Background: Olfactory training is the only evidence-based treatment for post viral olfactory dysfunction. Smell disorders after SARS-CoV-2 infection have been attributed to neuroinflammatory events within the olfactory bulb and the central nervous system. Therefore, targeting neuroinflammation is one potential strategy for promoting recovery from post-COVID-19 chronic olfactory dysfunction. Palmitoylethanolamide and luteolin (PEA-LUT) are candidate anti-inflammatory/ neuroprotective agents. Objective: To investigate recovery of olfactory function in patients treated with PEA-LUT oral supplements plus olfactory training versus olfactory training plus placebo. Methods: Multicenter double-blinded randomized placebo-controlled clinical trial. Eligible subjects had prior COVID-19 and persistent olfactory impairment >6 months after follow-up SARS-CoV-2 negative testing, without prior history of olfactory dysfunction sinonasal disorders. Participants were randomized to daily oral supplementation with ultramicronized PEA-LUT 770 mg plus olfactory training (intervention group) or olfactory training with placebo (control). Sniffin' Sticks assessments were used to test the patients at baseline and 90 days. Results: A total of 185 patients, including intervention (130) and control (55) were enrolled. The intervention group showed significantly greater improvement in olfactory threshold, discrimination, and identification scores compared to controls (p=0.0001). Overall, 92% of patients in the intervention group improved versus 42% of controls. Magnitude of recovery was significantly greater in the intervention group versus control (12.8 + 8.2 versus mean 3.2 + 3), with >10-fold higher prevalence of anosmia in control versus intervention groups at the 90-day endpoint. Conclusion: Among individuals with olfactory dysfunction post COVID-19, combining PEA-LUT with olfactory training resulted in greater recovery of smell than olfactory training alone. (ITALIAN; Clinicaltrials.gov number: NCT04853836).

Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo-Controlled Clinical Trial / Di Stadio, Arianna; D'Ascanio, Luca; Vaira, Luigi Angelo; Cantone, Elena; De Luca, Pietro; Cingolani, Cristina; Motta, Gaetano; De Riu, Giacomo; Vitelli, Federica; Spriano, Giuseppe; De Vincentiis, Marco; Camaioni, Angelo; La Mantia, Ignazio; Ferreli, Fabio; Brenner, Michael J. - In: CURRENT NEUROPHARMACOLOGY. - ISSN 1570-159X. - 20:(2022). [10.2174/1570159X20666220420113513]

Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo-Controlled Clinical Trial

Vaira, Luigi Angelo;Cantone, Elena;Motta, Gaetano;
2022

Abstract

Background: Olfactory training is the only evidence-based treatment for post viral olfactory dysfunction. Smell disorders after SARS-CoV-2 infection have been attributed to neuroinflammatory events within the olfactory bulb and the central nervous system. Therefore, targeting neuroinflammation is one potential strategy for promoting recovery from post-COVID-19 chronic olfactory dysfunction. Palmitoylethanolamide and luteolin (PEA-LUT) are candidate anti-inflammatory/ neuroprotective agents. Objective: To investigate recovery of olfactory function in patients treated with PEA-LUT oral supplements plus olfactory training versus olfactory training plus placebo. Methods: Multicenter double-blinded randomized placebo-controlled clinical trial. Eligible subjects had prior COVID-19 and persistent olfactory impairment >6 months after follow-up SARS-CoV-2 negative testing, without prior history of olfactory dysfunction sinonasal disorders. Participants were randomized to daily oral supplementation with ultramicronized PEA-LUT 770 mg plus olfactory training (intervention group) or olfactory training with placebo (control). Sniffin' Sticks assessments were used to test the patients at baseline and 90 days. Results: A total of 185 patients, including intervention (130) and control (55) were enrolled. The intervention group showed significantly greater improvement in olfactory threshold, discrimination, and identification scores compared to controls (p=0.0001). Overall, 92% of patients in the intervention group improved versus 42% of controls. Magnitude of recovery was significantly greater in the intervention group versus control (12.8 + 8.2 versus mean 3.2 + 3), with >10-fold higher prevalence of anosmia in control versus intervention groups at the 90-day endpoint. Conclusion: Among individuals with olfactory dysfunction post COVID-19, combining PEA-LUT with olfactory training resulted in greater recovery of smell than olfactory training alone. (ITALIAN; Clinicaltrials.gov number: NCT04853836).
2022
Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo-Controlled Clinical Trial / Di Stadio, Arianna; D'Ascanio, Luca; Vaira, Luigi Angelo; Cantone, Elena; De Luca, Pietro; Cingolani, Cristina; Motta, Gaetano; De Riu, Giacomo; Vitelli, Federica; Spriano, Giuseppe; De Vincentiis, Marco; Camaioni, Angelo; La Mantia, Ignazio; Ferreli, Fabio; Brenner, Michael J. - In: CURRENT NEUROPHARMACOLOGY. - ISSN 1570-159X. - 20:(2022). [10.2174/1570159X20666220420113513]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/883117
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