Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001226594
Ethics application status
Approved
Date submitted
18/09/2024
Date registered
9/10/2024
Date last updated
9/10/2024
Date data sharing statement initially provided
9/10/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Home strengthening exercise for knee osteoarthritis: the MULTI-ONE randomised controlled trial
Scientific title
MULTIple or ONE home strengthening exercise(s) for knee osteoarthritis: the MULTI-ONE randomised controlled trial (RCT)
Secondary ID [1] 312857 0
None
Universal Trial Number (UTN)
Trial acronym
MULTI-ONE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Knee osteoarthritis 334993 0
Condition category
Condition code
Musculoskeletal 331508 331508 0 0
Osteoarthritis
Physical Medicine / Rehabilitation 331901 331901 0 0
Physiotherapy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Active exercise groups

Participants will be randomly assigned a physiotherapist (stratified by group allocation - ‘one’ or ‘five’ exercise arm using random permuted block sizes) and research staff will book three consultation appointments (1, 2 and 6 weeks post-randomisation, 30 minutes each) on behalf of the participant.

The consultations with the physiotherapist will occur via telehealth (Zoom video- conferencing), for prescription, monitoring and progression of a home strength program that participants will be asked to undertake for 12 weeks, but encouraged to continue beyond that time up until 9 months. Physiotherapists will be permitted to use their clinical judgement to prescribe exercise(s) from a pre-determined list of allowed exercises that reflects the typical home strength exercises prescribed in the literature for knee OA and by physiotherapists in Australia. Physiotherapists will be asked to prescribe the exercise(s) that they think will be most beneficial in relieving pain and improving function for a given participant. Exercises will be selected from a list including quadriceps exercises (including weightbearing such as squats and non-weightbearing exercises such as seated knee extensions), hamstrings exercises (such as hamstring curls or seated knee flexion), hip exercises (such as crab walking or bridges) and calf exercises (such as calf raises). Participants will be asked to perform prescribed exercises at home (3 sets of 12 repetitions for each exercise), three times/week.

The only difference across trial arms is in the number of exercises that will be prescribed (one versus five as per the randomisation schedule). The physiotherapist will individualise the technique of each exercise (e.g. depth of knee bend, amount of body weight, hold time, colour of exercise band etc) to encourage the participant to work at an intensity of 5-7 out of ten (hard to very hard) on the modified Borg Rating of Perceived Exertion CR-10 scale for strength training. At subsequent consultations, physiotherapists may replace a prescribed exercise(s) for a different exercise(s) if required (eg because an exercise is too easy, too hard, aggravates the knee etc) as long as they adhere to the allocated number of exercises (ie a participant’s program contains only the allocated number of exercises of either one or five) and choose only from the defined list of exercises.

Consultations will occur via the video-conferencing facility of Zoom, a commercial cloud-based system accessible from any internet-connected computer, laptop or mobile device. Physiotherapists will consult from their clinic with participants based at home or wherever is suitable (e.g. work). Physiotherapists will be provided access to a website containing a video library of exercises to allow them to provide real-time demonstration of exercises to participants. This will be shared with the participants via a share-screen feature on Zoom so that the participant is able to view a demonstration of the exercise during the consultations. Participants will not have access to the online video library outside of the consultations. During each consultation, physiotherapists will email participant’s exercise handouts for how to perform each of their prescribed exercises (the research team will provide the physiotherapists with standardised digital instructions for each exercise on the allowed list of exercises to facilitate this).

Semi-structured electronic consultation notes will be recorded by the physiotherapist for each consultation and submitted to research staff at the completion of each consultation. Notes will be scrutinised by research staff for physiotherapist fidelity to exercise protocols.
Intervention code [1] 329436 0
Rehabilitation
Comparator / control treatment
Control group (usual care)

Participants allocated to this group will continue with their usual care/management approaches for their knee problem. They will not have any consultations with a trial physiotherapist and so will not be prescribed any home strength exercises.

Usual care for knee osteoarthritis in Australia may entail self-management strategies such as use of heat or medications (such as analgesics or anti-inflammatories) to manage pain as required. Participants may also use other medications as prescribed by their doctor.
Control group
Active

Outcomes
Primary outcome [1] 339305 0
Self-reported severity of knee pain during walking over the past week
Timepoint [1] 339305 0
Baseline, 3 months (primary timepoint) & 9 months after randomisation
Secondary outcome [1] 439401 0
Self-reported knee pain
Timepoint [1] 439401 0
Baseline, 3 months & 9 months after randomisation
Secondary outcome [2] 439402 0
Self-reported physical function
Timepoint [2] 439402 0
Baseline, 3 months & 9 months after randomisation
Secondary outcome [3] 439403 0
Quality of life
Timepoint [3] 439403 0
Baseline, 3 months & 9 months after randomisation
Secondary outcome [4] 439404 0
Self-efficacy
Timepoint [4] 439404 0
Baseline, 3 months & 9 months after randomisation
Secondary outcome [5] 439405 0
Exercise self efficacy
Timepoint [5] 439405 0
Baseline, 3 months & 9 months after randomisation
Secondary outcome [6] 439406 0
Fear of movement
Timepoint [6] 439406 0
Baseline, 3 months & 9 months after randomisation
Secondary outcome [7] 439407 0
Global rating of change in the knee overall
Timepoint [7] 439407 0
3 months & 9 months after randomisation
Secondary outcome [8] 439408 0
Quadriceps strength
Timepoint [8] 439408 0
Baseline, 3 months & 9 months after randomisation
Secondary outcome [9] 439409 0
Calf strength
Timepoint [9] 439409 0
Baseline, 3 months & 9 months after randomisation
Secondary outcome [10] 439410 0
Willingness to undergo knee joint replacement surgery
Timepoint [10] 439410 0
Baseline, 3 months & 9 months after randomisation

Eligibility
Key inclusion criteria
i) meet National Institute for Health and Care Excellence clinical criteria for Osteoarthritis (OA)
a. age 45 years or over;
b. activity-related knee joint pain;
c. no morning knee stiffness or morning knee stiffness duration of 30 mins or less;
ii) report history of knee pain of 3 months or longer;
iii) report knee pain on most days of the past month;
iv) report knee pain on walking over past week of 4 or more on 11-point (0-10 range) numerical rating scale (NRS);
v) report difficulty walking or climbing stairs;
vi) have an email address for receiving exercise instruction sheets;
vii) have access to a computer/laptop/tablet/smartphone with webcam and internet connection for Zoom consultations and;
viii) willing to participate in video consultations for physiotherapy appointments.
Minimum age
45 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i) inability to speak or read English;
ii) on waiting list for/planning knee/hip surgery in next 9 months;
iii) previous arthroplasty on affected knee;
iv) undergone knee surgery in the past 6 months;
v) is undertaking/has undertaken regular strengthening exercise (at least once per week) for knee problems at any stage in the past 6 months;
vi) intending to/planning to commence regular strengthening exercise (at least once per week) for knee problems in the next 3 months;
vii) self-reports any inflammatory arthritis (e.g., rheumatoid arthritis);
viii) self-reports any neurological condition that impacts their lower limb function or;
ix) self-reports any unstable/uncontrolled cardiovascular condition that could make exercise unsafe.

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)
The person who will determine if a potential participant is eligible for inclusion in the trial will be unaware, when this decision is made, to which group the participant will be allocated. The randomisation schedule will be concealed in a password protected computer database. A member of our research team will maintain and access the schedule and reveal allocation to the Trial Coordinator as each participant requires randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation schedule will be prepared by the biostatistician (permuted random block sizes) with physiotherapist allocation stratified by group
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
A biostatistician will develop a detailed Statistical Analysis Plan while blinded to intervention allocation. This will be written and published on the CHESM website prior to data analysis commencing.

Sample Size Calculation
A total sample size of 144 (48 per arm) is required. Sample size calculations were performed accounting for differential clustering between the ‘usual care’ and the ‘one’ or ‘five’ exercise arms where clustering in the exercise arm is due to the treating physiotherapist, assuming that the correlation between two repeated measurements is the same for both control and intervention arms. Assuming there will be 10 physiotherapists treating approximately 4 patients each, with an intra-cluster correlation of 0.05, 40 participants per arm are required to detect a minimal clinically important difference (MCID) of 1.8 NRS units in change in pain from baseline to 3 months with 80% power. This assumes a between-participant standard deviation of 2.4 and pre-post correlation of 0.41, with a two-sided alpha of 0.05 (split equally as 0.167 between the three pairwise comparisons). Accounting for 15% loss to follow-up, 48 participants per arm are required. This sample size of 144 participants provides greater than 80% power to detect a MCID of 1.8 NRS units in change in pain at 3 months from baseline between ‘one’ versus ‘five’ exercise arms with a two-sided alpha of 0.167, assuming a between-participant standard deviation of 1.9 and pre-post correlation of 0.36.

