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NCT Number: NCT07134244

Development of Computational Models to Predict the Short-, Medium- and Long-term Cartilage Degeneration and Pain for Patients With Early-stage Osteoarthritis or Anterior Cruciate Ligament Injury

Knee osteoarthritis is a complex condition, and selecting effective non-drug treatments like orthoses or exercise is often difficult and imprecise. This study will follow individuals with early-stage knee osteoarthritis or previous anterior cruciate ligament injury to develop computational models that predict cartilage degeneration and pain over time. The models will integrate data from medical imaging, movement analysis, muscle strength testing, pain assessments, questionnaires, and biomarkers to improve personalized treatment planning.

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Key information

Conditions

Osteoarthritis, Knee Anterior Cruciate Ligament Injuries Arthritis Joint Diseases Knee Injuries Leg Injuries Musculoskeletal Diseases Osteoarthritis Rheumatic Diseases Wounds and Injuries

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Aalborg University Hospital, Aalborg, North Denmark, Denmark

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

.3.1 ACL reconstruction group (n= 25) Inclusion criteria

  • Adults under 70 years
  • ACL injury within the last year and planned for ACL reconstruction at inclusion
  • Informed consent form signed Exclusion criteria (at inclusion)
  • Previous knee surgery before current knee trauma.
  • Severe ischemic or neurological sequelae.
  • BMI above 32.
  • Clinically significant joint disease (inflammatory or degenerative) to other joints than the ACL injured knee (according to the clinician).
  • Unsuitable for MRI (e.g. pacemaker or claustrophobia)
  • Participants not able to fit the MRI knee coil (Thigh circumference larger than 73.5 cm measured 10 cm above the kneecap and a maximum calf circumferences of 61.5 cm).
  • Drug addiction defined as the use of cannabis, opioids or other drugs as reported by the participant

ACL no reconstruction group (n= 25) Inclusion criteria

  • Adults under 70 years
  • ACL injury within the last year and with no plans for ACL reconstruction at inclusion
  • Informed consent form signed Exclusion criteria (at inclusion)
  • Previous knee surgery before current knee trauma.
  • Severe ischemic or neurological sequelae.
  • BMI above 32.
  • Clinically significant joint disease (inflammatory or degenerative) to other joints than the ACL injured knee (according to the clinician).
  • Unsuitable for MRI (e.g. pacemaker or claustrophobia)
  • Participants not able to fit the MRI knee coil (Thigh circumference larger than 73.5 cm measured 10 cm above the kneecap and a maximum calf circumferences of 61.5 cm).
  • Drug addiction defined as the use of cannabis, opioids or other drugs as reported by the participant

Early to moderate knee OA stage (n= 25) Inclusion criteria

  • Adults under 70 years
  • Diagnosis of knee OA (Kellgren Lawrence (KL) grade 1, 2 and 3 (Kohn et al., 2016). If there is no X-ray that is a maximum of 1 year old, a new one is taken.
  • Stress-related pain in the knee and knee stiffness
  • Informed consent form signed Exclusion criteria (at inclusion)
  • Previous knee surgery
  • Clinically significant joint disease (inflammatory or degenerative) of other joints than the knee at inclusion.
  • Severe ischemic or neurological sequelae in the lower extremities.
  • Clinically significant joint disease (inflammatory or degenerative) to other joints than the knees (according to the clinician).
  • BMI above 32.
  • Unsuitable for MRI (e.g., pacemaker or claustrophobia)
  • Participants not able to fit the MRI knee coil (Thigh circumference larger than 73.5 cm measured 10 cm above the kneecap and a maximum calf circumferences of 61.5 cm).
  • Drug addiction defined as the use of cannabis, opioids or other drugs as reported by the participant

Control groups (3 groups of 10 control participants matched for each of the patient groups, n=30) Inclusion criteria

  • Adults under 70 years
  • Informed consent form signed
  • No radiological changes on a knee x-ray (Arendt-Nielsen et al., 2015). Exclusion criteria (at inclusion)
  • Previous knee surgery
  • Self-reported Knee problems (pain, stiffness)
  • Clinically significant joint disease (inflammatory or degenerative) at inclusion.
  • Severe ischemic or neurological sequelae in the lower extremities.
  • BMI above 32.
  • Unsuitable for MRI (e.g., pacemaker or claustrophobia)
  • Participants not able to fit the MRI knee coil (Thigh circumference larger than 34.3-73.5 cm measured 10 cm above the kneecap and a maximum calf circumferences of 61.5 cm).
  • Drug addiction defined as the use of cannabis, opioids, or other drugs as reported by the participant

Treatment and study plan

Primary outcomes

  1. Change in Knee Cartilage Composition and Structure Assessed by Quantitative Magnetic Resonance Imaging

    Time frame: Data will be collected at three main time points: baseline, one-year follow-up, and three years follow-up. Additionally, a downscaled protocol will be used to follow the participants at 7- and 10 years follow-ups.

    Person-specific 3T MRI scans will be used to measure changes in knee cartilage, including T1ρ and T2 relaxation times and 3D geometry, as indicators of cartilage biochemical composition and structural integrity. Analyses will be used for predictive computational modeling of cartilage degeneration.

Secondary outcomes

  1. Knee Pain Intensity (Visual Analog Scale)

    Time frame: Baseline, 1-year, 3-year, 7-year, 10-year follow-up.

    Self-reported knee pain intensity using a 100-mm Visual Analog Scale anchored with "0 = no pain" and "100 = worst imaginable pain.

  2. Brief Pain Inventory Scores

    Time frame: Baseline, 1-year, 3-year, 7-year, 10-year follow-up.

    Severity and interference of pain over the past 24 hours, measured on a 0-10 scale using the Brief Pain Inventory questionnaire.

