Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000689471p
Ethics application status
Submitted, not yet approved
Date submitted
9/06/2025
Date registered
30/06/2025
Date last updated
30/06/2025
Date data sharing statement initially provided
30/06/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
ACTIVE KNEECAPs! tArgeted effeCTIVE treatments for adolescent KNEECAP pain
Scientific title
tArgeted effeCTIVE treatments for adolescent KNEECAP pain (ACTIVE KNEECAPs!): A multicentre randomised clinical trial evaluating the effectiveness of targeted physiotherapy, foot orthoses and advice for treating adolescents with patellofemoral pain
Secondary ID [1] 312282 0
None
Universal Trial Number (UTN)
Trial acronym
ACTIVE KNEECAPs!
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patellofemoral pain 334005 0
Condition category
Condition code
Musculoskeletal 330680 330680 0 0
Other muscular and skeletal disorders
Physical Medicine / Rehabilitation 333979 333979 0 0
Physiotherapy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The aim of this RCT is to compare the effectiveness and cost-effectiveness of foot orthoses or targeted physiotherapy, combined with advice, with advice alone, in adolescents with patellofemoral pain (PFP).

Participants will be randomised to one of three intervention arms:
(1) Foot orthoses + advice
(2) Targeted physiotherapy + advice; or
(3) Advice (control).

Arm 1: Foot orthoses + Advice

The foot orthoses intervention aims to provide adolescents with a simple device that can be worn in their everyday shoes, with minimal additional time and effort required by them. Participants will receive prefabricated contoured foot orthoses from a commercially available range (Vasyli Medical, Vionic Group LLC, Novato CA, USA) that is acceptable to adolescents with PFP. The orthoses have inbuilt arch support and varus wedging, with a variety of lengths and shapes to fit different footwear. Foot orthoses will be fit for comfort using our established algorithm. Participants will be fit with 2-4 pairs of foot orthoses in enclosed shoes they most commonly wear (e.g. school shoes, sports shoes [including running shoes, boots, cleats], casual shoes). The study practitioner fitting the foot orthoses (registered podiatrist or physiotherapist) will ensure that the adolescent’s footwear is appropriate to accommodate the foot orthoses, and will provide recommendations on suitable footwear if the adolescents and their parents wish to purchase new footwear. The orthoses can be transferred to other shoes (e.g. between different sports shoes) as needed. Foot orthoses will be fit to shoes as a pair (i.e. one in each shoe), regardless of whether the participant has unilateral or bilateral patellofemoral pain (PFP). Participants will be offered up to 3 appointments with the study practitioner in the first 3 months to fit the orthoses and make adjustments for comfort or to address any issues (e.g. rubbing, blisters), with the first appointment scheduled within 1-2 weeks after randomisation. One additional appointment will be offered over the remaining 6 months to refit or replace orthoses as needed (e.g. due to growth spurts). Each appointment will be approximately 30 minutes duration. If in-person attendance is not feasible for follow-up appointments where no foot orthoses prescription or adjustment is needed (e.g. due to transport issues), participants will be offered telehealth appointments. Participants will also be offered a pair of contoured flip-flops, slides or sandals to wear as an alternative to enclosed shoes and foot orthoses in warmer weather (Tide II Toe Post Sandal or Rejuvenate Recovery Sandal; Vionic, Vionic Group LLC, Novato CA, USA). Participants will be provided with a guide for using and adapting to the orthoses and contoured footwear (printed and electronic resources).

Participants in Arm 1 will also receive the Advice intervention. The advice intervention aims to give adolescents brief, credible information about their PFP, and simple strategies to manage it. Participants in all three trial arms will receive the same advice intervention. The resources will explain what PFP is and what it means, what causes PFP, and simple self-management strategies for their knee pain. The resources will include: (i) a 1-page written summary; (ii) a graphical summary of key points; and (iii) a video summary presented by a health professional (e.g. physiotherapist) and an adolescent. The advice intervention resources have been adapted from existing resources, in consultation with the trial Consumer and Stakeholder Advisory Groups. Participants will be given the resources at the baseline appointment, and asked to review them in their own time. A follow-up zoom or phone call will be scheduled within two weeks of the baseline appointment, with the same health professional who conducts the screening assessment and gives the adolescent a diagnosis of PFP. During the call, they will go through the resources with the participant and their parent/guardian (if applicable) and answer any questions.


