Synovium Brushing to Augmented Microfracture for Improved Cartilage Repair

Study Overview
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Brief Summary
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This is a proof-of-concept study to determine the safety and efficacy of a novel device to increase the reparative capacity of the knee. The discovery of a resident population of mesenchymal stem cells (MSCs) within synovial fluid (SF) was the first description of this reparative cell population having direct access to superficial cartilage and joint structures. The ready access of SF MSC to cartilage and other joint tissues offers a novel strategy for joint repair. Current arthroscopic procedures result in the removal of all SF MSCs due to continuous irrigation throughout the procedure. The current study would benefit the patient by greatly increasing the reparative capacity of the joint by bolstering MSC numbers and retaining those MSCs within the joint after surgery. By accessing MSCs from the synovium it is anticipated that these cells would be entrapped/migrate into the marrow clot formed by microfracture of the sub-chondral bone. These MSCs would supplement those from the marrow and may result in faster, better quality repair.

Detailed Description
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The synovium is a rich source of potent chondrogenic mesenchymal stromal cells (MSCs). Gaining access to this valuable source of regenerative cells could improve the outcome of joint restorative procedures. To avoid costly two-stage procedures and ex vivo manipulation, exploiting these autologous cells in a minimally invasive way with minimal manipulation could provide a novel cost-effective approach. This study will evaluate the safety, feasibility and efficacy of a novel medical device (a synovial brush) and procedure (synovial brushing) to increase the number of autologous minimally manipulated MSCs in the knee. Twenty patients undergoing microfracture for isolated chondral defects will be randomly assigned to either a control group (microfracture only, 10 patients) or the intervention group (microfracture plus synovial brushing, 10 patients). The device is intended to increase the number of MSCs within the joint as a final stage during surgery, aiding repair by bolstering those MSCs recruited from the bone marrow.

Official Title
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Safety and Efficacy of a Novel Synovium Brushing Method for Endogenous Mesenchymal Stem Cells Mobilisation During Knee Joint Microfracture for Cartilage Repair.

Conditions
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Defect of Articular Cartilage, Cartilage Injury, Osteoarthritis, Knee

Intervention / Treatment
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* Device: Arthroscopic synovial brushing
* Procedure: Microfracture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Isolated cartilage defects (<2cm2) Patients undergoing microfracture for repair of cartilage defects Exclusion Criteria: Septic arthritis Infectious disease Revision joint surgery Meniscal damage requiring repair Ligament damage requiring repair Cartilage defect greater than 2cm2 Contra-indications for MRI: Pacemakers, Implantable Cardioverter defibrillators, implantable cardiac loop recorders Surgical clips within the head Certain inner ear implants Neuro-electrical stimulators Metal fragments within the eye or head

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>Patients in this group will received conventional microfracture treatment as indicated for isolated cartilage defects and defined by the inclusion criteria. | Procedure: Microfracture<br>* Microfracture or marrow-stimulation is a surgical procedure to repair small isolated cartilage defects by recruiting bone marrow mesenchymal stromal cells by creating small holes ('micro fractures') in the sub-chondral bone. These cells are entrapped in the ensuing blood clot and contribute to partial repair of the cartilage.<br>* Other names: Marrow-stimulation;|
| Experimental: Intervention group<br>Patients in this group will also receive microfracture for the treatment of isolated cartilage defects in combination with arthroscopic synovial brushing to access and release synovial MSCs into the joint space. | Device: Arthroscopic synovial brushing<br>* The specific and novel surgical procedure that will be carried out here is synovial membrane brushing using a novel device that has been shown to release MSCs from the synovium in vitro. This technique will be carried out in the setting of therapeutic microfracture for cartilage defects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The mean change in the number of MSCs present in the knee pre- and post- microfracture/microfracture plus arthroscopic synovial brushing. |  | 2 weeds | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients whose clinical effusion scores improve at 3, 6 and 12 months |  | 3, 6 and 12 months | 
| Number of patients whose semi-quantitative MRI cartilage scores improve at 6 and 12 months |  | up to 12 months | 
| Median KOOS scores at 3, 6 and 12 months (pain; other symptoms; function in daily living; function in sport; knee-related QoL; average score) |  | 3, 6 and 12 months | 
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Median WOMAC scores at 3, 6 and 12 months (total; pain; stiffness; function) | 3, 6 and 12 months | 
| Visual Analogue Scale (VAS) |  | 3, 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous, Minimally manipulated, Cartilage, Mesenchymal stromal cell, Microfracture, Knee, Defect, Injury, Stem cell