  3. Knee Injury and Osteoarthritis Outcome Score (KOOS)

    Time frame: Baseline, 1-year, 3-year, 7-year, 10-year follow-up.

    Self-administered questionnaire assessing pain, symptoms, activities of daily living, sport and recreation function, and knee-related quality of life. Scores range from 0 (no problems) to 4 (extreme problems) for each domain.

  4. Hospital Anxiety and Depression Scale (HADS) - Total Score

    Time frame: Baseline, 1-year, 3-year, 7-year, 10-year.

    14-item self-report scale assessing anxiety and depression symptoms. Total score range: 0-42; higher scores indicate worse symptoms.

  5. Pittsburgh Sleep Quality Index (PSQI) - Global Score

    Time frame: Baseline, 1-year, 3-year, 7-year, 10-year.

    19-item questionnaire assessing sleep quality over the past month. Global score range: 0-21; higher scores indicate poorer sleep quality.

  6. Pain Catastrophizing Scale (PCS) - Total Score

    Time frame: Baseline, 1-year, 3-year, 7-year, 10-year.

    13-item scale assessing catastrophic thinking related to pain. Total score range: 0-52; higher scores indicate greater pain catastrophizing.

  7. Short Form-12 Health Survey (SF-12) - Physical Component Summary (PCS) Score

    Time frame: Baseline, 1-year, 3-year, 7-year, 10-year.

    Summary measure of physical health-related quality of life. Score range: 0-100; higher scores indicate better physical health status.

  8. Short Form-12 Health Survey (SF-12) - Mental Component Summary (MCS) Score

    Time frame: Baseline, 1-year, 3-year, 7-year, 10-year.

    Summary measure of mental health-related quality of life. Score range: 0-100; higher scores indicate better mental health status.

  9. 40-Meter Fast-Paced Walk Test - Time

    Time frame: Baseline, 1-year, 3-year.

    Time to walk 40 meters at fastest safe pace. Measured in seconds; lower scores indicate better performance.

  10. 30-Second Chair Stand Test - Number of Repetitions

    Time frame: Baseline, 1-year, 3-year.

    Number of full stands from a seated position completed in 30 seconds. Higher scores indicate better performance.

  11. Stair Climb Test - Time

    Time frame: Baseline, 1-year, 3-year.

    Time taken to ascend a standard set of stairs. Measured in seconds; lower scores indicate better performance.

  12. Timed Up-and-Go (TUG) Test - Time

    Time frame: Baseline, 1-year, 3-year.

    Time to rise from a chair, walk 3 meters, turn, return, and sit. Measured in seconds; lower scores indicate better performance.

  13. 3D Motion Capture - Kinematic Parameters

    Time frame: Baseline, 1-year, 3-year.

    Joint angles and Movements patterns during movement, measured in degrees, using 3D motion capture.

  14. 3D Motion Capture - Kinetics Parameters

    Time frame: Baseline, 1-year, 3-year.

    Inverse dynamics calculated from movement patterns and force plates during activities, using 3D motion capture.

  15. Motion capture Surface Electromyography (EMG)

    Time frame: Baseline, 1-year, 3-year.

    Muscle activation amplitude from selected lower limb muscles, measured in microvolts (µV) and processed per SENIAM guidelines.

  16. Pressure Pain Detection Threshold

    Time frame: Baseline, 1-year, 3-year.

    Minimum pressure at which a sensation becomes painful, measured in kilopascals (kPa) using a computer-controlled cuff algometer. Higher values indicate reduced sensitivity to pain.

  17. Pressure Pain Tolerance Threshold

    Time frame: Baseline, 1-year, 3-year.

    Maximum pressure a participant can tolerate, measured in kilopascals (kPa). Higher values indicate greater pain tolerance.

  18. Temporal Summation of Pain

    Time frame: Baseline, 1-year, 3-year.

    Increase in pain intensity in response to repetitive stimulation, measured as change in pain rating on a 0-10 numeric rating scale. Higher scores indicate greater central sensitization.

  19. Conditioned Pain Modulation Effect

    Time frame: Baseline, 1-year, 3-year.

    Percentage change in pain rating during a conditioning stimulus, indicating efficiency of endogenous pain inhibition. Higher percentages indicate stronger pain inhibition.

  20. Plasma Protein Biomarker Concentrations - Inflammatory Markers

    Time frame: Baseline, 1-year, 3-year, 7-year, 10-year.

    Quantitative concentrations of inflammatory biomarkers in plasma using LC-MS/MS and high-multiplex immunoassays (Olink). Higher or lower values indicate changes in inflammatory status.

  21. Plasma Protein Biomarker Concentrations - Cartilage Metabolism Markers

    Time frame: Baseline, 1-year, 3-year, 7-year, 10-year.

    Quantitative concentrations of cartilage metabolism biomarkers in plasma. Higher or lower values indicate changes in cartilage turnover.

  22. Synovial Fluid Protein Biomarker Concentrations - Inflammatory Marker

    Time frame: Baseline, 1-year, 3-year, 7-year, 10-year.

    Quantitative concentrations of inflammatory biomarkers in synovial fluid

  23. Synovial Fluid Protein Biomarker Concentrations - Cartilage Metabolism Markers

    Time frame: Baseline, 1-year, 3-year, 7-year, 10-year.

    Quantitative concentrations of cartilage metabolism biomarkers in synovial fluid

Sponsors and collaborators

Lead sponsor

Aalborg University

Other

Collaborators

  • Aalborg University Hospital
  • Lund University
  • University of Eastern Finland

Registry information

Acronym: MathKOA

Important dates

Study start
2024
Primary completion
2035
Study completion
2036
First posted
Aug 21, 2025
Registry last updated
Aug 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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