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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626001161314
Ethics application status
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Approved
Date submitted
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1/09/2026
Date registered
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17/09/2026
Date last updated
Help: Date last updated
17/09/2026
Date data sharing statement initially provided
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17/09/2026
Type of registration
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Prospectively registered

Titles & IDs
Public title
The immediate effects of ibuprofen compared to placebo on knee pain and knee joint loading during running in runners with patellofemoral pain
Scientific title
The immediate effect of a non-steroidal anti-inflammatory drug compared to placebo on knee pain and peak patellofemoral joint force during running in runners with patellofemoral pain
Additional trial identifiers [1] 318178 0
CT-2026-CTN-01575-1 v1
Universal Trial Number (UTN)
Trial acronym
STRIDE-NSAID
Related trial records

Health condition
Health condition(s) studied:
patellofemoral pain 343434 0
Chronic knee pain 343435 0
Condition category
Condition code
Musculoskeletal 339524 339524 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
Arm 1 (Ibuprofen):
Participants allocated to the ibuprofen group will receive a single oral dose of ibuprofen 400 mg. This dose is consistent with the recommended adult dose and is below the maximum non-prescription daily dose of 1200 mg. The ibuprofen formulation is classified as a non-prescription medicine in Australia. Immediately after completing the baseline assessments, participants will ingest one 400 mg tablet orally with water under the direct observation of a member of the research team.

Before receiving the intervention, participants will complete a baseline running assessment. They will first perform a 5-minute treadmill warm-up at 3.0–3.5 m/s. This will be followed by two familiarisation runs and eight acceptable 40-metre overground running trials while wearing standardised neutral running shoes. Participants will run at 3.0-3.5 m/s, with speed measured using timing gates positioned around the force plates. A trial will be considered acceptable when the participant runs within the prescribed speed range and both feet make clean contact with the embedded force plates. Participants will walk back to the starting position between trials, with additional rest and water provided as needed. Perceived exertion will be measured after the complete set of running trials using the 6–20 Borg Rating of Perceived Exertion scale.

The ibuprofen dose will be administered immediately after completion of the baseline running assessment and associated post-running measures. Participants will then rest quietly for approximately 35 minutes to allow for drug absorption. After this period, they will repeat the 5-minute treadmill warm-up at 3.0–3.5 m/s, followed by the same static calibration, two familiarisation runs and eight acceptable overground running trials at 3.0–3.5 m/s. Perceived exertion will again be measured using the Borg scale after completion of the post-dose running trials.
Intervention code [1] 335204 0
Treatment: Drugs
Description of the comparator or control
Arm 2 (Placebo)
Participants allocated to the placebo group will receive a single oral placebo tablet identical in appearance to the ibuprofen tablet but containing no active medication. Immediately after completing the baseline assessments, participants will ingest one placebo tablet orally with water under the direct observation of a member of the research team.

Before receiving the intervention, participants will complete a baseline running assessment. They will first perform a 5-minute treadmill warm-up at 3.0–3.5 m/s. This will be followed by two familiarisation runs and eight acceptable 40-metre overground running trials while wearing standardised neutral running shoes. Participants will run at 3.0–3.5 m/s, with speed measured using timing gates positioned around the force plates. A trial will be considered acceptable when the participant runs within the prescribed speed range and both feet make clean contact with the embedded force plates. Participants will walk back to the starting position between trials, with additional rest and water provided as needed. Perceived exertion will be measured after the complete set of running trials using the 6–20 Borg Rating of Perceived Exertion scale.

