Arthritis Foundation to Initiate a Network Model for Clinical Trials
The Arthritis Foundation’s OA-CTN is a $20M infrastructure investment to launch and execute randomized clinical trials in osteoarthritis.
At least 500 million people globally have clinically diagnosed osteoarthritis and need treatments that can slow or halt disease progression. The pursuit of such treatments has been challenging due to lack of funding and because the disease is heterogeneous and generally slow-moving. Leading the efforts to find a cure for this degenerative joint disease, the Arthritis Foundation, along with experts in clinical practice and academia, is preparing to launch the post-injury knee arthritis severity outcomes (PIKASO) clinical trial at the end of this year. This randomized phase II study will test if metformin, a drug widely used for managing Type 2 diabetes, can prevent osteoarthritis progression in people at elevated risk for developing post-traumatic osteoarthritis.
“The individual burden of osteoarthritis is tremendous and the burden to the health care system is overwhelming,” says Jason Kim, PhD, Vice President of Osteoarthritis Research Programs at the Arthritis Foundation. “We need to develop more treatments to stop or slow arthritis.”
The PIKASO Project is a collaborative effort of several top arthritis investigators and nine research institutions, including Cleveland Clinic, Emory University, Hospital for Special Surgery, Mass General Brigham, Ohio State University, University of Iowa, University of Kentucky, University of Nebraska and University of North Carolina, who make up the Osteoarthritis Clinical Trials Network (OA-CTN).
“For many years, the arthritis community at large has discussed the need for osteoarthritis research, and specifically post-traumatic osteoarthritis. After much consultation with institutional partners and our national board of directors, we determined that the Arthritis Foundation is well positioned to lead in this space,” says Steven Taylor, Arthritis Foundation President & CEO. “PIKASO is the biggest science initiative of the Arthritis Foundation to date and is the culmination of several important projects that the Foundation has recently supported.”
Once considered a single condition due to age-related “wear and tear” of the joint, osteoarthritis is recognized as a heterogenous disease characterized by variable genetic predispositions, metabolic pathways and biomechanical features. The alternative treatment to invasive major surgery are medications that provide only pain relief rather than disease-modification, in part due to the complexity of osteoarthritis pathology. Further, osteoarthritis progresses slowly, requiring expensive and prolonged follow-up to test new treatments. Among the clinical trials conducted so far, no disease-modifying medications have emerged.
“Traditionally, clinical interventions have focused on the later stages of osteoarthritis when there is extensive cartilage loss and it’s time for a joint replacement,” says Virginia Byers Kraus, MD, PhD, an Arthritis Foundation-funded investigator and professor at Duke University in Durham, North Carolina. “And so OA-CTN’s goal was to find a suitable cohort of individuals who have not yet developed osteoarthritis but who are at high risk for developing the disease within a few years.”
Interventional clinical trials are the gateway to evidence-based treatments for osteoarthritis. But the disease has frustrated scientists because it generally moves more slowly than the timeframe typically allowed for clinical trials. However, some vulnerable patients do show osteoarthritis symptoms within a 2-5-year window after a joint injury. The Arthritis Foundation, recognizing this important detail, launched the FastOA Initiative to identify specific individuals who could be studied in clinical trials. These people not only had a history of having a major joint injury but they also had other risk factors, like being overweight and having higher pain severity.
Over the past several years, and with the Arthritis Foundation’s support, the OA-CTN has been working on projects like MOCHA (montelukast as a potential chondroprotective treatment following anterior cruciate ligament reconstruction), the corticosteroid meniscectomy trial (CoMeT), and “Biomechanical Changes Following ACL Injury that Influence the Development of Posttraumatic Osteoarthritis” study, all crucial predecessors to the PIKASO Project.
After careful deliberation, OA-CTN members voted for metformin as the candidate drug for PIKASO. The medication is a front-runner among other therapeutics because of its excellent safety profile, low cost and mounting preclinical evidence in delaying the onset of osteoarthritis. Human studies with metformin also show potential for disease-modifying benefits in people diagnosed with osteoarthritis. However, PIKASO will be the first clinical trial to test if metformin can prevent or delay the onset of post-traumatic osteoarthritis.
“Through our multi-institutional collaboration, we will not just evaluate the effect of metformin in pain reduction, but we will also measure changes in joint structure using advanced imaging techniques and functional improvements using cutting-edge biomechanics measurements,” says David Felson, MD, MPH, the Chair of the Arthritis Foundation’s OA-CTN and professor at Boston University.
Key capabilities of this endeavor are the investment in network-based infrastructure. The Arthritis Foundation awarded Elena Losina, PhD, and Mass General Brigham to serve as the clinical coordinating center for the multisite PIKASO Project; Xiaojuan Li, PhD, and Cleveland Clinic to serve as the imaging center to coordinate collection and analysis of MRI data for the PIKASO Project; and Brian Pietrosimone, PhD, ATC, and the University of North Carolina at Chapel Hill to coordinate biomechanical and functional assessments.
“The Arthritis Foundation has invested much thought, time and resources into bringing the PIKASO project to fruition,” says Peggy Crow, MD, the Chair of the Arthritis Foundation’s Medical Science Advisory Committee and Physician-in-Chief Emeritus at Hospital for Special Surgery in New York. “We now eagerly look forward to the next stage of PIKASO, that is, executing a clinical trial that meets the highest standards of quality, ethics and integrity.”
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