Biomaterials and Mesenchymal Stem/Stromal Cells in the Treatment of Knee Articular Surface Lesions

Knee Injuries Clinical Trial

Official title:

Biomaterials and Mesenchymal Stem/Stromal Cells in the Treatment of Knee Articular Surface Lesions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06078072
• Other study ID #: University Medical Centre
• Status: Completed
• Start date: September 1, 2022
• Est. completion date: October 31, 2023

Study information

• Verified date: October 2023
• Source: University Medical Centre Ljubljana
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this observational study is to evaluate the combined single-step approach with biomaterials and mesenchymal stem/stromal cells in the treatment of knee articular surface lesions. The clinical analysis of the treatment outcomes, regarding postoperative improvements and safety, is going to be accompanied with laboratory analysis of the intraoperatively applied cellular products. The main hypothesis are: (1) such combined single-step procedure significantly improves patients' functioning and quality of life; (2) this therapeutic approach is safe; (3) cellular parameters of the applied filtered bone marrow aspirate (fBMA) impact treatment outcomes, among other potential predictors. Researchers will compare subjective (questionnaire) and objective (clinical examination) status of patients before and after the operation, record any potential complications and perform regression analysis to assess the influence of potential predictors on postoperative improvements.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: October 31, 2023
• Est. primary completion date: August 31, 2023
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• informed consent
• patients treated with combined single-step procedure (scaffold and fBMA) for knee articular surface lesions, between January 2013 and December 2020
• symptomatic knee articular surface lesions (International cartilage repair society (ICRS) grades 3-4, size = 1.5 cm2) unresponsive to conservative treatment,
• only mild concomitant osteoarthritis (Kellgren-Lawrence grades 1-2)

Exclusion Criteria:

• patients that refuse to participate in the study
• non responders to the invitation to answer PROMs at the follow-up
• associated medical conditions (inflammatory, metabolic, neoplastic, etc.) that could directly handicap the musculoskeletal system or indirectly impact the quality of life

Related Conditions & MeSH terms

• Cartilage Injury
• Knee Injuries
• Osteochondral Defect
• Wounds and Injuries

Intervention

Procedure:
• Biomaterials augmented with mesenchymal stem/stromal cells
Combined single-step procedure of treating knee articular surface lesions with biomaterials (scaffolds) and mesenchymal stem cells (filtered bone marrow aspirate concentrate)

