Olfactory Disfunction and Co-ultraPEALut
Study Details
Study Description
Brief Summary
Olfactory dysfunction is common among patients with Corona-Virus-Infection-Disease (COVID)-19, and up to 30% of patients may report persistent disorders of smell or taste as a long-term sequelae. This randomized-controlled study has addressed to compare the efficacy of neuro-protective and anti-inflammatory agents palmitoylethanolamide (PEA) and Luteolin(Treatment) with control (olfactory training) in a cohort of patients who present persistent smell disorders after resolution from Covid-19 and negative swab for 4 months at least.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 4 |
Detailed Description
Patients ages 18 to 90 years with confirmed history of COVID-19 (positive nasopharyngeal swab for SARS-CoV-2) and subjective olfactory dysfunction persisting ≥ 90 days after follow-up negative COVID-19 nasopharyngeal swab are eligible.
All patients will undergo nasal endoscopic examination to look for presence of polyps, masses, anatomic blockage, or other pathology which presence will require exclusion from the study. Patients then will be evaluated at the baseline with Sniffin' Sticks (Burghardt®, Wedel, Germany) prior to initiating olfactory training and/or supplement treatment/nasal spray (T0). Three groups received weekly olfactory training, and patients in the supplement group additionally received a daily oral tablet that contained PEA 700 mg and Luteolin 70 mg (Glialia ®, Epitech pharmaceutical, Milano, Italy), while the one in spray group -nasal cortisone.
Assessment of olfactory function will be repeated at 30 days, 60 and 90 and 120 days
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Placebo Comparator: Rehabilitation therapy only (control group) Olfactory training / stimulation through Sniffin' Sticks, administered twice every day (10 minutes session) |
Procedure: Olfactory Rehab
Olfactory Rehabilitation10 minutes twice a day for all the observation period
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Active Comparator: Rehabilitation and treatment with PEA Olfactory training / stimulation through Sniffin' Sticks, plus daily treatment with PEA/Luteolin oral supplement |
Combination Product: co-ultraPEALut
Olfactory rehab 10 minutes twice a day for all the observation period + co-ultraPEALut (700 PEA + 70 Luteolin) 1 dose daily.
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Outcome Measures
Primary Outcome Measures
- Recovery of smell [T1 (30 days), T2 (60 days), T3 (90 days)]
Change of Sniff scores from T0.The Sniffin' Sticks battery was administered following a previously established protocol, using pen-like devices filled with odorants.Three score subtests were conducted to measure olfactory function: detection threshold ("T", the lowest concentration at which an odor can be perceived), odor discrimination ("D", ability to distinguish between odors) and odor identification ("I" ability to assign names to odors). Possible scores ranged from 1-16 for the detection threshold subtest and 0-16 for both the discrimination and identification subtests. Adding these for yielded a TDI "Sniff score." Anosmia was defined as a score of <17, hyposmia by a score 17 to 30.75, and normosmia by a score of ≥31
Secondary Outcome Measures
- Parosmia after treatment [60 days (T2) and 90 days (T3)]
Prevalence of anosmia among the groups in the recovery
Eligibility Criteria
Criteria
Inclusion Criteria:
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18 to 90 years with confirmed history of COVID-19 (positive nasopharyngeal swab for SARS-CoV-2)
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subjective olfactory dysfunction persisting ≥ 90 days after follow-up negative COVID-19 nasopharyngeal swab
Exclusion Criteria:
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previous history of olfactory-gustatory disorders
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impaired cognitive function
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history of neurodegenerative disease
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medical therapy with possible effects on olfactory function
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presence of rhinological disorders (sinusitis, rhinosinusitis, sinonasal polyposis, atrophic rhinitis, allergy)
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history of chemo-radiotherapy of the head and neck region
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history of stroke or neurotrauma
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severe nasal blockage from stenosis of deformity
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severe psychiatric illness (e.g. schizophrenia, bipolar disorder, olfactory hallucination)
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previous sinonasal
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nasopharyngeal tumors.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Multicentric | Roma | Italy |
Sponsors and Collaborators
- University Of Perugia
- Azienda Ospedaliera Ospedali Riuniti Marche Nord, Italy
- Federico II University
- Humanitas Hospital, Italy
- San Giovanni Addolorata Hospital
- Policlinico Universitario, Catania
- Azienda Ospedaliero-Universitaria Careggi
- Azienda Ospedaliero Universitaria di Sassari
- Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
- Ospedale Universitario di Genova, Italy
- Istituto per la Sicurezza Sociale (ISS) della Repubblica di San Marino
- Ospedale Bufalini di Cesena, Italy
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Chiu A, Fischbein N, Wintermark M, Zaharchuk G, Yun PT, Zeineh M. COVID-19-induced anosmia associated with olfactory bulb atrophy. Neuroradiology. 2021 Jan;63(1):147-148. doi: 10.1007/s00234-020-02554-1. Epub 2020 Sep 15.
