Post-Traumatic Knee Osteoarthritis Following Anterior Cruciate Ligament Reconstruction

Profiling of Abnormal Knee Joint Loading to Reduce Risk of Post-Traumatic Knee Osteoarthritis Following Anterior Cruciate Ligament Reconstruction

The purpose of this trial is to define knee joint pathomechanics (KJPM) in the first 2 years after ACL reconstruction (ACLR) and relate these KJPM with changes in articular cartilage morphology and quality.

Study Overview

• Status: Recruiting
• Conditions: Anterior Cruciate Ligament Injuries; Post-Traumatic Osteoarthritis of Knee
• Intervention / Treatment: Other: Imaging - magnetic resonance imaging (MRI); Other: Blood sampling; Other: Assessment of functionality and strength; Other: Activity monitoring; Other: Imaging - x-ray scan (RX); Behavioral: Questionnaires

Detailed Description

This research project is a longitudinal prospective study. The investigators aim to define the KJPM longitudinally in the first 2 years following ACLR. The investigators relate these KJPM, combined with the cumulative mechanical exposure, to changes in articular cartilage/joint surface morphology and quality. To investigate the loading pattern on the knee joint, daily activities like walking, running and climbing stairs will be performed by the participants.

The overall goal of this research project is to investigate whether KJPM are related with early cartilage degeneration. This is a first major step towards reducing the risk for post-ACLR onset of Post-Traumatic Knee Osteoarthritis (PTOA).

Two work packages (WP) can be separated, that each have a separate aim:

WP1: The first aim of this WP (WP1.A) is to profile longitudinal changes in knee contact forces (KCFs) and knee contact pressure (KCP) distribution of the articular cartilage in the first 2 years following ACLR. Second, in WP1.B, the investigators will identify multivariate proxies of KCFs (and KCP) to improve clinical translation (for example by facilitating the development of prognostic tools for verifying KJPM in real life).

WP2: the second aim is to establish the relationship between KJPM at different time points following ACLR and (changes in) articular cartilage morphology and quality (WP2.A). Furthermore, the investigators will compare the biomechanical profile of "fast PTOA progressors" with "fast non-traumatic early osteoarthritis progressors" (WP2.B).

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Sabine Verschueren, PhD; Phone Number: 0032 16 32 90 70; Email: sabine.verschueren@kuleuven.be

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3001
      • Recruiting
      • Faculty of Kinesiology and Rehabilitation Sciences
      • Contact: Sabine Verschueren, Prof.; Phone Number: +32 16 32 90 70; Email: sabine.verschueren@kuleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult patients up until 35 years old with an ACL reconstruction (recruited at the outpatient clinic) Healthy controls (community sample recruited)

Description

Inclusion Criteria (healthy volunteers):

• Age: 18-35 years
• No previous anterior cruciate ligament (ACL) injury
• Body Mass Index (BMI) between 18-30
• Regular physical activity (active during work or practicing sports regularly)
• Signed informed consent to participate

Exclusion Criteria (healthy volunteers):

• Major injuries to the lower extremities with absence from sports or daily life activities longer than 2 weeks or that required surgery, less than 6 months before participation
• Pre-existing arthritic disease including inflammatory or infectious arthritis

Inclusion Criteria (ACL patients):

• Age: 18-35 years
• ACL tear which is recently reconstructed or will be reconstructed after enrollment in the current study (the reconstruction will take place within 6 months after injury) with a Hamstring autograft
• BMI between 18-30
• Regular physical activity (active during work or practicing sports regularly)
• Signed informed consent to participate

Exclusion Criteria (ACL patients):

• Major injuries to the lower extremities with absence from sports or daily life activities longer than 2 weeks or that required surgery, less than 6 months before participation
• Pre-existing arthritic disease including inflammatory or infectious arthritis
• Image based confirmation of local cartilage lesion grade 4 or major cartilage damage (Kellgren & Lawrence > 2)
• Medial collateral ligament damage (> grade 2)
• Intra-articular knee fractures
• Menisectomy with <80% remnant

