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Trial registered on ANZCTR


Registration number
ACTRN12618001436268
Ethics application status
Approved
Date submitted
14/08/2018
Date registered
28/08/2018
Date last updated
30/10/2018
Date data sharing statement initially provided
30/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
MS-SAFE: Stepping to Avoid Fall Events in Multiple Sclerosis
Scientific title
Training protective stepping responses to trips and slips in people with multiple sclerosis
Secondary ID [1] 295625 0
MS Research Australia 17-0291
Universal Trial Number (UTN)
U1111-1217-8527
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple sclerosis 308953 0
Condition category
Condition code
Neurological 307852 307852 0 0
Multiple sclerosis
Physical Medicine / Rehabilitation 307853 307853 0 0
Other physical medicine / rehabilitation
Injuries and Accidents 308109 308109 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Reactive step training sessions will be undertaken in 2 supervised individual sessions over 2 weeks. During each session, a participant will visit Neuroscience Research Australia for 50-minutes of training, focusing on balance recovery from mix of trips and slips (30 trials). A perturbation system built on a 10-m walkway consisting of 50cm x 50cm wooden decking tiles will be used to induce slips and trips (Okubo et al., 2018). Participants walk while being secured with a ceiling-mounted full body harness to avoid falling to the ground. Gait speed during this training will be individually set to approximately 80% (or 50-100% if adjustment is required) of usual speed using a metronome corresponding to individualised cadence. Interspersed with normal walk trials will be a series of trip and slip perturbations with increasing levels of unpredictability and 4 short breaks. A slip is induced by a movable tile on two hidden low-friction rails with linear bearings that result in a slide of 20-70cm upon foot contact. A trip is induced using a 7-14cm height tripping board that springs up from the walkway at mid-swing using a foot detection sensor. Unpredictability of perturbation will be progressively increased so that reactive stepping responses can be gradually and safely trained. Participant performance and anxiety status will be closely monitored and intensity of perturbation (i.e. trip height, slip distance/speed and gait speed) may be adjusted to appropriately progress the challenge and training effects. All training sessions will be conducted individually with an Exercise Physiologist and an assistant.
Intervention code [1] 301932 0
Rehabilitation
Intervention code [2] 301933 0
Treatment: Other
Comparator / control treatment
Participants allocated in the control group will undertake 2 50-minute sessions of sham training over 2 weeks (30 trials in a session). This group will be called "Obstacle avoidance training group". The participants (wearing a safety harness) will be instructed to walk and step over obstacles with increasing heights (7cm or 14cm) on the perturbation walkway with the beat of the metronome but without trip- and slip-perturbations. One of stepping tiles will be placed irregularly to mimic the recovery steps from trips and slips.
Control group
Active

Outcomes
Primary outcome [1] 306827 0
Perturbation-induced falls incidence will be assessed on the slip and trip walkway (Okubo et al., 2018).
Timepoint [1] 306827 0
Baseline (week 1) and after the intervention (week 2)
Secondary outcome [1] 349826 0
The choice stepping reaction time test standard version
(Lord et al., J Gerontol A Biol Sci Med Sci, 2001)
Timepoint [1] 349826 0
Baseline (week 1) and after the intervention (week 2)
Secondary outcome [2] 349828 0
The Falls Efficacy Scale-International
(Yardley et al., 2005)
Timepoint [2] 349828 0
Baseline (week 1) and after the intervention (week 2)
Secondary outcome [3] 349829 0
Dropout rate will be used as a measure of feasibility
Timepoint [3] 349829 0
During the 2-session intervention
Secondary outcome [4] 349830 0
Anxiety during training will be measured using a custom 5-point scale (1; no anxiety at all, 5: extreme anxiety).
Timepoint [4] 349830 0
During the 2-session intervention
Secondary outcome [5] 349831 0
Perceived benefit of the training will be assessed using a custom visual analog scale
Timepoint [5] 349831 0
After the intervention (week 2)
Secondary outcome [6] 350350 0
Postural sway on foam (Lord et al., J Am Geriatr Soc 1994). A sway meter that consists of a 40cm-long rod with a vertically mounted pen at its end will be attached at waist level.
Timepoint [6] 350350 0
Baseline (week 1) and after the intervention (week 2)
Secondary outcome [7] 350351 0
Knee extension strength will be measured using a digital dynamometer attached to the participant's leg using a webbing strap and affixed to a crossbar position behind the participant (Lord et al., J Am Geriatr Soc 1994).
Timepoint [7] 350351 0
Baseline (week 1) and after the intervention (week 2)
Secondary outcome [8] 350352 0
The simple reaction time test (Lord et al., J Am Geriatr Soc 1994). A hand-held electronic timer and a light as the stimulus and a switch will be used.
Timepoint [8] 350352 0
Baseline (week 1) and after the intervention (week 2)
Secondary outcome [9] 350605 0
Margin of stability (Hof et al., 2005) during the slip and trip trials (baseline and post-intervention) will be assessed using the vicon 3D motion analysis system with the full-body 38-marker model..
Timepoint [9] 350605 0
Baseline (week 1) and after the intervention (week 2)
Secondary outcome [10] 350606 0
Extrapolated centre of mass (Hof et al., 2005) during the slip and trip trials (baseline and post-intervention) will be assessed using the vicon 3D motion analysis system with the full-body 38-marker model..
Timepoint [10] 350606 0
Baseline (week 1) and after the intervention (week 2)
Secondary outcome [11] 350607 0
Step length during the slip and trip trials (baseline and post-intervention) will be assessed using the vicon 3D motion analysis system with the full-body 38-marker model..
Timepoint [11] 350607 0
Baseline (week 1) and after the intervention (week 2)
Secondary outcome [12] 350609 0
Range of trunk sway during the slip and trip trials (baseline and post-intervention) will be assessed using the vicon 3D motion analysis system with the full-body 38-marker model..
Timepoint [12] 350609 0
Baseline (week 1) and after the intervention (week 2)
Secondary outcome [13] 350612 0
A simplified kinematic model will be collected during the training sessions using the vicon 3D motion analysis system with 20 markers.
Timepoint [13] 350612 0
During the training sessions
Secondary outcome [14] 350613 0
Ground reaction forces during the slip and trip trials will be measured using AMTI and Kistler force plates.
Timepoint [14] 350613 0
Baseline (week 1) and after the intervention (week 2)
Secondary outcome [15] 351098 0
A pattern of muscle activation onset latency in the legs (rectus femoris, semitendinoss, tibialis anterior and vastus lateralis) during the slip and trip trials will be measured using surface electromyography. This is a composite outcome.
Timepoint [15] 351098 0
Baseline (week 1) and after the intervention (week 2)
Secondary outcome [16] 351099 0
Co-activation index in the legs (rectus femoris, semitendinoss, tibialis anterior and vastus lateralis) during the slip and trip trials will be measured using surface electromyography.
Timepoint [16] 351099 0
Baseline (week 1) and after the intervention (week 2)

