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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03497780
• Other study ID #: HUM00137279
• Status: Terminated
• Start date: November 8, 2018
• Est. completion date: March 25, 2021

Study information

• Verified date: March 2023
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: March 25, 2021
• Est. primary completion date: March 25, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• ACL - Anterior Cruciate Ligament Rupture
• ACL Injury
• Anterior Cruciate Ligament Injuries
• Healthy
• Rupture
• Wounds and Injuries

Intervention

Procedure:
• Anterior cruciate ligament reconstruction
Primary surgical reconstruction of the rupture anterior cruciate ligament

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	Peking University Health Science Center

Country where clinical trial is conducted

United States, 

Outcome

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