Randomized, double-blind, placebo-controlled study to evaluate the effect of treatment with an SPMs-enriched oil on chronic pain and inflammation, functionality, and quality of life in patients with symptomatic knee osteoarthritis: GAUDI study

Abstract

Background Specialized pro-resolving mediators (SPMs), including 18-HEPE, 17-HDHA, and 14-HDHA are recognized as potentially therapeutic in inflammatory diseases because SPMs regulate the inflammation process, which leads to, for example; swelling and the sensation of pain. In osteoarthritis (OA), chronic pain is described as the symptom that reduces patients´ quality of life (QoL). The GAUDI study evaluated the efficacy of SPMs supplementation in reducing pain in the symptomatic knee of OA patients. Methods This randomized, multicenter, double-blind, and placebo-controlled parallel-group pilot study was performed in Spain and conducted on adults 18–68 years old diagnosed with symptomatic knee OA. Patients were enrolled in the study for up to 24 weeks, which included a 12-week intervention period and a follow-up visit on week 24. The primary endpoint was pain change measured through a Visual Analog Scale (VAS). Secondary endpoints included: Pain change evaluation, stiffness, and function according to the WOMAC index; assessment of constant, intermittent, and total pain according to the OMERACT-OARSI score; evaluation of changes in health-related QoL parameters; the use or not of concomitant, rescue, and anti-inflammatory medication; and safety and tolerability assessments. Results Patients were enrolled in the study from May 2018 to September 2021. VAS pain score was evaluated in the per protocol population (n = 51 patients), in which we observed a statistically significant reduction after 8 weeks (p = 0.039) and 12 weeks (p = 0.031) of treatment in patients consuming SPMs (n = 23 subjects) vs. placebo (n = 28 subjects). In line with the OMERACT-OARSI score, intermittent pain was reduced after 12 weeks with statistical significance (p = 0.019) in patients treated with SPMs (n = 23 subjects) vs. placebo (n = 28 subjects). Functional status as WOMAC score did not significantly change after SPMs or placebo consumption. Notably, patients consuming SPMs showed improvements in all five aspects of the EUROQoL-5, including a significant improvement in the usual-activities dimension. None of the patients required rescue medication, nor were any adverse events reported. Conclusions These findings suggest that sustained SPMs consumption reduces pain in OA patients while also improving their Quality of Life. These results also support the safety profile of SPMs supplementation. Trial registration NCT05633849. Registered 1 December 1 2022. Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT05633849

Pharmacokinetics and Changes in Lipid Mediator Profiling after Consumption of Specialized Pro-Resolving Lipid-Mediator-Enriched Marine Oil in Healthy Subjects

“…RvD3 was reduced in the serum of rheumatoid arthritis patients [56]. Furthermore, in line with the increased levels of SPMs in circulation, a recent randomized clinical study by Möller et al revealed that oral supplementation of marine oils led to reduced pain in individuals with symptomatic knee arthritis when compared to a placebo group [57]. Also, RvD1 was significantly reduced in vulnerable regions of atherosclerotic plaques [58].…”

Reorganization of innate immune cell lipid profiles by bioinspired meroterpenoids to limit inflammation

“…This approach was inspired from the current understanding of inflammation as a biphasic process of initiation and active resolution, [1] the latter being essentially regulated by lipid mediators with pro-resolving activity. [2d] While there is still some debate as to whether tri-hydroxylated SPMs in particular are produced in sufficient quantities to elicit a physiological response, [15] there is also strong evidence from animal studies that excess SPMs (e.g., upon injection) are highly effective in alleviating inflammation, [2d, 13] and initial clinical trials on SPM analogs [59] or SPM precursors [60] support anti-inflammatory and/or analgesic activity. As a result, the challenge for small molecule inflammation-resolving drugs is not only to increase SPM levels, but to increase them sufficiently to produce a pronounced and long-lasting effect.…”

Omega-3 Supplementation and Its Effects on Osteoarthritis

“…SPMs reduce pro-inflammatory immune cells, increase the production of anti-inflammatory mediators, and counter-regulate pro-inflammatory mediators [ 56 ]. At the cellular level, this occurs through macrophage phagocytosis of pathogens, apoptotic cells, and cellular debris, and limits the infiltration of neutrophils and reduces chemokine and cytokine mediators to promote tissue repair and regeneration.…”