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

Primary Purpose

Osteoarthritis, Knee

Status
Recruiting
Phase
Not Applicable
Locations
Slovenia
Study Type
Interventional
Intervention
Knee aspiration + UCB-MSCs
Knee aspiration
Sponsored by
University Medical Centre Ljubljana
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoarthritis, Knee focused on measuring Knee, Osteoarthritis, Mesenchymal stem cells, Allogeneic

Eligibility Criteria

50 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University medical centre LjubljanaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intervention group

Control group

Arm Description

Knee aspiration and the application of UCB-MSCs

Only knee aspiration, without the application of UCB-MSCs

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

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.
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').
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.
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.
Serious Adverse Events (SAE)
Serious adverse events (SAE) are defined as any complication requiring hospitalization.

Full Information

First Posted
July 23, 2023
Last Updated
October 5, 2023
Sponsor
University Medical Centre Ljubljana
Collaborators
Blood Transfusion Centre of Slovenia
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1. Study Identification

Unique Protocol Identification Number
NCT06078059
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2022 (Actual)
Primary Completion Date
November 1, 2024 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Medical Centre Ljubljana
Collaborators
Blood Transfusion Centre of Slovenia

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis, Knee
Keywords
Knee, Osteoarthritis, Mesenchymal stem cells, Allogeneic

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention group
Arm Type
Experimental
Arm Description
Knee aspiration and the application of UCB-MSCs
Arm Title
Control group
Arm Type
Active Comparator
Arm Description
Only knee aspiration, without the application of UCB-MSCs
Intervention Type
Biological
Intervention Name(s)
Knee aspiration + UCB-MSCs
Intervention Description
Knee aspiration and the application of cultered allogeneic umbilical cord blood-derived mesenchymal stromal stem cells (UCB-MSCs).
Intervention Type
Other
Intervention Name(s)
Knee aspiration
Intervention Description
Knee aspiration
Primary Outcome Measure Information:
Title
Soluble biomarkers analysis with multiplex bead-based immunoassays Luminex in synovial fluid
Description
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.
Time Frame
After sampling
Title
Biomarkers analysis with Enzyme-linked immunosorbent assay (ELISA) in synovial fluid
Description
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.
Time Frame
After sampling
Title
Quantitative real-time PCR (qRT-PCR) analysis of gene expression in chondrocytes and synoviocytes
Description
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.
Time Frame
After sampling
Secondary Outcome Measure Information:
Title
Knee Injury and Osteoarthritis Outcome Score (KOOS)
Description
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.
Time Frame
4-6 prior to surgery and at admission
Title
Pain on Visual Analogue Scale (VAS)
Description
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').
Time Frame
4-6 prior to surgery and at admission
Title
EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaire
Description
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.
Time Frame
4-6 prior to surgery and at admission
Title
EuroQol self-rated health on Visual Analogue Scale (EQ-VAS)
Description
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.
Time Frame
4-6 prior to surgery and at admission
Title
Serious Adverse Events (SAE)
Description
Serious adverse events (SAE) are defined as any complication requiring hospitalization.
Time Frame
Until 1 month after the application of UCB-MSCs

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Matic Kolar, MD
Phone
+386 (0)40198367
Email
matic.kolar@kclj.si
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matej Drobnič, MD, PhD
Organizational Affiliation
University Medical Centre Ljubljana
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Urban Švajger, MPharm, PhD
Organizational Affiliation
Blood Transfusion Centre of Slovenia
Official's Role
Principal Investigator
Facility Information:
Facility Name
University medical centre Ljubljana
City
Ljubljana
ZIP/Postal Code
1000
Country
Slovenia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matic Kolar, MD
Phone
+386 40 198 367
Email
matic.kolar@kclj.si

12. IPD Sharing Statement

Plan to Share IPD
No

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

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