- D'Ascanio L, Pandolfini M, Cingolani C, Latini G, Gradoni P, Capalbo M, Frausini G, Maranzano M, Brenner MJ, Di Stadio A. Olfactory Dysfunction in COVID-19 Patients: Prevalence and Prognosis for Recovering Sense of Smell. Otolaryngol Head Neck Surg. 2021 Jan;164(1):82-86. doi: 10.1177/0194599820943530. Epub 2020 Jul 14.
- Guida F, Luongo L, Boccella S, Giordano ME, Romano R, Bellini G, Manzo I, Furiano A, Rizzo A, Imperatore R, Iannotti FA, D'Aniello E, Piscitelli F, Sca Rossi F, Cristino L, Di Marzo V, de Novellis V, Maione S. Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor. Sci Rep. 2017 Mar 23;7(1):375. doi: 10.1038/s41598-017-00342-1.
- Laurendon T, Radulesco T, Mugnier J, Gérault M, Chagnaud C, El Ahmadi AA, Varoquaux A. Bilateral transient olfactory bulb edema during COVID-19-related anosmia. Neurology. 2020 Aug 4;95(5):224-225. doi: 10.1212/WNL.0000000000009850. Epub 2020 May 22.
- Lee MH, Perl DP, Nair G, Li W, Maric D, Murray H, Dodd SJ, Koretsky AP, Watts JA, Cheung V, Masliah E, Horkayne-Szakaly I, Jones R, Stram MN, Moncur J, Hefti M, Folkerth RD, Nath A. Microvascular Injury in the Brains of Patients with Covid-19. N Engl J Med. 2021 Feb 4;384(5):481-483. doi: 10.1056/NEJMc2033369. Epub 2020 Dec 30.
- Levy JM. Treatment Recommendations for Persistent Smell and Taste Dysfunction Following COVID-19-The Coming Deluge. JAMA Otolaryngol Head Neck Surg. 2020 Aug 1;146(8):733. doi: 10.1001/jamaoto.2020.1378.
- Meinhardt J, Radke J, Dittmayer C, Franz J, Thomas C, Mothes R, Laue M, Schneider J, Brünink S, Greuel S, Lehmann M, Hassan O, Aschman T, Schumann E, Chua RL, Conrad C, Eils R, Stenzel W, Windgassen M, Rößler L, Goebel HH, Gelderblom HR, Martin H, Nitsche A, Schulz-Schaeffer WJ, Hakroush S, Winkler MS, Tampe B, Scheibe F, Körtvélyessy P, Reinhold D, Siegmund B, Kühl AA, Elezkurtaj S, Horst D, Oesterhelweg L, Tsokos M, Ingold-Heppner B, Stadelmann C, Drosten C, Corman VM, Radbruch H, Heppner FL. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci. 2021 Feb;24(2):168-175. doi: 10.1038/s41593-020-00758-5. Epub 2020 Nov 30.
- Paniz-Mondolfi A, Bryce C, Grimes Z, Gordon RE, Reidy J, Lednicky J, Sordillo EM, Fowkes M. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol. 2020 Jul;92(7):699-702. doi: 10.1002/jmv.25915.
- Ralli M, Di Stadio A, Greco A, de Vincentiis M, Polimeni A. Defining the burden of olfactory dysfunction in COVID-19 patients. Eur Rev Med Pharmacol Sci. 2020 Apr;24(7):3440-3441. doi: 10.26355/eurrev_202004_20797.
- Skaper SD, Facci L, Giusti P. Glia and mast cells as targets for palmitoylethanolamide, an anti-inflammatory and neuroprotective lipid mediator. Mol Neurobiol. 2013 Oct;48(2):340-52. doi: 10.1007/s12035-013-8487-6. Epub 2013 Jun 28. Review.
- Stoyanov GS, Petkova L, Dzhenkov DL, Sapundzhiev NR, Todorov I. Gross and Histopathology of COVID-19 With First Histology Report of Olfactory Bulb Changes. Cureus. 2020 Dec 4;12(12):e11912. doi: 10.7759/cureus.11912.
- Tan D, Yu X, Chen M, Chen J, Xu J. Lutein protects against severe traumatic brain injury through anti-inflammation and antioxidative effects via ICAM-1/Nrf-2. Mol Med Rep. 2017 Oct;16(4):4235-4240. doi: 10.3892/mmr.2017.7040. Epub 2017 Jul 20.
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