Cartilage Injury and Remodeling After ACL Rupture and Reconstruction: Functional Imaging and Biomarkers

Longitudinal Assessment of Cartilage Injury and Remodeling After Anterior Cruciate Ligament Rupture and Reconstruction: A Correlational Study of Functional Imaging and Biomarkers

The proposed study will establish novel relationships between intra-articular 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 PTOA after ACL injury and reconstruction.

Study Overview

• Status: Recruiting
• Conditions: Anterior Cruciate Ligament Injuries
• Intervention / Treatment: Procedure: ACL reconstruction

Detailed Description

In efforts to study the pathoetiology of post-traumatic osteoarthritis (PTOA), we propose a collaborative, prospective cohort study of 38 patients undergoing primary anterior cruciate ligament (ACL) reconstruction after ACL rupture. We will assess the longitudinal progression of patient-reported outcomes, knee laxity, MRI-based articular cartilage morphology and composition, and serum-borne biomarkers of cartilage degeneration up to 1 year of follow-up. Furthermore, stem cell mobilization, chemokine and pro-inflammatory cytokine concentrations, and inflammatory cell recruitment into synovial tissue will be measured from intraoperatively-collected samples. We will perform mixed multivariate linear regression modeling to elucidate potentially novel relationships between patient demographics, anatomy, biological factors, and downstream alterations in articular cartilage morphology and composition. We request $200,000 in funding over a two-year duration.

• Study Type: Observational
• Enrollment (Anticipated): 76

Contacts and Locations

• Study Contact: Name: yanfang jiang, MSc.; Phone Number: 15011420759; Email: anthea_jiang@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Recruiting
      • Peking University Third Hospital
      • Contact: yanfang jiang, MSc.; Phone Number: 15011420759; Email: anthea_jiang@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

Inclusion Criteria:

• - Males and females, aged 18 - 30 years
• 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 PCL injury or more than grade 1 injury to the MCL or LCL

Exclusion Criteria:

• - BMI < 18.5 or >35 kg/m2
• 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Volunteers; Volunteers were healthy people without ACL rupture
Patients with ACL Rupture; All patients will undergo a standardized single-bundle technique with a hamstring or bone-patellar tendon-bone autograft.	Procedure: ACL reconstruction; All patients will undergo a standardized single-bundle technique with a hamstring or bone-patellar tendon-bone autograft.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objectives measure of knee stability	Knee stability (anterior-posterior laxity) will be measured utilizing the KT-2000 arthrometer, based on the side-to-side difference (SSD) observed between the injured and the healthy, contralateral knee. Subjects will be tested at 90 days, 180 days, and 1 year after surgery, with maximum manual force performed at 30 and 90 degrees of knee flexion.	3 months, 6 months, 12 months
COMP	Cartilage Biomarker Analysis;	12 months after operation
Interleukin-1	Chemokines and Pro-Inflammatory Cytokines in Synovial Fluid;	12 months after operation
MMP-1	Soft Tissue Protease and Protease Inhibitor Analysis in Synovial Fluid	12 months after operation
colony-forming units (CFU)	The CFU assay is a common means of analyzing MSC concentration in bodily fluids	12 months after operation
Cartilage morphology	Quantitative MRI of cartilage morphology	12 months after operation
Magnetic resonance imaging	Quantitative MRI of Cartilage Composition	12 months after operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tegner Activity Scale	knee evaluation are commonly used to document a patient's activity level	12 months after operation
Lysholm Knee Scale	knee evaluation are commonly used to document a patient's functional outcomes	12 months after operation
International Knee Documentation Committee (IKDC) subjective Scale	knee evaluation are commonly used to document a patient's functional outcomes	12 months after operation

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Collaborators: University of Michigan
• Investigators: Study Director: yingfang ao, M.D., Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: June 27, 2021
• First Submitted That Met QC Criteria: July 12, 2021
• First Posted (Actual): July 21, 2021

Study Record Updates

• Last Update Posted (Actual): July 21, 2021
• Last Update Submitted That Met QC Criteria: July 12, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Leg Injuries; Knee Injuries; Wounds and Injuries; Rupture; Anterior Cruciate Ligament Injuries
• Other Study ID Numbers: M2017401

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