and the reference electrode (cathode) over the contralateral supraorbital region. Current intensity will be ramped up (0 mA to 1 mA) and down (1 mA to 0 mA) over 10 s at the beginning and end of the stimulation period. For the remainder of the 20 minute treatment, current intensity will be consistent at 1mA.

Exercise: Quadriceps strengthening exercises will be
performed with ankle cuff weights or elastic bands for resistance where necessary. Exercise intensity will be progressed by the physiotherapist as appropriate for each participant. Each session will last 30 minutes. A home exercise plan will be developed, monitored and progressed by the physiotherapist for each participant.
Intervention code [1] 288299 0
Rehabilitation
Intervention code [2] 288300 0
Treatment: Devices
Comparator / control treatment
Participants will receive 20 minutes of sham transcranial direct current stimulation (tDCS) immediately prior to exercise therapy 2 x per week for 8 weeks. The intervention will be delivered by a qualified physiotherapist trained in the use of sham tDCS. Participants will also complete home exercises 2 x per week to mimic typical clinical practice. Adherence to the home exercise program will be monitored using a log book.

Sham transcranial direct current stimulation (tDCS): will be delivered with electrodes placed in an identical position to that used for active tDCS. The current will be ramped up over 10 seconds (0 mA to 1 mA) and then ramped down (1mA to 0mA) over a further 10 seconds before being switched off. This is a standard sham approach in tDCS studies which ensures that participants feel the initial tingling
sensation associated with tDCS. The tDCS unit will be placed out of sight for both the active and sham interventions.

Exercise: Quadriceps strengthening exercises will be
performed with ankle cuff weights or elastic bands for resistance where necessary. Exercise intensity will be progressed by the physiotherapist as appropriate for each participant. Each session will last 30 minutes. A home exercise plan will be developed, monitored and progressed by the physiotherapist for each participant.
Control group
Active

Outcomes
Primary outcome [1] 290911 0
Knee pain will be measured using a 100 mm visual analogue scale (VAS) with pain on walking over the past week self-assessed with terminal descriptors of ‘no pain’ (score 0 mm) and ‘extreme pain’ (score 100 mm).
Timepoint [1] 290911 0
Assessed immediately before and immediately after the 8-week intervention.
Primary outcome [2] 290957 0
Knee function will be assessed using the function subscale of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index (Likert version 3.1).
Timepoint [2] 290957 0
Assessed immediately before and immediately after the 8-week intervention.
Secondary outcome [1] 305585 0
Feasibility will be measured as i) the number of sessions attended by each participant, ii) number of drop-outs in each group, iii) proportion of participants recruited from the total number screened, iv) willingness of each participant to undergo therapy on an 11-point numerical rating scale with ‘not at all willing’ at 0 and ‘very willing’ at 10 and v) recording of the type, severity and duration of any side-effects/adverse events (e.g. headache, fatigue, increased pain, dizziness, nausea).
Timepoint [1] 305585 0
Assessed immediately before and immediately after the 8-week intervention.
Secondary outcome [2] 305586 0
Central pain modulation (CPM): CPM is tested as a change in the pain perceived in one body region [electrical stimulation, 4 ms pulse duration, applied to the left upper arm] as a result of pain induced in another [heat pain, 30 pulses/minute to 1 degree celsius above pain threshold via a thermode, applied to the right forearm]. Twenty heat pain stimuli will be delivered to the left arm alone followed by 20 combined with electrical pain stimuli to the right arm.
Timepoint [2] 305586 0
Assessed immediately before and immediately after the 8-week intervention.
Secondary outcome [3] 305587 0
Pressure (PPT) and cold pain thresholds (CPT): PPT will be measured using a pressure algometer [probe size 1 cm2, rate 40 kPa/s]. CPT will be measured using the Thermotest system [preset to 30 degrees celsius, temperature change rate of 1.8 degrees celsius/s]. Participants will push a button when pressure or cold sensations first become painful. The average of three recordings will be analysed from the peripatellar region, tibialis anterior muscle (lower leg) and extensor carpi radialis longus muscle (wrist extensor).
Timepoint [3] 305587 0
Assessed immediately before and immediately after the 8-week intervention.
Secondary outcome [4] 305588 0
Nociceptive flexor withdrawal reflex (NFR): Surface stimulating electrodes will be positioned at a retromalleolar location along the right sural nerve. Recording electrodes will be positioned over the belly of the biceps femoris muscle. Stimulation will consist of pulse trains of 20 ms duration at an interval frequency of 300 Hz. The intensity needed to evoke a response of biceps femoris indicating activation of the NFR, and the subjective pain threshold will be recorded.
Timepoint [4] 305588 0
Assessed immediately before and immediately after the 8-week intervention.
Secondary outcome [5] 305676 0
The Global Perceived Effect Scale where each participant’s perceived response to therapy is assessed using a 7-point Likert scale ranging from “completely recovered” to “vastly worsened”.
Timepoint [5] 305676 0
Assessed immediately before and immediately after the 8-week intervention.
Secondary outcome [6] 305709 0
Treatment expectation will be assessed using a 5-point Likert scale ranging from 'No effect at all' to 'Completely recovered'.
Timepoint [6] 305709 0
Treatment expectation will be assessed at baseline, immediately before the 8-week intervention.

