Olfactory Disfunction and Co-ultraPEALut

NCT04853836 | Completed Phase 4

• 1 other identifier: 20112020PGFN
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Anosmia; Covid19; Hyposmia; Parosmia; Treatment Compliance

Outcome Measures

Primary Outcomes (1)

• 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: 1. detection threshold ("T", the lowest concentration at which an odor can be perceived), 2. odor discrimination ("D", ability to distinguish between odors) and 3. 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 Outcomes (1)

• Parosmia after treatment

  60 days (T2) and 90 days (T3)

Study Arms (4)

Rehabilitation therapy only (control group)

PLACEBO COMPARATOR

Olfactory training / stimulation through Sniffin' Sticks, administered twice every day (10 minutes session)

Procedure: Olfactory Rehab

Rehabilitation and treatment with PEA-LUT

ACTIVE COMPARATOR

Olfactory training / stimulation through Sniffin' Sticks, plus daily treatment with PEA/Luteolin oral supplement

Combination Product: co-ultraPEALut

Treatment with PEA-LUT one sachet daily

ACTIVE COMPARATOR

Patients in this group only used a single dose of PEA-LUT

Drug: PEA-LUT 1 sachet

Treatment with PEA-LUT two sachet daily

ACTIVE COMPARATOR

Patients in this group only used two doses of PEA-LUT

Drug: PEA-LUT 2 sachet day

Interventions

co-ultraPEALut COMBINATION_PRODUCT

Olfactory rehab 10 minutes twice a day for all the observation period + co-ultraPEALut (700 PEA + 70 Luteolin) 1 dose daily.

Rehabilitation and treatment with PEA-LUT

Olfactory Rehab PROCEDURE

Olfactory Rehabilitation10 minutes twice a day for all the observation period

Rehabilitation therapy only (control group)

PEA-LUT 1 sachet DRUG

Only 1 sachet day of PEA-LUT no olfactory training

Treatment with PEA-LUT one sachet daily

PEA-LUT 2 sachet day DRUG

2 sachets day of PEA-LUT no olfactory training

Treatment with PEA-LUT two sachet daily

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Multicentric

Roma, Italy

Location

Related Publications (13)

• 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. No abstract available.

  PMID: 32329813 BACKGROUND

• Meinhardt J, Radke J, Dittmayer C, Franz J, Thomas C, Mothes R, Laue M, Schneider J, Brunink S, Greuel S, Lehmann M, Hassan O, Aschman T, Schumann E, Chua RL, Conrad C, Eils R, Stenzel W, Windgassen M, Rossler L, Goebel HH, Gelderblom HR, Martin H, Nitsche A, Schulz-Schaeffer WJ, Hakroush S, Winkler MS, Tampe B, Scheibe F, Kortvelyessy P, Reinhold D, Siegmund B, Kuhl 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.

  PMID: 33257876 BACKGROUND

• 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. No abstract available.

  PMID: 32614399 BACKGROUND

• 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.

  PMID: 32662745 BACKGROUND

• 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.

  PMID: 32930820 BACKGROUND

• Laurendon T, Radulesco T, Mugnier J, Gerault 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. No abstract available.

  PMID: 32444492 BACKGROUND

• 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. No abstract available.

  PMID: 33378608 BACKGROUND

• 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.

  PMID: 33415060 BACKGROUND

• 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.

  PMID: 23813098 BACKGROUND

• 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.

  PMID: 32314810 BACKGROUND

• 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.

  PMID: 28336953 BACKGROUND

• 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.

  PMID: 28731190 BACKGROUND

• O'Byrne L, Webster KE, MacKeith S, Philpott C, Hopkins C, Burton MJ. Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction. Cochrane Database Syst Rev. 2022 Sep 5;9(9):CD013876. doi: 10.1002/14651858.CD013876.pub3.

  PMID: 36062970 DERIVED

MeSH Terms

Conditions

Anosmia; COVID-19; Olfaction Disorders; Patient Compliance

Interventions

co-ultraPEALut

Condition Hierarchy (Ancestors)

Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The investor will assign patients to one of the groups before Sniff test evaluation at T0
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Adjunct Professor

Model Details: Single-blinded randomized clinical trial

Study Record Dates

• First Submitted: April 16, 2021
• First Posted: April 21, 2021
• Study Start: November 15, 2020
• Primary Completion: October 28, 2021
• Study Completion: August 31, 2022
• Last Updated: November 16, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Access Criteria: request to PI

Locations

IT (1)