Arm 2: Targeted physiotherapy + Advice

The targeted physiotherapy intervention aims to provide adolescents with the skills to self-manage their PFP in the short- and long-term and build self-efficacy, using strategies tailored to their needs and impairments. The program uses education, behaviour change techniques and tools, exercise and pain-management strategies, and is based on interventions that have been tested in previous RCTs and cohort studies in adolescents with PFP, and adapted to the Australian context in consultation with the trial Consumer and Stakeholder Advisory Groups. The program consists of: (i) activity modification and load management; (ii) knee taping; (iii) exercise (tailored to the adolescent’s sport and physical activity demands, strength and movement impairments, and preferences); and (iv) psychologically informed videos (explaining pain; addressing beliefs about kinesiophobia, fear avoidance and pain catastrophising; explaining how to stay active; reframing negative thoughts into positive thoughts). Study practitioners (registered physiotherapists) will undergo training in how to select, tailor and prescribe each component of the program, to deliver an intervention that is targeted to each adolescent in terms of factors contributing to their PFP, sport and physical activity goals and demands, and acceptability to them (e.g. time commitment). Participants will be offered six sessions with the study practitioner over the 9-month trial. Up to 5 appointments will be scheduled over the first 3 months (initial appointment within 1-2 weeks of randomisation, subsequent appointments at 2 weeks, 1 month, 2 months and 3 months), with an additional appointment scheduled at approximately 6 months for longer-term follow-up and progression. Each appointment will be approximately 30 minutes duration. If in-person attendance is not feasible (e.g. due to transport issues), participants will be offered telehealth appointments (for some or all appointments). Participants will be provided with printed and electronic resources to accompany the components of the intervention.

Participants in Arm 2 will also receive the Advice intervention (detailed above).


Treatment adherence and fidelity

Treatment adherence will be monitored across all three trial arms (as described under secondary outcomes).
The fidelity of each of the three interventions will be evaluated by reviewing trial-specific treatment case report forms for each participant, and by observing a sample of participant intervention sessions during the first six months of the trial (video recorded; evaluated using a checklist of adherence and competence criteria specific to the intervention). General feedback points will be provided to all study practitioners based on outcomes of fidelity checks. Further training of study practitioners will be provided if issues with fidelity are identified early in the trial. Fidelity checks and feedback will be repeated in the second half of the intervention period.
Intervention code [1] 328745 0
Rehabilitation
Intervention code [2] 328746 0
Treatment: Devices
Intervention code [3] 331175 0
Treatment: Other
Comparator / control treatment
Arm 3: Advice (control)

The advice intervention aims to give adolescents brief, credible information about their PFP, and simple strategies to manage it. Participants in all three trial arms will receive the same advice intervention. The resources will explain what PFP is and what it means, what causes PFP, and simple self-management strategies for their knee pain. The resources will include: (i) a 1-page written summary; (ii) a graphical summary of key points; and (iii) a video summary presented by a health professional (e.g. physiotherapist) and an adolescent. The advice intervention resources have been adapted from existing resources, in consultation with the trial Consumer and Stakeholder Advisory Groups. Participants will be given the resources at the baseline appointment, and asked to review them in their own time. A follow-up zoom or phone call will be scheduled within two weeks of the baseline appointment, with the same health professional who conducts the screening assessment and gives the adolescent a diagnosis of PFP. During the call, they will go through the resources with the participant and their parent/guardian (if applicable) and answer any questions.

Participants randomised to the Advice group (Arm 3) will receive no additional intervention as part of the study, but will not be prohibited from seeking or receiving concomitant care or interventions outside of the trial. Other healthcare use will be recorded and described.
Control group
Active