Eligibility
Key inclusion criteria
Participants with knee OA (American College of Rheumatology criteria) will be recruited from the community. A minimum pain score of 40 on a 100 mm visual analogue scale (VAS) will be required.
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The main exclusion criteria are: (i) intra-articular corticosteroid injection or knee surgery in the past 6 months; (ii) systemic arthritic conditions; (iii) knee joint replacement or high tibial osteotomy; (iv) other muscular, joint or neurological conditions affecting lower limb function; (v) unable to walk unaided; (vi) currently undertaking a structured exercise program for knee
OA or (vii) contraindications to tDCS (e.g. epilepsy) or central pain modulation techniques (e.g. loss of sensation).

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)
Off-site concealed randomisation will be prepared by a researcher using a computer generated random number sequence. Consecutively numbered, randomly ordered opaque envelopes containing group allocation will be opened consecutively by the therapist implementing the two types of intervention. The person recruiting thus will not know to which group the subject will be allocated.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer generated random number will be used to generate the sequence.
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
Safety/efficacy
Statistical methods / analysis
This is a proof of concept study designed to generate data that can be used to inform a future large randomised controlled trial should the intervention appear feasible, safe and show trends of effectiveness. We have selected a sample size of 10 individuals per group, or 20 participants in total.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/02/2014
Actual
Date of last participant enrolment
Anticipated
31/10/2014
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 288288 0
Charities/Societies/Foundations
Name [1] 288288 0
Arthritis Foundation of Australia
Country [1] 288288 0
Australia
Primary sponsor type
Individual
Name
Dr Siobhan Schabrun
Address
University of Western Sydney, Campbelltown Campus, Locked Bag 1797, Penrith NSW 2751
Country
Australia
Secondary sponsor category [1] 287007 0
Individual
Name [1] 287007 0
Professor Paul Hodges
Address [1] 287007 0
School of Health and Rehabilitation Science, The University of Queensland, St Lucia 4072 QLD
Country [1] 287007 0
Australia
Secondary sponsor category [2] 287008 0
Individual
Name [2] 287008 0
Professor Kim Bennell
Address [2] 287008 0
Department of Physiotherapy
School of Health Sciences
University of Melbourne
Alan Gilbert Building, 161 Barry Street
Parkville, Vic 3010 Australia
Country [2] 287008 0
Australia
Secondary sponsor category [3] 287009 0
Individual
Name [3] 287009 0
Associate Professor Rana Hinman
Address [3] 287009 0
Centre for Health Exercise & Sports Medicine
Department of Physiotherapy
School of Health Sciences
Level 7 Alan Gilbert Building, 161 Barry Street
Parkville
Vic, 3010
Country [3] 287009 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290183 0
Human Research Ethics Committee, University of Western Sydney
Ethics committee address [1] 290183 0
Office of Research Services
Building K, Room K.1.45 Kingswood Campus
University of Western Sydney, Locked Bag 1797, Penrith NSW 2751
Ethics committee country [1] 290183 0
Australia
Date submitted for ethics approval [1] 290183 0
Approval date [1] 290183 0
30/05/2013
Ethics approval number [1] 290183 0
H10184

Summary
Brief summary
Osteoarthritis (OA) affects more than 20% of Australians aged over 55. The knee joint is commonly affected, resulting in knee pain and difficulty with everyday tasks such as walking or climbing stairs. Current treatments (e.g. medication, surgery, exercise) are only partially effective. Novel therapies that optimize the effects of current treatments are needed to reduce the social and economic burden on sufferers, caregivers and the wider community. Here we aim to conduct a ‘proof of concept’ study to investigate the use of an innovative non-invasive brain stimulation treatment to bolster the effects of exercise therapy in knee OA. We anticipate that the combination of non-invasive brain stimulation and exercise will have a greater effect on the biological mechanisms that contribute to pain, and thus provide greater benefits for pain and disability, than exercise alone.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44382 0
Dr Siobhan Schabrun
Address 44382 0
University of Western Sydney, Campbelltown Campus, Locked Bag 1797, Penrith NSW 2751, Australia
Country 44382 0
Australia
Phone 44382 0
+61 2 4620 3497
Fax 44382 0
+61 2 4620 3792
Email 44382 0
s.schabrunuws.edu.au
Contact person for public queries
Name 44383 0
Siobhan Schabrun
Address 44383 0
University of Western Sydney, Campbelltown Campus, Locked Bag 1797, Penrith NSW 2751, Australia
Country 44383 0
Australia
Phone 44383 0
+61 2 4620 3497
Fax 44383 0
+61 2 4620 3792
Email 44383 0
[email protected]
Contact person for scientific queries
Name 44384 0
Siobhan Schabrun
Address 44384 0
University of Western Sydney, Campbelltown Campus, Locked Bag 1797, Penrith NSW 2751, Australia
Country 44384 0
Australia
Phone 44384 0
+61 2 4620 3497
Fax 44384 0
+61 2 4620 3792
Email 44384 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23302Ethical approval-999999  

Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Plain language summaryNo A randomised, assessor- and participant-blind, sha... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseAddition of transcranial direct current stimulation to quadriceps strengthening exercise in knee osteoarthritis: A pilot randomised controlled trial.2017https://dx.doi.org/10.1371/journal.pone.0180328
N.B. These documents automatically identified may not have been verified by the study sponsor.