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Trial registered on ANZCTR


Registration number
ACTRN12616000415404
Ethics application status
Approved
Date submitted
21/03/2016
Date registered
31/03/2016
Date last updated
24/03/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Interventions to improve gait and reduce falls in people with multiple sclerosis (MS)
Scientific title
Do interventions targeting proprioceptive feedback and exercise improve functional gait and reduce falls and falls risk in people with MS?
Secondary ID [1] 288720 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 297956 0
Mobility 297957 0
Functional gait outcomes 297958 0
Condition category
Condition code
Neurological 298117 298117 0 0
Multiple sclerosis
Injuries and Accidents 298266 298266 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants in the intervention group will perform four exercises at home on a whole body vibration (WBV) board, at least 3 times a week for 10 weeks. Patients are allowed to perform the exercises more frequently if they wish but no more than once a day. Each exercise session should take ~30 minutes.

A trained research assistant will instruct participants on the exercises to be performed during the initial home visit. This should take ~1 hour.
All participants will be instructed to perform the following four exercises:
- Dynamic bilateral squats for 3 sets of 8 repetitions with 3 second holds
- Static bilateral squats for 3 sets with 30 seconds ‘hold’
- Bilateral marching for 30 seconds continuously
- Dynamic calf raises for 3 sets of 8 repetitions for each leg They can rest between exercises but for no more than 1 minute. The cool down and warm up will involve walking around their home at their own pace for 2 minutes.

Halfway into the 10-week intervention block participants will receive an additional 30 minute home visit for instructions to increase exercise progression as appropriate. This may include increasing duration, repetitions, sets, or the use of a weighted vest. Participants will also receive a phone call, lasting approximately 10 minutes, every ~4 weeks by the trained research assistant to ensure compliance and appropriate progression. The Fall Calendars will be collected ~monthly for 20 weeks.

The WBV group will be instructed in how to perform the exercises on the WBV platform and in the use of the SilverMink V-988 electrically controlled exercise system supplied by SaunaGem Australia. The SilverMink WBV system is registered with Australian Register of Therapeutic Goods (ARTG). The ARTG Number is 136007; the ARTG Product Number and Name: 222559 Massager, physical therapy.

Potential risks using the unit include the possibility of falling off the platform, which could result in other injuries. However, the WBV platforms have handles that participants are able to hold onto and a safety strap to prevent them from falling backwards off the unit. Participants may experience mild discomfort and/or fatigue during and after the testing and exercise sessions. Some people may develop mild soreness in some muscles one to two days after exercise.

If participants experience a relapse during participation they will be advised to stop exercise until after being reviewed by their physician and deemed ready to exercise again. The follow up measures for these participants will be conducted as their conditions allow.
Intervention code [1] 294157 0
Rehabilitation
Intervention code [2] 294310 0
Treatment: Other
Comparator / control treatment
For participants in the control group, the treatment will be the same as in the WBV group, except that participants will perform the same four exercises on a hard stable surface at least 3 times a week for 10 weeks. A trained research assistant will instruct them on the four exercises to be performed in an initial home visit. All other aspects of the control group will be the same as in the WBV group.
Control group
Active

