A Comparison of Two Different Treatment Approaches for Adolescents With Osgood Schlatter: A Randomized Controlled Superiority Trial (The SOGOOD Trial)
Phase: NA
Conditions: Osgood-Schlatter Disease, Apophysitis, Osteochondrosis; Tibia, Physeal Injury
Sponsor: Hvidovre University Hospital

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A comparison of two different treatment approaches for adolescents with Osgood-
Schlatter (the SOGOOD trial): Protocol of a randomized controlled superiority trial{1} 
 
Kasper Krommes, MSc1 
Study Director, Ph.D. fellow 
Per Hölmich, Professor1,2 
Investigator, main supervisor 
Kristian Thorborg, Professor1,2 
Investigator, co-supervisor 
Jens Lykkegaard Olesen, Professor3 
Investigator 
Michael Skovdal Rathleff, Professor3,4 
Investigator 
Mikkel Bek Clausen, Senior Associate Professor5 
Investigator 
Thomas Kallemose6 
Statistical consultant 
 
1 Sports Orthopedic Research Center – Copenhagen (SORC-C), Department of Orthopedic Surgery, Copenhagen University 
Hospital, Amager-Hvidovre, Denmark 
2 Department of Clinical Medicine, University of Copenhagen, Denmark 
3 Center for General Practice at Aalborg University, Aalborg, Denmark  
4 Department of Health Science and Technology, Aalborg University 
5 Department of Midwifery, Physiotherapy, Occupational Therapy and Psychomotor Therapy, Faculty of Health, University College 
Copenhagen, Copenhagen, Denmark 
6 Department of Clinical Research, Copenhagen University Hospital, Amager-Hvidovre, Denmark {5a} 
 
Site and sponsor{5b}  
Department of Orthopedic Surgery, Copenhagen University Hospital, Amager-Hvidovre, Denmark. 
Physiotherapist, PhD-fellow, and Primary Investigator (PI) Kasper Krommes.  
Email: ahh-fp-sogood@regionh.dk, Tel: +45 21 75 72 60, visiting address: Hvidovre Hospital, section 333, 
Kettegaard Alle 30, Hvidovre, Denmark. 
 
ClinicalTrials.gov registration and protocol repository{2a,2b}: NCT05174182 
Protocol identifier: H-21028912 
Supplementary materials: doi.org/10.6084/m9.figshare.c.5730008.v1 
 
Licensing: CC-BY-NC-ND 4.0  
Anyone can share this material, provided it remains unaltered in any way, this is not done for commercial 
purposes, and the original authors are credited and cited. 
 
Note: the numbers in curly brackets in this protocol refer to SPIRIT checklist item numbers.1 The order of the 
items has been modified to group similar items, as recommended by the TRIALS journal.2 
 
 
 

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Version:{3} 1.4, 04-APR-2024. Revision history: 
Version 
Date 
Amendment 
1.0 
30-MAR-2021 
• First draft submitted to ethical review board (Regional Committees on 
Health Research Ethics for The Capitol Region). 
1.1 
30-NOV-2021 
• Second draft (full protocol with embedded statistical analysis plan) with 
approval identifiers from the Capital Region Data Protection Agency, 
Denmark (P-2021-818) and the Regional Committees on Health Research 
Ethics for The Capitol Region, Denmark (H-21028912).  
• Registration submitted at ClinicalTrials.gov 
1.2 
30-DEC-2021 
• Updated with ClinicalTrials.gov registration identifier (NCT05174182) and 
full protocol submitted as supplementary document.  
1.3 
01-MAR-2023 
 
• Added pilot study results (n=15) and the consequential amendmends to 
trail procedures. 
• Added details on mediation analysis framework. 
• Added details on interventions (embargo lifted). 
• Added details on qualitative study. 
• Changed safety outcomes from “Serious adverse events” and “Adverse 
events” to “Any adverse events” in accordance with outline methods. 
1.4 
04-APR-2024 
• Full protocol submitted as supplementary document to ClinicalTrials.gov 
registration (NCT05174182). 
1.5 
05-APR-2024 
• Submitted (proofs) for peer-review publication in BMC Sports Science, 
Medicine and Rehabilitation in shorter journal format.  
 
Appendices and supplementary: 
Appendix 1 (page 75): Clinical test protocols 
Appendix 2 (page 82): Ultrasound protocol 
Appendix 3 (page 88): Exercise descriptors and populated CERT/TIDierR checklists 
Appendix 4 (page 91): Weekly monitoring via text-messages (Danish) 
Appendix 5 (page 95): Pragmatic-Explanatory trial indicators 
Appendix 6 (page 96): Directed acyclic graph 
 
Supplementary files doi.org/10.6084/m9.figshare.c.5730008.v1:  

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• REDCap instruments with all patient-reported outcomes and data-collection forms (Danish) 
• Written participant information (Danish) {32} 
• Informed consent forms (Danish) {24} 
• Approval from Ethical review board (Danish) {24} 
• Description and materials (Danish) for the interventions (previously under embargo) 
• Full directed acyclic graph for proposed causal framework for mediation and moderation analysis 
 
Abbreviations 
 
AEs = Adverse events 
AKPP-test = Anterior Knee Pain Provocation test 
CONSORT = Consolidated Standards of Reporting Trials 
EU = European Union 
EQ-5D-Y = EuroQol, five domains, Youth 
FINER = Feasible, Interesting, Novel, Ethical and Relevant 
GROC = Global rating for Change 
ICC = Intraclass Correlation Coefficient 
KOOS = Knee Injury and Osteoarthritis Outcome Score 
MCID = Minimially clinically important difference 
MVPA = Moderate to Vigorous Physical Activity 
NPRS = Numerical 0-10 pain rating scale 
PA = Physical Activity 
PASS = Patient Acceptable Symptom State 
PHV = Peak Height Velocity 
PICOT = Population, Intervention, Comparator, Outcome, Time 
frame 
PRE-SPEC = PRE-SPECifying a statistical analysis strategy in 
clinical trials 
PS-FS = Patient-Specific Functional Scale 
QRPs = Questionable Research Practices 
REDCap = Research Electronic Data Capture 
SPIRIT = Standard Protocol Items: Recommendations for 
Interventional Trials 
TSK-17 = Tampa Scale of Kinesiophobia, 17 items 
VAS = Visual Analogue Scale 
WHO = World Health Organization  
WIA = Working Alliance Inventory 

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 Table of contents 
 
Abbreviations .............................................................................................................................................. 3 
Table of contents ................................................................................................................................................. 4 
Abstract ............................................................................................................................................................... 8 
Introduction ......................................................................................................................................................... 9 
Background and rationale ............................................................................................................................... 9 
Need for a trial ............................................................................................................................................... 10 
Review of the current literature .................................................................................................................... 10 
Primary aim ................................................................................................................................................... 11 
Secondary aims .............................................................................................................................................. 12 
Timepoints ..................................................................................................................................................... 12 
Table 1. Objectives ........................................................................................................................ 12 
Trial design, reporting, and conduct ............................................................................................................. 14 
Patient involvement ...................................................................................................................................... 15 
Table 2. Prespeficied criteria for successful/failed pilot study ...................................................... 16 
Embedded pilot study: results and ammendments ...................................................................................... 16 
Table 3. Pilot objectives, criteria, results, and changes to trial conduct ....................................... 16 
Embedded qualitative study .......................................................................................................................... 17 
Written & verbal information ........................................................................................................................ 19 
Consent .......................................................................................................................................................... 20 
Figure 1. Flow of mixed-methods study ........................................................................................ 22 
Table 4. Depiction of progressive balance and alignment exercise levels .................................... 24 
Experimental intervention: A novel treatment approach (Arm A) ............................................................... 25 
Table 5. Depiction of hip- and knee exercises ............................................................................... 28 
Table 6. Short-form overview of the two treatments ................................................................... 29 
Table 7. Items for exercise evaluation forms as reported by the treating physiotherapist .......... 30 
Table 8. Adherence criteria for the intervention group ................................................................ 31 
Table 9. Adherence criteria for the comparator group ................................................................. 31 
Criteria for discontinuing or modifying allocated interventions ................................................................... 31 
Concomitant care during the trial ................................................................................................................. 32 
Outcomes ...................................................................................................................................................... 32 

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Table 10. Overview of outcome domains and prioritized hierarchy of outcomes ........................ 32 
Primary outcome ........................................................................................................................................... 34 
Adverse events .............................................................................................................................................. 37 
Participant demographics .............................................................................................................................. 38 
Study flow and participant timeline .............................................................................................................. 38 
Figure 2. Study flow ....................................................................................................................... 39 
Sample size considerations ........................................................................................................................... 39 
Figure 3. Effect size vs sample size plotted ................................................................................... 40 
Recruitment ................................................................................................................................................... 41 
Sequence generation ..................................................................................................................................... 41 
Concealment mechanism .............................................................................................................................. 41 
Implementation of allocation ........................................................................................................................ 42 
Assignment of interventions: Blinding .............................................................................................................. 42 
Who will be blinded ....................................................................................................................................... 42 
Procedure for unblinding if needed .............................................................................................................. 43 
Study personnel ............................................................................................................................................. 43 
Data collection and management ..................................................................................................................... 44 
Plans for assessment and collection of outcomes ........................................................................................ 44 
Table 11. Study schedule ............................................................................................................... 45 
Plans to promote participant retention and complete follow-up ................................................................. 46 
Data management ......................................................................................................................................... 46 
Statistical methods ............................................................................................................................................ 47 
Statistical methods for primary and secondary outcomes ........................................................................... 47 
Interim analyses ............................................................................................................................................ 51 
Handling of non-adherence and any statistical methods to handle missing data ........................................ 51 
Plans to give access to the full protocol, participant level-data and statistical code ................................... 52 
Figure 4. Visual example of mediator in the causal pathway ........................................................ 52 
Figure 5. Proposed directed acyclical graph for mediation analysis ............................................. 53 
Assumptions for causal mediation analysis ................................................................................................... 53 
Table 12. Proposed moderators and mediators ............................................................................ 54 
Statistical approach to mediation analysis .................................................................................................... 56 
Oversight and monitoring ................................................................................................................................. 56 

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Steps to minimize pain, risk, and inconveniences ......................................................................................... 58 
Justification of risks and drawbacks, and future therapeutic reward ........................................................... 58 
Compensation to patients ............................................................................................................................. 58 
Frequency and plans for auditing trial conduct ............................................................................................ 59 
Plans for communicating important protocol amendments to relevant parties .......................................... 59 
Dissemination plans ...................................................................................................................................... 59 
Acknowledgments ......................................................................................................................................... 59 
Authors’ contributions .................................................................................................................................. 60 
Table 13. Author contributions (CRediT Taxonomy) ..................................................................... 60 
Funding .......................................................................................................................................................... 60 
Trial status ..................................................................................................................................................... 61 
Availability of data and materials .................................................................................................................. 61 
Competing interests ...................................................................................................................................... 61 
References ......................................................................................................................................................... 62 
Appendix 1: Clinical test protocols .................................................................................................................... 75 
Knee extension strength: handheld dynamometry ....................................................................................... 76 
Pressure-pain threshold: handheld algometry .............................................................................................. 77 
Pain response to cumulative loading: The anterior knee pain provocation test .......................................... 78 
Sports function and power-production: Countermovement jump ............................................................... 79 
Rectus femoris flexibility: The modified Thomas test ................................................................................... 80 
Growth velocity offset: The anthropometrics-based Peak Height Velocity formula .................................... 81 
Appendix 2: Ultrasound protocol ...................................................................................................................... 82 
Table 14. Classification systems .................................................................................................... 83 
Table 15. Case Report form for ultrasound ................................................................................... 84 
Figure 6. Examples of ultrasound assessments ............................................................................. 86 
Figure 7. Examples of color doppler assessments at the tibial tubercle in the longitudinal and 
transversal plane ........................................................................................................................... 87 
Appendix 3: Exercise descriptors and populated CERT/TIDierR checklists ....................................................... 88 
Table 16. Exercise descriptors for the experimental intervention ................................................ 88 
Table 17. Collated populated TIDieR76 and CERT77 templates for the experimental treatment ... 89 
Appendix 4: Weekly monitoring via text-messages (Danish) ............................................................................ 91 
Figure 8. Flow of text-based monitoring in the experimental group from week 4 to 22 .............. 91 
Figure 9. Flow of text-based monitoring in the experimental group from week 0 to 4 ................ 92 

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Figure 10. Flow of text-based monitoring in the usual care group from week 0 to 22 ................. 93 
Appendix 5: Pragmatic-Explanatory indicators ................................................................................................. 94 
Figure 11. PRagmatic-Explanatory Continuum Indicator Summary – PRECIS ‘Wheel’ .................. 94 
Table 18. PRECIS-2 scores for trial domains .................................................................................. 94 
Appendix 6: Directed acyclig graph ................................................................................................................... 96 
 
 
 

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Abstract 
 
Background 
The most common growth-related injury is Osgood-Schlatter, which affects up to 1 in 5 physically active 
adolescents. It can cause long-term pain and potential discontinuation of sports and physical activity, with 
sequela well into adulthood. No effective treatments have been documented, and clinical practice is 
characterized by a wealth of conflicting advice and modalities. A novel treatment approach has shown 
promising results in a small single-cohort study. Therefore, we aim to compare this novel treatment with 
usual care in 10-16-year-old adolescents with Osgood-Schlatter. 
 
Methods 
This single-center pragmatic, double-blinded, randomized, controlled superiority trial, will have a two-group 
parallel arm design. Participants will undergo 3 months of treatment, followed by 2 months of self-
management with self-reported knee function (KOOS-child ‘Sport/play’) at 5 months as the primary 
endpoint. In this protocol, we outline the planned methods and procedures, including the statistical analyses 
plan.  
 
Discussion 
This trial comparing a novel treatment with usual care for adolescents with Osgood-Schlatter could result in 
an evidence-based treatment that is ready for implementation in clinical practice, thereby improving patient 
outcomes and guide clinicians in the management of Osgood-Schlatter patients. 
 
Trial registration and protocol repository: NCT05174182 
 
Keywords: Osgood-Schlatter, Apophysitis, Adolescents, Sport, Physical activity, Knee, Load management, 
Strength training, Accelerometer, Ultrasound 
 
Anticipated date of first recruitment: 03-JAN-2022 
Target sample size: 130 participants 
 
 
 
 

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Introduction 
 
Background and rationale {6a} 
Being physically active during adult life is key for health and prevention of disease and carries additional 
benefits during adolescence, such as improved academic abilities and cognitive function.3–6 Besides somatic 
advantages, participating in sports for adolescents fosters meaningful social networks, lowers the risk of 
criminal activity, drinking, and substance abuse.7–9 The levels of physical activity declines during early 
adolescence, and less than 20% are currently meeting recommendations for moderate-vigorous physical 
activity or sports participation.10 
 
As adolescence is a period of increased autonomy, behaviors established during this period could potentially 
last into adulthood.11,12 Several barriers exist to physical activity and sports participation during adolescence, 
such as the risk of injury and pain during activity. In line with this, lower limb pain is the most frequent cause 
for seeking primary care during adolescence,13 as 40% of active adolescents experience knee pain,14 and up 
to half of sports active adolescents regularly take pain medication for injury-related pain.15 In addition, 
almost a third of adolescents quitting their sport reports injuries or pain as the main reason.16  
 
Osgood-Schlatter affects up to 1 in 5 physically active adolescents and is the most common growth-related 
injury.17–21 The condition affects the knee, specifically the proximal tibial apophysis (the weakest part of the 
muscle-tendon-bone complex).22,23 Osgood-Schlatter can lead to long-term pain, swelling, and most notably, 
potential discontinuation of sports and physical activity, with potential sequela into adulthood.3,24–32 Osgood-
Schlatter might also predispose to maladaptation in the maturing bone,33,34 inhibition of muscle activation,35 
or more serious traumatic knee injuries, such as tendon-avulsion and ligament tear.29,36,37 Increased loading 
from sports participation seems to be a trigger as adolescents who practice more have a higher rate of 
Osgood-Schlatter.38 Data have also shown that adults who suffered sports-related injuries during youth are 
prone to musculoskeletal problems and poor health and having suffered knee pain before adulthood 
increase the risk of chronic pain later in life.39,40,41 In addition, investigations into longstanding knee pain in 
adolescence have shown that suffering from knee pain is related to lower quality of life, general health, and 
sports participation.31,42 
 
Research into Osgood-Schlatter and other lower limb apophysitis is only just emerging despite its first 
documentation in 1903.43,44 Only trials on injection therapy exists, and the recommended types of modalities 
for conservative management of Osgood-Schlatter is abundant and conflicting in the literature, reflecting the 
lack of evidence in this area for first-line conservative treatments.43,45–50 

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The notion that adolescent knee pain is self-limiting with a favorable prognosis is widespread but recent data 
suggest this is not the case, as even when treated, it can be long-lasting.42,45,47,51–54 This presumption might 
partly explain the state of the current management of Osgood-Schlatter, being characterized by a wealth of 
advice, from total cessation of sport, participation under the pain-limit, play-through-pain, wait-and-see, and 
cast-immobilization; to passive therapies such as shockwave therapy, ultrasound therapy, laser therapy, 
injections, surgery, vitamin-supplements, cryotherapy, dry-needling, massage, stretches, and manual 
manipulations.31,43,45–47,49,55–58 
 
Need for a trial 
This highlights the need for an effective conservative management approach. Our group recently published 
data from a cohort of adolescents with patellofemoral pain who received an intervention based on a self-
management approach containing gradual exposure to sports and physical activity using a guidance tool 
based on pain response and progressive exercise therapy.59 This was associated with a 86% rate of successful 
outcomes after 12 months, with 81% being back to sport and physical activity, and 67% being pain-free.59 In 
line with this, our group explored a similar intervention in a smaller cohort of adolescents with Osgood-
Schlatter and had comparable promising results.60  
 
With our current knowledge, a robust comparison of our novel approach to a standardized usual care 
treatment package in a well-powered randomized setting is highly warranted. This would also require a 
mapping and synthesis of the current usual care practice as no standards exist.  
 
Review of the current literature 
We have performed a basic systematic literature review on trials in adolescents with Osgood-Schlatter to 
ensure that the trial is not redundant or wasteful.61 We searched MEDLine, CENTRAL and EmBase using the 
search terms: (‘osgood’ OR ‘schlatter’) in June 2021. A systematic review that evaluated interventions for 
Osgood-Schlatter was found, concluding, “Carefully controlled studies on well-described treatment 
approaches are needed to establish which conservative treatment options are most effective for patients 
with OSD”.62 In addition, four trials are registered on clinicaltrials.gov. One aims to evaluate cast 
immobilization with complete rest (completed 2016), another myofascial massage over usual care (currently 
recruiting), and a third comparing stretching with cryotherapy, NSAIDs, and relative rest (last updated 2013). 
One recent trial-registration from a member of our study group, compares some of  the different 
components used in experimental intervention, in a 3-armed trial, thus comparing tailored progressive 

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loading and return to sport vs. pain guided activity vs. 4 week rest (recruitment started January 2023). 
Therefore, the rationale and scientific justification for this trial, remains.  
 
Primary aim 
The primary aim is to investigate the superiority of 3 months of a novel treatment approach compared to 
standardized usual care after 5 months, measured on the KOOS-child ‘Sport/play’ subscale, in adolescents 
with Osgood-Schlatter.  
 
Research question 
Therefore, we propose the following research question:  
Is a novel 3 month treatment approach superior to standardized usual care for improving patient-reported 
knee function after 5 months in patients with Osgood-Schlatter? 
 
