Evaluating the Effectiveness of Subchondroplasty for Treating Bone Marrow Lesions of the Knee

Study Overview
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Brief Summary
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The primary objective of this randomized pilot study is to evaluate whether subchondroplasty combined with knee arthroscopy is more effective at reducing knee pain and improving knee function compared to knee arthroscopy alone. All knee function outcomes will be assessed at initial presentation, 3 months, 6 months, 12 months, and 24 months following surgery using validated questionnaires. Patient-reported pain will also be recorded at 2 weeks after surgery. The secondary objective of the study is to determine whether the subchondroplasty and knee arthroscopy group has better bone quality and bone micro-architecture compared to the group receiving knee arthroscopy alone. Bone quality/micro-architecture will be evaluated at baseline, 3 months, and 12 months following surgery using Magnetic resonance imaging (MRI) and High-Resolution Peripheral Quantitative CT (HR-pQCT) imaging and at baseline, 3 months, 12 months, and 24 months after surgery using X-rays.

Detailed Description
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The investigators hypothesize that patients receiving subchondroplasty combined with arthroscopy will have reduced knee pain, improved knee function, and improved bone quality and micro-architecture compared to patients receiving arthroscopy alone who have symptomatic early osteoarthritis with the presence of at least one BML observed on MRI. Patients who provide informed consent to enroll in the study will be scheduled for knee surgery and randomized to receive subchondroplasty and arthroscopy or arthroscopy alone. Knee function outcomes will be assessed at initial presentation, 3 months, 6 months, 12 months, and 24 months following surgical intervention. Patient-reported pain will also be recorded at 2 weeks following surgical intervention. The evaluation of bone quality and micro-architecture will occur at baseline, 3 months, and 12 months following surgical intervention. X-rays will also be evaluated at the 24-month time-point.

Official Title
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Randomized Pilot Study Comparing the Effectiveness of Subchondroplasty Combined With Arthroscopy to Arthroscopy Alone for Treating Bone Marrow Lesions of the Knee

Conditions
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Osteoarthritis, Knee, Arthroscopy, Musculoskeletal Disease, Bone Marrow Edema, Subchondral Bone Edema, Knee Osteoarthritis

Intervention / Treatment
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* Procedure: Subchondroplasty and Knee Arthroscopy
* Procedure: Knee Arthroscopy Alone
* Biological: Subchondroplasty


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 40 years of age or older Kellgren-Lawrence grade 1-3 osteoarthritis in the affected knee Has experienced pain in the affected knee for at least 3 months Candidate for knee arthroscopy (moderate to severe symptoms, lack of response to non-operative care, and/or mechanical symptoms) Stable ligament exam No additional injuries affecting the study knee or contralateral knee Candidate for MRI (no pacemaker, aneurysmal clip, eye prosthesis, pregnancy, neurostimulator, implanted stimulator [e.g. diabetes pump]) Confirmed visualization of at least 1 bone marrow lesions using T2 weighted MRI Exclusion Criteria: Determined to not be a surgical candidate Kellgren-Lawrence grade 4 osteoarthritis Unable to fit in XtremeCT scanner (based on measurement at time of recruitment) Contraindications to MRI Any hardware present in either knee that could interfere with MRI signal Bone marrow lesion(s) caused by acute trauma prior to enrolment Radiographic mal-alignment defined by obvious valgus > 7° or obvious varus > 7° on measured hip-knee-ankle angle No bone marrow lesion detected on baseline (pre-operative) MRI Rheumatoid arthritis Septic arthritis Reactive arthritis Gout Osteochondritis dissecans of knee resulting in significant bone loss Collapse of subchondral bone Restricted knee range of motion: passive flexion < 110° or a flexion contracture > 30° Ligament instability in either knee History of other arthropathies (e.g. sickle cell or autoimmune disease) History of uncontrolled diabetes: HbA1C level of 8 or higher, measured within 3 months of enrollment Unable to perform a functional assessment of either knee Current smoker or stopped smoking for less than 3 months History of invasive malignancy (Unless treated in the past and has had no clinical signs or symptoms of malignancy for 5 years or longer) Has a primary bone tumor in the knee or adjacent to the knee Having surgery on another part of the lower limb in addition to the study procedure Taking prescription pain medication other than NSAIDs or acetominophen Active infection or a history of joint infection Pursuing action through the Workers' Compensation Board - Alberta BMI > 40

