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

NCT06078059 | Completed

• 1 other identifier: UMC Ljubljana
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Osteoarthritis, Knee

Keywords

Knee; Osteoarthritis; Mesenchymal stem cells; Allogeneic

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Knee Injury and Osteoarthritis Outcome Score (KOOS)

  4-6 prior to surgery and at admission

• Pain on Visual Analogue Scale (VAS)

  4-6 prior to surgery and at admission

• EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaire

  4-6 prior to surgery and at admission

• EuroQol self-rated health on Visual Analogue Scale (EQ-VAS)

  4-6 prior to surgery and at admission

• Serious Adverse Events (SAE)

  Until 1 month after the application of UCB-MSCs

Study Arms (2)

Intervention group

EXPERIMENTAL

Knee aspiration and the application of UCB-MSCs

Biological: Knee aspiration + UCB-MSCs

Control group

ACTIVE COMPARATOR

Only knee aspiration, without the application of UCB-MSCs

Other: Knee aspiration

Interventions

Knee aspiration + UCB-MSCs BIOLOGICAL

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

Intervention group

Knee aspiration OTHER

Knee aspiration

Control group

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with end-stage (Kellgren-Lawrence) knee osteoarthritis scheduled for knee arthroplasty
• Osteoarthritis of primary or post-traumatic etiology

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead
• Blood Transfusion Centre of Slovenia: collaborator

Study Sites (1)

University medical centre Ljubljana

Ljubljana, 1000, Slovenia

Location

Related Publications (1)

• Svajger U, Kolar M, Kobold A, Drobnic M. Mechanisms of treatment effects using allogeneic, umbilical cord-derived mesenchymal stromal stem cells (MSCs) in knee osteoarthritis: a pharmacological clinical study protocol. Trials. 2024 Aug 13;25(1):533. doi: 10.1186/s13063-024-08360-x.

  PMID: 39135209 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Matej Drobnič, MD, PhD

  University Medical Centre Ljubljana

  PRINCIPAL INVESTIGATOR

• Urban Švajger, MPharm, PhD

  Blood Transfusion Centre of Slovenia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2023
• First Posted: October 11, 2023
• Study Start: November 1, 2022
• Primary Completion: October 1, 2024
• Study Completion: December 1, 2024
• Last Updated: December 9, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)