Anterior Cruciate Ligament InjuryExeLoadBioPTOANCT06892899
Exercise Loading Biology Post-Traumatic OsteoArthritis Study - a Pilot and Feasibility Study
An observational study of Anterior Cruciate Ligament Injury and Quadriceps Dysfunction, run by May Arna Risberg at 1 site in Norway.
Trial summary
FROM RISK FACTORS TO THE PREVENTION OF LONG-TERM CONSEQUENCES AFTER CRUCIATE LIGAMENT INJURY (ACL injury) - This is a research project where we seek new knowledge about why some people have a high risk and others a low risk of developing long-term consequences such as persistent pain, thigh muscle dysfunctions and… Read more about this study
- Who is it for?
- Ages 16 to 40 years
- Conditions the study is for
- Anterior Cruciate Ligament Injury, Quadriceps Dysfunction, Knee Joint Loading
- How many people
- 40 participants
- Where
- 1 siteNorway
- Study dates
- 19 Sep 2024to Jul 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Participants will be recruited through the Norwegian Knee Ligament Registry (NKLR). Established in 2004, its current data show that between 1800 and 2000 individuals go through ACL reconstruction annually in Norway. The NKLR includes nationwide data in Norway with >90% coverage for surgical data.
Who may be able to join
- Unilateral ACL injury and ACLR (≤ one year between injury and surgery)
- Surgery performed using the BPTB or hamstring grafts
- Age between 16 and 40 years
- Isolated ACL or with concomitant meniscal injury/cartilage injuries at surgery
- Location (living) in the Oslo or Viken areas (due to the need for testing performed at the Norwegian School of Sport Sciences and Oslo University Hospital)
- Healthy, uninjured contralateral knee
Who cannot join
- Above 40 years and below 16 years of age
- Previous ACL injury (re-rupture of graft or an ACL injury more than one year between injury and surgery)
- MCL/LCL grade 3 injuries
- Other lower extremity injuries less than one year before inclusion, or previous inflammatory arthropathy or systemic infection or inflammation
- Participants with bilateral ACL injuries
Trial locations and contacts
1 site in 1 country.
Norway1 site
Department of Sport Medicine, Norwegian School Sport Sciences
Oslo, Oslo, 0806
About this study
Official title: Reducing the Burden of Post-traumatic Knee Osteoarthritis Targeting Persistent Abnormal Joint Loading and Quadriceps Muscle Dysfunctions in Young Adults With ACL Injury - a Pilot and Feasibility Study
FROM RISK FACTORS TO THE PREVENTION OF LONG-TERM CONSEQUENCES AFTER CRUCIATE LIGAMENT INJURY (ACL injury) - This is a research project where we seek new knowledge about why some people have a high risk and others a low risk of developing long-term consequences such as persistent pain, thigh muscle dysfunctions and osteoarthritis after ACL surgery. Through more knowledge about risk factors for persistent pain, thigh muscle dysfunctions, and, in the long term, osteoarthritis, we have a greater opportunity to tailor preventive treatment measures to the individual.
We know that a subgroup of those who have undergone ACL surgery does not regain the normal function of the quadriceps muscle, that it does not become as strong as it used to or not quite the same as on the other healthy side. Some may notice this very well, others may not notice as much in the short term. We know that quadriceps dysfunctions can affect the biomechanical joint loading in your knee and can be a contributing risk factor to developing long-term consequences such as persistent pain, thigh muscle function and osteoarthritis after ACL injury.
Read more
We have methods to measure joint loading conditions in the knee and to identify changes in the cartilage, in the underlying bone tissue of the knee joint, and to measure various aspects of quadriceps muscle strength and dysfunctions.
In this study, we want to develop new knowledge about whether there is a difference in knee joint loading conditions and quadriceps muscle function between those who have low risk and those with a higher risk of developing post-traumatic osteoarthritis and whether there is an association between joint loading conditions in the knee after ACL surgery and quadriceps muscle function and symptoms.
Read the detailed description
The main risk factors for knee OA disease are well-known: joint injuries and obesity. For those with ACL injury, systematic reviews have reported between 4 to 6 times increased risk of developing OA after ACL injury (PTOA). The following risk factors have been identified for PTOA in a recent systematic review by our OPTIKNEE group: ACL injury with concomitant injuries (meniscus and cartilage injuries), re-injuries after ACL injury, long-lasting quadriceps dysfunction, and inflammation after joint injury.
A better understanding of mechanisms to stratify the patients into different subgroups based on risk factors is critical. The mechanisms driving OA disease development are known to be 1) mechanical and 2) inflammatory. The mechanisms leading to PTOA combine mechanical, biological, structural, and neuromuscular factors.
