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

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

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.

Study Overview

• Status: Terminated
• Conditions: Healthy; ACL Injury; ACL - Anterior Cruciate Ligament Rupture
• Intervention / Treatment: Procedure: Anterior cruciate ligament reconstruction

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 13

Contacts and Locations

• Study Contact: Name: Elizabeth Enselman, ATC; Phone Number: 734-615-0768; Email: esiblisk@med.umich.edu
• Study Contact Backup: Name: Jaimee Gauthier, BA; Phone Number: 734-647-0050; Email: jaimeeg@med.umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Community sample

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ACL Tear; Patients with ACL tears	Procedure: Anterior cruciate ligament reconstruction; Primary surgical reconstruction of the rupture anterior cruciate ligament
Healthy Subjects; Healthy subjects

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Peking University Health Science Center

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2018
• Primary Completion (Actual): March 25, 2021
• Study Completion (Actual): March 25, 2021

Study Registration Dates

• First Submitted: March 23, 2018
• First Submitted That Met QC Criteria: April 12, 2018
• First Posted (Actual): April 13, 2018

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: March 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Healthy Volunteers; ACL (Anterior Cruciate Ligament) tear
• Additional Relevant MeSH Terms: Leg Injuries; Knee Injuries; Wounds and Injuries; Rupture; Anterior Cruciate Ligament Injuries
• Other Study ID Numbers: HUM00137279

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No