Arthritis Foundation to Initiate a Network Model for Clinical Trials

July 192023

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 diseasethe Arthritis Foundationalong with experts in clinical practice and academiais preparing to launch the Preventing Injured Knees from osteoArthritis: Severity Outcomes (PIKASO) clinical trial at the end of this year. This randomized phase II study will test if metformina drug widely used for managing Type 2 diabetescan 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 KimPhDVice 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 institutionsincluding Cleveland ClinicEmory UniversityHospital for Special SurgeryMass General BrighamOhio State UniversityUniversity of IowaUniversity of KentuckyUniversity of Nebraska and University of North Carolinawho make up the Osteoarthritis Clinical Trials Network (OA-CTN). 

“For many yearsthe arthritis community at large has discussed the need for osteoarthritis researchand specifically post-traumatic osteoarthritis. After much consultation with institutional partners and our national board of directorswe determined that the Arthritis Foundation is well positioned to lead in this space,” says Steven TaylorArthritis 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 jointosteoarthritis is recognized as a heterogenous disease characterized by variable genetic predispositionsmetabolic pathways and biomechanical features. The alternative treatment to invasive major surgery are medications that provide only pain relief rather than disease-modificationin part due to the complexity of osteoarthritis pathology. Furtherosteoarthritis progresses slowlyrequiring expensive and prolonged follow-up to test new treatments. Among the clinical trials conducted so farno disease-modifying medications have emerged.

“Traditionallyclinical 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 KrausMDPhDan Arthritis Foundation-funded investigator and professor at Duke University in DurhamNorth 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. Howeversome vulnerable patients do show osteoarthritis symptoms within a 2-5-year window after a joint injury. The Arthritis Foundationrecognizing this important detaillaunched 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 factorslike being overweight and having higher pain severity. 

Over the past several yearsand with the Arthritis Foundation’s supportthe 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” studyall crucial predecessors to the PIKASO Project.

After careful deliberationOA-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 profilelow 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. HoweverPIKASO will be the first clinical trial to test if metformin can prevent or delay the onset of post-traumatic osteoarthritis.

“Through our multi-institutional collaborationwe will not just evaluate the effect of metformin in pain reductionbut we will also measure changes in joint structure using advanced imaging techniques and functional improvements using cutting-edge biomechanics measurements,” says David FelsonMDMPHthe 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 LosinaPhDand Mass General Brigham to serve as the clinical coordinating center for the multisite PIKASO Project; Xiaojuan LiPhDand Cleveland Clinic to serve as the imaging center to coordinate collection and analysis of MRI data for the PIKASO Project; and Brian PietrosimonePhDATCand the University of North Carolina at Chapel Hill to coordinate biomechanical and functional assessments.

“The Arthritis Foundation has invested much thoughttime and resources into bringing the PIKASO project to fruition,” says Peggy CrowMDthe 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 PIKASOthat isexecuting a clinical trial that meets the highest standards of qualityethics and integrity.”