Mechanical stress with persistent abnormal joint loading is an undisputed mechanism driving OA disease development. Altering joint mechanics (underloading and overloading) after ACL injury and reconstruction (ACLR) can lead to uneven stress and changes in stress across the articular cartilage of the joint surfaces, contributing to abnormal joint function and muscular dysfunction over time.
Whether such persistent abnormal knee joint loading patterns differ between individuals categorized as high risk compared to those at low risk of PTOA has not been investigated.
We do not understand the main drivers of the shifts in joint loading (underloading or overloading) or biochemical changes and whether this knowledge can be translated into developing joint-loading therapeutic interventions. However, we do know that quadriceps muscle weakness is a modifiable risk factor for non-traumatic OA and PTOA. ACL injury has shown a decline in quadriceps muscle function, which mimics ageing, known as sarcopenia. Quadriceps muscle dysfunction persists for some individuals for several years after ACLR, even after the cessation of structured rehabilitation, and has been questioned if it ever returns to normal. Despite decades of high-quality rehabilitation, normalizing quadriceps function in all ACL-injured and reconstructed patients remains unsolved.
This study has an overall aim of understanding more of the mechanisms for abnormal knee joint loading and quadriceps muscle dysfunctions in individuals at high- compared to low-risk PTOA (those with concomitant injuries and persistent symptoms compared to those with isolated ACL injury).
This cross-sectional study includes 40 participants 9 months to 2 years after ACLR with an extensive test-protocol of biomechanical-, neuromuscular- and biological assessments and tests. Hence, it is also a feasibility study for a planned randomized controlled trial of the effect of joint-loading therapeutic interventions on changes in knee joint loading for those at risk of developing PTOA. Furthermore, a sample of 40 individuals will be included to investigate primary outcomes' mean and standard deviation needed to calculate sample size for future randomized controlled trials.
Specific aims for the cross-sectional study are:
- Investigate knee joint loading during gait, running and hopping, cellular, morphological, muscle inhibition and strength of the quadriceps muscle, and inflammatory knee joint markers in individuals who are 9 months to 2 years after an ACLR.
- Characterize biomechanical, neuromuscular, and inflammatory factors in individuals classified as high-risk (concomitant injuries, persistent symptoms) for developing PTOA compared to those classified as low-risk (isolated ACL injury and no or minimal knee pain).
- Explore the associations between abnormal knee joint loading, quadriceps muscle dysfunctions, and inflammatory markers in the knee joint 9 months to 2 years after ACLR
- Describe the feasibility of the study regarding the recruitment of an extensive test-protocol
- A pilot study for a future mechanistic RCT on the efficacy of a muscle- and joint-loading therapeutic exercise program on changes in knee joint loading and on surrogate outcomes of PTOA.
- Conditions
- Anterior Cruciate Ligament Injury, Quadriceps Dysfunction, Knee Joint Loading, Anterior Cruciate Ligament Reconstruction, Risk Factors
- Keywords
- knee injury, anterior cruciate ligament injury, knee joint loading, quadriceps muscle strength, quadriceps muscle function, post-traumatic knee osteoarthritis, risk factors, prevention
- Medical subject headings
- Anterior Cruciate Ligament Injuries, Knee Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: isolated injury | Group 2: combined injuries (concomitant injuries) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tibiofemoral contact forces
Medial and lateral contact forces as a function of time during the standing phase of gait and the loading phase of running and hopping:
- Walking and running over floor-embedded force plates (AMTI, Watertown, Massachusetts, USA)
- Vertical and horizontal single-leg countermovement jumps with take-off and landing on a force platform.
MSK modelling and Statistical Parametric Mapping (SPM) analysis will be used to provide a comprehensive understanding of the loading characteristics throughout the stance phase of gait and during the landing phases of each movement
Measured: The participant are tested once, as this is a cross-sectional study, 9 months to 2 years after ACLR
Secondary outcomes (4)
Patellofemoral contact forces
Walking, running and hopping - same as described for the Tibiofemoral contact forces.
Measured: The participant are tested once, as this is a cross-sectional study, 9 months to 2 years after ACLR
Quadriceps and hamstring isokinetic muscle strength tests
Maximal Isokinetic leg extension and flexion strength in a dynamometer (HUMAC Norm, CSMi, Stoughton, MA, USA) at 60°/s
Measured: The participant are tested once, as this is a cross-sectional study, 9 months to 2 years after ACLR
Leg press strength/power test
Seated leg press strength test: a Keiser Air300 horizontal pneumatic device with an A420 software (KeiserSport).
