Clinical trial NCT06078059: Mechanisms of Treatment Effects Using Cultured, Allogeneic Mesenchymal Stromal Stem Cells (MSCs) in Knee Osteoarthritis
Official title: Mechanisms of Treatment Effects Using Cultured, Allogeneic Mesenchymal Stromal Stem Cells (MSCs) in Knee Osteoarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteoarthritis, Knee
Keywords: Knee
Osteoarthritis
Mesenchymal stem cells
Allogeneic
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
Collaborators: name: Blood Transfusion Centre of Slovenia
First posted: 2023-10-11
Enrollment: 30
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Soluble biomarkers analysis with multiplex bead-based immunoassays Luminex in synovial fluid
timeFrame: After sampling
measure: Biomarkers analysis with Enzyme-linked immunosorbent assay (ELISA) in synovial fluid
timeFrame: After sampling
measure: Quantitative real-time PCR (qRT-PCR) analysis of gene expression in chondrocytes and synoviocytes
timeFrame: After sampling
Secondary outcomes:
measure: Knee Injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: 4-6 prior to surgery and at admission
measure: Pain on Visual Analogue Scale (VAS)
timeFrame: 4-6 prior to surgery and at admission
measure: EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaire
timeFrame: 4-6 prior to surgery and at admission
measure: EuroQol self-rated health on Visual Analogue Scale (EQ-VAS)
timeFrame: 4-6 prior to surgery and at admission
measure: Serious Adverse Events (SAE)
timeFrame: Until 1 month after the application of UCB-MSCs
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: University medical centre Ljubljana
Study officials:
affiliation: University Medical Centre Ljubljana
name: Matej Drobnič, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Blood Transfusion Centre of Slovenia
name: Urban Švajger, MPharm, PhD
role: PRINCIPAL_INVESTIGATOR
References: