Targeting Senescence to Reduce Osteoarthritis Pain and cartilagE Breakdown (ROPE)
Status:
Not yet recruiting
Trial end date:
2024-05-31
Target enrollment:
Participant gender:
Summary
Symptomatic knee osteoarthritis (OA) is the most common joint disorder in the U.S. and a
leading cause of disability. Increasing age, obesity, and previous injury increase the
lifetime risk of knee OA, but these factors are also independently associated with increased
cellular senescence. Senescent cells accumulate in many tissues and contribute to chronic
pathologies, linked to the secretion of pro-inflammatory factors collectively known as the
senescence-associated secretory phenotype. In OA, senescent cells promote production of
cytokines, chemokines, and matrix-degrading enzymes involved in progressive cartilage
breakdown. The senolytic supplement fisetin alters the inflammatory and catabolic cartilage
responses, which may clinically lessen OA pain while also slowing progressive cartilage
breakdown. The purpose of this double-blind, randomized clinical trial is to compare 2
fisetin dosing regimens versus placebo. Sixty patients with mild to moderate knee OA will be
assessed at baseline and 3 months in an effort to: determine if 2 different fisetin dosing
regimens lessen pain and functional impairment compared to placebo, compare progressive
changes in senescent cell activity and biomarkers of cartilage degradation between different
fisetin dosing regimens and placebo, and assess acceptability and feasibility of 2 fisetin
dosing regimens.