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Trial registered on ANZCTR


Registration number
ACTRN12614000952640
Ethics application status
Approved
Date submitted
21/08/2014
Date registered
4/09/2014
Date last updated
27/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Use of transcranial random noise stimulation (tRNS) as an adjunct to reaching training in chronic stroke survivors with severe arm paresis: An exploratory pilot study.
Scientific title
The effect of reaching training with active transcranial random noise stimulation (tRNS) on arm function compared to reaching training with sham tRNS in people with chronic stroke and severe arm paresis.
Secondary ID [1] 285200 0
Nil.
Universal Trial Number (UTN)
Nil.
Trial acronym
Nil.
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 292815 0
Condition category
Condition code
Physical Medicine / Rehabilitation 293105 293105 0 0
Physiotherapy
Stroke 293106 293106 0 0
Ischaemic
Stroke 293107 293107 0 0
Haemorrhagic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention group will receive 12 x 45-minute training sessions with a physiotherapist (trainer) over 4-weeks (3 sessions per week). Individualised training will involve repetitive and incrementally progressed task-oriented reaching in sitting. Participants will be instructed to push their arm along a linear slide at a comfortable speed while receiving real-time visual feedback of performance. To augment full range movement, electrical stimulation to muscles of the arm will be applied as required using the Empi 300PV unit (St Paul, MN, USA). Stimulation parameters will consist of a 1 second ascending ramp, and a 4 to 20 second duration of 200-sec pulse width biphasic stimulation at 35 Hz. All training will be recorded by the trainer in a logbook.
Training will be combined with transcranial random noise stimulation (tRNS). Stimulation will occur for the first 5-seconds of each movement attempt to augment voluntary motor drive. Stimulation will be delivered by a battery-driven non-invasive brain stimulator (Neuroconn, Germany) through conductive rubber electrodes, placed in saline soaked sponges. The noise signal will contain all frequencies (101 – 640 Hz) up to half the sampling rate (1280 sps). The electrodes will be positioned over C3/C4 as per the 10/20 international system for EEG electrode placement: the stimulation electrode positioned over the ipsilesional primary motor cortex (M1) and the reference electrode positioned over the contralateral supra-orbital region. All tRNS parameters will be recorded in a separate log by an unblinded intervener. The stimulating unit will be placed out of sight of the participant and trainer at all times.
Intervention code [1] 290071 0
Rehabilitation
Intervention code [2] 290072 0
Treatment: Devices
Comparator / control treatment
The control group will receive 12 x 45-minute training sessions with a physiotherapist (trainer) over 4-weeks (3 sessions per week). Individualised training will involve repetitive and incrementally progressed task-oriented reaching in sitting. Participants will be instructed to push their arm along a linear slide at a comfortable speed while receiving real-time visual feedback of performance. To augment full range movement, electrical stimulation to muscles of the arm will be applied as required using the Empi 300PV unit (St Paul, MN, USA). Stimulation parameters will consist of a 1 second ascending ramp, and a 4 to 20 second duration of 200-sec pulse width biphasic stimulation at 35 Hz. All training will be recorded by the trainer in a logbook.
Training will be combined with sham-tRNS. The electrodes will be positioned as per the intervention group, but no stimulation will be delivered during sham-tRNS application. The stimulating unit will be placed out of sight of the participant and trainer at all times.
Control group
Placebo

