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Trial registered on ANZCTR


Registration number
ACTRN12623000376640
Ethics application status
Approved
Date submitted
6/03/2023
Date registered
13/04/2023
Date last updated
8/12/2024
Date data sharing statement initially provided
13/04/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of non invasive auricular vagus nerve stimulation (taVNS) combined with physiotherapy on mobility and balance impairment after stroke.
Scientific title
The effect of non invasive auricular vagus nerve stimulation paired with physiotherapy on gait and balance impairments in chronic stroke: A randomised controlled feasibility study
Secondary ID [1] 309066 0
Nil Known
Universal Trial Number (UTN)
U1111-1288-9863
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 329141 0
Gait impairments 329142 0
Balance impairments 329309 0
Condition category
Condition code
Physical Medicine / Rehabilitation 326118 326118 0 0
Physiotherapy
Neurological 326119 326119 0 0
Studies of the normal brain and nervous system
Cardiovascular 326120 326120 0 0
Other cardiovascular diseases
Stroke 326253 326253 0 0
Ischaemic
Stroke 326254 326254 0 0
Haemorrhagic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Transcutaneous auricular vagus nerve stimulation (taVNS) will be applied using tVNS® R device (tVNSTechnologies GmbH, Reichenschwand, Germany) by a researcher who is a physiotherapist. Stimulation intensity will be individually adjusted to a level that is above the individual’s sensory threshold and below pain threshold (a tolerable stimulus). Participants will be allocated to one of two groups, active stimulation stream or sham stimulation stream. In addition, both groups will receive physical rehabilitation therapy concurrently with the taVNS active or sham stimulation. taVNS will be applied at every rehabilitation session. Physiotherapy intervention will be based on Stroke Foundation Clinical Guidelines (Australia) for Stroke Management. The following framework is based on motor learning principles and will be tailored to individuals’ impairments, rehabilitation goals, and level of mobility. Sessions can include the following components: 1) goal-oriented task-specific training (for example practice of walking components followed by practice of walking on land or on a treadmill, and balance training in sitting and in standing position), 2) aerobic exercise (for example, bicycle ergometer, walking on a treadmill or on land), and 3) core and lower limbs strengthening exercises. Each participant will receive 15 therapy sessions conducted over 6 weeks (2-3 x 1-hour sessions per week). This will be provided on a one-on-one basis by a qualified physiotherapist. All sessions will be conducted within the City West Health and Medical Clinic of the University of South Australia, Adelaide, Australia.

Stimulation parameters for active taVNS group will be as follow: electrode will be placed at cymba concha of the left ear. A pulse width of 0.3 ms, a frequency of 25 Hz, and a pulse pause ratio of 30 sec on: 30 sec off will be used. The stimulation will be delivered for up to 1 hour concurrent with physical rehabilitation.

Adherence to intervention will be monitored by auditing participants’ attendance checklist as well as details of physical rehabilitation intervention and stimulation parameters provided which will be documented in participants’ medical records.
Intervention code [1] 325523 0
Treatment: Devices
Intervention code [2] 325524 0
Rehabilitation
Comparator / control treatment
sham taVNS group: taVNS electrode will be attached to cymba concha of left ear but the device will be switched off and no electric current will be delivered for the entire duration of the rehabilitation session (1 hour). This group will also receive physical rehabilitation therapy.
Control group
Placebo

Outcomes
Primary outcome [1] 333987 0
The primary outcome of this study is the feasibility of taVNS as an adjuvant therapy to enhance balance and gait recovery in chronic stroke. This will be determined by measuring recruitment rates and compliance to intervention determined by study logs, patients' acceptability and satisfaction of the intervention (determine using 5-point Likert Scale), adverse events, and effectiveness of blinding. Two questionnaires have been developed to assess adverse events and effectiveness of sham methods (both are included in attached study protocol). All feasibility measures will be assessed as a composite primary outcome. If all feasibility criteria described in detail in Table 1 of attached study protocol met the requirement to "proceed" or "proceed with protocol amendment " then the study will be deemed feasible.
Timepoint [1] 333987 0
Within five days of last intervention session.
Secondary outcome [1] 418954 0
Safety: We developed an evidence-based adverse events questionnaire which will be used to assess adverse events at the end of each session (see Appendix 1 in attached study protocol). This was developed based on the findings from our recent scoping review investigating taVNS therapeutic application across all clinical populations including stroke (data has been synthesised but not yet published) and guided by two systematic reviews reporting on the safety of non-invasive taVNS. Common adverse events of taVNS include redness, pain and irritation at electrode site, but usually mild. Furthermore, participants will be asked to record and report falls incidences during the trial using a falls diary.
Timepoint [1] 418954 0
Participants will complete the AEs questionnaire at the end of each week of intervention. And participants will be asked to inform the researcher if they experienced any adverse events during the intervention.
Participants will be provided with a falls diary to document any falls during the six weeks of intervention.
Secondary outcome [2] 418955 0
10-meter walk test (10MWT) to assess gait speed.
Timepoint [2] 418955 0
1. At baseline
2. Within five days of last intervention session.
3. After 30 days from last intervention session.
Secondary outcome [3] 419449 0
6-minutes walk test to assess endurance.
Timepoint [3] 419449 0
1. At baseline
2. Within five days of last intervention session.
3. After 30 days from last intervention session.
Secondary outcome [4] 419450 0
Temporal and spacial parameters of gait will be assessed using GAITRite®
Timepoint [4] 419450 0
1. At baseline
2. Within five days of last intervention session.
3. After 30 days from last intervention session.
Secondary outcome [5] 419451 0
Brief Balance Evaluation System Test (BESTest) will be used to assess balance
Timepoint [5] 419451 0
1. At baseline
2. Within five days of last intervention session.
3. After 30 days from last intervention session.
Secondary outcome [6] 419452 0
Modified Rankin Score (mRS) to assess level of disability
Timepoint [6] 419452 0
1. At baseline
2. Within five days of last intervention session.
3. After 30 days from last intervention session.
Secondary outcome [7] 419453 0
Stroke Self-Efficacy Scale (SSES) to assess self-efficacy
Timepoint [7] 419453 0
1. At baseline
2. Within five days of last intervention session.
3. After 30 days from last intervention session.
Secondary outcome [8] 419454 0
Patient experience with taVNS will be assessed using a semi-structured, one on one interview conducted with a member of the research team. An interview guide which includes 9 questions will be used to guide the researcher (see Appendix 2 in attached study protocol). This qualitative data will help inform future research about treatment design, participants ‘acceptance, and compliance with taVNS.
Timepoint [8] 419454 0
Within five days of last intervention session.

Eligibility
Key inclusion criteria
Aged 18 years or older; first-ever haemorrhagic or ischaemic stroke at least 6 months earlier; can walk 10 meters with or without a gait aid and with or without assistance, no history of other neurological conditions; gait and/or balance impairment; ability to give informed consent and to understand instruction.

Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous vagus nerve surgery; cognitive impairment and/or language impairment that might impact the person's ability to consent or understand instructions (MOCA score of less than 18) ; severe pain in any joints of the affected limb; advanced cardiac, pulmonary, kidney or liver condition; pregnancy; active implants; cerebral shunts; open skin at the point of stimulation.

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)
Participants will be assigned a number from 1 to 40 and allocation to intervention (active or sham taVNS) will be randomised (1: 1 ratio). Randomisation will be completed using the web application available at https://www.randomizer.org/.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Sequence generation will be completed by simple randomisation created using the web application available at https://www.randomizer.org/.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
All participants will not be aware of the stimulation condition they are receiving for the duration of treatment. The sensory and pain threshold for taVNS stimulation will be measured for all participants in the first assessment session (baseline measures) and participants will be familiarised with the taVNS device. Prior to randomisation, all participants will be told that” In this study, we will use different stimulation parameters for different groups of participants. Depending on the parameters used in the group that you will be assigned to, you may feel the stimulus, normally a tingling/prickling/stinging/warmth/vibration sensation at electrode site, or feel nothing at all”.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The feasibility will be reported against the criteria in table 1 in the attached study protocol (Appendix 1). For efficacy outcomes, a linear mixed model analysis will be used to compare two groups (active and sham) and 3-time points (baseline, post-intervention, and follow-up). Safety outcomes will be summarised descriptively. Blinding will be assessed using a questionnaire (see Appendix 3 in attached study protocol ) and the effectiveness of the sham method in blinding participants will be summarised descriptively. Qualitative interviews will be analysed and reported using thematic analysis.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/04/2023
Actual
9/05/2023
Date of last participant enrolment
Anticipated
30/05/2024
Actual
19/03/2024
Date of last data collection
Anticipated
30/06/2024
Actual
18/06/2024
Sample size
Target
40
Accrual to date
Final
26
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 313271 0
University
Name [1] 313271 0
University of South Australia
Country [1] 313271 0
Australia
Primary sponsor type
University
Name
University of South Australia
Address
Corner of North Terrace and, Frome Rd, Adelaide SA 5001
Country
Australia
Secondary sponsor category [1] 315023 0
None
Name [1] 315023 0
Address [1] 315023 0
Country [1] 315023 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312502 0
University of South Australia Human Research Ethics Committee HREC
Ethics committee address [1] 312502 0
Ethics committee country [1] 312502 0
Australia
Date submitted for ethics approval [1] 312502 0
Approval date [1] 312502 0
20/12/2022
Ethics approval number [1] 312502 0

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

Contacts
Principal investigator
Name 124890 0
Mr Ashraf Gerges
Address 124890 0
University of South Australia City East Campus, Corner of North Terrace and, Frome Rd, Adelaide SA 5001
Country 124890 0
Australia
Phone 124890 0
+61 411896044
Fax 124890 0
Email 124890 0
ashraf.gerges@mymail.unisa.edu.au
Contact person for public queries
Name 124891 0
Ashraf Gerges
Address 124891 0
University of South Australia City East Campus, Corner of North Terrace and, Frome Rd, Adelaide SA 5001
Country 124891 0
Australia
Phone 124891 0
+61 411896044
Fax 124891 0
Email 124891 0
ashraf.gerges@mymail.unisa.edu.au
Contact person for scientific queries
Name 124892 0
Ashraf Gerges
Address 124892 0
University of South Australia City East Campus, Corner of North Terrace and, Frome Rd, Adelaide SA 5001
Country 124892 0
Australia
Phone 124892 0
+61 411896044
Fax 124892 0
Email 124892 0
ashraf.gerges@mymail.unisa.edu.au

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?




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.