Outcomes
Primary outcome [1] 297642 0
Falls risk will be assessed using the Physiological Profile Assessment (PPA) fall risk index score. This is a series of tests composed of weighted values from five sensorimotor and balance domains: quadriceps muscle strength, hand reaction time, proprioception, postural sway, and visual contrast sensitivity.
Timepoint [1] 297642 0
Falls risk will be measured at baseline and at 10 weeks after the commencement of the intervention for each of the 5 blocks. Assessments will occur at the University of Sydney Cumberland campus and Neuroscience Research Australia.
Secondary outcome [1] 322065 0
The reliability of the PPA will be analysed by correlation of test- retest scores. Using the intraclass correlation coefficient (ICC), the reliability for each measurement tool will be classified as low (ICC <0.4), good (ICC >0.4 and <0.75), and excellent (ICC >0.75) .
Timepoint [1] 322065 0
In 50 participants the PPA will be measured at the initial assessment and then again 1 week after at the start of each of the 5 assessment blocks.
Secondary outcome [2] 322225 0
The reliability of the choice stepping reaction time will be analysed by correlation of test-retest scores. Using the intraclass correlation coefficient (ICC), the reliability for each measurement tool will be classified as low (ICC <0.4), good (ICC >0.4 and <0.75), and excellent (ICC >0.75) .
Timepoint [2] 322225 0
In 50 participants the choice stepping reaction time will be measured at the initial assessment and then again 1 week after at the start of each of the 5 assessment blocks.
Secondary outcome [3] 322226 0
The reliability of the multiple sclerosis functional composite score (MSFC) will be analysed by correlation of test-retest scores. Using the intraclass correlation coefficient (ICC), the reliability for each measurement tool will be classified as low (ICC <0.4), good (ICC >0.4 and <0.75), and excellent (ICC >0.75) .
Timepoint [3] 322226 0
In 50 participants the MSFC scores will be measured at the initial assessment and then again 1 week after at the start of each of the 5 assessment blocks.
Secondary outcome [4] 322227 0
Prospective falls over six months will be monitored with monthly falls diaries which will be returned to the investigators, with monthly telephone follow-up if required.
Timepoint [4] 322227 0
The participants will start completing monthly falls calendars during the 10 weeks from baseline to the end of the intervention and then during the 14 weeks following the end of the intervention. In total, six months of monthly falls calendars will be completed by all participants in each of the 5 blocks.
Secondary outcome [5] 322228 0
Dynamic balance will be assessed by the Timed Up and Go Test and the choice stepping reaction time test.
Timepoint [5] 322228 0
Dynamic balance will be assessed at baseline and at 10 weeks following the commencement of the intervention for each of the 5 blocks.
Secondary outcome [6] 322229 0
Endurance will be assessed by the 6-minute Walk Test.
Timepoint [6] 322229 0
Endurance will be assessed at baseline and at 10 weeks after the commencement of the intervention for each of the 5 blocks.
Secondary outcome [7] 322230 0
Functional mobility will be measured by the multiple sclerosis functional composite score (MSFC) which is comprised of the symbol-digit test, 9-Hole Peg test, and the 10 meter walk test.
Timepoint [7] 322230 0
Functional mobility will be assessed at baseline and at 10 weeks after the commencement of the intervention for each of the 5 blocks.

Eligibility
Key inclusion criteria
Participants with MS, Expanded Disability Status Scale (EDSS) Level ranging from 2-6, and can walk independently (with or without the use of an assistive device) will be invited to participate.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be screened and excluded from the study if they have had a relapse within the last 3 months, corticosteroid treatment within 28 days of the study commencement, or have contra­indications for exercise.

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 concealment will be done with sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation to intervention or control groups will occur after completion of the baseline assessment. Permuted block randomisation will be performed using web-based randomisation software (i.e., a concealed randomisation system).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
This study is a randomised, single blind control trial using a pre-post intervention design targeting proprioceptive feedback and exercise training to improve functional gait and reduce falls and falls risk in people with multiple sclerosis.
100 subjects (age 18-65) will be randomly allocated to two groups, a control group and an intervention group (WBV group).

Over one year, five intervention blocks lasting 10 weeks will be delivered. 20 participants will be recruited for each block, 10 of which will receive a WBV platform delivered to their home. At the conclusion of the 10-week intervention block, the next 20 participants will begin the second 10-week block. This will be repeated three additional times (10-week intervention blocks 3, 4, and 5) bringing the total number of participants in each group to 50 at the end of one year.

In addition, reliability for the choice stepping reaction time test, the physiological profile assessment, and the multiple sclerosis functional composite score will be measured at the start of each intervention block. 50 participants with Expanded Disability Status Scale (EDSS) Levels ranging from 2-6 (n=10 for each of the five levels for a total of 50 participants) will return 1 week after the initial evaluation to be reassessed using the same testing protocol.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample size was selected based on several factors. First, the project’s primary aim is to assess falls risk as a pilot project. The falls risk as assessed by the PPA is a good predictor of prospective falls (2) and has been validated in people with MS (1). Using data from a previous study (1) showing that falls risk score using the PPA is 2.7 (+/- 1.38) for people with MS (Disease Steps 0-5), we conducted a power and sample size analysis in STATA (StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX: StataCorp LP). The result showed a sample size of 108 (N1 = 54; N2 = 54; ratio: 1:1) will give 90% power to detect ~30% difference for falls risk using the PPA, assuming the use of a two tailed independent samples t-test with alpha = 0.05 (In Stata: power twomeans 0, diff(.87) sd(1.38) power(0.9)). Next, based on the recent findings of Uszynski and colleagues (3) a sample size of 104 is recommended to show differences in our secondary outcome examining functional mobility using the 6 Minute Walk test. To confirm this, we again conducted a power and sample size analysis in STATA using data from a previous study showing that people with MS in Disease Step 3 (or EDSS = ~4.5 5.5) walk ~315 meters (SD = 85) in 6 minutes (4). The result showed a sample size of 88 (N1 = 44; N2 = 44; ratio: 1:1) will give 90% power to detect ~20% difference for the 6 minute walk test outcome variable, assuming the use of a two-tailed independent samples t-test with alpha = 0.05 (In Stata: power twomeans 0, diff(60) sd(85) power(0.9)).

