Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625001084471
Ethics application status
Approved
Date submitted
8/09/2025
Date registered
3/10/2025
Date last updated
3/10/2025
Date data sharing statement initially provided
3/10/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Home strengthening exercise for knee osteoarthritis: the FRESH randomised controlled trial
Scientific title
FREquency of Strength Home exercises for knee osteoarthritis: the FRESH non-inferiority randomised controlled trial
Secondary ID [1] 315182 0
None
Universal Trial Number (UTN)
Trial acronym
FRESH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Knee osteoarthritis 338626 0
Condition category
Condition code
Musculoskeletal 334921 334921 0 0
Osteoarthritis
Physical Medicine / Rehabilitation 334922 334922 0 0
Physiotherapy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomly assigned a physiotherapist (stratified by group allocation—‘once’ or ‘three’ times weekly exercise group using random permuted block sizes), and research staff will book one consultation appointment on behalf of the participant.

Each participant will have one online consultation (within 1-week post-randomisation, 30 minutes each) with the randomly allocated physiotherapist to prescribe a home strength program that participants will be asked to undertake for 3 months. Physiotherapists will prescribe the same five exercises to each participant. These exercises reflect the typical home strength exercises prescribed in the literature for knee osteoarthritis (OA) and by physiotherapists in Australia. Ahead of the physiotherapy consultations, the research team will post all participants two exercise resistance bands of different strengths (green and blue) along with an exercise booklet.

The trial arms differ in the frequency of exercise prescribed across the week (once versus three times per week). Other dosage parameters will be identical across the treatment groups. Prescription of each home strength program will be the same five standardised exercises, each to be performed as 3 sets of 12 reps, with 1-3 minutes rest between sets. The days home exercises are performed each week are up to the participants discretion.

The physiotherapist will individualise the colour of the exercise band (green or blue) for the seated knee extension exercise and the side leg raises in standing exercise to ensure the participant is working as close as possible to an intensity of 5-7 out of ten (hard to very hard) on the modified Borg Rating of Perceived Exertion Scale for strength training. Based on the Borg scale, the physiotherapist may also decide that an exercise band is not needed for one or both of these exercises. Physiotherapists will verbally advise participants whether they should perform their prescribed program once or three times per week (based on allocation), and this information will also be included in the participant’s exercise booklet. After the consultation, the physiotherapist will instruct the participant to perform the exercise program until their follow-up assessment at 3 months post-randomisation. Participants will be permitted to continue with their usual joint pain medications during that time.

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 demonstrations of exercises to participants. This will be shared with participants via a shared-screen feature on Zoom, allowing them to view a demonstration of the exercise during the consultation.

Semi-structured electronic consultation notes will be recorded by the physiotherapist and submitted to the research staff after the consultation. Notes will be scrutinised by research staff for physiotherapist fidelity to allocated exercise frequency. Participants will complete a one week log book recording their exercises in weeks 4, 8 and 12 with the data submitted to the researchers.
Intervention code [1] 331810 0
Rehabilitation
Intervention code [2] 331811 0
Treatment: Other
Comparator / control treatment
The study is comparing the same exercise program performed either three times per week or once per week.
Control group
Active

Outcomes
Primary outcome [1] 342561 0
Self-reported severity of knee pain during walking over the past week
Timepoint [1] 342561 0
Baseline & 3 months after randomisation
Secondary outcome [1] 451305 0
Self-reported knee pain severity
Timepoint [1] 451305 0
Baseline & 3 months after randomisation
Secondary outcome [2] 451306 0
Self-reported physical function
Timepoint [2] 451306 0
Baseline & 3 months after randomisation
Secondary outcome [3] 451307 0
Quality of life
Timepoint [3] 451307 0
Baseline & 3 months after randomisation
Secondary outcome [4] 451308 0
Self-efficacy
Timepoint [4] 451308 0
Baseline & 3 months after randomisation
Secondary outcome [5] 451309 0
Exercise self efficacy
Timepoint [5] 451309 0
Baseline & 3 months after randomisation
Secondary outcome [6] 451310 0
Global rating of change in the knee overall
Timepoint [6] 451310 0
3 months after randomisation
Secondary outcome [7] 451311 0
Physical function
Timepoint [7] 451311 0
Baseline & 3 months after randomisation
Secondary outcome [8] 451313 0
Patient acceptance of symptoms
Timepoint [8] 451313 0
3 months after randomisation
Secondary outcome [9] 451314 0
Quadriceps strength
Timepoint [9] 451314 0
Baseline & 3 months after randomisation
Secondary outcome [10] 451315 0
Calf strength
Timepoint [10] 451315 0
Baseline & 3 months after randomisation
Secondary outcome [11] 451316 0
Willingness to undergo knee joint replacement surgery
Timepoint [11] 451316 0
Baseline & 3 months after randomisation

Eligibility
Key inclusion criteria
i) meet the National Institute for Health and Care Excellence clinical criteria for OA
i. age 45 years or older;
ii. activity-related knee joint pain;
iii. no morning knee stiffness or morning knee stiffness duration of less than 30 mins;
ii) report history of knee pain for 3 months or more;
iii) report knee pain on most days of the past month;
iv) report knee pain on walking over the past week of at least 4 on an 11-point (0-10 range) NRS;
v) report difficulty walking or climbing stairs;
vi) have an email address and access to a computer/laptop/tablet/smartphone with webcam and internet connection for Zoom consultation and;
vii) willing to participate in a videoconferencing consultation for their physiotherapy appointment.
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 any knee/hip surgery in the next 6 months;
iii) previous arthroplasty on the affected knee;
iv) undergone knee surgery in either knee 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 (at screening) any inflammatory arthritis (e.g., rheumatoid arthritis);
viii) self-reports (at screening) any neurological condition that impacts their lower limb function;
ix) self-reports (at screening) any unstable/uncontrolled cardiovascular condition that could make exercise unsafe.
x) previously participated in a CHESM clinical trial in the prior four years, or is currently participating in another research study at CHESM or elsewhere.