Our research question fulfills the FINER-criteria, as it is considered both Feasible, Interesting, Novel, Ethical 
and Relevant.63 These criteria are important when attempting to optimize features of trial design to 
maximize the usefulness of clinical trials.64–66  
 
The research question is based on the PICOT model with the following denotations for each item: 
Population: 10-16-year-old adolescents with Osgood-Schlatter  
Intervention: 3 month of a novel treatment approach  
Comparator: 3 month of standardized usual care 
Outcome: Patient-reported knee function on KOOS-child ‘Sport/play’ subscale 
Time frame: Primary endpoint after 5 months 
 
Objectives 
This trial has several objectives that have been outlined according to the SMART-model (Specific, 
Measurable, Achievable, Relevant, Time Bound)67 in table 1. 
 
Hypothesis 
The hypothesis for the primary aim, is that the mean KOOS-child ‘Sport/play’ subscale change score at 
month 5 is larger for the novel treatment approach compared to standardized usual care in adolescents with 
Osgood-Schlatter. 
 
 

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Secondary aims 
• 
Compare secondary and exploratory patient-reported, clinical and objective measures of 
improvement and adverse effect, also at secondary timepoints at 3 months, and at long-term follow-
up after 8, 10, 12, 24, and 48 months (table 10 & 11).  
• 
Supply detailed trajectories of treatment response by collecting weekly self-reported measures and 
data from activity sensors during the entire 5 month core study period using visualizations and 
mixed effect analysis models. 
• 
Explore factors associated with effect moderation or mediation to determine who will potentially 
benefit more or less of treatment, and the pontential mechanisms responsible. 
• 
Investigate the experience of undergoing the intervention and identify potential barriers or 
facilitators to treatment and adherence. 
• 
Evaluate features and procedures of the trial in a pilot-setting to assess operational feasibility 
 
Timepoints 
The primary and secondary fixed endpoints are chosen based on the fact that our previous cohort had 
trajectories of pain, knee-function, and sports participation that were not fully recovered at 12 weeks,60 and 
that some participants had not progressed fully through the exercise regime. Thus, we decided to add a 
period of complete self-management by adding 2 months to the timeline before the primary endpoint. We 
have found this alteration to be feasible in clinical practice.68 This will also allow the novel treatment 
approach to work in a real self-management setting, rather than only during the course of the supervised 
treatment. To an overview of visits and timing of data collection, see figure 2 and table 11. 
 
Table 1. Objectives {7} 
Primary objective(s) 
Between-group compared endpoints related to primary objective(s) at month 5 
To assess the relative efficacy of the novel treatment 
approach on patient-reported knee function 
Patient-reported knee-function evaluated with the KOOS-child ‘Sport/play’ subscale 
 
 
 
Secondary objective(s) 
Between-group compared endpoints related to secondary objective(s) at month 5 
To assess the relative efficacy of the novel treatment 
approach on patient-reported outcomes 
Patient-acceptable Symptom-state question (Y/N) 
KOOS-child ‘Quality of Life’ 0-100 subscale (5 items) 
KOOS-child ‘Pain’ 0-100 subscale (8 items) 
4-week-average episodes of pain flares (≥4 on 0-10 NPRS) 
Worst pain past week (0-10 NPRS) 
Satisfaction with extent of sports participation 
Global rating of Change (7-point likert scale) 
Patient-specific function scale (NRS 0-10) 
Kinesiophobia (Tampa Scale of Kinesiophobia, 17 items) 
Self-rated health (EQ-D5-Y 0-100 VAS) 
Level of pain/discomfort (EQ-D5-Y 4) 
Pre knee pain level of sports participation 
Pre knee pain level of physical activity 

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Time to return to sport (week no.) 
Satisfaction with treatment (Y/N) 
Problems with usual activities (EQ-D5-Y 3) 
 
To assess the relative efficacy of the novel treatment 
approach on objective outcomes 
 
Anterior Knee Pain Provocation test (0-10 NPRS) 
Pain during knee extension test (0-10 NPRS) 
Pressure-pain threshold at the tibial tubcle (kPa) 
Maximal isometric knee extenstion strength (Nm/kg) 
Countermovement jump height (cm) 
4-week average hours of sports participation 
4-week average hours of physical activity 
Known pain during manual palpation 
Pain during countermovement jump (0-10 NPRS) 
Countermovement power (W) 
Knee extensor flexibility change (°) 
 
To assess the relative efficacy of the novel treatment 
approach on tissue morphology through ultrasound 
imaging 
 
Tendinosis signs (thickening or hyperemia) 
Hyperemia of the tibial tubercle ad modum Öhberg  
Infrapatellar bursitis signs (thickening or hyperemia) 
Flaviis composite severity score 
 
To assess the relative efficacy of the novel treatment 
approach on safety 
Any adverse events  
 
 
 
Variables analyzed for moderating the effect on selected outcomes 
To asses, if potential baseline variables moderates 
the effect of the intervention 
Treatment expectations 
Peak height velocity offset 
Timing of maturation  
Flaviis composite severity score 
Maturation stage of the apophysis 
Pain frequency: KOOS-child child question P1 on ‘Pain’ subscale (1-5 likert scale) 
Symptom duration 
Kinesiophobia (Tampa Scale of Kinesiophobia, 17 items) 
Worst pain past week (0-10 NPRS) 
 
 
 
 
Variables analyzed for mediating the effect on the primary outcome 
To asses, if potential intermediate variables 
mediates the effect of the intervention on the primary 
outcome 
Change in worst pain past week (0-10 NPRS) at week 4 
Change in pressure-pain threshold at the tibial tubcle (kPa) at week 4 
Controlled return to sport (<2 hours/week) at week  5 
Pain flare frequency (no.) at week 13 
Therapeutic Alliance (WAI) at week 13 
Change in kinesiophobia (Tampa Scale of Kinesiophobia, 17 items) at week 13 
Change in pain during knee extension test (0-10 NPRS) at week 13 
Change in maximal isometric knee extenstion strength (Nm/kg) at week 13 
Change in distal patella tendon hyperemia (ad modum Öhberg 1-4) at week 13 
Change in infrapatellar bursitis signs (thickening or hyperemia) at week 13 
 
 
Qualitative analysis 
Investigate the experience of undergoing the 
intervention and identify potential barriers or 
facilitators to treatment and adherence (n=24) 
Currently planned as analyses of experiences reported by participants in semi-structured 
interview group sessions stratified on group-allocation and age.  
 
 
 
Feasibility domains evaluated for first 15 participants until month 3 
Evaluated features and procedures of the trial to 
assess operational feasibility (n=15) 
Barriers to accepting enrollment or randomization 
Dropout rate and causes 
Incidents of staff og patient in-comprehension of procedures, measures or materials 

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Capacity 
Safety concerns 
Any unforeseen challenges by staff 
 
 
Variables collected 
Describe features of the included population sample 
Previous treatment and use of painkillers 
Health-related behaviors 
Anthropometrics 
Pubertal and skeletal maturaity, and predicted adult height 
 
 
 
Trial design, reporting, and conduct {8} 
The trial is a single-center pragmatic, double-blinded randomized controlled superiority trial, with a two-
group parallel arm design and 1:1 group allocation ratio.  
 
The full clinical trial protocol is based on the PREPARE Trial Guide and follows the reporting items from the 
SPIRIT checklist in the order proposed by the Trials Protocol Template, and is supplemented by items from 
the WHO protocol recommendations; the Danish Committee on Health Research Ethics, and the 
Transparency Checklist.1,2,69–72 The reporting of the results will adhere to the CONSORT (Consolidated 
Standards of Reporting Trials) guidelines for reporting a) pragmatic trials, b) harms, and c) non-
pharmacologic treatment interventions.73,74 Description of interventions follows current best-practice 
guidelines for reporting exercise-based interventions.75–77 The trial procedures will adhere to non-
pharmaceutical standards of Good Clinical Practice E6(R2).78 The embedded Statistical Analysis Plan will 
follow recommendations from the PRE-SPEC framework (PRE-SPECcification of statistical analysis strategies 
in clinical trials)79 complemented with guidelines from the EMA (E9), JAMA, and field guidelines.80–82 
Analytical code for the primary outcomes will be shared along the primary publication.83 Data will be 
reported in sufficient detail to allow inclusion in potential future meta-analyses.84  
 
To increase the transparency, validity, and robustness of the trial, we have posted this protocol as a 
timestamped pre-print publication to the ClinicalTrials.gov repository before commencement of data 
collection as a supplementary to the registration (NCT05174182). Pre-registration and pre-print publication 
of protocols ensures greater adherence to a priori decisions regarding data collection and analyses and is 
thus associated with higher dissemination rate85,86 and lower risk of bias.87 In addition, it appears to address 
prevalent QRPs (Questionable Research Practices)88,89 and produce more conservative estimates90,91 and 
increased rate of null-findings.92–94 However, sections describing the contents of the experimental 
intervention (and supplementary leaflets and precise descriptors) have been uploaded to the Figshare 
repository previously under embargo until final recruitment to prevent premature uptake of the 

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experimental intervention until data on its efficacy is established, and to prevent potential unblinding of 
group-content for potential future staff and participants (10.6084/m9.figshare.c.5730008.v1). However, as 
recruitment of personell is finalized and participant unblinding stemming from this version of the protocol is 
a minor concern at this stage is in the trial, the embargo has been lifted and intervention descriptions has 
been included in the protocol. 
 
We chose features of trial design based on the following: 
Superiority framework: As our preliminary study60 has shown promising results for patients having tried 
other treatments and with a significant duration of symptoms, we hypothesize that the experimental 
intervention is superior, and the trial design and analyses-plan reflects this hypothesis, e.g. by utilizing one-
sided hypothesis testing for statistical analysis.  
Two-group parallel-arm design: This design was chosen as the design is simple and therefore easier to 
understand and implement for patients and clinicians, is simple to include in meta-analyses, has higher 
external validity than other designs, and incurs fewer statistical issues.95  
Pragmatic framework: Using the PRECIS-2 tool (PRagmatic-Explanatory Continuum Indicator Summary) for 
categorizing our trial, we found our design to be mostly pragmatic (score 38 of 45) in terms of clinical 
domains (figure 11, table 18), making the potential results fit for real-world implementation with high 
ecological validity.96 This is in line with our own successful implementation of the intervention in the clinic.68 
Some domains, in terms of follow-up and adherence measuring, are more explanatory in nature, making 
these features less fit for a clinical setting.96,97  
 
Patient involvement 
Osgood-Schlatter patients undergoing treatment in our department have been involved in discussions of the 
design of this trial in relation to their visits at the department, which have both informed and changed initial 
decisions regarding trial design. In an unstructured open manner, patients have been asked about their 
preference, acceptability, and other inputs, mainly regarding 1) number and duration of appointments 
during an intervention, 2) duration of the entire intervention, 3) type of outcomes relevant for them, 4) 
contents of the experimental intervention, and 5) relevance and importance of the research question and 
comparisons, and have thus provided a valuable basis for this protocol which could lead to increased 
enrollment and retention.98 The nested qualitative study will incorporate the perspectives of trial-
participants. In addition, following the analysis, new patients will be invited to discuss the interpretation of 
the results of the trial, as well as dissemination aspects, and receive compensation for their inputs. Relevant 
public and clinical stakeholders will be engaged in a possible implementation process once dissemination via 

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peer-reviewed journal publication is completed. 
 
Embedded pilot study: results and ammendments 
As outlined in previous protocol versions, the initial 15 participants acted as pilot-participants. This did not 
incur any additional burden to participants or change their experience or procedures compared to the 
intended setup for subsequent participants, but trial personnel recorded extra data during months 0-3 on 
specific pilot objectives (table 3). Pilot studies are the best way to assess the feasibility of a large, expensive 
full-scale study and avoid any adverse consequences or unforeseen pitfalls during the large-scale trial, and 
ensure that all the different components 
work together.99–101 If the aim and features 
of the pilot trial is aligned with the main 
trial and participant data are deemed 
compatible such none or minimal 
amendments are needed for the main trial, 
their data be included in the analysis of the 
main trial.100 The key difference from a 
pilot study and the main study are 
feasibility objectives and criteria for 
success that should reflect an operational perspective and aim but otherwise run as a miniature version of 
the main study.99,101–103  We prespecified pilot objectives and criteria for either a success or failure of the 
pilot study (protocol version 1.2, table 2). The results and amendments are outlined in table 3, and the pilot-
trial were deemed as successful, as only minor changes were needed to procedures, and participant-data 
was considered compatible with inclusion in the main trial dataset (outcome number 3 from table 2). 
Besides the amendments denoted in table 3, a few other minor changes to procedures was also 
implemented:  
• 
Changes to the REDCap-project, such as removing obsolete fields, fixed validation values, change 
wrong field values. 
• 
Changed sequence of some clinical measures to increase time-efficiency 
• 
As a few participants performed fewer than the planned 3 attempts of maximal knee extension 
strength test due to knee pain, the analysis of pain during testing will now consider the most painful 
attempt during these trials, rather a mean measure of pain across trials.  
 
Table 3. Pilot objectives, criteria, results, and changes to trial conduct 
Prespeficied Objectives 
Prespeficied Criteria 
Results 
Changes 
Table 2. Prespeficied criteria for successful/failed pilot study 
 
 
 
Success 
 
Failure 
1. Amendments to trial procedures that cause 
delay of the main study 
 
X 
2. Amendments to trial procedures that cause 
inability to include pilot-participant data in main 
study analyses 
 
X 
3. Amendments needed to trial procedure that 
does not postpone ongoing trial recruitment, 
and pilot-participant data can still be included 
in the in main study analyses 
X 
 
4. No amendments needed to trial procedure 
and pilot-participant data can still be included 
in the in main study analyses 
X 
 

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Embedded qualitative study 
A qualitative study will be nested in the trial to understand barriers and facilitators to adhering to the 
interventions and describe the participant-perspective of undergoing the interventions as a whole.104 The 
interviewguide and analysis is based the Theoretical Domains Framework and constructs pertaining to 
behavior change,105 and the study conducted according to the COREQ checklist (consolidated criteria for 
reporting qualitative research.106 Interviews will be performed in group sessions stratified by group-
allocation. The planned sample size is 16 participants minimum, across 4-5 sessions with 4-5  participants in 
each sessions. The planned sample size is based on field-specific guidance from Malterud et. al regarding 
Information Power.107,108 All interviews will be conducted by the PI under supervision of an experienced 
qualitative researcher. Participants from the main trial will be invited to group-sessions after undergoing 
their visit at 5 months (primary endpoint assessment). They will be provided with a leaflet detailing how the 
Potential participants refuse to 
enroll due to information about the 
study, other than randomization 
≤50% (n=7/15) 
33%, n=5/15 
 
Dropout rate 
≤20% (n=3/15) 
20%, n=3/15.  
1 concussion 
2 stopped 
responding/showing up 
 
Participants attending inclusion 
appointment was included in the 
trial 
≥50% (n=8/15 
87%, n=13/15 
 
Potential participants accepted to 
be randomized 
≥50% (n=8/15) 
100%, n=15/15 
 
Incidents of in-comprehension of 
intervention delivery or intervention 
materials 
≤15% (n=2/15) 
0%, n=15/15 
 
Incidents of in-comprehension of 
outcomes or testing procedures 
≤15% (n=2/15) 
0%, n=15/15 
 
Incidents of faulty data collection 
procedures (REDCap entry, 
sensors, scan, clinical tests) 
≤5% (n=0/15) 
33%, n=5/15 
3 incidents of participants 
not fully using sensor-app 
1 scanning error 
1 REDcap error 
• As sensor-app compliance is the responsibility of 
participants, full compliance likely cannot be 
achieved. Data-loss is accepted and expected to 
occur at same rate during the main trial 
• Index knee was not scanned, as patient recalled 
wrong symptomatic leg. Index knee from hereon are 
noted in the appointment-text for testing-staff 
• Wrong link to REDcap survey was used. Name and 
timepoint is hereon piped at the top of every survey 
Safety incidents (major or minor) 
0% (n=0/15) 
33%, n=5/15 
4 (minor) incidents of 
sensor-adhesive causing 
skin irritation 
1 (minor) flare-up short-
term during strength test 
• New procedures for preventing and handling irritated 
skin 
• Added instructions to not push through pain during 
testing 
Capacity: how many patients can 
we logistically handle per 
day/week? 
 
≥5 enrollments weekly 
2 baseline, or 3-4 follow-
up appointments per day 
have been feasible 
 
Capacity: Are rooms and 
equipment available when 
needed? 
Yes, or readily 
manageable  
Yes, no issues 
 
Any unforeseen challenges by 
intervention- or outcome personnel 
No, or readily 
manageable 
Yes, no issues 
 
Inclusion criteria were deemed 
obvious and practical by inclusion 
staff 
Yes, or readily 
manageable  
Yes, no issues 
 

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session will take place and what themes questions are planned to revolve around. As compensation, 
participants will receive a voucher for movie theaters (280 dkr.) as well as generous refreshments during the 
session. The sessions will take place at Hvidovre Hospital in a standard meeting room. An adjacent room 
with refreshments will be made available for parents. The sessions are planned for 2 x 45 min. separated by 
a 45 min. break.  
 
Methods: Participants, interventions, and outcomes 
 
Study setting {9} 
All trial-related procedures will take place at Hvidovre Hospital, Capital Region, Denmark. Participants will 
attend procedures related to enrollment, imaging, and end-of-study visits at the Department of Orthopedic 
Surgery, while visits pertaining to intervention delivery and clinical outcome assessments will be performed 
at the Department of Physiotherapy, located adjacent to the latter. 
 
Key inclusion and exclusion criteria {10} 
The diagnosis of Osgood-Schlatter will be made by a trained physiotherapist according to the following 
diagnostic criteria:109 
▪ 
Pain or swelling of the tibial tuberosity for ≥6 weeks with a primary insidious onset, which is  
provoked by at least 2 of the following positions or activities; prolonged sitting or kneeling, 
squatting, running, hopping/jumping, stair walking, or during multidirectional sports 
▪ 
Tenderness on palpation of the tibial tuberosity or pain during resisted isometric knee 
extensions  
Adolescents aged 10-16 fulfilling these criteria at enrollment and report having either 1) markedly reduced 
sports participation, or 2) are severely affected by pain during participation during the past (representative) 
6 weeks, will be eligible for inclusion. This will be assessed by having potential participants answering two 
pres-specified questions on these two domains.  
 
Any other primary pathology or complaints from other structures of the knee will disqualify the participant 
from inclusion but will be allowed providing that primary complaints during the preceding ≥6 weeks are from 
the tibial tubercle. Previous fractures or avulsions of the tibial tubercle will disqualify patients. Any other 
injuries, complaints, or illnesses that may cause disability or specifically restricts levels of physical activity or 
sports participation will also be cause for exclusion. Previous surgery in the lower extremities or lumbar 
spine will be cause for exclusion. Congenital deformities, device implants, or cysts, or tumors of the knee will 

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also be cause for exclusion. If participants are currently being treated for Osgood-Schlatter and are not 
willing to cease this concomitant treatment, they will not be included. Participants and their parents should 
be able to understand and communicate in written and verbal Danish, and participants and at least one 
parent or guardian must be able to attend all visits together. The study director or their trained replacement 
will provide systematic verbal information to participants and their parents, answer any potential questions, 
and collect verbal and written informed consent from all participants and their parents/guardians at the 
enrollment visit (see the section ‘Consent’ for details). 
 