The seat position is adjusted for each participant to result in approximately 90° of knee flexion. Participants will extend both legs with maximal effort for each repetition during the 10-repetition protocol. Maximum power and maximal force from the force-velocity profile of each leg will be used for further analysis
Measured: The participant are tested once, as this is a cross-sectional study, 9 months to 2 years after ACLR
Voluntary quadriceps muscle activation test
The interpolated twitch technique (ITT) is used to evaluate voluntary muscle activation. Two percutaneous surface stimulation electrodes are placed over the distal and proximal parts of the quadriceps muscle belly
Measured: The participant are tested once, as this is a cross-sectional study, 9 months to 2 years after ACLR
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2025
- Study start19 Sep 2024
- Primary completionApr 2025 (estimated)
- Study completionJul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anterior Cruciate Ligament InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- May Arna Risberg
- Sponsor type
- University, hospital or other
- Collaborators
- Helse-Bergen HF, Oslo University Hospital
- Responsible party
- Sponsor-investigator, May Arna Risberg, Norwegian School of Sport Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06892899
- Sponsor's protocol ID
- REK sør-øst C #644970
- Acronym
- ExeLoadBioPTOA
- Status last verified
- Sep 2024
- First submitted
- 8 Feb 2025
- Last updated
- 25 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: As this is also a feasibility and pilot study. The PI, the co-PIs and the Scientific Advisory board will discuss this.
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reducing the Burden of Post-traumatic Knee Osteoarthritis Targeting Persistent Abnormal Joint Loading and Quadriceps Muscle Dysfunctions in Young Adults With ACL Injury - a Pilot and Feasibility Study
- ClinicalTrials.gov ID
- NCT06892899
- Acronym / sponsor ID
- ExeLoadBioPTOA / REK sør-øst C #644970
- Conditions
- Anterior Cruciate Ligament Injury, Quadriceps Dysfunction, Knee Joint Loading, Anterior Cruciate Ligament Reconstruction, Risk Factors
- Keywords
- knee injury, anterior cruciate ligament injury, knee joint loading, quadriceps muscle strength, quadriceps muscle function, post-traumatic knee osteoarthritis, risk factors, prevention
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- May Arna RisbergUniversity, hospital or other
- Collaborators
- Helse-Bergen HF, Oslo University Hospital
- Study start
- 19 Sep 2024 (actual)
- Primary completion
- Apr 2025 (estimated)
- Study completion
- Jul 2025 (estimated)
- First posted
- 25 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
FROM RISK FACTORS TO THE PREVENTION OF LONG-TERM CONSEQUENCES AFTER CRUCIATE LIGAMENT INJURY (ACL injury) - This is a research project where we seek new knowledge about why some people have a high risk and others a low risk of developing long-term consequences such as persistent pain, thigh muscle dysfunctions and osteoarthritis after ACL surgery. Through more knowledge about risk factors for persistent pain, thigh muscle dysfunctions, and, in the long term, osteoarthritis, we have a greater opportunity to tailor preventive treatment measures to the individual.
We know that a subgroup of those who have undergone ACL surgery does not regain the normal function of the quadriceps muscle, that it does not become as strong as it used to or not quite the same as on the other healthy side. Some may notice this very well, others may not notice as much in the short term. We know that quadriceps dysfunctions can affect the biomechanical joint loading in your knee and can be a contributing risk factor to developing long-term consequences such as persistent pain, thigh muscle function and osteoarthritis after ACL injury.
We have methods to measure joint loading conditions in the knee and to identify changes in the cartilage, in the underlying bone tissue of the knee joint, and to measure various aspects of quadriceps muscle strength and dysfunctions.
In this study, we want to develop new knowledge about whether there is a difference in knee joint loading conditions and quadriceps muscle function between those who have low risk and those with a higher risk of developing post-traumatic osteoarthritis and whether there is an association between joint loading conditions in the knee after ACL surgery and quadriceps muscle function and symptoms.
Detailed description
The main risk factors for knee OA disease are well-known: joint injuries and obesity. For those with ACL injury, systematic reviews have reported between 4 to 6 times increased risk of developing OA after ACL injury (PTOA). The following risk factors have been identified for PTOA in a recent systematic review by our OPTIKNEE group: ACL injury with concomitant injuries (meniscus and cartilage injuries), re-injuries after ACL injury, long-lasting quadriceps dysfunction, and inflammation after joint injury.
A better understanding of mechanisms to stratify the patients into different subgroups based on risk factors is critical. The mechanisms driving OA disease development are known to be 1) mechanical and 2) inflammatory. The mechanisms leading to PTOA combine mechanical, biological, structural, and neuromuscular factors.
Mechanical stress with persistent abnormal joint loading is an undisputed mechanism driving OA disease development. Altering joint mechanics (underloading and overloading) after ACL injury and reconstruction (ACLR) can lead to uneven stress and changes in stress across the articular cartilage of the joint surfaces, contributing to abnormal joint function and muscular dysfunction over time.
Whether such persistent abnormal knee joint loading patterns differ between individuals categorized as high risk compared to those at low risk of PTOA has not been investigated.
We do not understand the main drivers of the shifts in joint loading (underloading or overloading) or biochemical changes and whether this knowledge can be translated into developing joint-loading therapeutic interventions. However, we do know that quadriceps muscle weakness is a modifiable risk factor for non-traumatic OA and PTOA. ACL injury has shown a decline in quadriceps muscle function, which mimics ageing, known as sarcopenia. Quadriceps muscle dysfunction persists for some individuals for several years after ACLR, even after the cessation of structured rehabilitation, and has been questioned if it ever returns to normal. Despite decades of high-quality rehabilitation, normalizing quadriceps function in all ACL-injured and reconstructed patients remains unsolved.
This study has an overall aim of understanding more of the mechanisms for abnormal knee joint loading and quadriceps muscle dysfunctions in individuals at high- compared to low-risk PTOA (those with concomitant injuries and persistent symptoms compared to those with isolated ACL injury).
This cross-sectional study includes 40 participants 9 months to 2 years after ACLR with an extensive test-protocol of biomechanical-, neuromuscular- and biological assessments and tests. Hence, it is also a feasibility study for a planned randomized controlled trial of the effect of joint-loading therapeutic interventions on changes in knee joint loading for those at risk of developing PTOA. Furthermore, a sample of 40 individuals will be included to investigate primary outcomes' mean and standard deviation needed to calculate sample size for future randomized controlled trials.
Specific aims for the cross-sectional study are:
- Investigate knee joint loading during gait, running and hopping, cellular, morphological, muscle inhibition and strength of the quadriceps muscle, and inflammatory knee joint markers in individuals who are 9 months to 2 years after an ACLR.
- Characterize biomechanical, neuromuscular, and inflammatory factors in individuals classified as high-risk (concomitant injuries, persistent symptoms) for developing PTOA compared to those classified as low-risk (isolated ACL injury and no or minimal knee pain).
- Explore the associations between abnormal knee joint loading, quadriceps muscle dysfunctions, and inflammatory markers in the knee joint 9 months to 2 years after ACLR
- Describe the feasibility of the study regarding the recruitment of an extensive test-protocol
- A pilot study for a future mechanistic RCT on the efficacy of a muscle- and joint-loading therapeutic exercise program on changes in knee joint loading and on surrogate outcomes of PTOA.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group 1: isolated injury | – | –Group 2: combined injuries (concomitant injuries) |
Who may qualify
- Ages
- 16 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Participants will be recruited through the Norwegian Knee Ligament Registry (NKLR). Established in 2004, its current data show that between 1800 and 2000 individuals go through ACL reconstruction annually in Norway. The NKLR includes nationwide data in Norway with >90% coverage for surgical data.
Key inclusion criteria (6 listed)
- Unilateral ACL injury and ACLR (≤ one year between injury and surgery)
Key exclusion criteria (5 listed)
- Above 40 years and below 16 years of age
- Previous ACL injury (re-rupture of graft or an ACL injury more than one year between injury and surgery)
- MCL/LCL grade 3 injuries
- Other lower extremity injuries less than one year before inclusion, or previous inflammatory arthropathy or systemic infection or inflammation
- Participants with bilateral ACL injuries
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Tibiofemoral contact forces
Time frame: The participant are tested once, as this is a cross-sectional study, 9 months to 2 years after ACLR
Medial and lateral contact forces as a function of time during the standing phase of gait and the loading phase of running and hopping: * Walking and running over floor-embedded force plates (AMTI, Watertown, Massachusetts, USA) * Vertical and horizontal single-leg countermovement jumps with take-off and landing on a force platform. MSK modelling and Statistical Parametric Mapping (SPM) analysis will be used to provide a comprehensive understanding of the loading characteristics throughout the stance phase of gait and during the landing phases of each movement
4 secondary outcomes
Patellofemoral contact forces
Time frame: The participant are tested once, as this is a cross-sectional study, 9 months to 2 years after ACLR
Quadriceps and hamstring isokinetic muscle strength tests
Time frame: The participant are tested once, as this is a cross-sectional study, 9 months to 2 years after ACLR
Leg press strength/power test
Time frame: The participant are tested once, as this is a cross-sectional study, 9 months to 2 years after ACLR
Voluntary quadriceps muscle activation test
Time frame: The participant are tested once, as this is a cross-sectional study, 9 months to 2 years after ACLR
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2025.
- Individual participant dataSharing planned: Undecided. As this is also a feasibility and pilot study. The PI, the co-PIs and the Scientific Advisory board will discuss this.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anterior Cruciate Ligament Injury and Quadriceps Dysfunction, run by May Arna Risberg at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tibiofemoral contact forces (time frame: The participant are tested once, as this is a cross-sectional study, 9 months to 2 years after ACLR). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2025.