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients undergoing unilateral Anterior Cruciate Ligament Reconstruction (ACLR); 4 - 5 visits: Clinical examination, magnetic resonance imaging (MRI), 3D motion analysis, Strength assessment, EOS radiography (full leg X-ray scan), X-ray scan knee, Blood sample, Questionnaires and Activity monitoring.	Other: Imaging - magnetic resonance imaging (MRI); MRI knee - not standard of care; Other: Blood sampling; blood sample taken and analysis - not standard of care; Other: Assessment of functionality and strength; Movements and posture Analysis Laboratory Leuven measurement (3D motion analysis) and Biodex measurement - not standard of care; Other: Activity monitoring; Actigraph measurement- not standard of care; Other: Imaging - x-ray scan (RX); RX Knee and EOS radiography full leg - not standard of care; Behavioral: Questionnaires; Patient reported outcomes (PROMS)
Healthy controls without previous Anterior Cruciate Ligament (ACL) injury; 2 visits: Clinical examination, MRI, 3D motion analysis, Strength assessment, EOS radiography, X-ray scan knee, Blood sample, Questionnaires and Activity monitoring.	Other: Imaging - magnetic resonance imaging (MRI); MRI knee - not standard of care; Other: Blood sampling; blood sample taken and analysis - not standard of care; Other: Assessment of functionality and strength; Movements and posture Analysis Laboratory Leuven measurement (3D motion analysis) and Biodex measurement - not standard of care; Other: Activity monitoring; Actigraph measurement- not standard of care; Other: Imaging - x-ray scan (RX); RX Knee and EOS radiography full leg - not standard of care; Behavioral: Questionnaires; Patient reported outcomes (PROMS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee contact forces (KCF) will be measured using a 3D motion analysis system	The goal is to profile longitudinal changes in KCFs of the articular cartilage. Using a 3D motion analysis system (Vicon, Oxford Metrics, UK), marker trajectories, ground reaction forces (AMTI, MA, USA) and muscle activations (Wireless EMG Cometa, Italy) will be measured. Subsequently a musculoskeletal modelling workflow in OpenSim will be used to calculate Knee contact forces (KCF) of the articular cartilage.	2 years
Knee contact pressures (KCP) will be measured using a 3D motion analysis system	Using a 3D motion analysis system (Vicon, Oxford Metrics, UK), marker trajectories, ground reaction forces (AMTI, MA, USA) and muscle activations (Wireless EMG Cometa, Italy) will be measured. Subsequently a musculoskeletal modelling workflow in OpenSim will be used to calculate Knee contact pressures (KCP) of the articular cartilage.	2 years
The patient-specific cartilage thickness distribution.	The cartilage thickness will be measured using the semi-automatic segmentation from the high-resolution images (3D-FSE) of the tibiofemoral cartilage.	2 years
The patient-specific tibiofemoral cartilage quality.	The cartilage quality will be examined using compositional measures such as T1rho, T1p and T2 relaxation time.	2 years

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: KU Leuven
• Investigators: Principal Investigator: Sabine Verschueren, PhD, KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2021
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: January 26, 2023
• First Submitted That Met QC Criteria: December 28, 2023
• First Posted (Estimated): January 11, 2024

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: December 28, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: PTOA; ACLR; Anterior cruciate ligament injury; post-traumatic knee osteoarthritis; KJPM; knee joint pathomechanics
• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Knee Injuries; Osteoarthritis; Osteoarthritis, Knee; Anterior Cruciate Ligament Injuries
• Other Study ID Numbers: S65257

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The full pseudonymized dataset will be made available in RDR (KU Leuven tool) and will be shared upon written request after approval of the PI, for clearly defined research purposes.

Pseudonymized data and documentation will be available on request in RDR.

Data sharing can only happen when it is not for commercial use or it doesn't reveal the identity of the participants. Data will always be pseudonimized.

• IPD Sharing Time Frame: Upon publication of the research results and for an undetermined period of time.
• IPD Sharing Access Criteria: Data sharing can only happen when it is not for commercial use or it doesn't reveal the identity of the participants. Data will always be pseudonimized. A written request has to be submitted to the PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No