Outcomes
Primary outcome [1] 292973 0
Composite score of Motor Assessment Scale upper limb items 6-8, which measure upper arm function, hand movements and advanced hand movements.
Timepoint [1] 292973 0
Measured at pre training (week 0), post training (week 4), follow-up (week 12).
Secondary outcome [1] 310056 0
Muscle strength of elbow extension (triceps brachii) according to Manual Muscle Testing criteria.
Timepoint [1] 310056 0
Measured at pre training (week 0), post training (week 4), follow-up (week 12).
Secondary outcome [2] 310057 0
Muscle strength of wrist extension (extensor carpi radialis and ulnaris) according to Manual Muscle Testing criteria.
Timepoint [2] 310057 0
Measured at pre training (week 0), post training (week 4), follow-up (week 12).
Secondary outcome [3] 310058 0
Resistance to passive movement using the Modified ashworth scale for elbow and wrist flexors
Timepoint [3] 310058 0
Measured at pre training (week 0), post training (week 4), follow-up (week 12).
Secondary outcome [4] 310059 0
Spasticity using the tardieu scale for elbow and wrist flexors.
Timepoint [4] 310059 0
Measured at pre training (week 0), post training (week 4), follow-up (week 12).
Secondary outcome [5] 310060 0
Pain using the Ritchie Articular Index and 10-point Visual Analogue Scale.
Timepoint [5] 310060 0
Measured at pre training (week 0), post training (week 4), follow-up (week 12).
Secondary outcome [6] 310070 0
Real-world use of the arm in everyday tasks using the REACH (Rating of Everyday Arm-Use in the Community and Home) measure.
Timepoint [6] 310070 0
Measured at pre training (week 0), post training (week 4), follow-up (week 12).
Secondary outcome [7] 310295 0
Quality of life using the Stroke Specific Quality of Life Scale (normal and aphasia friendly version).
Timepoint [7] 310295 0
Measured at pre training (week 0), post training (week 4), follow-up (week 12).
Secondary outcome [8] 310296 0
Structural (diffuse tensor imaging [DTI]) and functional (resting state functional-magnetic resonance imaging [fcMRI]) connectivity of cortical motor regions using a 3T MRI.
Timepoint [8] 310296 0
Measured at pre training (week 0) and post training (week 4).

Eligibility
Key inclusion criteria
All participants will be first time adult (greater than 18 years) stroke survivors who are 6 to 24 months post stroke who demonstrate severe upper limb paresis (as indicated by a Motor Assessment Scale item 6 score of less than 4 out of a possible 6 points). A minimum level of active movement consistent with a triceps brachii score of 2- is required, along with the ability to understand single stage commands. All participants will not have participated in any rehabilitation services for their arm for at least 2-weeks prior to commencement of training.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria include: 1) any contraindications to tRNS or MRI, 2) presence of neurological conditions other than stroke e.g., Parkinson’s disease, or upper limb comorbidities that could limit functional recovery e.g., arthritis, 3) elbow contracture greater than 15 degrees, or 4) currently taking medication/s that could alter cortical excitability (e.g., antiepileptic medications, antidepressants) or have a presumed positive or negative effect on neural plasticity (e.g., dopamine, dexamphetamine).

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)
An independent person will prepare the concealed randomisation using a computer generated random number sequence: 1) intervention group, reaching training + active tRNS or 2) control group, reaching training + sham-tRNS. Consecutively numbered opaque envelopes containing group allocation will be collected by the tRNS intervener from an independent person after initial assessment. People involved in assessment and training, along with all participants will be blinded to group allocation for the duration of the study. Group allocation will only be known by the unblinded person applying the tRNS.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer generated random number sequence 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
NA
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Analysis will be performed on an intention-to-treat basis using SPSS software (SPSS Inc, Chicago, USA) and an a of 0.05. Descriptive statistics will be used to ensure comparability of scores between participants at baseline and to describe performance at each phase.
To determine the effect of tRNS on clinical outcome measures, a non-parametric, mixed effects model in a 2 group (active tRNS, sham-tRNS) × 3 phases (0, 4, 12 weeks) design will be implemented for each variable. This will be followed by between-groups comparisons.
The imaging sequences will be used to determine the structural and functional connectivity of specific nodes in the cortical motor network, pre and post training.