Statistical Analysis Plan
Analysis will be undertaken while biostatisticians are masked to intervention name. Main comparative analyses between groups will be performed using intention-to-treat. A constrained longitudinal data analysis (cLDA) model will be fitted to examine differences in change in walking pain (primary outcome) between the three intervention arms. The response will consist of all walking pain scores (baseline, 3 months, 9 months) and the model will include factors representing intervention arm, time (categorical), and an intervention arm-by-time interaction with random effects for participant and accounting for clustering by physiotherapist as appropriate, with the restriction of a common baseline mean across intervention arms. The primary hypotheses will be evaluated by obtaining the estimated differences in mean change in pain score between each pair of intervention arms (five exercises versus control; one exercise versus control; five exercises versus one exercise) from baseline to 3 months (primary time point), two-sided multiplicity-adjusted 95% confidence intervals and p-values. These models provide valid inference in the presence of missing data if the data are missing at random. An analysis will be conducted using the delta-adjustment method under the pattern-mixture modelling framework in the context of multiple imputation to assess sensitivity to missingness not at random.

A similar approach will be used for continuous secondary outcomes. Binary secondary outcomes will each be compared between groups using risk differences and risk ratios calculated from a logistic regression model fit using generalized estimating equations to account for clustering, including a term for week and an interaction between week and treatment group. Assumptions will be assessed using standard diagnostic plots and methods. Since these are all secondary analyses, p-values for these assessments will not be adjusted for multiple comparisons. We will conduct exploratory analyses to evaluate moderation of treatment effects on the primary outcome by pre-specified potential moderators. This will be assessed by including appropriate interaction terms between the moderators and the intervention arms.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
4/11/2024
Actual
Date of last participant enrolment
Anticipated
31/03/2026
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
144
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 317300 0
Government body
Name [1] 317300 0
National Health and Medical Research Council (NHMRC) Investigator Grant
Country [1] 317300 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 319677 0
None
Name [1] 319677 0
Address [1] 319677 0
Country [1] 319677 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316033 0
University of Melbourne Central Human Research Ethics Committee
Ethics committee address [1] 316033 0
Ethics committee country [1] 316033 0
Australia
Date submitted for ethics approval [1] 316033 0
19/07/2024
Approval date [1] 316033 0
12/09/2024
Ethics approval number [1] 316033 0
2024-29890-58015-3

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

Contacts
Principal investigator
Name 136570 0
Prof Rana Hinman
Address 136570 0
Centre for Health, Exercise and Sports Medicine Department of Physiotherapy Level 7, Alan Gilbert Building The University of Melbourne, Victoria 3010 Australia
Country 136570 0
Australia
Phone 136570 0
+61 3 8344 3223
Fax 136570 0
Email 136570 0
[email protected]
Contact person for public queries
Name 136571 0
Penny Campbell
Address 136571 0
Centre for Health, Exercise and Sports Medicine Department of Physiotherapy Level 7, Alan Gilbert Building The University of Melbourne, Victoria 3010 Australia
Country 136571 0
Australia
Phone 136571 0
+61 3 9035 5401
Fax 136571 0
Email 136571 0
[email protected]
Contact person for scientific queries
Name 136572 0
Rana Hinman
Address 136572 0
Centre for Health, Exercise and Sports Medicine Department of Physiotherapy Level 7, Alan Gilbert Building The University of Melbourne, Victoria 3010 Australia
Country 136572 0
Australia
Phone 136572 0
+61 3 8344 3223
Fax 136572 0
Email 136572 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All data presented in the published results paper, available in XLSX format.
When will data be available (start and end dates)?
A period of 15 years from publication
Available to whom?
Data will be made available as required for specific, approved analyses by researchers. Data will be provided from locked, cleaned, and de- identified study database. Requests will be reviewed by the Principal Investigator prior to approval.
Available for what types of analyses?
The investigators endorse the concept of data sharing to advance medical science. All requests for data sharing will be reviewed by the Principal Investigator to ensure no conflict with any planned sub analyses and to ensure that the data are shared in an ethical and protected manner.

Analyses aimed to improve treatment of knee osteoarthritis for non-commercial purposes are eligible.
How or where can data be obtained?
By emailing the Principal Investigator at [email protected]. Data will be made available after review and approval by the Principal Investigator. Before any analysis, a signed Confidentiality Agreement and/or Data Sharing Agreement is required.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
24206Data dictionary    The Data Dictionary will be supplied with the de-i... [More Details]



Results publications and other study-related documents

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