Autologous Bone Marrow Aspirate Concentrate in Patients Undergoing Meniscectomy

Study Overview
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Brief Summary
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The proposed research study aims to evaluate the effects of autologous bone marrow aspirate concentrate (BMAC) on the development and progression of osteoarthritis (OA) in patients undergoing meniscectomy. This prospective, randomized, double-blind clinical trial will compare patient-reported outcomes, specifically IKDC scores between patients who receive BMAC post-meniscectomy and those who receive a saline control injection. The study will also compare physical examination, MRI, radiographs, and synovial fluid analysis. Our hypothesis is that those who receive the autologous BMAC injection after the procedure will have better outcomes than those who do not.

Detailed Description
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Recent studies have demonstrated both the safety of BMAC intra-articular injection and improvements in subjective, patient reported outcomes in patients with existing knee OA. Unfortunately these studies were largely uncontrolled, underpowered, and/or retrospective in nature. Additionally, a recent prospective, randomized clinical study of allograft mesenchymal stem cells (MSCs) injected at a separate time point post surgical intervention has highlighted the ability of MSCs to increase meniscal volume and improve knee pain following injection. This will be the first study to examine the effects of autograft BMAC intra-articular injection in a single-stage procedure and in a prospective, randomized, double-blind fashion. The results of this study, if the null hypothesis is rejected, will have far-reaching implications for the standard of care in meniscal treatment and on OA progression in the knee. Additionally, if the results of this study are favorable in reduction of OA progression this study will change the surgical approach to all axial, synovial joints including the shoulder, elbow, wrist, hip, and ankle.

Official Title
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Prospective, Randomized, Double-blind Clinical Trial to Investigate the Efficacy of Autologous Bone Marrow Aspirate Concentrate Post-Meniscectomy

Conditions
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Osteoarthritis Post-meniscectomy

Intervention / Treatment
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* Biological: Bone Marrow Aspirate Concentrate
* Procedure: Standard Meniscectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is greater than 18 years old Written informed consent is obtained Subject is determined to have a symptomatic meniscal tear requiring a meniscectomy Meniscal pathology is confirmed through MRI and arthroscopically Subject agrees to all follow-up evaluations Osteoarthritis Kellen-Lawrence grade 1-3 on flexion PA and extension AP views Exclusion Criteria: Any subject lacking decisional capability Unwillingness to participate in the necessary follow-up Subject is pregnant or may become pregnant History of diabetes mellitus History of rheumatoid arthritis or other autoimmune disorder History of solid organ or hematologic transplantation Diagnosis of a non-basal cell malignancy within the preceding 5 years Infection requiring antibiotic treatment within the preceding 3 months Osteoarthritis Kellen-Lawrence grade 4 on flexion posterior-anterior (PA) or extension anteroposterior (AP) views Prior surgery on the index meniscus Concomitant surgery such as ligament surgery or cartilage repair or restoration Infection Prior cortisone/viscosupplementation/ (platelet rich plasma) PRP injection within 6 weeks

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Meniscectomy with Bone Marrow Aspirate Concentrate (BMAC)<br>Subjects will undergo the scheduled meniscectomy procedure. Following the procedure the investigator will make a small incision and create the marrow access channel in the proximal tibia. The experimental group will then have bone marrow harvested and BMAC will be prepared using a BMAC harvesting system. The automated centrifuge system rapidly concentrates cellular contents and growth factors in bone marrow aspirate using flow cytometry. The BMAC will be injected intra-articularly. | Biological: Bone Marrow Aspirate Concentrate<br>* Subjects undergoing autologous bone marrow aspirate concentrate will receive an intra-articular injection into the affected knee.<br>Procedure: Standard Meniscectomy<br>* All subjects will undergo either a partial or complete meniscectomy to treat the torn meniscus.<br>|
| Placebo Comparator: Meniscectomy with Placebo<br>Subjects will undergo the same meniscectomy procedure and will also have an incision and marrow access channel made in the proximal tibia, however no bone marrow will be harvested. The control group will have a placebo injection of saline into the affected knee. | Procedure: Standard Meniscectomy<br>* All subjects will undergo either a partial or complete meniscectomy to treat the torn meniscus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Knee Documentation Committee (IKDC) Score | The primary outcome measure will be the IKDC score at one year follow-up | One Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient reported outcomes throughout follow-up period | Patient reported outcomes will include change in scores from preoperative to Postoperative Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) | 7-10 days, 6 weeks, 3 months, 6 months, 1 year, 2 years | 
| Synovial fluid analysis | To investigate any changes in synovial fluid markers of osteoarthritis. | 2 weeks, 6 weeks | 
| Radiographic analysis | The degree of OA will be examined in all patients preoperatively and at subsequent follow-up visits at 1 and 2 years. | 1 year, 2 years | 
| Patient reported outcomes throughout follow-up period (VAS) | Visual Analog Score (VAS) | 7-10 days, 6 weeks, 3 months, 6 months, 1 year, 2 years | 
| Patient reported outcomes throughout follow-up period (IKDC) | International Knee Documentation Committee form (IKDC) | 7-10 days, 6 weeks, 3 months, 6 months, 1 year, 2 years | 
| Patient reported outcomes throughout follow-up period (KOOS) | Knee injury and Osteoarthritis Outcome Score (KOOS) | 7-10 days, 6 weeks, 3 months, 6 months, 1 year, 2 years | 
| Patient reported outcomes throughout follow-up period (SF-12) | (Short Form Health Survey) SF-12 | 7-10 days, 6 weeks, 3 months, 6 months, 1 year, 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal stem cells, Bone marrow aspirate concentrate