Eligibility
Key inclusion criteria
1) Aged between 18 years or older,
2) Living in the community,
3) Confirmed diagnosis of MS,
4) Expanded Disability Status Scale (EDSS) between 1 and 5.5,
5) No apparent cognitive impairment,
6) Being able to understand and follow test instructions,
7) Stable MS (with or without disease modifying drugs) with no exacerbation in the past 30 days.
8) Exercising for 60 minutes per week (e.g. fitness class, walking, strength training, Tai Chi, etc) for the past 3 months.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Unable to walk 5 minutes without a bilateral mobility aid,
2) Existing conditions that prevent exercise (e.g. severe pain, heel ulcers, severe spasticity, excessive fatigue, exercise intolerance),
3) A relapse of MS in the past 30 days
4) Advised by a medical practitioner not to exercise.
5) History of fracture in the past 3 years or joint replacement in the past 12 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)
Allocation of participants will not be conducted until the individual have been enrolled and completed the baseline assessment. Following the baseline assessment, research staff will access a web-based randomisation service to perform random allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random block size randomisation using a web-based randomisation service. The randomisation will be stratified by EDSS (1-3 and 4-5.5).
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)
Efficacy
Statistical methods / analysis
Sample size calculation (with Poisson regression, significance levels of 0.05, power of 0.8, control falling rate of 70%, 10% dropouts) revealed that 44 eligible participants would need to be recruited initially (22 per group) for a significant reduction by 50% in the number of laboratory falls in the intervention group.

