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

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.

Study Overview

• Status: Recruiting
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Biological: Knee aspiration + UCB-MSCs; Other: Knee aspiration

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Matic Kolar, MD; Phone Number: +386 (0)40198367; Email: matic.kolar@kclj.si

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Recruiting
    • University Medical Centre Ljubljana
    • Contact: Matic Kolar, MD; Phone Number: +386 40 198 367; Email: matic.kolar@kclj.si

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; Knee aspiration and the application of UCB-MSCs	Biological: Knee aspiration + UCB-MSCs; Knee aspiration and the application of cultered allogeneic umbilical cord blood-derived mesenchymal stromal stem cells (UCB-MSCs).
Active Comparator: Control group; Only knee aspiration, without the application of UCB-MSCs	Other: Knee aspiration; Knee aspiration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Serious Adverse Events (SAE)	Serious adverse events (SAE) are defined as any complication requiring hospitalization.	Until 1 month after the application of UCB-MSCs

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana
• Collaborators: Blood Transfusion Centre of Slovenia
• Investigators: Principal Investigator: Matej Drobnič, MD, PhD, University Medical Centre Ljubljana; Principal Investigator: Urban Švajger, MPharm, PhD, Blood Transfusion Centre of Slovenia

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: July 23, 2023
• First Submitted That Met QC Criteria: October 5, 2023
• First Posted (Actual): October 11, 2023

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Osteoarthritis; Knee; Allogeneic; Mesenchymal stem cells
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: UMC Ljubljana

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No