Outcomes
Primary outcome [1] 338436 0
Knee pain
Timepoint [1] 338436 0
Baseline (T1), 1.5 months (T2), 3 months (T3, primary timepoint), 6 months (T4), 9 months (T5) post-commencement of intervention
Secondary outcome [1] 435937 0
Knee symptoms
Timepoint [1] 435937 0
Baseline (T1), 1.5 months (T2), 3 months (T3), 6 months (T4), 9 months (T5) post-commencement of intervention
Secondary outcome [2] 435938 0
Self-reported function
Timepoint [2] 435938 0
Baseline (T1), 1.5 months (T2), 3 months (T3), 6 months (T4), 9 months (T5) post-commencement of intervention
Secondary outcome [3] 435939 0
Self-reported function
Timepoint [3] 435939 0
Baseline (T1), 1.5 months (T2), 3 months (T3), 6 months (T4), 9 months (T5) post-commencement of intervention
Secondary outcome [4] 435940 0
Knee-related quality of life
Timepoint [4] 435940 0
Baseline (T1), 1.5 months (T2), 3 months (T3), 6 months (T4), 9 months (T5) post-commencement of intervention
Secondary outcome [5] 435941 0
Patellofemoral symptoms and knee-related quality of life
Timepoint [5] 435941 0
Baseline (T1), 1.5 months (T2), 3 months (T3), 6 months (T4), 9 months (T5) post-commencement of intervention
Secondary outcome [6] 435942 0
Knee pain severity
Timepoint [6] 435942 0
Baseline (T1), 0.5 months, 1 month, 1.5 months (T2), 2 months, 3 months (T3), 4 months, 5 months, 6 months (T4), 7 months, 8 months, 9 months (T5) post-commencement of intervention
Secondary outcome [7] 435943 0
Perception of change
Timepoint [7] 435943 0
1.5 months (T2), 3 months (T3), 6 months (T4), 9 months (T5) post-commencement of intervention
Secondary outcome [8] 435944 0
Patient Acceptable Symptom State (PASS)
Timepoint [8] 435944 0
Baseline (T1), 0.5 months, 1 month, 1.5 months (T2), 2 months, 3 months (T3), 4 months, 5 months, 6 months (T4), 7 months, 8 months, 9 months (T5) post-commencement of intervention
Secondary outcome [9] 436285 0
Treatment Failure (TF)
Timepoint [9] 436285 0
1.5 months (T2), 3 months (T3), 6 months (T4), 9 months (T5) post-commencement of intervention
Secondary outcome [10] 445460 0
Pain self-efficacy
Timepoint [10] 445460 0
Baseline (T1), 1.5 months (T2), 3 months (T3), 6 months (T4), 9 months (T5) post-commencement of intervention
Secondary outcome [11] 445578 0
Pain catastrophising
Timepoint [11] 445578 0
Baseline (T1), 1.5 months (T2), 3 months (T3), 6 months (T4), 9 months (T5) post-commencement of intervention
Secondary outcome [12] 448938 0
Health-related quality of life
Timepoint [12] 448938 0
Baseline (T1), 1.5 months (T2), 3 months (T3), 6 months (T4), 9 months (T5) post-commencement of intervention
Secondary outcome [13] 448939 0
Physical activity
Timepoint [13] 448939 0
Baseline (T1), 1.5 months (T2), 3 months (T3), 6 months (T4), 9 months (T5) post-commencement of intervention
Secondary outcome [14] 448940 0
Use of analgesia
Timepoint [14] 448940 0
Baseline (T1), 1.5 months (T2), 3 months (T3), 6 months (T4), 9 months (T5) post-commencement of intervention
Secondary outcome [15] 448941 0
Health economics
Timepoint [15] 448941 0
Baseline (T1), 1 month, 1.5 months (T2), 2 months, 3 months (T3), 4 months, 5 months, 6 months (T4), 7 months, 8 months, 9 months (T5) post-commencement of intervention

Eligibility
Key inclusion criteria
i) Age 10-19 years
ii) Diagnosis of PFP according to consensus-based criteria: insidious onset anterior or retro-patellar knee pain aggravated by patellofemoral joint loading activities (e.g. squatting, stairs, running)
Minimum age
10 Years
Maximum age
19 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i) Other primary source of anterior knee pain (e.g. Osgood Schlatter Disease, Sinding-Larsen-Johansson Syndrome, patellar instability, patellar tendinopathy, referred pain from lumbar spine or hip)
ii) Other pain or injury in their lower limbs or lower back that is worse than their anterior knee pain
iii) Conditions precluding foot orthoses use (e.g. impairments in foot sensation)
iv) Neurological conditions (e.g. traumatic brain injury, cerebral palsy)
v) Inflammatory arthritis (e.g. Juvenile Idiopathic Arthritis)
vi) Acute knee injury or trauma in the past 3 months (e.g. ligament injury, meniscal injury, fracture)
vii) Knee injections or use of foot orthoses in the last 3 months
viii) Recent commencement of new physiotherapy treatment for their knee pain (i.e. new intervention, or modifications to an existing intervention such as exercise therapy)
ix) Planned or previous surgery to the lower limb or lumbar spine
x) Inability to understand consent and trial documents and procedures (written in English) to the satisfaction of the potential participant, their consenting parent/guardian and trial personnel.

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer-generated randomisation schedule using permuted blocks (large size) will be generated. The allocation ratio will be 1:1:1.
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
Accounting for 10% dropout in each group by 3 months, randomising 336 participants 1:1:1 to 3 groups will provide complete data for 100 participants per group. This will provide >80% power to detect a standardised mean difference of at least 0.4 between foot orthoses plus advice vs. advice only, and targeted physiotherapy plus advice vs. advice only, in KOOS-Child pain subscale score at 3 months using a t-test (two-sided, 5% significance level). For the primary outcome, this corresponds to detecting a difference if the true mean at 3 months is 74 (SD 15) in the advice only group and 80 (SD 15) in the foot orthoses plus advice group or targeted physiotherapy plus advice group (KOOS-Child pain subscale score range 0-100, where 100 = no knee pain).