Ages Eligible for Study
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Minimum Age: 40 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
Interventional Model Description: The control group will be patients receiving knee arthroscopy alone and the intervention group will be patients receiving subchondroplasty and knee arthroscopy.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Subchondroplasty and Knee Arthroscopy<br>Patients randomized to the Subchondroplasty and Knee Arthroscopy group will receive the subchondroplasty procedure before or after knee arthroscopy that will be completed based on current standard of care guidelines. | Procedure: Subchondroplasty and Knee Arthroscopy<br>* Subchondroplasty® (SCP®) is a procedure performed along with minimally-invasive arthroscopy. The bone marrow lesion(s) will be located using pre-operative MRI combined with fluoroscopy (intra-operative X-ray) and a small, drillable AccuPort® Delivery Cannula will be placed in the appropriate position. The cannula will then be drilled into the bone marrow lesion(s) and a flowable, synthetic, calcium phosphate bone substitute (AccuFill® Bone Substitute Material, Zimmer Biomet) will be injected into the lesion(s). The calcium phosphate bone substitute will then harden, improve the structural integrity of the damaged subchondral bone, and will gradually be resorbed and replaced with new bone.<br>Biological: Subchondroplasty<br>* Subchondroplasty® (SCP®) is a procedure performed along with minimally-invasive arthroscopy. The specific biological component of the procedure involves the injection of the AccuFill® Bone Substitute Material (Zimmer Biomet), which is a a flowable, synthetic, calcium phosphate bone substitute, into the bone marrow lesion(s).<br>* Other names: SCP® (Zimmer);|
| Sham Comparator: Knee Arthroscopy Alone<br>Patients randomized to the Knee Arthroscopy Alone group will receive the knee arthroscopy that will be completed based on current standard of care guidelines. | Procedure: Knee Arthroscopy Alone<br>* Knee arthroscopy is a surgical procedure that involves the orthopaedic surgeon making small incisions in the knee and then inserting a small camera into the joint. Following the insertion of the camera, multiple procedures can be completed to treat a number of different conditions such as repair or partial/complete removal of the meniscus, debridement, lavage, removal of a loose body among others.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire scores | The primary outcome measure will be the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire scores for knee pain and knee function. The KOOS questionnaire consists of 5 different sub-scales including Symptoms (7 questions), Pain (9 questions), Activities of Daily Living (17 questions), Sports/Recreation (5 questions), and Quality of Life (4 questions). A normalized score from 0-100 (100 indicates no problems/symptoms and 0 indicates extreme problems/symptoms) is calculated for each sub-scale individually. | Baseline (pre-surgery), 3 months, 6 months, 12 months, 24 months post-surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form scores | Knee pain and function will also be evaluated using the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form scores. The IKDC includes three different domains including Symptoms (7 questions), Sports Activities (2 questions, 1 multi-part question), and Function (1 multi-part question). A total score from 0-100 (100 indicates no problems/symptoms and 0 indicates extreme problems/symptoms) is calculated. | Baseline (pre-surgery), 3 months, 6 months, 12 months, 24 months post-surgery. | 
| Change in Patient-Reported Pain scores on the Visual Analog Scale (VAS) | Knee pain will also be evaluated using the Visual Analog Scale (VAS) scores for patient-reported pain. The Visual Analog Scale (VAS) consists of a 10 cm long straight line that starts from the lowest value of 0 (no pain) at one end, and the highest value of 10 (worst pain possible) at the other. Patients are asked to mark a place on the line that represents the severity of their pain. Scores are recorded in millimetres from 0-100 with 0 indicating no pain and 100 indicating the worst pain possible. | Baseline (pre-surgery), 2 weeks, 3 months, 6 months, 12 months, 24 months post-surgery. | 
| Change in bone quality/micro-architecture evaluated using magnetic resonance imaging (MRI) | The bone quality and micro-architecture of the bone marrow lesion(s) in the knee, and the knee overall, will be evaluated using magnetic resonance imaging (MRI). MRI will be used to identify the presence of bone marrow lesion(s) in the knee at baseline before surgery using a T2 weighted fat-suppression sequence and evaluate the bone marrow lesion(s) post-surgery. | Baseline (pre-surgery), 3 months, 12 months post-surgery | 
| Change in bone quality/micro-architecture evaluated using High-Resolution Peripheral Quantitative CT (HR-pQCT) imaging | The bone quality and micro-architecture of the bone marrow lesion(s) in the knee, and the knee overall, will also be evaluated using High-Resolution Peripheral Quantitative CT (HR-pQCT) imaging. HR-pQCT imaging will be used to evaluate the bone micro-architecture of the knee and the bone marrow lesion(s) before and after surgery. | Baseline (pre-surgery), 3 months, 12 months post-surgery | 
| Change in bone quality/micro-architecture evaluated using X-rays | The bone quality and micro-architecture of the bone marrow lesion(s) in the knee, and the knee overall, will also be evaluated using X-ray. X-ray imaging will be used to evaluate bone quality and osteoarthritis status before and after surgery. | Baseline (pre-surgery), 3 months, 12 months, 24 months post-surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bone Marrow Lesion, Subchondroplasty, Knee Function, Knee Pain, Bone Quality, Bone Micro-architecture