Olfactory Disfunction and Co-ultraPEALut

Covid19 Clinical Trial

Official title:

Olfactory Disfunction After COVID-19: Conventional Therapy Versus Intervention Treatment With Co-ultraPEALut

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04853836
• Other study ID #: 20112020PGFN
• Status: Completed
• Phase: Phase 4
• Start date: November 15, 2020
• Est. completion date: August 31, 2022

Study information

• Verified date: November 2022
• Source: University Of Perugia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Patients ages 18 to 70 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 (T0). One group received daily olfactory training, 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), or 1 dose of PEA-LUT only or aTwo Dose of PEA-LUT.

Assessment of olfactory function will be repeated at 30 days, 60 and 90 and 120 days

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: August 31, 2022
• Est. primary completion date: October 28, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• 18 to 90 years with confirmed history of COVID-19 (positive nasopharyngeal swab for SARS-CoV-2)

• subjective olfactory dysfunction persisting = 90 days after follow-up negative COVID-19 nasopharyngeal swab

Exclusion Criteria:

• previous history of olfactory-gustatory disorders

• impaired cognitive function

• history of neurodegenerative disease

• medical therapy with possible effects on olfactory function

• presence of rhinological disorders (sinusitis, rhinosinusitis, sinonasal polyposis, atrophic rhinitis, allergy)

• history of chemo-radiotherapy of the head and neck region

• history of stroke or neurotrauma

• severe nasal blockage from stenosis of deformity

• severe psychiatric illness (e.g. schizophrenia, bipolar disorder, olfactory hallucination)

• previous sinonasal

• nasopharyngeal tumors.

Related Conditions & MeSH terms

• Anosmia
• COVID-19
• Covid19
• Hyposmia
• Olfaction Disorders
• Treatment Compliance

Intervention

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.

Procedure:
• Olfactory Rehab
Olfactory Rehabilitation10 minutes twice a day for all the observation period

Drug:
• PEA-LUT 1 sachet
Only 1 sachet day of PEA-LUT no olfactory training
• PEA-LUT 2 sachet day
2 sachets day of PEA-LUT no olfactory training

Locations

Country	Name	City	State
Italy	Multicentric	Roma

Sponsors (12)

Lead Sponsor

Collaborator

University Of Perugia

Azienda Ospedaliera Ospedali Riuniti Marche Nord, Italy, Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo, Azienda Ospedaliero Universitaria di Sassari, Azienda Ospedaliero-Universitaria Careggi, Federico II University, Humanitas Hospital, Italy, Istituto per la Sicurezza Sociale (ISS) della Repubblica di San Marino, Ospedale Bufalini di Cesena, Italy, Ospedale Universitario di Genova, Italy, Policlinico Universitario, Catania, San Giovanni Addolorata Hospital

Country where clinical trial is conducted

Italy, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recovery of smell	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	T1 (30 days), T2 (60 days), T3 (90 days)
Secondary	Parosmia after treatment	Prevalence of anosmia among the groups in the recovery	60 days (T2) and 90 days (T3)