The placebo tablet will be administered immediately after completion of the baseline running assessment and associated post-running measures. Participants will then rest quietly for approximately 35 minutes. After this period, they will repeat the 5-minute treadmill warm-up at 3.0–3.5 m/s, followed by the same static calibration, two familiarisation runs and eight acceptable 40-metre overground running trials at 3.0–3.5 m/s. Perceived exertion will again be measured using the Borg scale after completion of the post-dose running trials.
Control group
Placebo

Outcomes
Primary outcome [1] 346705 0
Knee pain intensity after running
Timepoint [1] 346705 0
Baseline (after running trials) Post-intervention (after running trials)
Primary outcome [2] 346706 0
Peak patellofemoral joint force during running
Timepoint [2] 346706 0
Baseline (during running) Post-intervention (during running)
Secondary outcome [1] 467128 0
Knee confidence
Timepoint [1] 467128 0
Baseline (after running trials) Post-intervention (after running trials)
Secondary outcome [2] 467129 0
Perceived exertion
Timepoint [2] 467129 0
Baseline (after running trials) Post-intervention (after running trials)
Secondary outcome [3] 467130 0
Pressure pain threshold: Patella
Timepoint [3] 467130 0
Before and after baseline running trials Before and after post-intervention running trials
Secondary outcome [4] 467131 0
Pattelofemoral joint force impulse
Timepoint [4] 467131 0
Baseline (during running) Post-intervention (during running)
Secondary outcome [5] 467894 0
Pressure pain threshold: Elbow
Timepoint [5] 467894 0
Before and after baseline running trials Before and after post-intervention running trials
Secondary outcome [6] 467895 0
Patellofemoral joint force loading rate
Timepoint [6] 467895 0
Secondary time point: Baseline (during running) Post-intervention (during running)
Secondary outcome [7] 467896 0
Ankle sagittal-plane angle
Timepoint [7] 467896 0
Secondary time point: Baseline (during running) Post-intervention (during running)
Secondary outcome [8] 467897 0
Ankle sagittal-plane joint moment
Timepoint [8] 467897 0
Secondary time point: Baseline (during running) Post-intervention (during running)
Secondary outcome [9] 467898 0
Knee sagittal-plane angle
Timepoint [9] 467898 0
Secondary time point: Baseline (during running) Post-intervention (during running)
Secondary outcome [10] 467899 0
Knee sagittal-plane joint moment
Timepoint [10] 467899 0
Secondary time point: Baseline (during running) Post-intervention (during running)
Secondary outcome [11] 467900 0
Hip sagittal-plane angle
Timepoint [11] 467900 0
Secondary time point: Baseline (during running) Post-intervention (during running)
Secondary outcome [12] 467901 0
Hip sagittal-plane joint moment
Timepoint [12] 467901 0
Secondary time point: Baseline (during running) Post-intervention (during running)
Secondary outcome [13] 467902 0
Hip frontal-plane angle
Timepoint [13] 467902 0
Secondary time point: Baseline (during running) Post-intervention (during running)
Secondary outcome [14] 467903 0
Hip frontal-plane joint moment
Timepoint [14] 467903 0
Secondary time point: Baseline (during running) Post-intervention (during running)
Secondary outcome [15] 467904 0
Trunk sagittal-plane angle
Timepoint [15] 467904 0
Secondary time point: Baseline (during running) Post-intervention (during running)