Clinical examination during the enrollment process will consist of:  
1. History taking: 
▪ 
Onset, nature, location of pain, mechanical symptoms (catching, locking, clicking, giving 
way), history of growth, history of patella luxations or apophysitis 
▪ 
Previous clinical and para-clinical examinations,  treatment modalities, advice, or self-
imposed management.  
▪ 
Painful situations, and current restrictions and level of participation in sports and physical 
activity 
 
2. Physical examination: 
▪ 
Pain location in predefined anatomical sites (circum patella, quadriceps tendon, patella 
tendon, Hoffas fat pad, anterior joint-line, pes anserinus, tibial condyle, tibial tubercle, 
Gerdy’s tubercle) identified by palpation.  
▪ 
Clinical testing of menisci (Meniscal stress test or Thessalys test), anterior cruciate 
ligament (Lachmanns test or anterior drawer test), medial and lateral collateral ligaments 
(varus- and valgus stress-test), Hoffas fat pad (Fat pad impingement test), knee joint 
edema (Ballottement Test) and isometric knee extension against manual resistance. 
 
Written & verbal information  
The study and enrollment process will be carried out in accordance with the principles of the Declaration of 
Helsinki. We supply verbal information in an undisturbed setting (similar to a regular medical consultation) 
for all participants and their parents/guardians, during which we go over the purpose, flow, tests, and self-
reported measures, present the risk and benefits, and their rights as participants in a research project. The 
personnel giving verbal information and obtaining consent have extensive experience with treating and 
communicating with minors. Afterwards they can provide verbal and written consent if they wish to waive 

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their right to >24-hour extra consideration. If they wish to take their >24 hours consideration time or have 
an additional bystander present, they will reschedule for another similar appointment. In cases where only 
one parent/guardian can attend the enrollment visit, a written ‘power of attorney’ (Danish: fuldmagt) from 
the other parent/guardian will be required. All eligible participants will be provided with written information 
about the study >48 hours before a possible enrollment visit.  
 
Consent {26a,26b} 
We aim to observe the fullest possible degree of patient- and guardian consent.110 The study director will 
obtain consent from parents/guardians to participate in the trials and to publish the results based on their 
pseudo-anonymous data. Participants over the age of 15 will also be asked to sign a written consent form 
themselves. Written and verbal information will be supplied to participants and their parents prior to 
consent. Verbal information will be delivered in an undisturbed setting, similar to a usual medical 
consultation. All participants will be informed of their additional rights as research participants, including 
that 1) they have the right to withdraw from the study at any time and does not have to provide a reason, 
and that this decision will not affect future care 2) that they can consider consenting to participate for at 
least 24 hours after having received written and in-person verbal information 3) they have the right to bring 
a by-stander/guardian before consenting 4) all information captured is confidential, and 5) that their data 
will be stored according to current laws and regulations, they can request access to all their documentation 
and data and request it deleted entirely, and 6) that they are eligible to potentially seek compensation in the 
event of unintended or unexpected injury or harm. 
 
Interventions  
 
The number and length of therapeutic visits will be equal across both groups and delivered in the same 
setting, to minimize performance bias and balance contextual factors that might add to the cumulative 
effect.111,112  
 
Comparator intervention: Usual Care (Arm 1) {6b} 
The literature from Denmark and internationally is conflicting in recommendations for management of 
Osgood-Schlatter, and no specific guidelines exist.113 Using a standardized usual care intervention as a 
comparator increase generalizability and have the potential to have clinical and policy impact.114 An 
international study consisting of surveys and interviews with clinicians with a special interest in Osgood-
Schlatter, found that 1 in 4 of these clinicians employed a wait-and-see approach, and the rest an active 
approach.58 Most recommended advice on load management, exercises, compression strap, stretches, pain 

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medication, and cryotherapy. Other reports from patients or the literature suggest even more variation in 
approaches.31,43,57 We have therefore performed a step-wise sub-study (figure 1) to investigate current 
standard of care in the most common settings in Denmark (Sports Physiotherapists mainly from private 
primary practice, and Orthopedic Surgeons caring for these patients invited from all public secondary care 
orthopedic departments in Denmark). Results were then combined with reports from patients seen in our 
clinic (n=34) who were questioned in detail on what modalities and advice they had previously received.115 
The results were mostly compatible with the recent international survey of clinicians treating Osgood-
Schlatter.58 With the findings from this process, we have developed a patient-aimed leaflet, which will 
contain vignettes and elaborations of the multimodal approaches included in the standardized usual care 
package (figure 1), which will be implemented through four visits (at months 0, 1, 2, 3) with a 
physiotherapist (mirroring the plan of care of the experimental group). 
 
 

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Figure 1. Flow of mixed-methods study 
Flow of mixed-methods study 
with clinicians and patients 
using step-wise 
inclusion/exclusion of modalities 
and approaches to comprise a 
usual care treatment package 
 

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1) Progressive balance and alignment exercises 
Participants will be performing one exercise incorporating balance and alignment every other day. The 
exercise can be one of 6 exercises on progressively more challenging levels. The exercise levels has been 
sourced or inspired by sections from a leading sports rehabilitation textbook47 and subsequently adjusted 
and refined with an experienced clinician utilizing this type of modality with Osgood-Schlatter patients (23 
years practiced, seeing appx. 40 Osgood-Schlatter patients/year).  
 
If the participant continuously experience pain during any of the exercises, the participant is advised to stop 
performing the exercise regress to a previous pain-free level of exercise. If participants have bilateral 
Osgood-Schlatter, the exercises will be performed with double dosage, with each leg as the supporting leg 
interchangeably. For all the exercise levels, the participant must focus on stability/balance and hip-knee-foot 
alignment on the supporting/landing leg, defined as the symptomatic leg. When each exercise can be 
performed with a sufficient level of alignment and stability, the participant can progress to the next level. 
The participants will be instructed through their leaflet and visits with a physiotherapist on how to evaluated 
exercise qualities and when to progress exercises. During each visit, the physiotherapists will also evaluate 
the current exercise level. All exercises levels are depicted in table 4. 
 
Alignment in this context is defined as the ability to  
1) keep the pelvis horizontal in the coronal plane, neutral in the sagittal plane, and not twist around the 
center of mass in the axial plane 
2) keep the knee from going into varus or valgus, and  
3) keep the foot and midfoot arch from going into pronation or supination  
Stability and balance in this context are defined as the ability to perform movement or holds without 
excessive perturbations, corrections, or otherwise inability to perform the movement with intended form or 
tempo.  
 
Level 1 exercise “Standing on one leg”: The exercise is performed by standing upright on one leg for 2 
repetitions of 30 seconds.  
Level 2 exercise “Side lifts”: Standing upright on one leg, participants slowly and controlled lifts their 
contralateral straight sideways out in the coronal plane into hip abduction, and then back again, without the 
foot touching the ground. The exercise is performed for 2 sets of 10 repetitions in a slow controlled 
movement.  
Level 3 exercise “Half moons”: Standing upright on one leg, participants slowly and controlled tracks their 
contralateral foot just off the floor, drawing half-circles around themselves. The exercise is performed for 2 

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sets of 10 repetitions in a slow controlled movement.  
Level 4 exercise “Side twists”: Standing upright on one leg, the participant lifts the contralateral leg by 
grabbing their knee with one hand, tucks it toward their abdomen, and then rotates in the hip around their 
center of mass in the axial plane. Thereby the leg is slowly rotated to the side, all while keeping sufficient 
alignment on the supporting leg and sufficient stability and balance. The exercise is performed for 2 sets of 
10 repetitions.  
Level 5 exercise “Standing Superman”: Standing upright on one leg with both arms flexed at the shoulder, 
and positioned straight in front them, they slowly and controlled lean forward with stretched arms while 
also lifting the other (asymptomatic) leg up behind themselves. The exercise is performed for 2 sets of 10 
repetitions. 
Level 6 exercise: Participants perform hops by setting off on the asymptomatic leg and landing on the 
symptomatic leg, and alignment and balance/stability are then evaluated during landing. The hop is 
performed in three different directions; straight forward, sideways, and diagonally. After each hop, 
participants takes a step back to the starting position. The exercise is performed for 3 repetitions of 8 hops 
to each direction, totaling 24 hops.  
 
Table 4. Depiction of progressive balance and alignment exercise levels 
 
 
 
 
 
Exercise level 1:  
“Standing on one leg” 
Exercise level 2: “Side lifts” 
Exercise level 3: “Half-moons” 
 
 
 
 
 
 
Exercise level 4: “Side twists” 
Exercise level 5: “Superman” 
Exercise level 6: 
“One-legged hops” 
 
 
 

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2) Stretching of the quadriceps muscle 
On the symptomatic leg(s), 2 sets of 30 seconds of the stretching for quadriceps muscle exercise are 
performed daily. The participants are instructed in standing stretches but can select a stretching exercise for 
the quadriceps muscle of their own choosing if desired. 
 
3) Use of a patella strap 
Each participant is given and instructed in the use of a patella strap according to manufacturer instructions 
(item 992, Mueller Sports Medicine Inc., Prairie du Sac, USA). The participants are instructed to use the 
patella strap if they are experiencing pain and find relief in using of the patella strap. They are also instructed 
to use the patella strap during sport or physical activity if they experience it as beneficial.  
 
4) Advice on other modalities 
Cryotherapy: ”Utilize after participating in sports or physical activity if you experience pain or swelling. Apply 
the icepack for 15-20 minutes, and repeat if necessary”. In addition, instructions on exactly what to use as an 
ice-pack and how to wrap it, and how to apply it safely.   
Taping: “Specific taping of the knee can be useful for some if you have access to it. Maybe you have previous 
experience with applying sports-tape for your knee pain either on your own/with your parents, or by a 
coach, teammate, or health professional at your club.” 
 
5) Advice on load, pain, and prognosis 
Prognosis: “The prognosis is good. It will pass on its own, and the condition is not dangerous. It can, 
however, have some non-serious long-term consequences.” 
Pain and sport: “We advise that you adjust your level of participation in sports and physical activity so that 
you participate with little pain or to your pain limit. If you experience pain, it can be helpful to take a short 
break (lasting from a few hours to a few days).” 
 
Experimental intervention: A novel treatment approach (Arm A) {11a}  
 
Rationale and scientific background 
The experimental intervention was first comprised and tested in a large cohort of 10-14-year-old adolescents 
with a similar condition (patellofemoral pain) and was associated with a successful outcome after 12 
weeks.59 Afterwards, the intervention was changed slightly to target adolescents with Osgood-Schlatter and 
then pilot-tested in a cohort of 51 participants.60 In this cohort, most participants needed more time to 

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progress through exercises and sport, and we have therefore piloted extending the intervention further in 
the clinic, with more success on these aspects.68 We have also found that adolescents with Osgood-Schlatter 
had markedly decreased strength in knee extension and hip abduction compared to a control group or even 
to a group of adolescents with patellofemoral pain.116 
 
Exercises with pain have been shown superior to pain-free exercises in short-term management of chronic 
pain,117, and pain of up to 5 NPRS is usually tolerated in exercise programs for tendon-related conditions in 
adults.117,118 Exercises with pain is a safe and effective way to increase gradual tolerance to loading activities 
and to decrease pain-response by inducing hypoalgesia and mitigating central and peripheral 
sensitization.119,120 It has also been shown that exercise as a modality is effective for pain-related beliefs, 
such as kinesiophobia (fear of exercise), pain self-efficacy, and fear-avoidance behavior.121,122 In adolescents 
with knee pain performing simple knee extension and flexion, increased kinesiophobia seems to necessitate 
additional neurological resources to compensate for pain-disrupted processing.123 
Experimental studies have shown reductions in pain sensitivity after exercise,124,125 including dynamic 
(concentric and eccentric contractions) and isometric resistance training.125 Just a few weeks of resistance 
training can improve pain and function in musculoskeletal pain conditions,126 and seems superior to other 
non-pharmacological modalities.127 Patella tendon pain or damage can lead to quadriceps inhibition,35 a 
disorder that responds well to resistance training.128 In addition to being an appropriate and safe modality 
for Osgood-Schlatter, strength training also carries a wealth of other health and performance benefits,129–137 
especially for adolescents.138 
 
In line with this, isometric exercises with a long time under tension (10-30 s) can be a good initial loading 
mode as it allows a high exercise volume with lower peak joint forces and has been shown to improve tissue 
quality in the patella tendon, induce strength and hypertrophy,139,140 whilst allowing athletes to continue 
their sports participation.139,141,142 Short rest periods (≤30 s) stimulates metabolic load and results in lower 
mechanical load and are, therefore, a safe and effective way to promote adaptations through 
anabolic/metabolic pathways.143,144 Moreover, tendons have high collagen turnover during adolescence, 
with no turnover in the remaining lifespan;145 and especially the distal part of the patella-tendon is 
susceptible to adaptations from exercise.142 This highlights the need for a healthy stimulus during this phase 
of maturation.  
 
Taking away the pain-evoking stimuli of loading from sports and vigorous physical activity while 
simultaneously introducing high volume exercise is therefore likely a key to allow subsequent gradual 
exposure to sports more successfully. The guidance through the return-to-sport process will be based on the 

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clinical exposure therapy, which is defined “by repeatedly and systematically approaching stimuli that trigger 
pain-related distress or symptom preoccupation is counteracted, and the participant will gradually gain an 
increased tolerance to pain and pain-related distress”146 and aims to stop or slow the cycle of preoccupation 
with symptoms, avoidance behavior, and pain. Exposure-based interventions are particularly effective in 
reducing pain-related fear and the perceived harmfulness of physical activity, also by challenging 
catastrophic interpretations of movements or activities.147–151 
 
Adolescents thus have to self-manage the dose of exercise and loading from sports and physical activity 
through the NPRS, putting decision-making on regression/progression in their hands. A self-management 
approach aimed at behavior-change has been identified as key for patients to adapt when facing social, 
emotional, and physical challenges when suffering from persistent musculoskeletal pain or pain disorders, 
and shifting the expectations of a cure to an active approach is central to continued management and is 
suggested to prevent long-term disability and pain.152–156 In addition, Pain Self-efficacy, that is the belief in 
one’s ability to manage and complete a task despite pain, seems to improve by employing self-management 
strategies.122 The approach also supports participants in the step-wise path towards reaching self-
management mindsets- and behavior change.157  
 
Incorporating the parents is important during the intervention, as data have shown parents’ protectiveness, 
catastrophizing, and mood is predictors of youth pain intensity, unpleasantness, and catastrophizing.158 
Further, parents play a critical role in managing pain in their children and improving function.153 The 
intervention will be delivered with age-appropriate language and incorporate vignettes during adjunctive 
pain management education.159,160  
 
Arm A will therefore contain an active approach with self-management of load and progressive exercise 
therapy, delivered through 4 one-on-one visits lasting approximately 20 minutes (at months 0, 1, 2, 3) over 3 
months with a physiotherapist and an accompanying leaflet with written and illustrated exercise description, 
and advice and information. 
 
This intervention will also align with the high-value care recommendations for care in musculoskeletal pain 
and sports medicine.161–163 
 
1) Exercises 
For targeting the insertion site of the quadriceps femoris, the tibial tubercle, exercises at around 75° knee 
flexion will be performed, starting with the mild “knee-press” exercise during the first month, after which 

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participants will be instructed to proceed to the heavier weight-bearing wall-squats at appx 90° knee flexion, 
followed by unilateral lunges at approximately 125° knee flexion (table 5). The tensile force on the patella 
tendon is approximately half that during a bodyweight squat compared to a lunge with high range of 
motion.164,165 The regression/progression of exercises will depend upon the pain experienced during and 
until the morning after performing the exercise – if pain has not exceeded NPRS 2, the standardized 
exercise-dose should be progressed. Alternatively, the exercise dose should be maintained or regressed until 
NPRS ≤2 is achieved. Besides knee-dominant exercises, the hip abductor bridge will be prescribed, with the 
same dose throughout months 0-3. 
 
Table 5. Depiction of hip- and knee exercises 
 
 
Knee press 
Wall squats 
 
 
Hip abductor bridge 
Lunges 
 
2) Loading from sport and physical activity 
Participants will be asked to take a complete break from weight-bearing sports and rigorous physical activity 
during the first month. After month 1, gradual exposure to sport will begin, using the same pain-model to 
progress or regress loading, as well as sport-specific advice from a physiotherapist based on load-markers 
such as intensity, frequency, duration. Once full or maximum-possible sports participation has been 

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achieved, progression of load from rigorous physical activity will follow in the same manner.    
 
3) Advice and education 
The leaflet and conversations during visits will contain information and advice regarding the following 
domains: 1) Aetiology 2) Pain management 3) Effects of exercise and knee loading activities 4) Prognosis 5) 
Self-management decision-making tools and addressing real-world challenges for the participant. From 
month 3 to 5, the participants will completely self-manage their condition and is encouraged to maintain 
some level of self-chosen exercise dose (advice of 1-3 sets of lunges and hip abductor bridge, 2-3 times 
weekly) 
 
Table 6. Short-form overview of the two treatments 
 
Experimental 
Comparator 
Month 0-1 
 
Phase 1 
▪ 
Break from sports and moderate-to-vigirous physical 
activity 
▪ 
Daily high-volume low load isometric training 
▪ 
High-load hip-abductor training every other day 
▪ 
Introduction to a pain-model for progression of exercises 
and exposure to sport/moderate-to-vigirous physical 
activity 
▪ 
Education on pain science and management 
▪ 
Introductionof progressive balance and alignment 
exercises every other day and continued 
▪ 
Introduction of daily progressive quadriceps stretching 
▪ 
Advice on approaches for preventing/treating pain flares: 
▪ 
Cryotherapy after activity if painful 
▪ 
Sports taping 
▪ 
Handout and instructions in using a patella strap 
▪ 
Advice on potential prognosis 
▪ 
Advice participation in sports and physical activity when 
experiencing pain 
 
 
 
Months 2-3  
 
Phase 2 
▪ 
Self-managed introduction of gradual exposure to sport 
based on the pain-model 
▪ 
Once acceptable sport-level achieved, self-managed 
gradual exposure to vigorous physical activity is 
introduced 
▪ 
Introduction of progressively more loaded isometric and 
subsequent dynamic weight-bearing exercises for the 
knee extensors 
▪ 
Continued high-load hip-abductor training every other 
day 
Months 4-5  
 
Self-management phase 
▪ 
Complete self-management of pain vs. loading from 
participation in sports and physical activity  
▪ 
Potential self-management of self-chosen exercise dose  
Self-management phase 
▪ 
Complete self-management of pain vs. loading from 
participation in sports and physical activity  
▪ 
Potential self-management of self-chosen exercise dose 
 
 
Criteria for discontinuing or modifying allocated interventions {11b} 
If scheduling or the availability of equipment (surface, chair) hinders the participant from following the 
exercise dosage, the treating physiotherapist will, together with the participant, try to amend the 
programme to better suit the preferences and context of the participant while still aiming for the correct 
dose and form in accordance with the original approach to the fullest extent possible.  

