Mechanisms of Treatment Effects Using Cultured, Allogeneic Mesenchymal Stromal Stem Cells (MSCs) in Knee Osteoarthritis

Osteoarthritis, Knee Clinical Trial

Official title:

Mechanisms of Treatment Effects Using Cultured, Allogeneic Mesenchymal Stromal Stem Cells (MSCs) in Knee Osteoarthritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06078059
• Other study ID #: UMC Ljubljana
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2022
• Est. completion date: March 31, 2025

Study information

• Verified date: October 2023
• Source: University Medical Centre Ljubljana
• Contact: Matic Kolar, MD
• Phone: +386 (0)40198367
• Email: matic.kolar[@]kclj.si
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to pharmacologically evaluate the effects of culturued allogeneic umbilical cord blood-derived mesenchymal stromal stem cell (UCB-MSCs) in the treatment of end-stage knee osteoarthritis (Kellgren-Lawrence grade 4) with the analysis of soluble biomarkers and expression of key genes, as well as the evaluation of clinical outcomes with patient-reported outcome measures (PROMs) and recording of potential complications.

Patients will be randomized in the intervention and control groups. In both groups, the knee aspiration will be performed 4-6 weeks prior to the knee arthroplasty to analyse baseline synovial fluid characteristics. The intervention group will receive the injection of UCB-MSCs. All patients will complete PROMs questionnaires and maintain a pain diary on visual analogue scale (VAS) at home until the surgery. On the day of admission to hospital for knee arthroplasty, the same questionnaires will be administered again. During the operative procedures, the samples of synovial fluid, synovial membrane and resected cartilage will be obtained and analysed afterwards.

It is anticipated that the study results will contribute to elucidate the mechanisms of action of MSCs in the treatment of knee osteoarthritis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 31, 2025
• Est. primary completion date: November 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients with end-stage (Kellgren-Lawrence) knee osteoarthritis scheduled for knee arthroplasty

• Osteoarthritis of primary or post-traumatic etiology

Exclusion Criteria:

• Secondary arthritis of other etiology

• Rheumatic diseases

• Uncontrolled metabolic disorders

• Crystalopathies

• Coagulopathy

• Anticoagulant therapy

• Heart failure

• Renal failure

• Other conditions that may affect immune response or pose additional risk during cell application

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Biological:
• Knee aspiration + UCB-MSCs
Knee aspiration and the application of cultered allogeneic umbilical cord blood-derived mesenchymal stromal stem cells (UCB-MSCs).

Other:
• Knee aspiration
Knee aspiration

Locations

Country	Name	City	State
Slovenia	University medical centre Ljubljana	Ljubljana

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana	Blood Transfusion Centre of Slovenia

Country where clinical trial is conducted

Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Soluble biomarkers analysis with multiplex bead-based immunoassays Luminex in synovial fluid	Luminex assay is a type of immunoassay that precisely measures multiple analytes in one sample. It is a bead-based immunoassay that allows for multiplex detection of analytes simultaneously. Color-coded microspheres or beads are internally dyed with different proportions of red and infrared fluorophores that correspond to a distinct spectral signature or bead region. The quantification of multiple cytokines and other biomarkers in samples provides critical information about biological processes and diseases.	After sampling
Primary	Biomarkers analysis with Enzyme-linked immunosorbent assay (ELISA) in synovial fluid	Enzyme-linked immunosorbent assay (ELISA) is the main approach for the sensitive quantification of protein biomarkers in body fluids and is currently employed in clinical laboratories for the measurement of clinical markers. It also constitutes the main methodological approach for biomarker validation and further qualification.	After sampling
Primary	Quantitative real-time PCR (qRT-PCR) analysis of gene expression in chondrocytes and synoviocytes	Quantitative real-time PCR (qRT-PCR) is a major development of PCR technology that enables reliable detection and measurement of products generated during each cycle of PCR process. The detection of changes in fluorescence intensity during the reaction enables to follow the PCR reaction in real time. qRT-PCR is comprised of several steps: 1. RNA is isolated from target tissue/cells, 2. mRNA is reverse-transcribed to cDNA, 3. modified gene-specific PCR primers are used to amplify a segment of the cDNA of interest, following the reaction in real time, 4. the initial concentration of the selected transcript in a specific tissue or cell type is calculated from the exponential phase of the reaction.	After sampling
Secondary	Knee Injury and Osteoarthritis Outcome Score (KOOS)	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 of 0 indicating the worst possible knee symptoms and 100 indicating no knee symptoms.	4-6 prior to surgery and at admission
Secondary	Pain on Visual Analogue Scale (VAS)	The Visual Analogue Scale (VAS) measures pain intensity. The VAS consists of a 10cm line, with two end points representing 0 ('no pain') and 10 ('the worst pain imaginable').	4-6 prior to surgery and at admission
Secondary	EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaire	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.	4-6 prior to surgery and at admission
Secondary	EuroQol self-rated health on Visual Analogue Scale (EQ-VAS)	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.	4-6 prior to surgery and at admission
Secondary	Serious Adverse Events (SAE)	Serious adverse events (SAE) are defined as any complication requiring hospitalization.	Until 1 month after the application of UCB-MSCs