Eligibility
Key inclusion criteria
- Insidious onset of anterior or peripatellar knee pain, with a duration of at least 2 months.
- Worst pain intensity equal or greater than 30 on a 0-100 numerical rating scale during the previous month.
- Pain around or behind the patella during at least two of the following activities: sitting for a prolonged period, rising from sitting, squatting, kneeling, running, walking up stairs, walking down stairs, jumping, landing, heavy household activities and after sports and recreational activities.
- Individuals who have maintained an average running volume of at least 5 km per week during the past 2 months.
- Individuals must be able to understand and speak English.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
- Known allergy or hypersensitivity to ibuprofen or history of adverse ibuprofen reactions.
- Known hypersensitivity to aspirin and other NSAIDs.
- Asthma that is aspirin or NSAID-sensitive.
- Active gastrointestinal bleeding or peptic ulceration.
- Renal, hepatic or any known cardiac impairment.
- Use of medicines known to interact with Ibuprofen, including current use of other NSAIDs or salicylates, anticoagulants (e.g., warfarin), lithium, methotrexate, antihypertensive agents (angiotensin-converting enzyme inhibitors, beta-blockers, diuretics), oral corticosteroids (e.g., prednisone, prednisolone, cortisone), zidovudine, medicines used to treat diabetes.
- Failure to meet pre-defined washout periods: no NSAIDs or aspirin in the 72 hours before testing, no oral corticosteroids in the 7 days before testing, no weekly methotrexate in the 7 days before testing.
- Recent use of other analgesics, anti-inflammatory, or psychoactive medications within 3 days of testing (to avoid confounding effects or drug interactions).
- History of knee surgery.
- History of patellar dislocation.
- Clinical evidence of meniscal injury or ligamentous instability.
- Self-reported current or recent hip, ankle, or foot pain (>30 on a 0-100 point NRS).
- Use of any knee injection (e.g., PRP, hyaluronic acid, cortiscosteroid) in the previous 6 months
- Pregnant.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The allocation sequence will be uploaded to and securely stored within REDCap and will not be accessible to researchers responsible for participant recruitment, eligibility assessment, consent, or baseline data collection. Participants will be randomised only after eligibility has been confirmed, informed consent has been obtained, and all baseline assessments have been completed. The treatment allocation will be revealed only after the participant has been irrevocably entered into the trial and randomised.

Each ibuprofen (400 mg) and placebo tablet will be pre-packed in sequentially numbered, opaque, sealed containers, each containing a single, indistinguishable tablet labelled solely with a unique study code corresponding to the randomisation list.

During testing, the blinded investigator will provide participants with the next numbered container in sequence. Because the tablets are identical and the randomisation codes remain securely stored and inaccessible to the research team, neither participants nor investigators will be aware of treatment allocation. This process ensures complete allocation concealment and preserves double-blind integrity throughout the trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated allocation sequence prepared by an independent statistician. Participants will be allocated in a 1:1 ratio to the ibuprofen (400 mg) or placebo group using permuted blocks of fixed size (block size = 4) to ensure balanced group allocation throughout recruitment. Randomisation will be stratified by sex to maintain equal representation of male and female participants and by symptom duration greater or lower than 2 years.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size calculation:
The trial has two primary outcomes: peak PFJ force and knee pain during running, both assessed immediately following administration of ibuprofen or placebo. A statistically significant effect on either primary outcome will be sufficient to demonstrate efficacy. To control the family-wise type I error rate at 5%, each primary outcome will be tested at a two-sided significance level of 0.025. Sample size requirements were calculated separately for each primary outcome based on the prespecified analysis of covariance models, which will compare post-intervention outcomes between groups while adjusting for the corresponding baseline measurement.
For peak PFJ force, the calculation was based on a target between-group difference of 0.40 BW and an SD of 0.75 BW, informed by an immediate experimental study of runners with patellofemoral pain. Assuming a baseline-to-post-intervention correlation of 0.60, these parameters corresponded to a baseline-adjusted effect size of Cohen’s (f=0.33). With 80% power, a two-sided significance level of 0.025 and equal allocation, 90 participants are required (45 per group).

For knee pain during running, the calculation was based on a target between-group difference of 10 point and an SD of 20 points on an 0-100-point numerical pain rating scale, informed by an immediate laboratory-based running study in adults with patellofemoral pain. Assuming a baseline-to-post-intervention correlation of 0.60, these parameters corresponded to a baseline-adjusted effect size of Cohen’s (f=0.31). With 80% power, a two-sided significance level of 0.025 and equal allocation, 100 participants are required (50 per group).
The larger sample-size requirement, based on knee pain during running, determined the overall sample size. The trial will therefore randomise 100 participants, with 50 assigned to each group. Sample-size calculations were performed using G*Power, version 3.1.9.7. Because baseline and post-intervention assessments occur during the same laboratory visit, loss to follow-up is expected to be negligible. No separate allowance for attrition was therefore incorporated into the sample size calculation. Nevertheless, the target sample of 100 participants provides a margin of 10 participants above the 90 evaluable participants required for the peak PFJ force outcome to accommodate occasional unavailable outcome data resulting from technical or biomechanical data-quality issues.