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Intervention adherence {11c} 
Making exercises enjoyable, social, and convenient has been identified as the most likely barriers to exercise 
adherence in adolescents with musculoskeletal pain.166 In line with this, the exercises prescribed in both 
groups are designed to be performed with only little if any exercise-equipment and are time-efficient (1- 20 
minutes per day/every other day). We also encourage the participants to attend their regular sports team 
practices and perform the exercises in that environment, rather than potentially skipping practice 
altogether, and thereby gaining a social aspect of performing the exercises.167 In both groups, the 
intervention personnel will remind participants to adhere to their respective interventions at visits at 
months 0, 1, 2, and 3. Reminders will firstly focus on the importance of adhering to dose and form of 
exercises and to the advice on loading by their own autonomy.167 Secondly, the personnel will engage 
participants in potential context-based barriers to adherence and foster realistic expectations. Through 
weekly monitoring, participants are asked about their adherence to exercise and other group-specific 
modalities the past week (table 7-9 and figures 8-10). Also, we ask if they have currently returned to sports 
participation. In addition to weekly reports on adherence, participants will be asked at visits at months 1 and 
3 about their current exercise dose and to demonstrate the exercises, which will then be rated by the 
observing therapist on a standardized form (table 7). To ensure honest answers regarding adherence, data 
from weekly monitoring will be unavailable to the treating physiotherapist, and the participant will be 
informed of this blinding at enrollment. Capturing detailed adherence of participants will allow post-hoc 
interpretation of the study results beyond the intention-to-treat approach.168 
 
Table 7. Items for exercise evaluation forms as reported by the treating physiotherapist 
 
Balance/alignment 
exercises 
Stretching 
Hip abduction 
Knee exercise 
 
Comparator group 
Experimental group 
Sufficient focus on knee alignment 
X 
 
 
 
Sufficient focus on hip alignment 
X 
 
 
 
Sufficient attention to progression 
X 
 
X 
X 
Sufficient range of motion 
X 
X 
X 
X 
Sufficient load (RM) 
 
 
X 
X 
Accurate tempo and time under tension 
X 
X 
X 
X 
Sufficient form to target to intended muscles or qualities 
X 
X 
X 
X 
Intended pain level (<3 NPRS) 
 
 
X 
X 
 
Compliance criteria 
Adherence will be determined in 3 different epochs, which will vary between groups, as the experimental 
intervention is divided into two phases. In the experimental group, two epochs will be set from month 0-1 
(phase 1) and month 1-5 (phase 2 and the self-management period). The comparator group will only have 1 

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epoch lasting the whole core study period (month 0-5). We have outlined criteria for weekly adherence 
criteria below (table 7-9 and figures 8-10). For phase 1 in the intervention group, 3 out of 4 weeks of full 
adherence is considered as compliant, and for phase 2 (week 4-13), 7 out of 9 weeks of full adherence is 
considered compliant. For the whole treatment period in the comparator group (week 0-13), 10 out of 13 
weeks with full adherence is considered compliant, this mirroring the total count in the same period in the 
intervention group. For the self-management period (months 3-5), in both groups, the criteria for exercises 
are the same as during treatment, but the dose is self-chosen. For participants in either group, the 
compliance criteria must be achived in every epoch, the to be catogrized as compliant over the entire study 
periode (month 0-5) 
 
Table 8. Adherence criteria for the intervention group  
Epoch 
Modality 
Criteria for epoch 
Measurement 
Month 0-1 (phase 1) 
Break from sports and  
MVPA 
≤15 min of VPA and ≤30 
min of MPA every day 
Sensor-based 
Daily isometric knee-extensor 
exercise 
4≥ full sessions per week  
Weekly text: “How many sessions did you complete of 
your knee exercise this past week?” 
Month 1-3 (phase 2): 
Gradual exposure to sport with 
limitation of pain flares 
Non-negative 4 week 
moving average of MVPA 
minutes (calculated from 
week 8) 
Sensor-based 
Weightbearing knee-extensor 
exercise every other day 
2≥ full sessions per week 
Weekly text: “How many sessions did you complete of 
your knee exercise this past week?” 
Month 0-3 (phase 1 & 2) 
Hip-abductor exercise 
every other day 
2≥ full sessions per week 
Weekly text: “How many sessions did you complete of 
your hip exercise this past week?”  
Month 3-5 (Self-
management phase) 
 
Self-chosen dose of knee-
extensor exercise  
2≥ sessions per week 
Weekly text: “How many sessions did you complete of 
your knee exercise this past week?” 
 
Self-chosen dose of any hip-
abductor exercise 
2≥ sessions per week 
Weekly text: “How many sessions did you complete of 
your hip exercise this past week?” 
 
No dramatic short-term 
changes in sports and 
physical activity 
≤100% change in 4 week 
moving average of MVPA 
minutes  
Sensor-based 
 
Table 9. Adherence criteria for the comparator group  
Epoch 
Modality 
Criteria 
Measurement 
Month 0-5 
Balance and alignment 
exercises every other day  
2≥ full sessions per week 
Weekly text: “How many sessions did you complete of 
your balance exercise this past week?”  
Daily quadriceps 
stretching 
4≥ full sessions per week 
Weekly text: “How many sessions did you complete of 
your stretching exercise this past week?” 
Cryotherapy, sports taping, or 
patella strap 
Utilized >1 times per 
week 
Asked during visits: “How many times weekly have you 
used icepacks, taping, or straps?” 
 
 
Criteria for discontinuing or modifying allocated interventions {11b} 

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If scheduling or the availability of equipment hinders the participant from following the exercise dosage, the 
treating physiotherapist will, together with the participant, try to amend the programme to better suit the 
preferences and context of the participant while still aiming for the correct dose and form in accordance 
with the original approach to the fullest extent possible.  
 
Concomitant care during the trial {11d,30} 
Participants will be encouraged only to receive treatment as outlined in their allocated group for the 
duration of the treatment (first 3 months) and the self-management period (month 3-5). Concomitant 
treatment will not be course for exclusion, but will be recorded at visits months 1, 3, and 5. We do not 
expect a high occurrence of concomitant treatment, but if this should occur, we will explore potential post-
hoc moderation or subgroup analysis to better understand this aspect and its implications on the results of 
the trial. Participants will be instructed to not take any pain medication on the same day of testing to ensure 
that this does not affect any measurements. No post-trial treatment is planned. 
 
Outcomes {12} 
Besides long-term digital follow-up, patient-reported and clinical measures will be recorded at 5 possible 
time points; at baseline and months 1, 3, 5, and 8. Weekly monitoring will be done from baseline to month 5. 
Imaging will be performed at enrollment and at months 3, 5, and 8. Long-term patient-reported follow-up is 
planned for 1, 2, and 4 years after enrollment. All data, besides text-message, ultrasound images, and 
sensor-data, will be captured in REDCap (Research Electronic Data Capture, Vanderbilt Universit,y, USA),169 a 
logged secure system designed to capture sensitive non-commercial clinical data hosted at Hvidovre 
Hospital. REDCap contains options for valid values, range checks, data validation, branching, scheduling, and 
stop-rules to increase data quality. Pain during all clinical tests will be recorded in addition to the primary 
measure. Ultrasound will be performed during the enrollment visits and again at months 3, 5, and 8. For a 
visual overview of data collection schedule, see table 11. We have reported our outcomes in a prioritized 
order in addition to designations as primary, secondary or exploratory, which also reflects the order of 
hypothesis-testing, analyses, and intentional order of reporting, with all primary and secondary outcomes 
intended for the primary report.170 Note that for this reason, the order and count of outcomes below reflect 
the total number of variables of interest within each outcome. No core outcome set exists for this or similar 
populations, and the outcomes are chosen based on current literature and clinical experience.171 
 
 
Table 10. Overview of outcome domains and prioritized hierarchy of outcomes 
Outcome domain 
 
Specific outcome variables 

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Primary outcome 
 
 
 
Sport function 
 
1. 
KOOS-child ‘Sport/play’ 0-100 subscale (7 
items) 
 
 
 
Secondary outcomes 
 
Patient-acceptable Symtom-
state 
2. 
PASS question (Y/N) 
 
 
Knee-related Quality of Life  
3. 
KOOS-child ‘Quality of Life’ 0-100 subscale (5 
items) 
 
 
Pain intensity and frequency 
(Pain flares) 
4. 
4-week-average episodes of pain flares (≥4 
on 0-10 NPRS) 
5. 
Worst pain past week (0-10 NPRS) 
11. 
 
12. 
KOOS-child question P1 on ‘Pain’ subscale (1-5 Likert 
scale) 
Level of pain/discomfort (EQ-D5-Y 4) 
Participation in sports and 
physical activity 
6. 
4-week average hours of sports participation 
 
13. 
14.
15. 
16. 
17. 
4-week average hours of MVPA 
Satisfaction with extent of sports participation  
Pre knee pain level of sports participation 
Pre knee pain level of physical activity 
Time to return to sport (week no.) 
Osgood-Schlatter morphology 
(ultrasound imaging) 
7. 
Flaviis composite severity score 
18. 
19. 
20. 
Tendinosis signs (thickening or hyperemia) 
Infrapatellar bursitis signs (effusion or hyperemia 
Hyperemia of the tibial tubercle ad modum Öhberg 
Pain during knee loading  
8. 
Anterior Knee Pain Provocation test (0-10 
NPRS) 
21. 
22. 
23. 
24. 
25. 
Pain during knee extension test (0-10 NPRS) 
Pressure-pain threshold at the tibial tubercle (kPa) 
KOOS-child ‘Pain’ 0-100 subscale (8 items) 
Known pain during manual palpation 
Pain during countermovement jump (0-10 NPRS) 
Objective knee function 
 
26. 
27. 
28. 
29. 
Maximal isometric knee extension strength (Nm/kg) 
Countermovement jump height (cm) 
Countermovement power (W) 
Knee extensor flexibility change (°) 
Global rating of change 
9. 
7-point Likert scale 
30. 
Satisfaction with treatment (Y/N) 
Usual activities 
10. Patient-specific function scale (NRS 0-10) 
31. 
Problems with usual activities (EQ-D5-Y 3) 
Pain beliefs 
 
32. 
Kinesiophobia (Tampa Scale of Kinesiophobia, 17 items) 
Health 
 
 
33. 
Self-rated health (EQ-D5-Y 0-100 VAS) 
 
Safety outcomes 
 
 
 
 
1. 
Any adverse events 
 
 
 
 
 

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Primary outcome 
KOOS-child ‘Sport/play’ subscale 
The primary between-group difference will be evaluated using the KOOS-child (Knee injury and 
Osteoarthritis Outcome Score – Child), designed specifically for adolescents and youths aged ≥10 years 
experiencing knee problems.172 The KOOS-child contains 5 independent subscales with domains ‘Pain’ (11 
items), ‘Symptoms’ (7 items), ‘Activities of Daily Living’ (11 items), ‘Sport/play’ (7 items), and ‘Quality of Life’ 
(6 items). The questions are answered on Likert scales from 0 to 4 points and pertains to the prior week. The 
scoring of each subscale is normalized to a 0-100 score, 0 being extreme symptoms and 100 being no 
symptoms. Four subscales (excluding ‘Activities of Daily Living’ due to low responsiveness68,116) will be 
recorded and presented, but the subscale ‘Sport/play’ will be prioritized based on study aims and feedback 
and preferences from patient representatives and will thus provide properties for sample size calculation. 
The four included subscales have low detectable change on the group level (1.86-2.66 points), acceptable 
standard error of measurement (5.69-8.14 points), and substantial/near-perfect test-retest reliability (ICC 
0.78-91). 
 
Secondary and exploratory outcomes 
 
Patient Acceptable Symptom State 
The question pertaining to Patient Acceptable Symptom State (PASS) is designed in collaboration with 
patient representatives. The recall period will be one week, and the outlook period a ‘few months’ as in 
previous applications in musculoskeletal conditions with fluctuating symptoms.173 The phrasing of the PASS 
will be (approximate English translation): ”If you consider your knee pain during the past week, and how it 
affects your ability to do activities of daily living (for example participating in school, in sports, and socially), 
would you consider your current symptom state acceptable for the next few months?”. The proportions of 
yes/no in each group will be captured and compared at designated time points. 
 
KOOS-child Quality of Life’, ‘Symptoms’ and ‘Pain’ subscales 
The above subscales will be collected and change scores compared in the same manner as the primary 
‘Sport/play’ subscale.  
 
Frequency and intensity of pain flares 
A pain flare in this study is defined as any time a participant reports episodes of pain of NPRS ≥4 through 
weekly monitoring. As an outcome, a 4-week median of number of pain flares during week 19-22 (frequency 
of pain flares) and the worst pain the past week at week 22 (intensity of pain) will be calculated and 

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compared. In adult populations with knee pain, the 0-10 numerical pain rating scale has shown near-perfect 
test-retest reliability of ICC 0.95 and low detectable change of 1.33 points.174 Frequency will also be captured 
using the P1 question from the KOOS-child ‘Pain’ subscale: “During the past month, how often have you 
experienced knee pain?” with potential responses “Never” (1), “Rarely” (2), “Sometimes” (3), “Often” (4), 
“All the time” (5). Finally, participants will rate their problems with Pain/Discomfort in the 3-point Likert EQ-
D5-Y. 
 
Participation in sports and physical activity 
According to WHO recommendations, a daily minimum of 60 min of moderate to vigorous physical activity 
(MVPA, such as biking, running/exercising/high-intensity training) is needed to stay healthy for 5-17-year-
olds.175 Thus, being at either under or above this cutoff during a 4-week average from week 18-22 will be 
assessed, in addition to a continuous comparison between the two groups of minutes of MVPA during the 
same time period. Self-reported levels of physical activity are highly under-reported from trials-participants, 
and sensors increase the precision.176 Minutes of MVPA will be captured using waterproof threeaaxis12 Hz 
accelerometers (SENS®, Copenhagen, Denmark) applied once to the participant’s thigh during the 
enrollment visit using an adhesive patch (35 cm2, 8 g). The sensors have shown 92±5% discriminate 
agreement when distinguishing between different activities (light sleep, deep sleep, lying/sitting, standing, 
sporadic walking/slow biking, walking, biking, running/exercising/high-intensity training).177 Physical activity 
data will also allow posthoc analyses of exposure.  
 
In addition to physical activity, the level of participation in sports will be captured through weekly 
monitoring. Participants will be asked how many hours they have been participating in sports in the 
preceding week. Return to sport time will be defined as the first week participating in sports, followed by 
one more week also with sports participation. Participants will also be asked during clinical visits if their 
return to sport was at their pre-injury level or less/more and if they are satisfied with the current extent of 
their sports participation. 
 
Morphology 
Involvement of the tendon is common in patients with Osgood-Schlatter,178,179 and associated signs of 
bursitis and severity have shown to be prognostic of a worse outcome.32 A series of Osgood-Schlatter 
patients has been described for whom less hyperemia on color doppler ultrasound was associated with 
milder symptoms.109 Hyperemia on color doppler ultrasound (ad modum modified Öhberg 1-4) will therefore 
be assessed for the patella tendon and tibial tubercle (yes/no) at baseline, month 3, month 5, and month 8. 
High inter-rater reliability of color doppler evaluations in the patella tendon has been established,180, and we 

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are currently investigating the reliability and clinical relevance of the full ultrasound protocol being 
employed in the study.178  
 
Knee pain during loading 
The pain evoked from loading the affected tissue will be measured in four different ways. Firstly, by rating 
the pain level after performing the Anterior Knee Pain Provocation test (we have recently shown this test to 
be associated with KOOS-child ‘Sport/play’ and NPRS, and response over time for adolescents with knee 
pain).181 Secondly, by a NPRS 0-10 rating from performing the maximal isometric knee extension strength 
test and the countermovement jump (maximum pain during any of three trials). Thirdly, by manual palpation 
of the tibial tubercle for known pain (y/n). Finally, to evaluate local hyperalgesia, specifically at the tibial 
tubercle, we will use handheld algometry to detect the pressure (kPa) needed to evoke pain (going from no 
pain to the slightest sensation of pain) on the tibial tubercle on both knees. The intra-day and intra-tester 
reliability has been found to be >0.98 (ICC 3.1) for two similar sites; the center of the patella and the muscle 
belly of the tibialis anterior in young adults with longstanding knee pain.182  
 
Knee function 
Knee pain is known to reduce muscle function.183 To evaluate the capacity of the quadriceps femoris muscle 
inserting at the site of pain, handheld dynamometry will be used to measure maximal isometric force 
generation, which will be normalized to body weight and lever-length (Nm/kg). This test has shown inter-
tester reliability of ICC: 0.76-0.96184,185 with a low standard error of measurement (5-11%)185 and good 
validity compared to the gold standard of isokinetic strength assessment.184,186,187 We have recently 
investigated the inter-tester reliability of this test in an Osgood-Schlatter cohort and found acceptable 
reliability.188 As a measure of power and a sports-specific skill, a countermovement jump will be performed 
to record jump height (cm) and power-production (watts), using high-speed video analysis via a smartphone 
app (My Jump 2). The test has been found feasible in adolescents,189 been validated against the gold 
standard of using a force-plate,190–192 and is highly reliable.190,192–195 Adolescents with Osgood-Schlatter have 
been reported to have tighter knee-extensor muscles, but it’s unclear if this is thought to be a contributing 
cause or derived effect or if this is merely is a characteristic of increased musculoskeletal maturation.38 We 
will compare the change in knee flexion angle, assessed by smartphone-inclinometry during a modified 
Thomas Test. Different apps based on the standard smartphone level-function have been investigated with 
near-perfect validity with other digital methods (video-analysis, digital inclinometers) and with good to 
excellent inter-and intra-tester reliability and low error of measurement and detectability.196 However, we 
will utilize the built-in level app in iPhone 7 (Apple, USA) as the apps investigated in the literature are no 
longer available for download. We have recently investigated the inter-tester reliability of using the built-in 

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level app in the iPhone 7 to measure the knee flexion angle in an Osgood-Schlatter cohort and found 
acceptable reliability.188 
 
Global rating of change 
To assess patient-assessed improvement or worsening, we will ask participants to rate their perceived level 
of change from their first visit on a 7-point Likert scale ranging from ‘Much worse’ to ‘Much better’. GROC-
scales have been found to have sufficient reproducibility and responsiveness.197 
 
Usual Activities 
We will ask participants to rate their problems with an important activity using the Patient-Specific 
Functional Scale. They are asked to name a single important activity of their own choosing. Participants then 
rate their functional limitation with activity on a 0 to 10 scale, where 0 corresponds to being unable to 
perform activity and 10 is being able to perform activity at same level as before knee pain. At follow-up 
assessments, participants are asked to rate the previously nominated activity on the same scale.198 For other 
conditions, the PS-FS has shown to be valid, reliable, and responsive.199 In addition, the EQ-D5-Y question on 
problems with ‘Usual Activities’ will be collected. 
 