Locations

Country	Name	City	State
Slovenia	University medical centre Ljubljana	Ljubljana

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana

Country where clinical trial is conducted

Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Knee injury and Osteoarthritis Outcome Score (KOOS) subscale Pain postoperative improvement	Knee injury and Osteoarthritis Outcome Score (KOOS) assesses patients' pain (9 items), other symptoms (7 items), function in daily living (17 items), function in sport and recreation (5 items), and knee related quality of life (4 items). Scores range from 0 to 100 with a score 0 being the worst score and 100 indicating no impairment.; KOOS subscale Pain postoperative improvement will be calculated as difference between preoperative and postoperative scores at the final follow up.; Paired Student t test will be applied to compare preoperative and postoperative values of KOOS subscale Pain.	At least 24 months after the operation
Secondary	Knee injury and Osteoarthritis Outcome Score (KOOS) subscales postoperative improvements	Originally published in 1998, the Knee injury and Osteoarthritis Outcome Score (KOOS) assesses patient pain (9 items), other symptoms (7 items), function in daily living (17 items), function in sport and recreation (5 items), and knee related quality of life (4 items). Scores range from 0 to 100 with a score 0 being the worst score and 100 indicating no impairment.; KOOS subscales postoperative improvements will be calculated as differences between preoperative and postoperative scores at the final follow up. As secondary outcome measures will be calculated all KOOS subscales improvements, beside KOOS subscale Pain, which is determined as the primary outcome measure.; Paired Student t test will be applied to compare preoperative and postoperative values of all KOOS subscales.	At least 24 months after the operation
Secondary	Complications (SAE and GF)	Serious adverse events (SAE) are defined as any hospitalization or revision surgery (arthrofibrosis, synovitis, infection, hardware problem, pulmonary embolism, etc.), while graft failures (GF) as revision surgery to the lesion or confirmed indication for it. SAE will be further classified as related (arthrofibrosis, synovitis, graft hypertrophy/delamination, etc.) or unrelated (hardware removal, meniscus or ligament injuries, new cartilage lesions, pulmonary embolism, etc.) to the graft.	Recording until the final follow up (minimum 24 months after the operation)
Secondary	Cellular parameters of intraoperatively applied filtered Bone Marrow Aspirate (fBMA)	Samples for cell counting (100 µl), fibroblast colony forming units (CFU-F) assay (1-2 ml) and flow cytometry (1-2 ml) will be taken before and after BMA processing with filter-based separation device. The total nucleated cell (TNC) count will be determined by counting white blood cells with hematology analyzer COULTER® Ac·T diff2™ (Beckman Coulter, Fullerton, CA, USA). MSCs content will be estimated with flow cytometry (FACSCalibur, BD Biosciences, San Jose, CA, USA) by determining CD271+ and CD45-cells, and concomitant assessment of their viability using 7-amino-actinomycin D (7-AAD) dye. Also, the CFU-F assay, which is a functional assay for measuring the frequency of MSCs with the colony forming abilities, will be performed. Briefly, cells will be seeded at least in duplicates into well culture plates and cultured in standard conditions: 37 °C, 5% CO2. After 14 days, colonies containing = 50 fibroblastic cells will be manually counted under the stereomicroscope.	Finsihed in 14 days after the procedure
Secondary	Tegner Activity Scale (TAS) postoperative improvement	Tegner Activity Scale (TAS) is a one-item score that graded activity based on work and sports activities on a 11-level scale from 0 to 10. Zero represents disability because of the knee problems and 10 represents national or international level soccer.; TAS postoperative improvement will be calculated as difference between preoperative and postoperative scores at the final follow up.; Paired Student t test will be applied to compare preoperative and postoperative values of TAS.	At least 24 months after the operation
Secondary	European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L) postoperative improvement	EQ-5D-3L descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression . Each dimension has 3 levels: no problems, some problems, and extreme problems. The respondent is asked to indicate his or her health state by ticking the box that marks the most appropriate level of problems in each dimension. A unique health state can be described according to the responses to the 5 questions. Health states defined in this way may be converted into a single summary index by applying a formula that attaches values to each of the levels in each dimension. States can be converted to a single value where 1 is equivalent to full health and 0 to a state equivalent to death.; EQ-5D-3L postoperative improvement will be calculated as difference between preoperative and postoperative scores at the final follow up.; Paired Student t test will be applied to compare preoperative and postoperative values of EQ-5D-3L .	At least 24 months after the operation
Secondary	EuroQol Visual Analogue Scale (EQ-VAS) postoperative improvement	EQ-VAS records the patient's self-rated health on a vertical visual analogue scale from 0 to 100, where 0 represents the worst health state imaginable and 100 represents the best health state imaginable.; EQ-VAS postoperative improvement will be calculated as difference between preoperative and postoperative scores at the final follow up.; Paired Student t test will be applied to compare preoperative and postoperative values of EQ-VAS5.	At least 24 months after the operation
Secondary	Potential predictors (patients' demographics, medical history, joint and lesions' characteristics, surgical and cellular parameters) of the clinical outcomes (KOOS subscales, EQ-5D-3L, EQ-VAS, TAS)	Regression models will be used to assess the influence of proposed predictors (patients' demographics, medical history, joint and lesions' characteristics, surgical and cellular parameters) on the postoperative improvements in clinical outcome measures (KOOS subscales, EQ-5D-3L, EQ-VAS, TAS). Statistical analysis will be performed with SPSS (version 25.0; IBM, Chicago, IL, USA).	At the time of statistical analysis