Statistical analysis
Analyses will follow a prespecified statistical analysis plan finalised before database lock and unblinding. Participants will be analysed according to their randomised group, irrespective of adherence or protocol deviations. Baseline characteristics will be summarised descriptively without significance testing.
Each primary outcome, knee pain during running and peak PFJ force will be analysed using an analysis of covariance (ANCOVA) model with the post-administration measurement as the dependent variable, treatment group as a fixed effect, and the corresponding baseline measurement as a continuous covariate. Prespecified variables used to stratify randomisation will also be included as covariates. Adjusted between-group mean differences, calculated as ibuprofen minus placebo, will be estimated with heteroskedasticity-robust standard errors. Model-based adjusted means for each treatment group will also be reported.

Because efficacy on either primary outcome is sufficient for trial success, the family-wise type I error rate will be controlled at 5% using a Bonferroni adjustment. Each primary hypothesis will be tested using a two-sided significance level of 0.025. Adjusted treatment effects will be reported with multiplicity-adjusted 97.5% confidence intervals; 95% confidence intervals may additionally be presented to aid estimation and clinical interpretation. The trial will be considered to demonstrate efficacy if the null hypothesis is rejected for at least one primary outcome at the two-sided 0.025 significance level and the corresponding treatment effect is in the prespecified direction favouring ibuprofen.

Secondary outcomes will be analysed using regression models appropriate to their scale and distribution and reported as treatment effect estimates with 95% confidence intervals. These analyses will be considered supportive or exploratory, and no adjustment for multiplicity will be applied; accordingly, secondary outcome findings will not be interpreted as confirmatory evidence of efficacy.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/10/2026
Actual
Date of last participant enrolment
Anticipated
3/12/2027
Actual
Date of last data collection
Anticipated
3/12/2027
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 322743 0
Government body
Name [1] 322743 0
National Health and Medical Research Council (NHMRC)
Country [1] 322743 0
Australia
Primary sponsor type
University
Name
La Trobe University
Address
Country
Australia
Secondary sponsor category [1] 325796 0
None
Name [1] 325796 0
Address [1] 325796 0
Country [1] 325796 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 321183 0
La Trobe University Human Ethics Committee
Ethics committee address [1] 321183 0
Ethics committee country [1] 321183 0
Australia
Date submitted for ethics approval [1] 321183 0
18/11/2025
Approval date [1] 321183 0
22/12/2025
Ethics approval number [1] 321183 0
HEC25556

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

Contacts
Principal investigator
Name 152938 0
A/Prof Danilo De Oliveira Silva
Address 152938 0
La Trobe University, Kingsbury Drive, Bundoora, 3086, Melbourne, VIC
Country 152938 0
Australia
Phone 152938 0
+61426188766
Fax 152938 0
Email 152938 0
[email protected]
Contact person for public queries
Name 152939 0
Danilo De Oliveira Silva
Address 152939 0
La Trobe University, Kingsbury Drive, Bundoora, 3086, Melbourne, VIC
Country 152939 0
Australia
Phone 152939 0
+61426188766
Fax 152939 0
Email 152939 0
[email protected]
Contact person for scientific queries
Name 152940 0
Danilo De Oliveira Silva
Address 152940 0
La Trobe University, Kingsbury Drive, Bundoora, 3086, Melbourne, VIC
Country 152940 0
Australia
Phone 152940 0
+61426188766
Fax 152940 0
Email 152940 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Anyone
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
What individual participant data might be shared?
• All de-identified individual participant data
What types of analyses could be done with individual participant data?
• Any type of analysis (i.e. no restrictions on data re-use)
When can requests for individual participant data be made (start and end dates)?
From:
At the end of the study
To:
As determined by the trial ethics application.

Where can requests to access individual participant data be made, or data be obtained directly?
• Email of trial custodian, sponsor or committee: [email protected]

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


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.