Pain Beliefs 
To capture the level of kinesiophobia, that is, the fear of pain due to movement or exercise, a type of fear-
avoidance behavior, the patient-reported 17-item Tampa Scale of Kinesiophobia (TSK-17) will be used.200 The 
instrument has good reliability and validity,201,202 and has demonstrated good psychometric properties when 
used by adolescents.203 
 
Self-rated Health 
Recent studies have shown that self-rated adolescent health is associated with death, multimorbidity, 
primary care utilization, medicine use, social welfare benefits,204–207 as well as persistent musculoskeletal 
pain.208 Self-rated health will be collected through the 0-100 VAS for general health. The EQ-D5-Y questions 
pertaining to ‘Self-care’ and ‘Mobility’ will be omitted due to low responsivenes68 and the question on 
‘Anxiety/depression’ will only be used for mediation/moderator analysis and baseline descriptives. Our 
application of the questions on ‘Usual Activities’ and ‘Pain/discomfort’ is described early in this section. Test-
retest reliability of the EQ-D5-Y has shown a percentual agreement of 70-99%.209 
 
Adverse events 
The potential occurrence of adverse events (AEs) in either treatment group will be reported as amount and 

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proportions, and described in prose regarding severity, timing, and duration.210 If sufficient data is observed 
to complete contingency tables, the odds ratio will also be reported.211 See the section “Adverse event 
reporting and harms“ for a more detailed definition of AE. Adverse events will be collected in a 
systematically rather than spontaneous reporting by participants by utilizing a pre-specified instrument in 
REDCap for each clinical visit and the telephone consultation at month 2.210  
 
Participant demographics 
The baseline survey will also include questions on age, body weight, stature, participation in sports and 
physical activity, previous care, bilateral pain, concomitant conditions (anterior knee pain conditions), 
symptom duration, health-related behaviors, anthropometrics, pubertal and skeletal maturity, and predicted 
adult height. Per CONSORT guidelines, we will not perform statistical comparisons of baseline 
charactistics.73,212  
 
Study flow and participant timeline {13} 
Patients will undergo pre-trial procedures (phone screening, examination, and history, oral and written 
information, signed consent) before enrollment and treatment start (baseline), which will then last 3 months 
(13 weeks). A telephone consultation with the treating physiotherapist is planned for month 2 (week 9), that 
can also result in a clinical visit if needed. Two months (9 weeks) after end-of-treatment, participants will 
attend the primary clinical follow-up visit at 5 months (22 weeks), followed by the final clinical visit at 8 
months. Subsequently, long-term digital-only follow-up will be captured at months 10, 12, 24, and 48. See 
figure 2 for detailed study-flow, and table 11 for the study schedule.  
 
 
 

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Figure 2. Study flow 
 
 
Sample size considerations {14} 
The properties of the primary outcome measure KOOS-child and the “Sport/rec” subscale have been well 
investigated, with a validation study including adolescent participants with Osgood-Schlatter amongst other 
overuse- and acute knee disorders.172 A small cohort of patients in our clinic (n=16) who 1) were eligible for 
inclusion in the trial at baseline, 2) received the intervention in question and 3) attended follow-up, reported 
their global rating of improvement on a 7 point Likert scale ranging from 'much worse (7)' to 'much better 
(1)'. Patients who reported ‘much better (1)’ or ‘better (2)’ had a mean improvement on KOOS-child 

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‘Sport/play’ subscale of 12.7±16 points, whereas patients reporting less improvement (‘little’ improvement 
or ‘no change’) only had a 3.57 point increase. In absence of more robust specific data in terms of severity, 
intervention, and length of follow-up,213 we will utilize this 9 point difference as a threshold for determining 
superiority. We consider this to be a meaningful change and a relevant between-group difference, and is 
within the recommended range of 8-10 points (heartbeat-med.com/resources/knee-injury-and-
osteoarthritis-outcome-score-koos). This change also exceeds the smallest detectable group-level change 
(2.66 points) and the standard error of measurement (8.02 points).172 
 
In order to detect such a change with a standard deviation of 16 points an α level (type I/false positive error 
rate) of 5% and power (β-1, or probability of avoiding type II/false negative error rate) of 90%, 55 (54.8) 
participants per group would be needed based on an independent one-sided t-test (R 4.0.2, Foundation for 
Statistical Computing, Vienna, Austria; RStudio 1.0.153, power.t.test package). To account for a potential 
15% dropout rate59 a total of 130 participants will be included. 
 
Figure 3. Effect size vs sample size plotted  
 
 
 
This will correspond to a 0.56 Cohens d 'medium' effect size at 90% power (figure 3). The smallest effect size 
reliably detectable will thus be >0.482 (Cohens d ‘small’ effect size) at ≥80% power (Jamovi 1.2.25, jpower 
module), surpassing the trivial (<0.2) and small (>0.2) effect size thresholds. We also consider this sample 
size to be operationally feasible within the given timeframe and with the resources available to our group. 

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Recruitment {15}  
Participants will be recruited through a combination of convenience and consecutive sampling from the 
uptake area of the Capital Region of Copenhagen, Denmark (1.8M inhabitants), through two different 
approaches; 1) patients referred to the secondary care specialized outpatient Orthopedic Department at 
Hvidovre Hospital, and 2) postings to our website encouraging parents of adolescents with anterior knee 
pain below the knee to contact the study director, which will be also be shared with sports clubs in the 
uptake area through our organizational network. Based on historical patient flow and past studies in this 
population, the planned recruitment rate is expected to be around 10-15 participants per month during non-
holiday periods. Thus, inclusion is expected to last up to two years, from January 1st 2022 to December 31st 
2023. 
 
First contact 
Accordingly, all 10-16-year-old patients referred for potential Osgood-Schlatter complaints to the 
department from other hospitals or general practice, or having contacted the study director themselves, will 
be screened for eligibility by telephone by the study director before potentially being invited to enrollment 
visit.  
 
Assignment of interventions: allocation 
 
Sequence generation {16a} 
Participants will be allocated to either standardized usual care or the experimental intervention with a 1:1 
allocation ratio. To perform adequate sequence generation, we will use The Robust Randomization App214 
(RRApp v3.0.1, https://clinicalresearch-apps.shinyapps.io/rrapp/) for a computer-generate sequence in 
random sized blocks with no stratifications, extracted by a person not otherwise involved in the trial. 
 
Concealment mechanism {16b} 
To conceal allocation and prevent selection bias, the sequence will be implemented using sequentially 
numbered in sealed opaque envelopes. A person not otherwise involved in the trial will be given the 
randomization sequence and 65 envelopes containing a paper reading ‘group 1’ and 65 envelopes containing 
a paper reading ‘group b’. The paper is sandwiched between two black pieces of cardboard, making it 
impossible to see through even with strong under-lighting. The envelopes have been sealed with glue. They  
will then order and number the envelopes according to the order from the randomization sequence. 
 

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Implementation of allocation {16c} 
During the study period, staff involved in data collection and analysis will be blinded to randomization 
sequence and block size. Only the personnel responsible for including participants will have the ability to 
view group allocation, but only after the participant is irreversibly included in the study and have been 
allocated to their group. 
 
Assignment of interventions: Blinding 
 
Who will be blinded {17a} 
Outcome assessors and the statistician performing analysis will be blinded in every way to group allocation.  
To yield valid results from the trial, we will blind intervention-receivers (participants) to treatment allocation 
and contents of the intervention they are not receiving. This will be done by providing minimal information 
to participants about the contents of either intervention until after group allocation, nor will they be 
informed if they are in the experimental (Group A) or usual care group (Group 1). The written and verbal 
information prior to inclusions will state that the two groups both contain first line treatment modalities 
such as different advice and exercises, offered as current practice based on the most recent literature. 
 
One reason for not informing participants about the contents of the interventions is that knowledge about 
the actual content would increase the likelihood of contamination, as participants might want to implement 
parts of one intervention into the other or vice versa, for example, by doing stretches in addition to the 
exercises in the experimental group. This would contaminate the experimental intervention leading to a 
possible underestimation of the efficacy of the intervention in question. Secondly, by keeping participants 
blinded to treatment allocation, the adverse effects, such as disappointment of not receiving one or the 
other intervention, could be avoided. This is important because these effects could negatively affect the 
outcomes, with a risk of an overestimation of the relative efficacy of the intervention in question. This 
blinding aspect of participants with minimal information about treatment contents will increase the validity 
of the results. We consider this blinding aspect ethically warranted, as firstly, no current standardized 
recommendations or best practice of care for Osgood-Schlatter exists, and secondly, there is a considerable 
variation in the current type and extent of treatment modalities offered for Osgood-Schlatter patients.58,115 
 
To minimize bias (performance- and verification bias), the intervention personnel will not be aware which, if 
any, of the two treatments is the experimental or the comparator, or if the trial is investigating 
superiority/non-inferiority/equivalence. Different personnel will deliver each intervention and will not be 

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aware of the contents of the intervention in the opposite arm. However, due to the nature of the 
interventions, it is required that they are aware of the group allocation of participants in order to deliver 
their assigned intervention, and they also need to engage participants in conversations about their current 
pain and symptoms, and their level of physical activity and sports, in order to guide participants through 
their respective treatments. Blinding intervention personnel to group allocation and some outcomes is 
therefore not feasible and is not performed, but they will not have access to any data collected by the 
outcome assessor during clinical testing and ultrasound scanning, nor the patient-reported instruments. 
 
Procedure for unblinding if needed {17b} 
As the study director and the Medical Advisor is unblinded to group allocation, unblinding is not expected to 
be necessary during the trial. 
 
Study personnel 
Intervention personnel will be 6-10 different trained physiotherapists, not be involved in other aspects of 
the trial. Personnel responsible for doing outcome collection will be 1-2 physiotherapists, not involved in 
other aspects of the trial and will be blinded to group allocation. Personnel responsible for diagnosis, 
inclusion, end-of-study visit will be one physiotherapist (KK) and a potential trained replacement, who will 
not be blinded to either group allocation or outcome measures. The Medical Advisor will be a Chief 
Orthopedic Surgeon (PH), who will examine participants in need of a second opinion regarding initial 
diagnosis, AEs, or other sudden health deterioration in participants. A biostatistician (TK) blinded to group 
allocation in the dataset will perform the analyses.  
 
Study training 
The PI has extensive experience delivering the experimental intervention, with all the chosen clinical 
outcome assessments from previous trials,32,59,68,116,181,188,195 and clinical work in the target population. In 
addition, the PI have managed the process of constructing the usual care-intervention through investigation 
with clinical field experts.115 Therefore, the PI will train the other physiotherapists in the respective 
interventions and clinical outcome assessments. All personnel will be trained in the nature of contamination 
effect and be trained in how to avoid unblinding when engaging participants. 
 

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Data collection and management 
 
Plans for assessment and collection of outcomes {18a} 
Depending on the time point, participants will answer between 85 (baseline) and 38 questions (month 1) in 
their surveys. In table 11 we have described the schedule of data collection of all outcomes. All outcome 
data, both clinically obtained by an outcome assessor or patient-reported directly from the participants, will 
be entered into REDCap. Weekly monitoring will be performed using text-based service (SMS-track®, Esbjerg, 
Denmark) similarly starting the following Monday after the baseline visit and the following 22 weeks, 
totaling 23 weekly monitoring questionnaires containing 4-6 questions.  
 
 

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Table 11. Study schedule 
Study phase 
Pre-allocation 
Baseline 
Intervention period 
Primary 
endpoint 
Clinical 
follow-up 
Long-term 
follow-upd 
Timepoint 
 
Mo 0 
Weekly 
Mo 1 
Mo 2 
Mo 3 
Mo 5 
Mo 8 
Mo 10, 12, 24, 
48 
Enrollment procedures 
 
 
 
 
 
 
 
 
 
Clinical visit 
 
X 
 
X 
 
X 
X 
X 
 
At home 
X 
 
X 
 
X 
 
 
 
X 
Phone screening 
X 
 
 
 
 
 
 
 
 
Written information 
X 
X 
 
 
 
 
 
 
 
Verbal information 
X 
X 
 
 
 
 
 
 
 
Written consent 
 
X 
 
 
 
 
 
 
 
Allocation 
 
X 
 
 
 
 
 
 
 
Clinical assessments 
 
 
 
 
 
 
 
 
 
Clinical examination 
 
X 
 
 
 
 
X 
 
 
Peak Height Velocity 
 
X 
 
 
 
X 
X 
X 
 
Adverse events 
 
X 
 
X 
X 
X 
X 
X 
 
Previous & concomitant treatments 
 
X 
 
X 
X 
X 
X 
X 
 
Clinical tests 
 
 
 
 
 
 
 
 
 
Pressure-Pain threshold 
 
X 
 
X 
 
X 
X 
X 
 
Knee extension strength 
 
X 
 
X 
 
X 
X 
X 
 
Countermovement jump 
 
X 
 
X 
 
X 
X 
X 
 
Modified Thomas test 
 
X 
 
X 
 
X 
X 
X 
 
Anterior knee pain provocation test 
 
X 
 
X 
 
X 
X 
X 
 
Objective longitudinal measures 
 
 
 
 
 
 
 
 
 
Physical activity (sensors) 
 
 
 
 
 
 
 
 
 
Imaging 
 
 
 
 
 
 
 
 
 
Ultrasound scanning 
 
X 
 
 
 
X 
X 
X 
 
Patient-reported questionnaires 
 
 
 
 
 
 
 
 
 
KOOS-child 4 subscales 
 
X 
 
X 
X 
X 
X 
X 
X 
Acceptable Symptom State (PASS) 
 
X 
 
X 
X 
X 
X 
X 
X 
Global rating of change 
 
 
 
X 
X 
X 
X 
X 
X 
Sport & Physical activity  
 
X 
X 
X 
X 
X 
X 
X 
X 
Pain history 
 
X 
X 
X 
X 
X 
X 
X 
X 
Self-rated health (EQ-5D-Y) 
 
X 
 
 
 
X 
X 
X 
X 
Kinesiophobia (Tampa) 
 
X 
 
 
 
X 
X 
 
 
Therapeutic Alliance (WIA) 
 
 
 
 
 
X 
 
 
 
Miscellaneous healtha 
 
X 
 
 
 
 
 
 
 
Pubertal stage (Tanner) 
 
X 
 
 
 
X 
X 
 
 
Adherence to treatments 
 
 
X 
X 
 
X 
X 
X 
 
Intervention 
 
 
 
 
 
 
 
 
 
Experimental or usual care treatment 
 
 
 
 
 
 
 
 
 
Complete self-management 
 
 
 
 
 
 
 
 
 
 
aSleep duration and problems, vitamin and supplement consumption, PA = Physical activity, QoL = Quality of Life, d = digital 
 

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Plans to promote participant retention and complete follow-up {18b} 
When capturing electronic questionnaire responses, participants will receive 2 reminders if having not 
responded and will subsequently be telephoned to ensure responses. We will continue data collection 
irrespective of adherence to interventions. Data collection will only discontinue if participants explicitly wish 
to withdraw from the study and not attend further visits. In such cases, we will offer participants the option 
to only complete electronic patient-reported forms or having treatments delivered by telephone or video 
chat, however, every reasonable effort will be made to retain all participants and collect all outcomes for 
every patient enrolled in the study.  
 
Data management {19} 
The study director will manage and curate data in collaboration with the blinded statistician (TK). 
Sonographs, videos (jump testing requires analyses of high-speed videos), or images (participants might 
occasionally be asked to send a picture of their knee with painful areas drawn up as part of inclusion or 
reporting of AEs) will be uploaded to a secure logged server with access restrictions. All other data will be 
entered directly into REDCap. REDCap users (study personnel) will only have access to their respective 
relevant instruments and data within the REDCap project to maintain blinding to group allocation, outcomes, 
and contents of interventions. Written consent forms and other hardcopy data will be stored in locked steel 
cabinets in a locked room and will be stored for 3 years after completion of the long-term follow-up of the 
study. 
 
Data protection & Confidentiality {27,33} 
In addition to data captured as outlined, we will keep standard confidential health records and store data in 
accordance with local laws and healthcare regulations: Our management and storing of data will comply 
with the articles of General Data Protection Regulation of May 20th 2018, under the EU, Regulation No 
2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection of natural 
persons with regard to the processing of personal data and on the free movement of such data, the Data 
Protection Act (in Danish: “databeskyttelsesloven”) and the Danish Health Care Act (in Danish: 
“sundhedsloven”). In addition, our plans (and sub-contractors) for use and handling of patient data have 
been reviewed and approved by the Capital Region Data Protection Agency, Denmark (P-2021-818) after the 
protocol was approved by the Capital Region Committee on Health Research Ethics, Denmark. Data will only 
be shared within the study group after unblinding at the pseudo-anonymized level and externally at the fully 
anonymized level. We plan for only the study director to hold access to the de-identifier key. We only expect 
to use this prematurely if participants wish to withdraw and have their data irrevocably deleted. As per usual 

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care, information regarding clinical findings, treatment plans, and delivery, will be noted in the participants 
regular electronic medical records to support possible post-trial care. No biological material will be obtained. 
 
Statistical methods 
 
Statistical methods for primary and secondary outcomes {20a} 
Analyses will be performed by a statistician blinded to group allocation and will be performed using (R 
Foundation for Statistical Computing, Vienna, Austria) in the Rstudio interface (RStudio Team, Boston, USA).  
 
Change scores for KOOS-child ‘sport/play’ score (△KOOS) from baseline to month 5 will be calculated for all 
participants. We will fit a linear regression model using the ‘lm’ function for △KOOS-child as the dependent 
variable and including group allocation as an independent variable. Covariates are described with their 
measurement, timing and justification in table 12, and will potentially be added to the model.82(p9),215 In 
order to not introduce unnecessary bias in the model, covariates will however only be included if doing so 
changes the primary estimate meaningfully, as we expect a equal distribution of these pre-specified 
covariates given the sample size. Significance level will not determine the inclusion of covariates. The linear 
model will be evaluated for linearity, multicollinearity, homogeneity of variance, distortion of outliers, 
homoskedasticity, correlation of variables, distribution of residuals using histograms. If these model 
assumptions are not met non parametric bootstrap estimation and tests will be used instead. Below we have 
outlined the intended steps with reproducible R code for Rstudio (version 3.6, 2021.09.0+351) 
 
Statistical code example 
Step 1: load necessary packages 
#installs and loads all necessary packages 
 
install.packages("stargazer") 
library("stargazer") 
install.packages("ggplot2") 
library("ggplot2") 
install.packages("performance") 
library("performance") 
install.packages("lindia") 
library("lindia") 
install.packages("see") 
library("see") 
install.packages("patchwork") 
library("patchwork") 
install.packages("readr") 

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library(readr) 
 
Step 2: import data 
#imports csv file into dataframe titled fu_data 
 
fu_data <- read_delim("R/win-library/3.6/fu_data.csv", ";", escape_double = FALSE, trim_ws = TRUE) 
 
Step 3: run regression model 
#runs linear regression model with ‘koos_spor’t as the dependent outcome variable  
#and ‘group’ as the independent predictor variable. The model is named lm_koos_sp 
#‘timing’ of maturation is included as a covariate.  
 
lm_koos_sp <- lm(koos_sport~group + timing, data=fu_data) 
 
Step 4: produce plots for model evaluation 
#produce plots used for evaluation of model fit and assumptions  
 
gg_diagnose(lm_koos_sp) 
check_model(lm_koos_sp) 
 
Step 5: evaluate model from plots 
 
 
 

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Step 6: print model output  
#prints output from model from summary and stargazer function 
 
summary(lm_koos_sp) 
stargazer(lm_koos_sp, type = "text", style="all", title="Linear regression of KOOS-child 
sport/rec") 
 
 
Step 6: evaluate model output from console 
Residuals: 
    Min      1Q  Median      3Q     Max  
-4504.4 -2863.1   485.1  2421.4  4720.6  
 
Coefficients: 
            Estimate Std. Error t value Pr(>|t|)   
(Intercept)   4541.2     2215.4   2.050   0.0498 * 
group         1050.6     1145.6   0.917   0.3670   
timing       -1056.5      776.5  -1.360   0.1845   
--- 
Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1 
 
Residual standard error: 3105 on 28 degrees of freedom 
  (2 observations deleted due to missingness) 
Multiple R-squared:  0.07503, 
Adjusted R-squared:  0.008959  
F-statistic: 1.136 on 2 and 28 DF,  p-value: 0.3356 
 
Linear regression of KOOS-child sport/rec 
================================================== 
                         Dependent variable:       
                    ------------------------------ 
                              koos_sport           
-------------------------------------------------- 
group                         1,050.577            
                             (1,145.632)           
                              t = 0.917            
                              p = 0.367            
timing                        -1,056.458           
                              (776.549)            
                              t = -1.360           
                              p = 0.185            
Constant                     4,541.163**           
                             (2,215.364)           
                              t = 2.050            
                              p = 0.050            
-------------------------------------------------- 
Observations                      31               
R2                              0.075              
Adjusted R2                     0.009              
Residual Std. Error      3,104.971 (df = 28)       

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F Statistic         1.136 (df = 2; 28) (p = 0.336) 
================================================== 
Note:                  *p<0.1; **p<0.05; ***p<0.01 
 
We expect only to modify these procedures if more suitable methods, packages, or software is developed 
and will describe and justify these potential deviations from the pre-specified strategy in the final report. 
Intention-to-treat analyses, that is, analysis according to group allocation, will be performed as the standard 
analysis strategy unless otherwise denoted, to 1) investigate the relative effectiveness of being offered the 
experimental intervention over usual care, and 2) to maintain the balance of known and unknown 
confounders from randomization. 
 
