Clinical trial NCT04970706: Cartilage Injury and Remodeling After ACL Rupture and Reconstruction: Functional Imaging and Biomarkers
Official title: Longitudinal Assessment of Cartilage Injury and Remodeling After Anterior Cruciate Ligament Rupture and Reconstruction: A Correlational Study of Functional Imaging and Biomarkers
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Anterior Cruciate Ligament Injuries
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
Collaborators: name: University of Michigan
First posted: 2021-07-21
Enrollment: 76
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: 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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objectives measure of knee stability
timeFrame: 3 months, 6 months, 12 months
measure: COMP
timeFrame: 12 months after operation
measure: Interleukin-1
timeFrame: 12 months after operation
measure: MMP-1
timeFrame: 12 months after operation
measure: colony-forming units (CFU)
timeFrame: 12 months after operation
measure: Cartilage morphology
timeFrame: 12 months after operation
measure: Magnetic resonance imaging
timeFrame: 12 months after operation
Secondary outcomes:
measure: Tegner Activity Scale
timeFrame: 12 months after operation
measure: Lysholm Knee Scale
timeFrame: 12 months after operation
measure: International Knee Documentation Committee (IKDC) subjective Scale
timeFrame: 12 months after operation
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking university third hospital
state: Beijing
Study officials:
affiliation: Peking University Third Hospital
name: yingfang ao, M.D.
role: STUDY_DIRECTOR
References: