Multi-Center Pilot Study to Evaluate Concentrated Bone Marrow Aspirate (cBMA) as a Treatment to Modify Post-Traumatic Osteoarthritis (PTOA) Following Revision Anterior Cruciate Ligament Reconstruction (ACLR)
Overview
- Phase
- Phase 4
- Intervention
- Concentrated Bone Marrow Aspirate Injection
- Conditions
- Anterior Cruciate Ligament Injuries
- Sponsor
- Hospital for Special Surgery, New York
- Enrollment
- 40
- Locations
- 2
- Primary Endpoint
- Change from baseline in patient reported knee pain
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
The goal of this pilot randomized clinical trial is to look into the efficacy of concentrated bone marrow aspirate (cBMA) in improving post traumatic osteoarthritis (PTOA) symptoms in patients undergoing revision anterior cruciate ligament reconstruction surgery. The main questions it aims to answer are whether clinical outcomes, such as pain, are improved in patients who get cBMA with surgery, if there is a change in circulating markers of inflammation and what part of the cellular and molecular composition of cBMA may explain its effects.
Detailed Description
Anterior cruciate ligament reconstruction (ACLR) surgery is considered a relatively safe and effective procedure, however, up to 18% of grafts will fail and require revision surgery. Some studies have shown that these patients may be at increased risk of worse clinical outcomes, including fast progression toward post-traumatic osteoarthritis (PTOA). This is likely in part due to the inflammatory environment created within the joint. Concentrated bone marrow aspirate (cBMA) is a regenerative medicine therapy that contains soluble factors and connective tissue progenitor cells which may have immunomodulatory and pro-regenerative potential. The use of this therapy in conjunction with standard of care surgical treatment may help reduce the inflammatory microenvironment inside the joint, therefore modifying the conditions that might lead to developing long term complications such as PTOA. The investigators hypothesize that cBMA treatment at the time of revision ACLR may improve clinical outcomes at 1 year after surgery and reduce the risk of developing PTOA-associated symptoms. Participants will be randomized to either get a cBMA injection (investigational arm) at the time of surgery or a placebo incision (control arm). Biological specimens (blood, urine, synovial fluid), imaging data, functional tests and patient reported clinical outcomes will be measured at different time points during the study, for up to two years after the surgery. This will allow the investigators to evaluate the effect of cBMA in clinical outcomes. Biological specimens will be analyzed using molecular biology techniques to determine their composition, including the concentration of cells and other inflammatory markers.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males and Females
- •Age 18 to 55
- •Previous unilateral ACLR (Anterior Cruciate Ligament Reconstruction) within the last 5 years, and identified as having experienced failure of the primary ACLR
- •Scheduled to have a revision ACLR surgery, with any graft type (including patellar tendon, hamstring, quad or allograft)
- •Able to complete all study procedures and participate in a standardized physical therapy program
Exclusion Criteria
- •History of inflammatory arthritis or joint sepsis
- •Prior or concurrent total or sub-total meniscectomy
- •Prior or present avascular necrosis of the index knee
- •Oral or intra-articular corticosteroid injection within 3 months
- •Hyaluronic acid or PRP (Platelet-Rich Plasma) injection within 6 months
- •Use of duloxetine, doxycycline, indomethacin, glucosamine and/or chondroitin (ongoing or within 2 months)
- •Any clinical or laboratory abnormality greater than grade 3 CTCAE, which in the view of the investigator, will compromise the participant's safety.
- •Planned arthroplasty in the index knee
Arms & Interventions
Investigational Arm
Patients undergoing revision anterior cruciate ligament reconstruction surgery will get an intraoperative injection of concentrated bone marrow aspirate (cBMA).
Intervention: Concentrated Bone Marrow Aspirate Injection
Investigational Arm
Patients undergoing revision anterior cruciate ligament reconstruction surgery will get an intraoperative injection of concentrated bone marrow aspirate (cBMA).
Intervention: Revision Anterior Cruciate Ligament Reconstruction
Control Arm
Patients undergoing revision anterior cruciate ligament reconstruction surgery will get a sham incision in lieu of bone marrow harvesting.
Intervention: Sham Incision
Control Arm
Patients undergoing revision anterior cruciate ligament reconstruction surgery will get a sham incision in lieu of bone marrow harvesting.
Intervention: Revision Anterior Cruciate Ligament Reconstruction
Outcomes
Primary Outcomes
Change from baseline in patient reported knee pain
Time Frame: Baseline, 6 weeks, 6 months, 12 months and 24 months post-operative
The primary outcome measured for this study will be postoperative knee pain. This will be achieved using the Knee Injury and Osteoarthritis Outcome Score (KOOS) standardized questionnaire, which will be electronically delivered to participants at baseline and at 6-weeks, 6-months, 12-months and 24-months postoperatively. This questionnaire measures 42 items in a Likert scale for 5 different dimensions: pain, other symptoms, activities of daily living, function in sports and recreation and knee-related quality of life. The questionnaire is scored as a percentage from 0 to 100, with 0 representing extreme knee problems and 100 indicating no knee related symptoms, and therefore better outcomes.
Secondary Outcomes
- Change from baseline in articular cartilage relative proteoglycan content and collagen fibril organization(Baseline, 12 months postoperative)
- Expression of local inflammatory biomarkers(Baseline and 6 weeks post-operative)
- Concentration of circulating inflammatory biomarkers(Baseline, 6 weeks and 12 months post-operative)
- Change from baseline in cartilage morphology(Baseline, 12 months post-operative)