We will employ a similar analysis strategy for other numerical outcome variables. For non-numeric variables, 
differences between groups will be analyzed by logistic regression models, and non-normally distributed 
residuals for ratio-interval scale outcomes will be compared by non parametric boot strap tests. To supply 
detailed trajectories and inferences of treatment response over time, we will fit mixed-effects models for the 
imaging outcomes (months 0, 3, 5, 8); time-to-return to sport, weekly hours of sports participation, pain-
flares, and sensor-based physical activity (weeks 0 to 22); clinical outcomes (months 0, 1, 3, 5, 8); and 
remaining patient-reported outcomes (months 0, 1, 3, 5, 8, 12, 24, 48). 
 
Mean and SD values will be reported if data appear approximately normally distributed. If data are non-
normally distributed, they will be presented as median and interquartile range (IQR). We will report 95% 
confidence intervals, exact p-values to the third decimal, and discussions of minimal detectable change 
(MDC) and minimal important change (MIC) when relevant/possible. Frequency data will be reported as "No. 
(%)". 
 
Our standard option for all variables, is to be analyzed with the highest resolution possible, meaning no 
collapsing or dichotomization to retain as much information as possible in the dataset. However, some 
assessor-dependent scales, such as ultrasound scoring of the (non-normal maturation-related) 
fragmentation quality of the tibial tubercle bone, contains the potential values “none” (1), “unclear”, (2), 
“little”, or “apparent/extensive” (4). The same applies to some other ultrasound measures and clinical 
examination findings. Depending on the distribution of responses into these categories, we might choose to 
exclude data from the “unclear” category or collapse the “little” and “apparent/extensive” categories if we 
estimate the number of responses to be too low to make meaningful inferences.   
 
Once the primary data have been analyzed, we will also compute and report the RCT-Fragility Index (how 

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many patients would need to change from success to non-success to render the potential experimental 
effect non-significant or equal) based on the PASS outcome for easier clinical interpretation of the 
robustness of results.216 
 
Superiority framework and controlling error rates 
The analysis will be evaluated based on a one-sided hypothesis as the trial employs a superiority design, 
meaning that if a one-sided test of significance fails in the direction of the experimental group, the null-
hypothesis is rejected for our sample, and the level of significance in opposite direction is therefore not of 
interest.217,218 To further safeguard this choice, we have made the decision to obtain 90% power (up to 
94.6% if all participants retained), corresponding to a 10% false negative error rate). By default, we will not 
perform adjustments for multiple comparisons as we have arranged our hypotheses in a prioritized order, 
and we will also conduct and report hypotheses testing in this pre-specified order.170,219 We will however 
adjust for multiple comparisons using Bonferroni corrections when multiple tests are performed for 
outcomes within the same construct or objective (e.g. the effect of group on acute pain response during 
loading, measured through 2 different outcomes: pain [0-10 NPRS] during maximal isometric knee extension 
test, and pain [0-10 NPRS] evoked from the Anterior Knee Pain Provocation test). 
 
Interim analyses {21b} 
No interim analyses or stopping rules are planned, due to very low safety concerns and to preserve statistical 
power. However, an evaluation of feasibility outcomes will be performed after including n=15 participants to 
decide if potential study amendments will result in these 15 participants being included in the primary 
dataset (see “Embedded pilot study” section). 
 
Methods for additional analyses (e.g. subgroup analyses) {20b} 
Besides the sensitivity analyses otherwise specified (covariate adjusted, mixed-effects, moderation, 
mediation), we will perform per-protocol analyses to test the robustness of the primary intention-to-treat 
analysis, by examining the effect of adherence according to the pre-specified compliance criteria.  
 
Handling of non-adherence and any statistical methods to handle missing data {20c} 
Assuming that data will be missing at random, multiple imputations using chain equations will be used to 
handle missing data. Imputation models for missing variables will be fitted using linear, logistic or 
polytomous regression models. All available variables will  be included in the imputation models, unless a 
specific reason is given for exclusion. Imputation will only be performed for varialbes included in the 

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analysis. Multiple imputation will be done using R-package mice[].220 
 
Plans to give access to the full protocol, participant level-data and statistical code {31c} 
To increase transparency and dissemination, all statistical code and fully anonymized dataset will be shared 
to an open-access repository (such as YODA, Zenodo, or Figshare) with a digital objective identifier once all 
planned publications are accepted or published as pre-print.221,222 Publication-specific datasets will 
potentially be posted along with published manuscripts in line with journal policies. If full anonymity cannot 
be achieved by removing unique data and identifies, a synthetic dataset will be created, which will mimic the 
original dataset by preserving the statistical properties and the relationships between variables.223 Specific 
funding for Open-Access publication fees will be sought to allow dissemination to clinicians lacking 
institutional access or funding for journal access.  
 
Effect moderation and mediation 
As secondary analyses, we will perform moderation and mediation (if a superior treatment response in arm 
A is observed) analyses, which will be conducted and reported in accordance with the AGReMA 
Statement.224 Through mediation analysis, the total effect of exposure to treatment groups 1 vs A  (i.e. 
between-group difference) on the outcome, will be parsed into indirect effect pathways from exposure to 
mediator, and from mediator to the primary outcome (KOOS child ‘Sport/play’ subscale), which are the 
effects of interest in this mediation analysis (figure 4).225,226 This will allow inference about the underlying 
responsible mechanisms for a potential effect. Such knowledge is key when optimizing or developing 
treatments, and for implementation efforts.224,227 As the sample size is not planned specifically for mediation 
analysis, these analyses are considered secondary and should be interpreted with caution mainly based on 
its effect size and precision.228 Although potential limitations of suboptimal power, this mediation analysis 
provides a novel preliminary step for potential identification of causal mechanisms for improvement in 
Osgood-Schlatter patients. 
 
Figure 4. Visual example of mediator in the causal pathway 
 
 
 
 

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Mediators are represented by variables measured after randomization and before collection of outcome 
data, which are thought or known to be influenced by the treatment allocated to participants.225,227 As large-
scale randomization balances known and unknown confounders that can potentially influence the outcome 
as well as the exposure-mediator pathway, randomized trials are the optimal setting to perform causal 
mediation analysis.225,226,229  
 
The assumed cauasal model we are investigating is illustrated as a directed acyclic graph below (figure 5) 
using the Dagitty software.225,230 
 
Figure 5. Proposed directed acyclical graph for mediation analysis 
 
 
Assumptions for causal mediation analysis 
The four assumptions for unconfounded analysis of parsed mediation pathways require 1) no unmeasured 
exposure-outcome confounders, 2) no unmeasured mediator-outcome confounders, 3) no unmeasured 
exposure-mediator confounders, 4) no mediator-outcome confounder affected by exposure.225,227,229 
Assumption 1 and 3 should be mitigated by randomization and potential covariate adjustment. Because 
mediators are not randomized it is possible for the mediator-outcome pathway to be confounded 

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(assumption 2 and 4). To address  assumption 2, we will include pre-treatment confounders based on 
available evidence and clinical expertise. This includes potential covariates/moderator variables outline 
(table 12) and baseline levels of the mediator-variables. Assumption 4 will be addressed by using 
interventional effects in the mediation analysis231 along with inclusion of confounders. In addition, to 
address the assumption of no positivity, that is, a zero risk of any participant exhibiting a positive 
characteristic of a mediation variable at baseline,227 all mediator variables with this potential issue, will be 
change-scores calculated from baseline.  
 
Number of predictors for mediations analysis 
Based on our sample size of n=130 and the use of multiple regression models, power of >80% and alpha level 
of 5% (t = 1.658, Df = 109), we calculated the potential number of predictors as 16 based on Fritz & 
MacKinnon sample size recommendations for mediation analysis (G*power 3.1.9.7, Düsseldorf University, 
Germany).228,232,233 In our current model, we have included 15 predictors (8 mediators and 7 potential 
covariates/moderators). 
 
Table 12. Proposed moderators and mediators 
Variables  
Measurement 
Justification  
Potential moderators/covariates 
Growth velocityw0 
Offset from predicted age at peak height velocity in 
years, calculated from clinically measured 
anthropometrics: sitting height, bodyweight, total 
stature, biological age.234 Participants will be 
categorized into pre- (<-1.0 years offset), circa- (-1.0 to 
+0.5 years offset), and post-PHV (>+0.5 years offset), 
corrected for timing of the primary endpoint, resulting in 
a 5 month subtraction.  
 
Overuse knee injuries, as well as injuries to the growth plate, in 
sports active adolescents are higher during peak height velocity 
and the year leading up to this point,235–239 which is thought to be 
primarily due to vulnerable growth-related conditions, such as 
Osgood-Schlatter.235 This has been supported by data showing 
higher growth velocity for Osgood-Schlatter patients than 
controls.240  
Growth timingw0 
Based on algorithms for calculating anticipated age of 
peak height velocity which incorporates data on parents 
adult stature, we will classify participants as early 
maturers, average maturers, and late maturers (girls: 
<10.94, 10.94-12.94, and >12.94 years, respectively; 
boys: <12.64, 12.64-14.64, and >14.64 years, 
respectively).241,242 
 
Reaching skeletal maturity either late or on average is a risk factor 
for developing Osgood-Schlatter compared to early 
maturation.21,243 
Fear of movementw13 
Fear of movement will be captured by participants filling 
in the 17 items Tampa Scale of Kinesiophobia, each 
item scored on a 4-point likert scale with a score 
ranging from 0 to 68.200,201 
Avoidance behavior might be related to a too apprehensive 
approach to gradual exposure and exercise therapy resulting in 
the patient not achieving a higher degree of participation in sports 
and physical activity. Osgood-Schlatter patients exhibits a high 
degree of kinesiophobia.68  
 
 
Pain intensityw0 
Self-reported “worst pain past week” on the 0-10 
NPRS.  
Pain intensity has shown to be related to a worse prognosis for 
adolescents with anterior knee pain54 
 
Pain frequencyw0 
Self-reported on the P1 question of the KOOS-child 
Pain subscale on frequency of experience knee pain, 
answered on a 0-4 scale ranging from “Never” to “All 
the time”.172 
 
Pain frequency have shown to be related to a worse prognosis for 
adolescents with anterior knee pain.52,54 
Treatment 
expectationsw0 
Self-reported through the question on change in “my 
ability to self-manage my knee pain” answered on a 1-4 
likert scale from ‘worse’, ‘no difference’, ‘little 
improvement’, to ‘large improvement’. 
Treatment expectations have been shown to moderate outcomes 
in trials of several different musculoskeletal conditions and chronic 
pain conditions.244–248 

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Tibial tubercle 
maturationw0 
Rated by sonographers ad modum Sailly109,249 from on 
a 1-4 scale depending on features of cartilage, potential 
secondary ossification center, tendon, and the 
infrapatellar bursa.  
The level of maturation of the apophysis has been shown to be 
related to the prevalence of Osgood-Schlatter symptoms with 
early (exhibiting no metaphysis-physis junction or apophyseal 
attachment of the patella tendon) and late stages (denoting full 
unification of metaphysis-physis junction and matured attached of 
the patella tendon) being low-risk stages, and the intermediate 
stages (exhibiting open metaphysis-physis junction, apophyseal 
attachment of the patella tendon, active ossification center) have 
a higher association to symptoms109,250,251 
 
Severityw0 
Rated by sonographers ad modum Flaviis251 from 
‘cartilage attachment’ to ‘mature attachment’ on a 
nominal 1-4 scale. 
  
Severity on the Flaviis scale has been associated with a worse 
prognosis.32,251 
Potential mediators 
Pain intensityw4 
Self-reported “worst pain past week” change from 
baseline on the 0-10 NPRS. 
The aim of the sports break (week 0-4) is to calm the sensitivity of 
the condition to achieve a more successful graded exposure to 
sports and physical activity.59,60,68 One way to measure decreased 
sensitivity to load is by asking patients their worst level of pain 
during the past week.  
 
Pressure sensitivityw4 
Through handheld algometry, the patient denotes when 
pressure applied to the symptomatic tibial tubercle goes 
from feeling as “pressure” to “pain”, and the kPa at this 
threshold is recorded. Change score is calculated from 
baseline.  
The aim of the sports break is to calm the sensitivity of the 
condition to achieve a more successful graded exposure to sports 
and physical activity.59,60,68 Besides pain intensity, one way to 
measure decreased sensitivity of the condition is through 
pressure-pain detection threshold  
to evaluate local hyperalgesia specifically at the tibial tubercle. 
 
Controlled return to 
sportw5 
Sports participation in the preceding week is self-
reported through weekly text messages, ranging from 0 
to >7 hours. <2 hours of sports participation in week 5 
will be considered as a controlled return to sport.  
Graded exposure requires a gradual introduction to sports, 
although this trajectory quickly can be accelerated if it appears to 
be tolerated. In the very first week of a gradual return to sports, 
modest sports participation should be a marker of adhering to the 
recommendation of gradual return.  
 
Pain flare frequency 
during return to sportw13 
Number of pain flares (episodes of NRPS ≥4) in the 
preceding week is self-reported through weekly text 
messages.  
Graded exposure according to the pain-model aims to both 
prevent pain flares, and to mitigate their intensity to NRPS ≤3. 
Therapeutic Alliancew13 
Therapeutic Alliance will be captured by participants 
filling in the 12 item short-form Working Alliance 
Inventory, each item scored on a 7-point likert scale 
with a score ranging from 0 to 84 points.252 
 
Achieving a strong therapeutic alliance has been shown to be 
related to improved outcomes in trials across several 
musculoskeletal conditions.253,254 
Fear of movementw13 
Fear of movement will be captured by participants filling 
in the 17 items Tampa Scale of Kinesiophobia, each 
item scored on a 4-point likert scale with a score 
ranging from 17 to 68.200,201 
Avoidance behavior might be related to a too apprehensive 
approach to gradual exposure and exercise therapy resulting in 
the patient not achieving a higher degree of participation in sports 
and physical activity. Osgood-Schlatter patients exhibits a high 
degree of kinesiophobia.68  
 
Pain during maximal 
knee loadingw13 
Participants will rate their pain using NRPS 0-10 during 
strength testing, that is, a 5 second maximal voluntary 
isometric contraction of the knee extensor muscles at 
60˚ knee flexion. 
Pain during loading is a key symptom of Osgood-Schlatter and is 
related to self-reported measures of quality of life, satisfaction with 
sports participation and hyperemia in the tendon.68,109,116 The 
intervention aims to improve capacity to loading activities and 
should thus be better tolerated at this timepoint.  
 
Knee extension 
strengthw13 
Knee extension strength will be measured in newtons 
by handheld dynamometry during a 5 second maximal 
voluntary isometric contraction at 60˚ knee flexion. 
Newtons will be normalized to lever-length and 
bodyweight and expressed as Nm/kg.  
 
Knee pain is known to reduce muscle function,116,255 and strength 
training contribute to alleviate these deficits.59,60 
Distal patella tendon 
hyperemiaw13 
Rated by sonographers ad modum Öhberg from ‘no 
neovessels’ to ‘5 or more neovessels’ on a 1-4 
scale.180,256–258  
 
A series of Osgood-Schlatter patients has been described for 
whom less hyperemia on color doppler ultrasound was associated 
with milder symptoms.109 Neovessels can generate and diminish 
rather quickly and could therefore be highly responsive to change 
in condition.259–261  
 
Infrapatellar bursitis 
signw13 
Either denoted as thickened bursa (yes/no) or 
appearing with doppler as rated by sonographers (1-4 
nominal scale).  
In our previous cohort at 2-year follow-up, almost all participants 
still experiencing knee-pain also had Flaviis grade 4 (associated 
infrapatellar bursitis) at baseline, whilst participants classified as 
grade 1 (normal) were less likely to report pain at follow-up.32 
Thus, the sole finding of bursitis signs in the infrapatellar bursa 
will be tested as mediator.  
 

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Outcome 
Knee-related Function in 
Sport/Recw22 
Self-reported on KOOS-child ‘Sport/play’ subscale, 
which measure how painful certain movements related 
to sports- and recreational activities are perceived on 7 
items ranging from ‘no pain’ to ‘extreme pain’ on a 1-5 
Likert scale, normalized to a 0-100 score.  
 
Primary outcome outcome collected at 22 weeks. 
 
 
Statistical approach to mediation analysis 
Mediation analysis will be based on interventional effects, this will allow for the inclusion of multiple 
mediators and account for dependence between mediators.231 With estimation done by Monte-Carlo based 
regressionmodels.Covariates will be included as moderators in the full model. For each mediator, we will 
calculate and report effect size as odds ratios and p-values, as well as 95% confidence intervals We will 
calculate and report estimated effect and percentage contribution to total effect for each mediator variable 
included in the final model, based of the mean indirect effect.  The model will only include mediators that 
fulfill the temporal sequence of a causal relationship, that is exposure, mediator, outcome. 
 
 
Oversight and monitoring 
 
Composition and roles of the trial steering committee and data monitoring committee {5d, 21a} 
The Sports Orthopedic Research Center – Copenhagen (SORC-C), specifically PhD-fellow Kasper Krommes 
(Study Director) and Professor Per Hölmich (Main Supervisor and Medical Advisor) and Professor Kristian 
Thorborg (Co-supervisor) at the Department of Orthopedic Surgery at Amager-Hvidovre Hospital has 
initiated and will manage the trial. Together, they also form the steering- and writing committee, which will 
oversee the trial and decide on authorships and assume stewardship of the data. No specific data monitoring 
committee is convened. 
 
Adverse event reporting and harms {22}  
In our published pilot-study60 and during pilot-testing the intervention in the clinic,68 we have not observed 
any adverse events suspected to be linked to undergoing the treatment, although this was not assessed 
systematically. Participants will be informed in writing and verbally about the blinding aspects and potential 
risks and discomforts of participating in the study prior to enrollment. As with usual activites, participants’ 
symptoms may similarly temporarily flare up during testing. Especially the anterior knee provocation test is 
designed to provoke anterior knee pain symptoms, specifically. Also, the algometric pressure will inflict 
short-term low levels of pain when going from 0 to 1 on the numeral pain rating scale (0 being ‘no pain’ and 
10 being ‘worst pain imaginable’). The imaging used in the study is diagnostic ultrasound that uses high-

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frequency soundwaves, with no ionizing radiation exposure and no discomfort during the scan. Usual care 
sometimes consists of invasive therapies such as injections and surgery, or other painful modalities, such as 
shockwave or dry-needling , however, the treatments and advice in the in the current study are solely based 
on straps, cryotherapy, exercises, and advice and education, and no adverse events are expected.262 As such, 
the potential benefits (on the individual and public level) of the study far outweigh the potential risks. 
 
To assess potential or any suspected harms and adverse events (AEs), participants will be asked during all 
clinical visits and the telephone consultation at month 2, through open-ended questioning about any new 
symptoms or illnesses, accidents, reasons for care-seeking, and knee-related questions on pain, locking, 
swelling, discoloration, or clicking experienced during exercises or other trial-related procedures, whether it 
can be attributed to the treatment or not. In addition, Serious (grade 3-5) unexpected side effects or AEs will 
be reported to the Capital Regional Ethics Committee in Denmark within 7 days after the study director has 
become aware of the incident. All AEs will be assessed by the study director and the Medical Advisor (PH) for 
possible relations with the assessments and/or intervention to consider whether there is a reasonable 
possibility that the AE can be caused by either. The study director will be notified of new AEs by personnel 
responsible for interventions or outcome assessments (at month 0, 1, 2, or 13) and will telephone the 
participant as soon as possible thereafter for further investigation; or when consulting the participants in 
person at month 0, 5 or 8. When needed, the participant will be seen by the Medical Advisor (PH). Adverse 
events will be categorized and graded by two independent reviewers according to the severity on from 
Grade 1-5 Using the Common Terminology Criteria for Adverse Events (CTCAE) grading:263 
1. Mild: Asymptomatic or minor symptoms; clinical or diagnostic observations only; no intervention 
needed  
2. Moderate: Minimal, local, or non-invasive intervention indicated 
3. Severe: Medically significant but not immediately life-threatening; hospitalization or prolongation of 
hospitalization indicated; disabling 
4. Life-threatening consequences (i.e., immediate risk of death); urgent intervention indicated 
5. Death related to adverse event 
The occurrence will be reported according to the Council for International Organizations of Medical Sciences 
thresholds of occurrence,264 however, the anticipated sample (n=130) will only allow to inferences regarding 
very common or common harms: 
• 
Very common ≥ 1/10 
• 
Common (frequent) < 1/10 AND ≥ 1/100 
• 
Uncommon (infrequent) < 1/100 AND ≥ 1/1000 

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• 
Rare < 1/1000 AND ≥ 1/10000 
• 
Very rare < 1/10000 
 
Steps to minimize pain, risk, and inconveniences  
To minimize pain during testing, the participants are told that they can always abort the test if the pain is felt 
as ‘too much’ or they start feeling fearful or uncertain of their symptoms during testing, but are ultimately 
told that potential pain felt during testing are not harmful and will subside within 24 hours, as is our 
experience from >1000 tests. During knee extension strength test, if the adolescent feels the metal of the 
gauge on their shinbone through the padding of the dynamometer, extra padding will be placed on the shin. 
During the algometric test, we will use an upper boundary of 1000 kPa not to cause any bruises if 
participants does not report pain at this level of pressure (corresponding to 1 newton/mm2 or 10 kg/cm2).  
 
Justification of risks and drawbacks, and future therapeutic reward  
There are no anticipated severe risks or drawbacks. All potential risks and drawbacks have been described 
and are considered minimal, with potential benefits far outweighing these both on the individual participant 
level and the public level. The choice to include 10-16-year-olds was made, as this is the age where Osgood-
Schlatter occurs. The current sample of adolescents will receive a state-of-the-art examination, treatment, 
and follow-up care, superior to the current standard of care, which often is non-evidence based, sometimes 
invasive or painful, and with potential side-effects; or even minimal or no care at all. If the experimental 
intervention shows relative efficacy, it could easily be implemented in current practice, potentially benefiting 
the many adolescents suffering from Osgood-Schlatter in the future. In addition, this study will uncover the 
potential effect of the two different interventions on other central outcomes such as pain mechanisms, 
performance, tissue morphology, as well as potential moderating factors and potential mechanisms 
responsible for success through mediation analysis. Finally, the long-term follow-up assessments will help 
clarify if the effects are sustained with a potential for better quality of life, disease prevention, health, etc. 
through increased participation in sports and physical activity.  
 
Compensation to patients 
No participants will receive reimbursement for their travel expenses related to participation in the study, nor 
will participants be offered compensation of any kind. During treatment at Hvidovre Hospital, the 
participants will be covered under the Danish Patient Compensation Act (LBK no 995 of 14/06/2018, chapter 
3 §19) (In Danish: Patienterstatningen), which is a scheme that deals with compensation claims of patients 

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treated in the public health system in Denmark who has sustained an unintended or unexpected injury or 
harm.  
 
Frequency and plans for auditing trial conduct {23} 
No trial audit is planned.  
 
Plans for communicating important protocol amendments to relevant parties {25} 
Amendments to the trial will be reported to the review board (Regional Committees on Health Research 
Ethics for The Capitol Region), and the amendments will be reported with justifications in the main report. If 
amendments affect trial participants during their participation, they will be informed by telephone or email.  
 
Dissemination plans {31a} 
All members of the study group will be invited as co-authors on the specific publications according to the 
International Committee of Medical Journal Editors (ICMJE) recommendations and The Danish Code of 
Conduct for Research Integrity codec.265,266 All findings and results are planned to be published in 
international peer-reviewed scientific journals. Furthermore, the results will be presented at national and 
international conferences; as part of our collaborations with the Danish Society of Sports Physical Therapy, 
Danish Sports Medicine Association, Clinical-Academic Groups (CAGs) across Copenhagen University and 
University Hospitals; and as our capacity as IOC Research Center. The results will be posted to 
ClinicalTrials.gov once the primary results have been published. In addition, we will utilize appropriate social 
media channels to increase dissemination.267 The results will be published regardless of positive, negative, or 
inconclusive findings. Kasper Krommes and Per Hölmich will enforce publications as first and senior authors 
respectively, unless other publication-specific contributions warrants or are otherwise agreed upon by the 
study group. We will frame the main conlusion based on the potentiel primary endpoint between-group 
difference, in line with the superiority framework, which will take into account the MCID (9 points), width of 
the confidence interval, the overlap of the confidence interval, and the statistical significance.  
 
Acknowledgments 
Patients and their parents attending meetings regarding objectives, design, and the practical 
implementation of the trial. Colleagues Mathias Fabricius Nielsen and Lasse Ishøi for ongoing valuable input. 
Pre-graduate students that have assisted in in performing studies and other preperational work for this 
protocol: Frederikke Villumsen, Amalie Bjerre Jørgensen, Oliver Olsen, Nickoline Andersen, Line Holm, 
Caroline Schad, Hjalte Nørremark. Ph.d. Candidate Marie Skov Breum and Professor Torben Martinussen for 

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valuable input and review of prespecified approach to mediation analysis. Senior Researcher Jeanetter 
Wassar Kirk for methodological guidance in designing and planning qualitative substudy.  
 
Authors’ contributions {31b} 
All authors contributed to the protocol. Contributions are visualized in table 13. 
Table 13. Author contributions (CRediT Taxonomy) 
 
KK 
PH 
KT 
JL 
MR 
MC 
TK 
Conceptualization 
 
 
 
 
 
 
 
Funding acquisition 
 
 
 
 
 
 
 
Supervision 
 
 
 
 
 
 
 
Resources 
 
 
 
 
 
 
 
Draft of protocol 
 
 
 
 
 
 
 
Review and edit of protocol 
 
 
 
 
 
 
 
Methods: Trial design 
 
 
 
 
 
 
 
Methods: Analyses plan  
 
 
 
 
 
 
 
Methods: Imaging  
 
 
 
 
 
 
 
Methods: Interventions  
 
 
 
 
 
 
 
Methods: Outcomes 
 
 
 
 
 
 
 
 
Funding {4} 
Sports Orthopedic Research Center – Copenhagen will provide, facilities, local operational support, some 
equipment, and 100% funding for statistical support. The following funders have provided grants to the 
project for other costs: Fysioterapipraksisfonden (dkr. 678.200), Østifterne (dkr. 599.958), Helsefonden (dkr. 
350.000), Købmand Ferdinand Sallings Mindefond (dkr. 219.480), Hvidovre Hospitals Frie Forskningsmidler 
(dkr. 100.000), Beckett Fund (dkr. 70.000), FLSmidth Donation Fund (dkr. 50.000), Frimodt-Heineke Fonden 
(dkr. 50.000), Danish Association of Physiotherapists Research Fund (dkr. 36.600) and the Danish Society of 
Sports Physical Therapy (dkr. 6.000). Additional funding is being sought to secure the total operational costs 
of the trial, but the completion of the trial does not depend on additional funding. The local financial 
department will manage all funding. No funding body will have any control or involvement in data collection, 
analyses, interpretation, writing the report, or deciding whether to publish. The primary supervisor and 
responsible party, Per Hölmich, participates in the form of his affiliation with the University of Copenhagen 
as Professor and his role as Chief Surgeon at Arthroscopic Center at Hvidovre Hospital. Per Hölmich does not 
receive any financial support for his involvement in the project. 
 

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Trial status 
We have piloted the intervention in three stages; in an original small published cohort59 (n=51), in a case-
series68 (n=34) in our regular clinical setting, and for the initial 15 patients we have examined true 
operational feasibility of the trial. Patients and their parents attending our department have collaborated on 
key aspects of trial design. In addition, we have performed a stepwise mixed-methods study to determine 
the comparator usual care intervention with patients and clinicians (n=97). Inclusion for the trial is currently 
at 100% (n=130 of 130) 
 
Availability of data and materials {29} 
Materials are available at https://doi.org/10.6084/m9.figshare.c.5730008.v1. No additional data or materials 
is connected to conception of this protocol. For plans regarding data and materials for the trial, see section 
“Plans to give access to the full protocol, participant level-data and statistical code”.  
 
Competing interests {28} 
Some of the authors have previously published in this area and have designed the experimental intervention 
being tested and are therefore prone to self-citation incentives and confirmation bias. Thomas Kallemose is 
paid dkr. 25.000 for statistical consultation and performing blinded analyses. There are no other conflicts of 
interest to declare. 
 
 
 
 

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Appendix 1: Clinical test protocols{18a} 
 
Objective tracking of physical activity: Activity motion sensors 
 
One waterproof SENS® motion sensor patch (35 cm2, 8 g) will be applied laterally on the preferred thigh, 
appx 10 cm from the knee joint during the inclusion visit.  
 
The activity intensity is calculated as the average vector magnitude of the high-pass filtered 3 axis 
accelerometer measurements at 12 Hz sampling frequency, with subtracting the noise present on each 
measurement axis, and done on each 5-second epoch. Every epoch is categorized as a particular activity 
(light sleep, deep sleep, lying/sitting, standing, sporadic walking/slow biking, walking, biking, 
running/exercise/high-intensity training; 92±5% agreement).177 Data is collected for up to 23 weeks after 
application through a blutooth connection to an app installed on the participant’s or their parent’s 
smartphone and onto a web-based secured private cloud. Sensor data will be analyzed at the 15-minute 
level and categorized into weekly and daily sedentary (lying, sitting, standing), light physical activity (sporadic 
walking, walking, light bicycling), and moderate/vigorous physical activity (cycling, running, high-intensity 
exercise), in addition to sleep activity. Participants will be instructed to wear the patch for the entire study 
period, change the adhesion patches when required weekly, and document physical activity at any periods 
where the sensor might have been taken off or lost.  
 
 
 
SENS motion sensor and adhesive patch 
Applying adhesive patch on the thigh 
The adhesive patch and sensor is placed 
approximately 10 cm proximal to the knee 
 
 
 
 
 

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Knee extension strength: handheld dynamometry 
 
With the participant sitting on the side of the examination bed, a handheld dynamometer is fixed anteriorly 
on the shin with a belt corresponding to app 4 cm proximal to the lateral malleolus. The participant is asked 
to hold on to the other side of the bed behind them with both hands and keep their upper body upright. 
Before testing, the following instructions a given: 
“In this test, you must push a hard as you possible can without it being too painful, that is, 100% / maximum, 
from the moment I say “go” until I say “stop”. So, I am going to say “3-1-2-go-press-press-press-press-stop.” 
We are doing up to 3 trials on each leg after a familiarization trial at appx 50% of your maximum effort. 
There is going to be 30 seconds between trials, and let me know if you feel any pain during testing.“ 
 
The assessor holds the leg in the starting position to allow full rest between trials. If the participant feels any 
pain during testing, they are asked to rate it on the NPRS. The position will be at 60° knee flexion and the 
angle of the belt on the dynamometer/shin will be 90º, both verified by handheld goniometry. This test has 
shown an inter-tester reliability of ICC: 0.76-0.96 with a low standard error of measurement (5-11%)185 and 
good validity compared to the gold standard of isokinetic strength assessment.186 
 
The dynamometer used is a MicroFet 2 (Hoggan, Scientific L.L.C., Salt Lake City, USA) with a sampling rate of 
100hz. The force (newtons) obtained from the dynamometer will be normalized to lever length (knee joint 
line to the point of fixation in meters) and body weight (kg) to allow appropriate comparisons between 
participants (Nm/kg). The best of three trials will be analyzed, as well as the maximum pain rating.  
 
 
Marking the probe placement 4cm proximal to 
the lateral malleolus 
Measuring lever length from the knee joint line 
to the line of probe placement 
Knee extension strength test position 
 
 
 

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Pressure-pain threshold: handheld algometry 
 
To assess the localized tissue hyperalgesia, e.g., sensitivity to pressure, a handheld pressure algometer 
(Algometer Type II; Somedic AB, Hörby, Sweden) will be used to measure the pain-pressure threshold, that 
is, the minimum pressure required to induce a painful sensation at the tibial tubercle. The probe measuring 
1 cm2 will be placed perpendicular on the pre-palpated tibial tubercle and pressure applied at appx 30 kPa/s. 
To minimize the risk of the probe sliding during testing, the skin is stretched to the side. To avoid excessive 
pressure applied, 1000 kPa will be used as a safety threshold. 
 
Participants will be lying supine with a solid tube under the knee during testing, while at appx 20˚ knee 
flexion. The participants will be instructed to press the button as soon as the pressure evokes pain, which 
will alarm the assessor to cease the application of pressure. Each knee will be measured twice with a 
minimum of 10 seconds between trials,268 starting with the non-index. The mean of the two trials will be 
used in analyses.   
 
 
 
 
 
 

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Pain response to cumulative loading: The anterior knee pain provocation test 
 
The AKPP-test is a 45-second unilateral test designed to provoke known anterior knee pain. The test is self-
performed and self-rated. Prior to the test, participants are instructed in using the NPRS. The test is then 
performed in a static single-legged squat position with 60 degrees of knee flexion, which is held for 45 
seconds. Participants provide their pain intensity immediately before and after completing the 45 s hold.181 
The test has been studied in a population of adolescents with longstanding knee pain and was associated 
with the current KOOS-child ‘Sport/play’ subscale and worst pain last 24 hours, as well as responsive to 
changes in these measures over time.181 
 
Anterior Knee Pain Provocation test 
 
 
 
 

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Sports function and power-production: Countermovement jump 
 
Increased countermovement jump height is associated with increased sprint performance, lower-body 
power, and enhanced force-velocity profile.189,269,270 The test has also been found feasible in adolescents.189 
Calculating the power-output and jump height from anthropometric data and contact- and flight-time has 
been validated against the gold standard of using a force-plate,190,191,195 and using a specific smartphone app 
providing the variable from a slow-motion video analysis is highly reliable.190,193–195  
 
Thus, participants will perform 3 trials of the countermovement jump while being recorded on a smartphone 
camera (>240 frames per second) and subsequently analyzed for jump height and power  using the MyJump 
2 smartphone application.190 Participants will perform a test trial, followed by 3 recorded trials. Participants 
will be asked to keep their hands on their hips and jump as high as possible.  
 
Data will be normalized per Myjump 2 procedures to push-off distance (distance from the floor to trochanter 
major in a 90˚ squat position) combined with leg length (measured prone from the superior anterior iliac 
spine to the tip-toes in full plantar flexion). The mean of three trials will be used, and potential pain during 
testing will be recorded on the NPRS. 
 
 
Countermovement jump test and video-recording (take-off position) 
Countermovement jump test and video-recording (in the air) 
 
 
 
 
 

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Rectus femoris flexibility: The modified Thomas test  
 
To assess the change in flexibility of the rectus femoris muscle between legs, participants will be asked to sit 
at the end of the examination bed with their thighs halfway off the bed. From here, participants will be 
instructed to lie back down and grab their index knee and hold it towards their chest, while the non-index 
leg is fully relaxed. In this position, the distal muscle belly of the quadriceps femoris is gently palpated and 
shaken to ensure there is no palpable tension. Then, by using a digital goniometer centered on the anterior 
tibial crest at the midpoint between the malleolus and the knee joint, the offset angle from horizontal is 
measured. The same assessment is the done for the index knee. The difference in degrees is then compared 
between the two knees, and for single knees over time.  
 
The built-in ‘Measure’ app with a level function on the iPhone will be used (Apple Inc., San Jose, USA). 
Different apps based on the same level-function have been investigated with near-perfect validity with other 
digital methods (video-analysis, digital inclinometers) and good to excellent inter-and intra-tester reliability 
and low error of measurement and detectability.196 Optimally, we would use an app that had specific 
evidence for its properties, but in a systematic review of studies of goniometer apps from May 2019, most of 
the included apps were at present (December 2020) not available for purchase/download. Therefore, the 
decision to use the underlying ‘Measure’ app was taken in light of the measure needed is also fairly simple 
and passive, and we found acceptable inter-tester reliability of this method in a recent study.188 
 
Modified Thomas test position 
Measuring angle using the level function in a smartphone 
 
 
 

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Growth velocity offset: The anthropometrics-based Peak Height Velocity formula  
 
To assess somatic maturation and growth velocity, participants offset from ‘Peak Height Velocity’ in years 
will be measured.234 This method is non-invasive and uses only the following anthropometric variables: sex, 
chronological age, height, weight, and sitting height.234 Height will be measured with a stadiometer with 
participants in their most upright positions with no shoes on and head placed in the Frankford plane. 
Similarly, sitting height will be measured from a flat box of 60 cm, also with a stadiometer.271 Age is reported 
by the participants, and weight is measured with clothes (shirt, shorts, and no shoes) on a standard 
bathroom scale. The singular measures part of this composite measure has shown high reliability.271 
 
Measuring sitting height with head in the Frankford Plane 
 
 
 
 

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Appendix 2: Ultrasound protocol 
 
We have investigated the inter-tester reliability of novice operators performing the original outline of this 
protocol and found a moderate or substantial agreement for most measures (κ =0.41-0.79).178 We have since 
improved or simplified the least reliable measures. The protocol is performed on each knee at baseline, 
starting with the right knee. All positive findings will be documented, and the sonographs and videos saved. 
The protocol consists of primarily longitudinal sonographs from the patella pole to the tibial tubercle. 
Although Osgood-Schlatter is a condition of the tibial tubercle or the adjacent tissue, our clinical experience 
is that a secondary proximal involvement of either the proximal patella tendon or the patella pole is not 
uncommon, and we have thus included measures within this region as well, to also assess these structures 
systematically at baseline. At follow-up, only the index-knee will be scanned. 
 
