Osteoarthritis clinical trials at UCLA

Anterior cruciate ligament (ACL) injuries are extremely common. On average, 50% of individuals suffering an ACL injury will develop radiographic osteoarthritis (OA) 10 to 20 years after injury. Unfortunately, ACL reconstruction does not prevent risk of future OA. Interleukin-1 (IL-1) levels in the human knee joint increase transiently after an ACL injury. In animal experiments, if interleukin-1 levels are increased in the joint, this alone causes arthritis to occur. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1. However, in ACL injuries the balance of these two proteins is disturbed transiently after injury, with the effects of IL-1 dominating this balance. In a large animal model of ACL injury, injection of IL-1Ra into the knee joint after ACL injury significantly decreased the amount of arthritis that was later observed. Thus, the investigators hypothesize that early injection of IL-1 inhibitor (IL-1Ra) into the knee joint of patients suffering recent ACL injury will decrease the incidence of cartilage damage later in life. After appropriate IRB approval, a total of 32 active patients will be randomized into one of two treatment groups. Group 1 will receive removal of the knee joint fluid (aspiration of hemarthrosis) using a needle and syringe within 1 to 2 weeks of injury. Following aspiration of the knee joint, an injection of 5 milliliters (mls) of sterile saline (as a placebo control) will be administered. In addition, a second knee aspiration procedure and an injection of 5mls of sterile saline into the injured knee joint will be performed at 3 to 5 days after the initial injection. Group 2 will receive aspiration of the knee hemarthrosis as described in group 1 as well as intra-articular administration of 150mg (~5mls) of anakinra (rhIL-1Ra) within 1 to 2 weeks of ACL injury. In addition, a second knee aspiration and intra-articular administration of 150mg (~5mls) of anakinra (rhIL-1Ra) will be performed at 3 to 5 days after the initial injection. Thus, all patients in this randomized placebo-controlled trial will undergo two injection procedures prior to surgery. Investigators will analyze subjects self-reported function and pain scores as well as urinary levels of cartilage breakdown products over time. Additionally, MRI studies will be used to compare MRI findings among patients in these 2 treatment groups. Urine samples will be obtain prior to surgery, at the time of surgery and at multiple time points after surgery (3, 6, 9, 12 and 24 months after surgery). Subjective outcome measure assessments (surveys) will be completed by participants prior to surgery and then again at 6, 9, 12 and 24 months post-operatively. MRI studies will be obtained at 1 year and 2 years following surgery. Additional, MRI studies at time points are optional and highly encouraged. These additional MRIs are at no cost to the patient.

Knee osteoarthritis is a debilitating disease that can cause severe knee pain and significant limitations to patients' activities of daily living. Total knee arthroplasty (TKA), also known as knee replacement surgery, is a well-established and successful procedure for treatment of end-stage knee osteoarthritis. Over the years, TKA surgical techniques and implant technology have improved, resulting in better patient outcomes and implant survivorship. Despite continuous improvements being made to this high demand procedure, malalignment of component position is a well-known cause of post-operative complications, including knee pain, component loosening, and failure requiring revision surgery. Advanced techniques that utilize computer navigation or robotic-arm assistance have been developed in an attempt to avoid malalignment. Both technologies were created with the goal of improving the precision of implant positioning and implant sizing in order to improve lower limb alignment and joint line alignment. The OrthoAlign KneeAlign computer assisted navigation system is a commercially available device that uses gyroscopic limb position sensing technology mounted to intramedullary and extramedullary jigs to measure bone resection cuts in TKA that ultimately dictate implant position. The Zimmer Biomet ROSA Knee System is a commercially available, FDA-approved robotic assistant for performing TKA. It uses pre-operative x-rays to create a three-dimensional image of the patient's knee anatomy, which is used to create a pre-operative template of the implants to be used and provides intra-operative guidance for bone cuts during the TKA. The robotic system also assesses the soft tissue envelope around the knee and can assist with the soft tissue balancing of the knee arthroplasty. Alternatively, it can also be used in an imageless mode where bone cuts are performed based on intra-operative mapping using anatomic landmarks. To date, there have been no prospective studies comparing the implant positioning and patient outcomes directly of the KneeAlign system with the ROSA system and conventional TKA instrumentation techniques.