Analysis of primary and secondary outcomes: A detailed statistical analysis plan (SAP) will be developed by the Senior Trial Statistician and the Trial Management Group and approved by the Trial Steering Committee, including use of linear mixed-models for repeated follow-up measures for continuous outcomes, adjusting for baseline. Analysis code will be written and agreed using pooled data before knowledge of group allocation is provided (blinded analysis). To address issues of multiple testing involving 3 groups, ‘gate-keeping’ global tests (on 2 d.f.) [testing H0: no difference between any group] will be reported, as well as between-group comparisons.

Health economic analysis: Utility scores will be derived from the CHU-9D using the Australian algorithm. Quality adjusted life years (QALYs) for each group will be calculated using the utility score multiplied by time in the trial. Cost-effectiveness will be modelled using an appropriate model to account for the non-normal nature of cost and effect data, such as a generalised linear model. A final parsimonious model will be selected following data examination and measures of model fit. One-way and probabilistic sensitivity analyses will be conducted to explore variability in the sampling and population. A full Health Economics Analysis Plan (HEAP) will be prepared to detail the analysis plan.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2025
Actual
Date of last participant enrolment
Anticipated
1/08/2027
Actual
Date of last data collection
Anticipated
1/05/2028
Actual
Sample size
Target
336
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC

Funding & Sponsors
Funding source category [1] 316671 0
Government body
Name [1] 316671 0
Australian Government Department of Health and Aged Care - Medical Research Future Fund (MRFF)
Country [1] 316671 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
Country
Australia
Secondary sponsor category [1] 321637 0
None
Name [1] 321637 0
Address [1] 321637 0
Country [1] 321637 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 315449 0
The University of Queensland Human Research Ethics Committee A
Ethics committee address [1] 315449 0
Ethics committee country [1] 315449 0
Australia
Date submitted for ethics approval [1] 315449 0
11/03/2025
Approval date [1] 315449 0
Ethics approval number [1] 315449 0
Ethics committee name [2] 317230 0
La Trobe University Human Ethics Committee
Ethics committee address [2] 317230 0
Ethics committee country [2] 317230 0
Australia
Date submitted for ethics approval [2] 317230 0
30/06/2025
Approval date [2] 317230 0
Ethics approval number [2] 317230 0
Ethics committee name [3] 317231 0
Macquarie University Human Research Ethics Committee Medical Sciences
Ethics committee address [3] 317231 0
Ethics committee country [3] 317231 0
Australia
Date submitted for ethics approval [3] 317231 0
30/06/2025
Approval date [3] 317231 0
Ethics approval number [3] 317231 0
Ethics committee name [4] 317232 0
University of Tasmania Human Research Ethics Committee
Ethics committee address [4] 317232 0
Ethics committee country [4] 317232 0
Australia
Date submitted for ethics approval [4] 317232 0
30/06/2025
Approval date [4] 317232 0
Ethics approval number [4] 317232 0

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

Contacts
Principal investigator
Name 134738 0
A/Prof Natalie Collins
Address 134738 0
School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane Qld 4072
Country 134738 0
Australia
Phone 134738 0
+61 7 3365 2124
Fax 134738 0
Email 134738 0
[email protected]
Contact person for public queries
Name 134739 0
Dr Natalie Dos Santos
Address 134739 0
School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane Qld 4072
Country 134739 0
Australia
Phone 134739 0
+61 7 3443 6401
Fax 134739 0
Email 134739 0
[email protected]
Contact person for scientific queries
Name 134740 0
Associate Professor Natalie Collins
Address 134740 0
School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane Qld 4072
Country 134740 0
Australia
Phone 134740 0
+61 7 3365 2124
Fax 134740 0
Email 134740 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:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a scientifically sound proposal or protocol
What individual participant data might be shared?
• De-identified individual participant data:
• All outcomes data
What types of analyses could be done with individual participant data?
• Systematic reviews and meta-analyses
• Studies exploring new research questions
• Health economic analyses
When can requests for individual participant data be made (start and end dates)?
From:
After publication of the trial results and agreed publications from the trial publication plan.

To:
Not yet decided
Where can requests to access individual participant data be made, or data be obtained directly?
• Data repository: UQ eSpace

• Email of trial custodian, sponsor or committee: Expressions of interest to access study data, made out to the Lead Chief Investigator (Associate Professor Natalie Collins, [email protected]).

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


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
No additional documents have been identified.