Some of the singular measures collected are contained in the classification systems used. Thus, all singular 
measures collected will be (table 15): 
• 
Cartilage thickening of patella pole and the tibial tubercle (Yes [1] or no [0]).109,249,251,272 
• 
Tendon thickening: thickening of the proximal patella tendon or distal patella tendon: the subjective 
rating of the tendon appearing thickened (1) or not (0).251,273 
• 
Bursitis signs of the infrapatellar bursa: If the infrapatellar fat pad appears either with fluid build up 
or with hyperemia, raters will denote signs of bursitis (1), and none if nothing abnormal is detected 
(0).54,251 
• 
Un-united ossicle: If the secondary ossification center or an ossicle (deemed as cortical bone, rather 
than a more irregular calcified fragment) appears unattached superficial to site of fusion of the 
metaphysis and physis on the tibial tubercle (1) or not (0). 251,274 
• 
Bone fragmentation of the patella pole and the tibial tubercle: subjective rating of the fragmentation 
quality of the bone surface (excluding normal fragmented/fissuring maturation-related appearance 
of the metaphysis-physis junction) as either unclear (0), none (1), apparent (2).251,272,274 
 
Classification systems (table 14): 
• 
Severity ad modum Flaviis: We will use the Flaviis cumulative system to grade participants in 
severity-stages, as described in table 14, depending on swollen cartilage (1), swollen cartilage 
combined with a fragmented or hypoechoic outline of the ossification center, tendon thickening (3), 
and infrapatellar bursitis (4)).32,251 If participants does not fall into any of these stages, they will be 
graded as ‘normal’ (0).  

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• 
Maturation ad modum Sailly: The maturation of the tibial tubercle will be graded based on the 
attachment of the patella tendon as either cartilage attachment without ossicle (1), cartilage 
attachment with ossicle (2), insertional cartilage (3), or mature (4).109,249 
• 
Hyperemia of the patella, proximal patella tendon, distal patella tendon, infrapatellar bursa, tibial 
tubercle (excluding potential vessels located in the metaphysis-physis junction). Using color-doppler 
the level of hyperemia will be rated in the regions of interest according to the Öhberg score as used 
in previous studies in relevant tissues examining reliability in adults: None (1), 1-2 vessels or spots 
(2), 3 vessels, or spots (3), 4> vessels or spots (4).180,256–258 
 
Table 14. Classification systems 
Measure 
Stage 1 
Stage 2 
Stage 3 
Stage 4 
Sailly (Maturation)  
Cartilage attachment 
without ossicle 
Cartilage attachment with 
ossicle 
Insertional cartilage 
Mature 
Öhberg (Doppler) 
None 
Mild / 1-2 vessels or spots 
Moderate  / 3 vessels or 
spots / <30% of ROI 
Severe / 4≥ vessels or 
spots / >50% of ROI 
Flaviis severity classification 
 
Swollen cartilage 
Irregularity or 
fragmentation of the 
ossification center 
Thickening of the tendon 
Infrapatellar  
bursitis signs 
1 
X 
 
 
 
2 
X 
X 
 
 
3 
 
 
X 
 
4 
 
 
 
X 
 
 
 

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Table 15. Case Report form for ultrasound 
ROI 
Measure 
Scale 
Right knee 
Left knee 
Proximal insertion 
(flexed knee) 
Cartilage thickened 
1/0 
 
 
Severity of fragmentation 
0-2 
 
 
Tendon thickened 
1/0 
 
 
Distal insertion 
(flexed knee) 
Tendon thickenedF 
1/0 
 
 
Infrapatellar bursa thickenedF 
1/0 
 
 
Cartilage thickenedF 
1/0 
 
 
Uninited ossicleF 
1/0 
 
 
FragmentationF 
0-2 
 
 
Ducher/Sailly (Maturation) 
1-4 
 
 
Proximal insertion 
(color doppler, 
extended knee) 
Bone: Doppler Öhberg 
1-4 
 
 
Tendon: Doppler Öhberg 
1-4 
 
 
Distal insertion 
(color doppler, 
extended knee) 
Infrapatellar bursa: Doppler ÖhbergF 
1-4 
 
 
Tendon: Doppler Öhberg 
1-4 
 
 
Bone: Doppler Öhberg 
1-4 
 
 
 
Ultrasound operators  
The ultrasound operator will be a post-graduate physiotherapist that is also doing a PhD-thesis related to 
musculoskeletal imaging. The physiotherapist is a certified sonographer from the Danish Association of 
Sports Physical Therapy and has 3 months of experience performing the protocol in adolescents with 
anterior knee pain, primarily in Osgood-Schlatter patients. He has been trained and supervised in performing 
the protocol and interpreting the sonographs by a professor (JLO) in rheumatology specialized within the 
field of using ultrasound as a diagnostic modality of overuse injuries in muscle-tendon tissue. If needed, a 
replacement will be trained.  
 
Ultrasound equipment, settings, and position 
Participants position: Participants will be seated in a resting position, halfway lying on their back with the 
headrest raised at approximately 70°, knees resting on a plint at about 30° knee flexion, and resting their 
feet on the heels. During color doppler assessment, participants will have their knees fully extended, and for 
evaluation of the infrapatellar bursa, the sonographer can choose to flex the knee to approximately 90° 
flexion at their discretion to acquire the best view and sonograph of a suspected positive finding. 
Participants will be able to co-view the sonographs during scanning.  
 

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Rater position: During the scanning of both knees, the rater is seated next to the participant, operating the 
probe with their right dominant hand.  
 
Probe placement: The probe is placed on the midportion of the patella tendon in the longitudinal/sagittal 
plane centered along with the continuity of the patella tendon. The probe is moved distally/proximally until 
the apex of the patella is in the proximal part of the sonograph. From here, the probe is moved distally until 
the tibial tubercle is in the middle/distal part of the sonograph, and measures are collected and rated along 
the way. All findings are confirmed by performing sweeps in medial-lateral plane and transerval sweeps, and 
the rater saves the best representation of the finding on the longitudinal plane, potentially supplemented by 
transveral sonographs. During doppler evaluation, minimal pressure is applied to the probe, and a thick 
visible layer of gel is applied to not constrict potential vessels.  
 
Equipment and settings: All ultrasound imaging will be captured using an Arrieta V70 (Hitachi, Japan) scanner 
and an L64 linear probe at 18–5 MHz (Hitachi, Japan). In collaboration with a consultant from the equipment 
supplier, an optimized preset was made for the study allowing only changes in depth, gain and focus. The 
settings for the preset are as follows: 
• 
Depth: 2.0 cm (usually adjusted to 3.0 cm when assessing doppler) 
• 
Gain: 80 
• 
Focus: 1.1 cm 
• 
Doppler speed: 2.03 cm/s 
• 
Doppler frequency: 10.42 MHz 
• 
CG: 140 
• 
Placement of doppler ROI window: Anteriorly and maximized 
• 
Frequency: High (approximately 18 MHz) 
 
 
 
 

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Figure 6. Examples of ultrasound assessments 
 
Color doppler: 3, swollen cartilage: 0, maturation: 2, unnited 
ossicle (1)  
Fragementation: 2 (apex patella) 
 
 
Fragmentation: 2. Maturation: 2 
Fragmentation: 2. Maturation: 3 
 
 
Tendon thickening (1), doppler (4) (apex patella) 
Doppler (4), tendon thickening (1), tendon hypoechoic (1) at the 
tibial tubercle (transverse) 
 
 
 
 

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Figure 7. Examples of color doppler assessments at the tibial tubercle in the longitudinal and transversal plane 
 
 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 

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Appendix 3: Exercise descriptors and populated CERT/TIDierR checklists  
Exercise in the experimental intervention described by parameters proposed by Toigo & Boutellier75 (table 
16) followed by a table of collated domains from CERT77 (Checklist for Exercise Reporting Template) and 
TIDieR76 (Template for Intervention Description and Replication) (table xx).  
 
Table 16. Exercise descriptors for the experimental intervention 
Exercise descriptors 
Knee-press 
Hip abduction bridge 
Wall-squat 
Lunges 
Continuous dose 
Continuous dose 
Start dose 
Target dose 
Start dose 
Target dose 
 
 
 
 
 
 
 
Load magnitude 
 
Unknown 
≥12RM 
1RM 
5RM 
1RM 
12RM 
Number of repetitions 
 
10 
12 
1 
5 
1 
12 
Number of sets 
 
10 
2 (per leg) 
1 
1 
1 (per leg) 
3 (per leg) 
Rest between sets 
 
30 s 
30 s 
30 s 
30 s 
30 s 
30 s 
Sessions per week 
 
7 
3.5 
3.5 
3.5 
3.5 
3.5 
Duration of the 
experimental period 
 
1 month  
(phase 1) 
3 months  
(phase 1 & 2) 
0-2 months  
(phase 2) 
0-2 months  
(phase 2) 
0-2 months 
(phase 2) 
0-2 months 
(phase 2) 
Duration of contraction modes per repetition 
 
 
 
 
 
- Eccentric 
None 
2 s 
2 s 
2 s 
2 s 
2 s 
- Isometric 
30 s 
4 s 
2 s 
30 s 
2 s 
2 s 
- Concentric 
 
None 
2 s 
2 s 
2 s 
2 s 
2 s 
Rest between repetitions 
 
30 s 
0 s 
30 s 
30 s 
0 s 
0 s 
Time-under-tension 
(TUT) per repetition 
 
30 s 
8 s 
8 s 
34 s 
6 s 
6 s 
Volitional muscular 
failure 
 
 
 
No 
Yes, or 12 reps 
Yes, or stopping 
due to pain >2 
NPRS 
Yes, or stopping 
due to pain >2 
NPRS 
Yes, or stopping 
due to pain >2 
NPRS 
Yes, or stopping 
due to pain >2 
NPRS 
Range of motion 
 
 
 
 
Fixed at 60° knee 
flexion 
Appx 0-30° hip abduction 
From 0-90° knee 
flexion, depending 
on pain >2NPRS 
90° knee flexion 
0-100° knee 
flexion 
0-100° knee 
flexion 
Recovery time between 
exercise sessions 
 
1 day 
2 days 
2 days 
2 days 
2 days 
2 days 
Anatomical definition of 
the exercise (exercise 
form) 
Sitting in a chair 
without shoes, and 
toes appx 15 cm from 
a wall, the participant 
puts their heel on the 
floor and toes on the 
wall and presses in the 
direction of the lower 
limb, and alternates 
between legs while 
resting one leg. 
Lying on the side with 
legs together and knees 
flexing at appx 70-50°, 
the participant maintains 
their body in a straight 
line from head to knees 
while lifting their upper 
body on their elbow by 
having the lower arm in 
appx 90° shoulder 
abduction. From here, 
they simultaneously 
abduct both hips to appx. 
30° hip abduction, thus 
lifting their lower body 
upwards. 
While maintaining contact between the 
back and the buttocks onto the wall, the 
participant places their heels at 1½ foot 
length from the wall in shoulder-width, 
pointing straight ahead. The participant 
then lowers their upper body by sliding 
down the wall to appx 90° knee flexion, 
keeping the tension for x-seconds, and 
returns to the starting position. 
Participants takes a long stride and 
stands with straight legs and appx 
45° hip flexion for the front leg and 
45° hip extension for the rear leg. 
Feet are pointing straight ahead and 
no more than shoulder-width apart. 
The participant maintains this 
position through the set. From here, 
the upper body is maintained in an 
upwards position is lowered directly 
downwards between the legs to appx 
100° knee flexion of the front leg and 
without touching the ground.  
Red numbers and golden lines indicate the order and type of progression steps. NPRS = 0-10 numerical pain rating scale; RM = repetition maximum 
 
 
 
 
 
 

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Table 17. Collated populated TIDieR76 and CERT77 templates for the experimental treatment 
Item no. 
Collated adapted item description 
TIDieR 
CERT 
1 
- 
Provide the name or a phrase that describes the intervention. 
 
 
Self-management approach 
 
2 
- 
Describe any rationale, theory, or goal of the elements essential to the intervention 
 
 
Page 20-27 
 
3 
1 
Materials and equipment: Describe any physical or informational materials used in the intervention, including those 
provided to participants or used in intervention delivery or in training of intervention providers. Provide information on 
where the materials can be accessed (e.g. online appendix, URL). 
 
 
A leaflet detailing exercise form, dose and progression rules for both treatment-arms are supplied at baseline 
Folders and leaflets for the usual care intervention: doi.org/10.6084/m9.figshare.17099984 
Folders and leaflets for the experimental intervention: doi.org/10.6084/m9.figshare.17099954 
 
5 
2 
For each category of intervention provider (e.g. psychologist, nursing assistant), describe their expertise, background and 
any specific training given / teaching/supervising expertise 
 
 
See “study training” section page 43 
 
6 
3, 4 
Describe the modes of delivery (e.g. face-to-face or by some other mechanism, such as internet or telephone) of the 
intervention and whether it was provided individually or in a group. Detail of supervised/unsupervised, and mode of 
delivery 
 
 
The intervention-instructions are delivered face-to-face at an individual level, and are done at home unsupervised by 
study personnel, however, parents are encouraged to supervise exercises when possible. By requests of participants, 
instructions by phone will be available. At each visit, participants are asked to perform their prior exercises, in order to 
rate if sufficient exercise-form was adhered to. 
 
11 
5 
Planned: If intervention adherence or fidelity was assessed, describe how and by whom, and if any strategies were used 
to maintain or improve fidelity, describe them. 
 
 
Page 30-32 
 
4 
6 
Detailed description of motivation strategies / Describe each of the procedures, activities, and/or processes used in the 
intervention, including any enabling or support activities 
 
 
Page 30 
- 
7a 
Detailed description of the decision rule(s) for determining exercise progression 
 
 
Page 23-29 
 
- 
7b 
Detailed description of how the exercise program was progressed 
 
 
Page 23-29 
 
- 
8 
Detailed description of each exercise to enable replication (e.g. photographs, illustrations , video etc) 
 
 
Page 27-28, 23-24 
 
7 
9 
Where / Detailed description of any home program component (e.g. other exercises, stretching etc) 
 
 
All exercises are to be performed at home. 
 
- 
10 
Describe whether there are any non-exercise components (e.g. education, cognitive behavioural therapy, massage etc) 
 
 
Pages 25, 29 
 
 
11 
Describe the type and number of adverse evens that occurred during exercise  
 
 
See a priori plans for collection and reporting of harms on page 57-58 
 
7 
12 
Describe the setting in which the exercises are performed. Describe the type(s) of location(s) where the intervention 
occurred, including any necessary infrastructure or relevant features. 
 
 
All exercises are to be performed at home. 
 
8, 4 
13 
Detailed description of the exercise intervention including, but not limited to, number of exercise repetitions/sets/sessions, 
session duration, intervention/program duration. Describe each of the procedures, activities, and/or processes used in the 
intervention, including any enabling or support activities + the number of times the intervention was delivered and over 
what period of time including the number of sessions, their schedule, and their duration, intensity or dose 
 
 
See table 4,5,6. Exercise instructions are performed at the Department of Physiotherapy, and exercises are performed at 
home. Instructions are received a months 0, 1, 2, and 3.  
 
9 
14a, 14b 
Describe whether the exercises are generic (one size fits all) or tailored whether tailored to the individual + Detailed 
description of how exercises are tailored to the individual 

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If the intervention was planned to be personalized, titrated or adapted, then describe what, why, when, and how 
 
 
The exercise intervention is not personalized but are adapted to fit the individuals capacity for load, muscular endurance 
and pain in terms of starting point and progression. If, for some reason, a participant is not able to perform a specific 
exercise, alternatives will be provided by the treating physiotherapist.  
 
- 
15 
Describe the decision rule for determining the starting level at which people commence an exercise program (such as 
beginner, intermediate, advanced etc.)  
 
 
All participants start with 1 month of de-loading, with only the knee-press exercise, and the hip abduction bridge with a 
set dose (see table 5). Participants are instructed to do 12 reps of the hip abduction bridge, or as many as they can, until 
they reach the 12-repetition level, which is then to be maintained throughout the intervention. After month 1, knee-press 
is substituted with a new knee exercise, the wall squat. During instructions, participants perform 1 repetition at (up to) 90º 
knee flexion, with a duration of up to 30 s hold, if they can, without NPRS >2. This determines their starting knee flexion 
angle and duration of the wall-squat exercise. After reaching the target dose for wall squats, they proceed to the start 
dose of lunges, which as many repetitions possible in one set with NPRS <3, or up 12 repetitions on each leg. See table 
16 for further detailed descriptions and order of exercise progression parameters.   
 
11 
16 
Describe how adherence or fidelity to the exercise intervention is assessed/measured 
 
 
Page 30-31 
 
NPRS = 0-10 numerical pain rating scale; TIDieR = Template for Intervention Description and Replication; CERT = Checklist for Exercise 
Reporting Template. Omitted items due to being post hoc: TIDieR: 10, 12; CERT: 16b 
 
 
 
 
 
 
 

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Appendix 4: Weekly monitoring via text-messages (Danish) 
Figure 8. Flow of text-based monitoring in the experimental group from week 4 to 22 
 

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Figure 9. Flow of text-based monitoring in the experimental group from week 0 to 4  
 
 
 
 

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Figure 10. Flow of text-based monitoring in the usual care group from week 0 to 22 
 
 
 
 

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Appendix 5: Pragmatic-Explanatory indicators 
 
Figure 11. PRagmatic-Explanatory Continuum Indicator Summary – PRECIS ‘Wheel’ 
 
 
Table 18. PRECIS-2 scores for trial domains 
 
Domain  
Score  
Rationale  
1  
Eligibility Criteria  
 4 
Participants included will resemble those that present in the clinic to a 
large degree, and concomitant complaints are also allowed to some 
degree.  
2  
Recruitment Path  
 4 
As there are limited treatment options, participants are usually not 
contained in the health care system. For those that do seek treatment, 
we will supply nearby GP clinics and private physio clinics with contact 
information for potential participants. Similarly, nearby sports clubs will 
be provided the same material. Moreover, all patients who are referred 
for specialized care in the uptake area of our orthopedic department 
will be screened for eligibility. Finally, we will supplement the above 
recruitment channels with social media adverts for those that are not 
currently in the health care system, targeting 40-55-year-old (potential 
parents) in the uptake area. As such, we are attempting to potentially 
offer recruitment to the entirety of the local potential population. 
3  
Setting  
 3 
The intervention and outcome assessments will take place at the 
physiotherapy department in the hospital.  
4  
Organization 
 4 
The intervention is comprised by field experts, but the personnel 
trained to deliver the intervention will not have extensive experience 
with either the intervention or the target-population. Post-trial 
dissemination to other clinicians will consists of leaflets, intervention 
descriptions, and a clinician manuscript.  
5  
Flexibility of experimental intervention  
– Delivery  
 2 
Only one mode of delivery will be used in the trial (in-person visits, 
combined with information leaflets), but the actual contents of the visits 

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will vary based on the progress and context of the individual 
participant. The treatments are standardized. 
6  
Flexibility of experimental intervention  
– Adherence  
 5 
All patients will be included in the final analyses, regardless of 
adherence levels.  
7  
Follow up  
 4 
The number of clinical follow-up visits (4 visits) will likely be the same 
as in a physiotherapy clinic, however trial-related follow-up will exceed 
what could be expected in general settings. 
8  
Outcome  
 5 
The primary outcome is self-reported validated measured of knee-
function, supplemented by level and satisfaction with sport and 
physical activity participation levels. 
9  
Analysis  
 5 
Intention-to-treat analysis is planned for all outcomes as the standard 
approach 
 
 
 

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Appendix 6: Directed acyclig graph