With respect to reliability of outcome tests, a sample size of 50 participants provides an adequate sample size and narrow confidence intervals to sufficiently analyse reliability of the choice stepping reaction time test, the physiological profile assessment, and the multiple sclerosis functional composite score for people with MS.

Between group comparisons of final test performance for the outcome measures will be made using General Linear Models (ANCOVA) controlled for pre-test performance. Significance is set at 0.05. Change scores (pre minus post) and effect sizes will be calculated. An estimate of the effect on falls will also be calculated to inform sample size calculations for any future trial to determine the effect on the intervention on fall rates. Participants can withdraw from the study at anytime. However, this is an intention to treat study and thus, all data collected will be included in the final analysis.

References:
1. Hoang PD, Cameron MH, Gandevia SC, and Lord SR. Neuropsychological, Balance, and Mobility Risk Factors for Falls in People With Multiple Sclerosis: A Prospective Cohort Study. Arch Phys Med Rehabil 95: 480-486, 2014.
2. HLord SR, Menz HB, and Tiedemann A. A physiological profile approach to falls risk assessment and prevention. Phys Ther 83: 237-252, 2003
3. Uszynski MK, Purtill H, Donnelly A, and Coote S. Comparing the effects of whole-body vibration to standard exercise in ambulatory people with Multiple Sclerosis: A randomised controlled feasibility study. Clin Rehabil 0269215515595522, 2015.
4. Hoang PD, Gandevia SC, and Herbert RD. Prevalence of joint contractures and muscle weakness in people with multiple sclerosis. Disabil Rehabil 36: 1588-1593, 2014.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
4/04/2016
Actual
18/04/2016
Date of last participant enrolment
Anticipated
28/03/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 5423 0
Westmead Hospital - Westmead
Recruitment hospital [2] 5500 0
Neuroscience Research Australia (NeuRA) - Randwick
Recruitment hospital [3] 5501 0
Brain and Mind Centre - University of Sydney - Camperdown
Recruitment hospital [4] 5515 0
Multiple Sclerosis Ltd (MS Ltd) - Studdy MS Centre - Lidcombe
Recruitment postcode(s) [1] 12954 0
2141 - Lidcombe
Recruitment postcode(s) [2] 12955 0
2031 - Randwick
Recruitment postcode(s) [3] 12956 0
2145 - Westmead
Recruitment postcode(s) [4] 12957 0
2000 - Sydney

Funding & Sponsors
Funding source category [1] 293088 0
Charities/Societies/Foundations
Name [1] 293088 0
Multiple Sclerosis Research Australia
Country [1] 293088 0
Australia
Funding source category [2] 296017 0
Government body
Name [2] 296017 0
NHMRC Motor Impairment Project Grant
Country [2] 296017 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
The University of Sydney
NSW 2006
Australia
Country
Australia
Secondary sponsor category [1] 291872 0
None
Name [1] 291872 0
Address [1] 291872 0
Country [1] 291872 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294595 0
University of Sydney Human Research Ethics Committee
Ethics committee address [1] 294595 0
Ethics committee country [1] 294595 0
Australia
Date submitted for ethics approval [1] 294595 0
13/11/2015
Approval date [1] 294595 0
04/03/2016
Ethics approval number [1] 294595 0
2016/02

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 812 812 0 0
/AnzctrAttachments/370297-MS Study PIS Clinical Trial V3.docx
Attachments [2] 813 813 0 0
/AnzctrAttachments/370297-Application Outcome 2016_002.pdf
Attachments [3] 814 814 0 0
/AnzctrAttachments/370297-MS Study Clinical Trial protocol V4.docx

Contacts
Principal investigator
Name 64246 0
Dr David Kennedy
Address 64246 0
Discipline of Physiotherapy
Faculty of Health Sciences
University of Sydney,
East St
Lidcombe. NSW. 2141
Country 64246 0
Australia
Phone 64246 0
+61 2 9351 9589
Fax 64246 0
Email 64246 0
[email protected]
Contact person for public queries
Name 64247 0
David Kennedy
Address 64247 0
Discipline of Physiotherapy
Faculty of Health Sciences
University of Sydney,
East St
Lidcombe. NSW. 2141
Country 64247 0
Australia
Phone 64247 0
+61 2 9351 9589
Fax 64247 0
Email 64247 0
[email protected]
Contact person for scientific queries
Name 64248 0
David Kennedy
Address 64248 0
Discipline of Physiotherapy
Faculty of Health Sciences
University of Sydney,
East St
Lidcombe. NSW. 2141
Country 64248 0
Australia
Phone 64248 0
+61 2 9351 9589
Fax 64248 0
Email 64248 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseInterventions for preventing falls in people with multiple sclerosis.2019https://dx.doi.org/10.1002/14651858.CD012475.pub2
N.B. These documents automatically identified may not have been verified by the study sponsor.