Recruitment
Recruitment status
Completed
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 in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 289819 0
Charities/Societies/Foundations
Name [1] 289819 0
National Stroke Foundation
Address [1] 289819 0
Level 7, 461 Bourke St, Melbourne VIC 3000
Australia.
Country [1] 289819 0
Australia
Funding source category [2] 289820 0
University
Name [2] 289820 0
Centre for Advanced Imaging, The University of Queensland
Address [2] 289820 0
The University of Queensland, St Lucia QLD 4072, Australia.
Country [2] 289820 0
Australia
Primary sponsor type
Individual
Name
Dr Kathryn Hayward
Address
Division of Physiotherapy, School of Health and Rehabilitation Sciences, The University of Queensland, St Lucia QLD 4072, Australia.
Country
Australia
Secondary sponsor category [1] 288511 0
Individual
Name [1] 288511 0
Professor Sandra Brauer
Address [1] 288511 0
Division of Physiotherapy, School of Health and Rehabilitation Sciences, The University of Queensland, St Lucia QLD 4072, Australia.
Country [1] 288511 0
Australia
Other collaborator category [1] 278118 0
Individual
Name [1] 278118 0
Professor Richard Carson
Address [1] 278118 0
School of Psychology & Trinity College Institute of Neuroscience, Lloyd Building, Trinity College, Dublin 2, Ireland.
Country [1] 278118 0
Ireland
Other collaborator category [2] 278119 0
Individual
Name [2] 278119 0
Kathy Ruddy
Address [2] 278119 0
Department of Health Sciences and Technology, Eidgenossische Technische Hochschule Zurich, Ramistrasse 101, 8092 Zurich, Switzerland
Country [2] 278119 0
Switzerland
Other collaborator category [3] 278120 0
Individual
Name [3] 278120 0
Dr David Lloyd
Address [3] 278120 0
Queensland Brain Institute, The University of Queensland, St Lucia QLD 4072, Australia.
Country [3] 278120 0
Australia
Other collaborator category [4] 278121 0
Individual
Name [4] 278121 0
Dr Ruth Barker
Address [4] 278121 0
Community Rehab northern Queensland, Townsville Mackay Medicare Local, 16 Ryan Street, Belgian Gardens QLD 4810, Australia.
Country [4] 278121 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291550 0
The University of Queensland Medical Research Ethics Committee
Ethics committee address [1] 291550 0
The University of Queensland St Lucia QLD 4072
Ethics committee country [1] 291550 0
Australia
Date submitted for ethics approval [1] 291550 0
Approval date [1] 291550 0
21/03/2014
Ethics approval number [1] 291550 0
2014000263

Summary
Brief summary
Stroke survivors with severe upper limb paresis have the poorest functional prognosis. There is growing evidence of the benefits of repetitive training to promote recovery of upper limb function. In addition, there is accumulating evidence that non-invasive brain stimulation techniques, such as tRNS, can augment activity within the cortical areas that are engaged during various forms of training. The aim of this study is to investigate the therapeutic and neuroplastic effects of combining repetitive training with tRNS in stroke survivors with chronic and severe upper limb paresis. A triple-blind randomised controlled pilot trial will be conducted. Ten stroke survivors will be randomly allocated to 4-weeks of SMART Arm training with active tRNS or sham-tRNS. To determine the clinical benefit, all participants will be assessed pre- and post-training and 2-months follow-up using a range of impairment, activity, participation and quality of life measures. To determine the structural (DTI) and functional (resting state fMRI) connectivity of cortical motor regions, all participants will undergo a 3T MRI pre- and post-training.
Trial website
NA
Trial related presentations / publications
NA
Public notes
NA

Contacts
Principal investigator
Name 50818 0
Dr Kathryn Hayward
Address 50818 0
Division of Physiotherapy, School of Health and Rehabilitation Sciences, The University of Queensland, St Lucia, QLD, Australia 4072
Country 50818 0
Australia
Phone 50818 0
+61 7 3365 2779
Fax 50818 0
+61 7 3365 1622
Email 50818 0
k.hayward@uq.edu.au
Contact person for public queries
Name 50819 0
Dr Kathryn Hayward
Address 50819 0
Division of Physiotherapy, School of Health and Rehabilitation Sciences, The University of Queensland, St Lucia, QLD, Australia 4072
Country 50819 0
Australia
Phone 50819 0
+61 7 3365 2779
Fax 50819 0
+61 7 3365 1622
Email 50819 0
k.hayward@uq.edu.au
Contact person for scientific queries
Name 50820 0
Dr Kathryn Hayward
Address 50820 0
Division of Physiotherapy, School of Health and Rehabilitation Sciences, The University of Queensland, St Lucia, QLD, Australia 4072
Country 50820 0
Australia
Phone 50820 0
+61 7 3365 2779
Fax 50820 0
+61 7 3365 1622
Email 50820 0
k.hayward@uq.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary