Longitudinal Assessment of Cartilage Injury and Remodeling After Anterior Cruciate Ligament Rupture and Reconstruction:

Study Overview
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Brief Summary
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The proposed study will establish novel relationships between intra-articular mesenchymal stem cell (MSC) recruitment, synovial inflammation, biomarkers of cartilage degeneration and joint inflammation, clinical patient factors, and downstream alterations in cartilage composition and morphology to provide novel insights into the pathoetiology of post-traumatic osteoarthritis (PTOA) after ACL injury and reconstruction. The study aims to enroll N=38 total patients with primary, isolated rupture to their anterior cruciate ligament (ACL), who have agreed to participate in the study and who will undergo primary surgical reconstruction by an orthopaedic physician at our two sites. Patients will undergo baseline magnetic resonance imaging (MRI), baseline clinical evaluation, and undergo a baseline blood draw. Subsequent imaging and clinical evaluations will be longitudinally performed at several postoperative timepoints up to 12 months postoperatively.

Detailed Description
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Overall Study Design: This is a prospective, longitudinal cohort study of patients undergoing primary ACL reconstruction following ACL rupture. Surgical treatment and treatment timelines do not deviate from the national and international standards of care. Enrolled patients for study participation will undergo assessments involving blood, urine, and synovial fluid collection, clinical evaluation involving questionnaires and joint laxity testing, and MRI analysis. Patient Selection and Enrollment: The participating physicians at each site will identify potential subjects from their clinics' patients according to the inclusion/exclusion criteria listed below. Based on surgical volumes at both sites, patients generally undergo ACL reconstruction 8-12 weeks after initial screening. In the preoperative timeframe, all patients will undergo standard physical therapy to address pain, swelling, and motion deficits, as is standard of care at both institutions. Arthroscopic ACL reconstruction will be performed by Dr. Bedi at the University of Michigan, by Professor Ao at Peking University, and by 5 additional surgeons at Peking University. All surgeons will utilize a standardized single-bundle technique with a hamstring or bone-patellar tendon-bone autograft.

Official Title
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Longitudinal Assessment of Cartilage Injury and Remodeling After Anterior Cruciate Ligament Rupture and Reconstruction: A Correlational Study of Synovial Inflammation, Functional Imaging, Clinical Outcomes, and Cartilage Biomarkers

Conditions
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ACL - Anterior Cruciate Ligament Rupture, ACL Injury, Healthy

Intervention / Treatment
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* Procedure: Anterior cruciate ligament reconstruction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Isolated, traumatic primary anterior cruciate ligament rupture requiring surgical reconstruction Surgical reconstruction performed using a single-bundle technique utilizing an autograft No history of ipsilateral traumatic knee injury or fracture No evidence of Posterior Cruciate Ligament injury or more than grade 1 injury to the Medial or Lateral Collateral Ligament Exclusion Criteria: Body Mass Index < 18.5 or >35 - Injury occurred longer than 4 weeks before enrollment Intra-articular steroid injection within 3 months of injury Chondral defects greater than 3 cm2 or Outerbridge grade II or higher lesions Pregnant women as they are not eligible for surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ACL Tear<br>Patients with ACL tears | Procedure: Anterior cruciate ligament reconstruction<br>* Primary surgical reconstruction of the rupture anterior cruciate ligament<br>|
| Healthy Subjects<br>Healthy subjects | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Articular cartilage surface roughness | One-year change in articular cartilage surface roughness based on quantitative morphological assessment with 3D MRI. | Baseline (preop), 12 months | 
| Change in Serum Cartilage Oligomeric Matrix Protein (COMP) concentration | One-year change in the serum concentration of COMP, a biomarker of articular cartilage degeneration. | Baseline (preop), 12 months | 
| Change in International Knee Documentation Committee (IKDC) score | One year change in IKDC, a patient-reported outcome measure specific to knee injuries. | Baseline (preop), 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in quantitative T2 mapping and T1rho mapping relaxation times from MRI. |  | Baseline (preop), 12 months | 
| Change in concentration of biomarkers of inflammation and cartilage metabolism. |  | Baseline (preop), 12 months | 
| Change in patient-reported outcome measures |  | Baseline (preop), 12 months | 
| Change in knee laxity | Knee laxity will be measured with KT-2000 testing | Baseline (preop), 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteers, ACL (Anterior Cruciate Ligament) tear