A Double-Blind, RandoMised, Placebo-Controlled Study to Assess the Efficacy and Safety of oRal deliVery of sodium Pentosan Polysulfate (PPS) compared to placebo in participants with symptomatic kneE osteoarthritis (OA) and dysLipidemia (MaRVeL Study)

Estimated to affect one in eight adults, osteoarthritis (OA) is a highly disabling disease resulting in the unsurpassed risk for mobility disability, especially in those above 65 years of age. Medical treatments for OA have mainly targeted the symptoms of the disease, rather than the underlying pathologies responsible. Pain management with analgesics and steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) were, and still remain, the mainstay of treatment with joint replacement the only option for end-stage OA. There is no evidence that steroidal or NSAIDs provide any beneficial effects on the underlying pathologic abnormalities which exist in OA joints. Dyslipidaemia is the presence of abnormal concentrations of lipoproteins in the blood; more specifically, high levels of low-density lipoproteins (LDLs) and, usually, low levels of high-density lipoproteins (HDLs). Hypercholesterolemia was associated with both unilateral and bilateral knee OA and high serum cholesterol and/or triglycerides were associated with both knee and generalized OA. PPS mediates the release, from endothelial cells and the liver, of lipoprotein lipases which split triglycerides into free fatty acids and glycerol providing a lipolytic effect. PPS has other useful properties for the amelioration of the pathophysiology and symptoms of OA. It inhibits the formation of activated factor Xa resulting in a limited anti-coagulant activity. In human patients, a recent pilot open-label study (ACTRN12619000047190) conducted by the University of Sydney aimed to target dyslipidemia in OA participants by oral administration of PPS. Pain and function information from participants were collected to determine if improvements in dyslipidemia would also result in clinical improvements of symptoms associated with knee osteoarthritis. The study outcomes revealed oral PPS significantly improved pain, stiffness, and other functional measures in these patients. The study's secondary outcomes also showed a statistically significant decrease in total and LDL cholesterol and a positive change in self-reported outcomes and severity knee pain score, measured using KOOS and NRS scale together. The self-reported pain, stiffness, and functional outcomes show a significant positive improvement. This indicates good potential for the further randomized double-blinded placebo-controlled study to demonstrate the beneficial effects of PPS in knee osteoarthritis clinical outcomes.