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 is based on detecting non-inferiority of a once-a-week home exercise program prescription relative to a three-times-a-week home exercise program prescription at 3-month post-randomisation. For change in pain, a non-inferiority margin (NIM) of 0.95?NRS points was chosen as this is less than the lowest of the range (1.0–2.0?units) reported as the minimum clinically important difference (MCID) by people with chronic pain, and less than the MCID of 1.8 points (extrapolated from a 100?mm visual analogue scale, VAS67) for OA by clinician consensus. Assuming a standard deviation (SD) of 1.9 NRS points for pain and a correlation of 0.36 between baseline and follow-up,64 15% loss to follow-up, 90% power, and a one-sided 2.5% significance level, we need 89 participants/arm (178 participants total).

Primary analyses will be conducted according to intention-to-treat principles, including all participants according to their allocated study arm, irrespective of adherence.

Data will be managed via REDCap. All analyses will be described a priori in a Statistical Analysis Plan, which will be developed while blinded to group allocation and published on our website before the analyses commence. Between-group differences in mean change (baseline minus 3-month follow-up) in average walking pain (primary outcome) will be compared using linear mixed-effects models, adjusting for the outcome at baseline and including a random effect for physiotherapists. Non-inferiority will be demonstrated if the lower bound of the two-sided 95% confidence interval (CI) for the between-group difference (once weekly exercise prescription minus three times weekly exercise prescription) is above -0.95. The 95% CIs correspond to testing a null hypothesis of non-inferiority at a one-sided significance level of 2.5%. Multiple imputation will be used to account for missing data if required (i.e., if >5% missing values for primary outcome at 3 months).

Secondary continuous outcomes will also be analysed using linear mixed-effects models and reported as mean (95% CI) between-group differences, and interpreted relative to a superiority framework since no NIMs have been specified for these outcomes. Binary outcomes will be analysed using logistic mixed effects models with a random effect for physiotherapist, with effects summarised as relative risks and risk differences with corresponding 95% CIs, and interpreted relative to a superiority framework. Exploratory analyses of a priori moderators of treatment effect on the primary outcome will be examined by including an interaction between pre-specified potential moderators and treatment in the linear mixed-effects model, with interpretation using the superiority framework.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
5/11/2025
Actual
Date of last participant enrolment
Anticipated
5/05/2027
Actual
Date of last data collection
Anticipated
5/08/2027
Actual
Sample size
Target
178
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 319754 0
Government body
Name [1] 319754 0
National Health and Medical Research Council (NHMRC) Investigator Grant
Country [1] 319754 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 322261 0
None
Name [1] 322261 0
Address [1] 322261 0
Country [1] 322261 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 318309 0
University of Melbourne STEMM 1 ethics committee
Ethics committee address [1] 318309 0
Ethics committee country [1] 318309 0
Australia
Date submitted for ethics approval [1] 318309 0
14/08/2025
Approval date [1] 318309 0
08/09/2025
Ethics approval number [1] 318309 0
2025-33625-70160-2

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

Contacts
Principal investigator
Name 143770 0
Dr Travis Haber
Address 143770 0
Centre for Health, Exercise and Sports Medicine Department of Physiotherapy Level 7, Alan Gilbert Building The University of Melbourne, Victoria 3010 Australia
Country 143770 0
Australia
Phone 143770 0
+61 3 83440425
Fax 143770 0
Email 143770 0
[email protected]
Contact person for public queries
Name 143771 0
Ben Metcalf
Address 143771 0
Centre for Health, Exercise and Sports Medicine Department of Physiotherapy Level 7, Alan Gilbert Building The University of Melbourne, Victoria 3010 Australia
Country 143771 0
Australia
Phone 143771 0
+61 3 83448127
Fax 143771 0
Email 143771 0
[email protected]
Contact person for scientific queries
Name 143772 0
Travis Haber
Address 143772 0
Centre for Health, Exercise and Sports Medicine Department of Physiotherapy Level 7, Alan Gilbert Building The University of Melbourne, Victoria 3010 Australia
Country 143772 0
Australia
Phone 143772 0
+61 3 83440425
Fax 143772 0
Email 143772 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• 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.

Conditions for requesting access:
• -

What individual participant data might be shared?
• All data presented in the published results paper, available in XLSX format.

What types of analyses could be done with individual participant data?
• 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.

When can requests for individual participant data be made (start and end dates)?
From:
After publication of main results
To:
A period of 15 years from publication

Where can requests to access individual participant data be made, or data be obtained directly?
• 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.

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Data dictionary    The Data Dictionary will be supplied with the de-i... [More Details]


Results publications and other study-related documents

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