Clinical trial NCT03497780: Longitudinal Assessment of Cartilage Injury and Remodeling After Anterior Cruciate Ligament Rupture and Reconstruction:
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
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: ACL - Anterior Cruciate Ligament Rupture
ACL Injury
Healthy
Keywords: Healthy Volunteers
ACL (Anterior Cruciate Ligament) tear
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Peking University Health Science Center
First posted: 2018-04-13
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Community sample

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Articular cartilage surface roughness
timeFrame: Baseline (preop), 12 months
measure: Change in Serum Cartilage Oligomeric Matrix Protein (COMP) concentration
timeFrame: Baseline (preop), 12 months
measure: Change in International Knee Documentation Committee (IKDC) score
timeFrame: Baseline (preop), 12 months
Secondary outcomes:
measure: Change in quantitative T2 mapping and T1rho mapping relaxation times from MRI.
timeFrame: Baseline (preop), 12 months
measure: Change in concentration of biomarkers of inflammation and cartilage metabolism.
timeFrame: Baseline (preop), 12 months
measure: Change in patient-reported outcome measures
timeFrame: Baseline (preop), 12 months
measure: Change in knee laxity
timeFrame: Baseline (preop), 12 months
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
References: