Up to 18% of patients undergoing ACL reconstruction experience graft failure and require revision surgery, which is known to increase the risk of developing post-traumatic osteoarthritis (PTOA). A new trial led by the Center for Regenerative Medicine at Hospital for Special Surgery (HSS) with a sub-site at Emory University will investigate whether using concentrated bone marrow aspirate (cBMA) can help patients to heal more effectively and prevent PTOA after revision surgery. This translational research study comes from HSS’ new Center for Regenerative Medicine-based trial to utilize a cell-based therapy.

The new single-blind, randomized, pilot, clinical trial, part of the Arthritis Foundation 2023 FastOA Interventional Pilot Studies, will harness the expertise of surgeons, radiologists, biostatisticians, and cellular and molecular biologists to determine whether cBMA may prevent the chronic inflammation that can lead to pain and stiffness following surgery, and can also contribute to post-traumatic osteoarthritis. Previous studies have suggested that cBMA injections may improve surgical outcomes, but this approach has not yet been evaluated in rigorous clinical trials in patients undergoing ACL revision surgery.

The cBMA used in these procedures is the patient’s own and is collected from the pelvic bones. The participating patients will be randomized to receive either cBMA injections at the time of revision surgery or standard care.

The goal of the trial is not only to establish whether the addition of cBMA reduces the risk of PTOA, but also to understand the underlying mechanisms of cBMA therapy and to look for biomarkers in the joint microenvironment that might help to refine the approach and further improve outcomes. Given the lack of effective non-surgical interventions for the prevention and treatment of PTOA, this study is expected to provide valuable insights that could guide care in the future.

To determine whether any differences observed between the two arms of the trial are clinically meaningful, the primary measure of the treatment’s success will be the patients’ self-reported pain levels 12 months after surgery. This will be determined by using the Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain. As a secondary measure, the investigators will deploy advanced, quantitative MRI scans to look for changes in the cartilage. “We will leverage clinical outcomes and imaging to evaluate the efficacy of adding cBMA to standard treatment,” said co-primary investigator Miguel Otero, PhD, scientist in the Orthopedic Soft Tissue Research Program, co-director of the Derfner Foundation Precision Medicine Laboratory, and of the HSS Research Institute Histopathology Service.

“Depending on what we learn about whether cBMA reduces the risk of PTOA, the results generated by this study may have the potential to change clinical practice,” adds co-primary investigator Scott Rodeo, MD, Vice Chair of Orthopaedic Research, co-director of the Orthopaedic Soft Tissue Research Program, and director of the Center for Regenerative Medicine at HSS.

By analyzing the cellular and molecular make-up of the cBMA as well as synovial fluids collected during and after the ACL revision surgery, the investigators also hope to gain insight into the populations of immune cells present within the joint microenvironment and the link between certain immune components and clinical outcomes. The researchers hypothesize that cBMA’s functionally relevant immune-modulatory and disease-modifying effects depend on the fluid’s cellular and molecular composition. They expect that these biospecimens may yield clues about how to further improve patient outcomes.

The FastOA2023 trial will harness strength of two Arthritis Foundation OACTN Clinical Trial Units that are also participating in the Post-Injury Knee Arthritis Severity Outcomes (PIKASO) Study and will use parallel instruments and dataset management. PIKASO is an ongoing, multicenter, randomized phase II clinical trial examining the use of metformin in patients who are at high-risk for developing PTOA in the knee after ACL reconstruction.

To learn more about the study and when enrollment opens in FastOA2023, visit https://clinicaltrials.gov/study/NCT06311513?locStr=New%20York,%20NY&country=United%20States&state=New%20York&city=New%20York&cond=ACLR&intr=BMAC&rank=1

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