Triamcinolone Treatment In Patients with Acute ACL Tear and Painful Effusions: Follow-up 2 Years Post-ACL Reconstruction

Anterior cruciate ligament (ACL) injuries occur frequently and the majority of individuals with partial or complete rupture of the ACL will develop post-traumatic osteoarthritis (PTOA) 5-15 years after the initial injury [1, 2]. The long-term consequences of PTOA include arthrofibrosis, pain, limited motion, and recurrent instability. Because ACL injuries occur most often in younger individuals (age 14-29 years), pain and other debilitating symptoms occur most often during patients’ most productive years costing society upwards of 3.06 billion dollars annually [2, 3]. Current surgical and non-surgical treatment options for ACL injury, while relatively successful in restoring function and stability in the short term, do little or nothing to reduce or prevent the development of PTOA later in life. ACL rupture, with or without accompanying damage to nearby cartilage and bone, initiates a persistent cascade of inflammation and catabolic enzyme activity leading to OA of the knee joint. We propose to disrupt the initial inflammation-driven cascade with a low dose intra-articular injection of triamcinolone acetonide (Kenalog). We hypothesize that triamcinolone acetonide administered intra-articularly during the early phase of acute ACL injury will decrease inflammatory and cartilage degradation products in synovial fluid and improve patient reported outcomes 2 years following initial injury and reconstruction. We have tested our hypothesis in a multicenter, randomized, placebo controlled, double blinded, clinical trial indicating a marked reduction of collagen break down products and increase of chondroprotective markers within the first 4 weeks after ACL injury. In this proposal we seek funding to evaluate this clinical trial cohort at 2 years after the initial treatment in order to determine the long-term effect of early anti-inflammatory therapy after ACL injury. Specific Aims will: 1. test the efficacy of a treatment protocol using triamcinolone acetate and knee arthrocentesis to improve patient-reported outcomes (PRO) following ACL rupture in a randomized, placebo controlled, double blinded, clinical trial at 2 years. All knees have undergone arthrocentesis and have received either the study drug or placebo within 1 week of ACL injury. For the purpose of this grant proposal we aim to evaluate patients at the 2 year time point following ACL reconstruction using established validated instruments for ACL injuries and PTOA (KOOS, IKDC, MARX). 2. determine if specific synovial fluid biomarker levels and their response to early intervention with triamcinolone acetonide (Kenalog) correlates with improved clinical outcomes as measured by the KOOS. Early clinical trial results demonstrate that the collagen break down product CTX-II, the chondroprotective cross-linking molecule TSG-6 and cartilage oligomeric protein COMP show synovial fluid patterns similar to established models of early Osteoarthritis in humans and mice in patients treated with placebo. These patterns reverse in patients who received Kenalog at one or two time points prior to surgery. The goal of this aim is to identify if these biomarker levels may be predictive of better or worse outcome as measured by the KOOS at 2 years. 3. determine if joint health as evaluated by MRI at 2 years after ACL injury is influenced by the initial treatment with Kenalog. Two years following ACL injury MRI analysis using standardized T2-mapping will be performed will be performed on 10 control subjects and 10 subjects who have received Kenalog injections. This proposal constitutes the 2 year follow-up examination of a GCP-level randomized clinical trial cohort (Clinical trials.gov No: NCT01692756). In our preliminary data we identified significant differences in synovial biomarker levels between patients who received Kenalog post injury versus arthrocentesis only. Synovial biomarker profiles indicated that patients who suffer an ACL tear undergo matrix and collagen degradation that parallels those of mouse models of osteoarthritis and those of humans with progressive OA [2]. Patients that received Kenalog showed a reversal of this trend. We therefore believe that an early administration of Kenalog may be beneficial to our ACL injured patients. However, we would like to identify if these early biomarker findings correlate with 2 year PROs and some basic structural changes as measured on MRI.