Recruitment
Recruitment status
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 in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 11484 0
Neuroscience Research Australia (NeuRA) - Randwick
Recruitment postcode(s) [1] 23506 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 300205 0
Charities/Societies/Foundations
Name [1] 300205 0
MS Research Australia
Address [1] 300205 0
Level 19, Northpoint, 100 Miller Street, North Sydney NSW 2060
Country [1] 300205 0
Australia
Funding source category [2] 300206 0
Government body
Name [2] 300206 0
National Health and Medical Research Council
Address [2] 300206 0
GHD Building Level 1
16 Marcus Clarke St
Canberra ACT 2601
Country [2] 300206 0
Australia
Primary sponsor type
Individual
Name
Prof Stephen Lord
Address
Neuroscience Research Australia
Margarete Ainsworth Building
Barker Street
Randwick NSW 2031
Country
Australia
Secondary sponsor category [1] 299610 0
Individual
Name [1] 299610 0
Dr. Yoshiro Okubo
Address [1] 299610 0
Neuroscience Research Australia
Margarete Ainsworth Building
Barker Street
Randwick NSW 2031
Country [1] 299610 0
Australia
Secondary sponsor category [2] 299611 0
Individual
Name [2] 299611 0
Dr Phu Hoang
Address [2] 299611 0
Neuroscience Research Australia
Margarete Ainsworth Building
Barker Street
Randwick NSW 2031
Country [2] 299611 0
Australia
Secondary sponsor category [3] 299612 0
Individual
Name [3] 299612 0
Dr Daina Sturnieks
Address [3] 299612 0
Neuroscience Research Australia
Margarete Ainsworth Building
Barker Street
Randwick NSW 2031
Country [3] 299612 0
Australia
Secondary sponsor category [4] 299613 0
Individual
Name [4] 299613 0
Dr Jasmine Menant
Address [4] 299613 0
Neuroscience Research Australia
Margarete Ainsworth Building
Barker Street
Randwick NSW 2031
Country [4] 299613 0
Australia
Secondary sponsor category [5] 299614 0
Individual
Name [5] 299614 0
Dr. Matthew Brodie
Address [5] 299614 0
Neuroscience Research Australia
Margarete Ainsworth Building
Barker Street
Randwick NSW 2031
Country [5] 299614 0
Australia
Secondary sponsor category [6] 299615 0
Individual
Name [6] 299615 0
Ms Angeliki Stivactas
Address [6] 299615 0
Neuroscience Research Australia
Margarete Ainsworth Building
Barker Street
Randwick NSW 2031
Country [6] 299615 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301031 0
University of New South Wales Human Research Ethics Committee
Ethics committee address [1] 301031 0
UNSW Grants Management Office
Rupert Myers Building, Level 3, South Wing
University of New South Wales
NSW
2052
Ethics committee country [1] 301031 0
Australia
Date submitted for ethics approval [1] 301031 0
05/03/2018
Approval date [1] 301031 0
04/05/2018
Ethics approval number [1] 301031 0
HC180128

Summary
Brief summary
This project will examine feasibility, mechanisms and efficacy of reactive step training as a fall-prevention strategy for people with MS. Forty-four people with MS will be recruited and assessed for balance recovery responses after slips and trips. Equipped with a full-body safety harness and foot protectors, People with MS will be exposed to a slip (70cm length) and a trip (14cm height) using our perturbation system. Twenty-two participants randomized to the intervention group will undertake 2 weekly individual 50-minute sessions (100 minutes in total) with each session focusing on balance recovery from a mix of trips and slips (week 2). Intensity of the training (e.g. gait speed, slip distance/speed and trip height) will be individualized and progressed according to participant ability. The control group will undertake 2 weekly 50-min session of sham training. Following training/sham, balance recovery response to slips and trips will be assessed. Kinematic, kinetic and physiological data will be collected to explore mechanisms for how people with MS improve their balance recovery responses.
Trial website
https://www.neura.edu.au/clinical-trial/ms-safe/
Trial related presentations / publications
Public notes
Following assessments are not outcomes of this study but will be used during the baseline assessments to document participant characteristics.

Physical activity level will be assessed through the Incidental and Planned Activity Questionnaire for the elderly (Delbaere et al., Br J Sports Med, 2010)

Disability will be assessed using the Expanded Disability Status Scale (EDSS).

Walking ability will be assess using the Twelve Item MS Walking Scale (MSWS-12).

Modified Fatigue Impact Scale (MFIS) will be used to assess the effects of fatigue on physical, cognitive and psychosocial functioning (Fisk et al, 1994).

Generalized Anxiety Disorder 7-item (GAD-7) scale will be used to assess the general anxiety (Spitzer et al., 2006)

Proprioception will be measured using the lower-limb matching task (Lord et al., 2003: DeDominaco et al., 1987).

Vision will be assessed using the Melbourne Edge Test (Lord et al., 2003; Verbaken et al., 1986).

The Trail-making Test (Wechsler, 1981) will be assessed using an iPad app NeuRA Trails.

Data from the first participant, who was treated under the initially registered protocol, will be excluded from analysis. Randomisation re-started under the updated protocol.

Contacts
Principal investigator
Name 63466 0
Prof Stephen Lord
Address 63466 0
Neuroscience Research Australia
Barker St
Randwick
NSW
2031
Country 63466 0
Australia
Phone 63466 0
+61 2 9399 1061
Fax 63466 0
+61 2 9399 1120
Email 63466 0
s.lord@neura.edu.au
Contact person for public queries
Name 63467 0
Prof Stephen Lord
Address 63467 0
Neuroscience Research Australia
Barker St
Randwick
NSW
2031
Country 63467 0
Australia
Phone 63467 0
+61 2 9399 1061
Fax 63467 0
+61 2 9399 1120
Email 63467 0
s.lord@neura.edu.au
Contact person for scientific queries
Name 63468 0
Prof Stephen Lord
Address 63468 0
Neuroscience Research Australia
Barker St
Randwick
NSW
2031
Country 63468 0
Australia
Phone 63468 0
+61 2 9399 1061
Fax 63468 0
+61 2 9399 1120
Email 63468 0
s.lord@neura.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
The ethics requires the IPD to be kept confidential.
What supporting documents are/will be available?
No other documents available
Summary results
No Results