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| Name | Class |
|---|---|
| Azienda Ospedaliera Ospedali Riuniti Marche Nord, Italy | UNKNOWN |
| Federico II University | OTHER |
| Humanitas Hospital, Italy | OTHER |
| San Giovanni Addolorata Hospital |
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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rehabilitation therapy only (control group) | Placebo Comparator | Olfactory training / stimulation through Sniffin' Sticks, administered twice every day (10 minutes session) |
|
| Rehabilitation and treatment with PEA-LUT | Active Comparator | Olfactory training / stimulation through Sniffin' Sticks, plus daily treatment with PEA/Luteolin oral supplement |
|
| Treatment with PEA-LUT one sachet daily | Active Comparator | Patients in this group only used a single dose of PEA-LUT |
|
| Treatment with PEA-LUT two sachet daily | Active Comparator | Patients in this group only used two doses of PEA-LUT |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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:
| T1 (30 days), T2 (60 days), T3 (90 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Parosmia after treatment | Prevalence of anosmia among the groups in the recovery | 60 days (T2) and 90 days (T3) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Multicentric | Roma | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32329813 | Background | 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. | |
| 33257876 | 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. |
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Shared, only anonymized data directly requested to PI
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request to PI
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| ID | Term |
|---|---|
| D000086582 | Anosmia |
| D000086382 | COVID-19 |
| D000857 | Olfaction Disorders |
| D010349 | Patient Compliance |
| ID | Term |
|---|---|
| D012678 | Sensation Disorders |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
Not provided
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| ID | Term |
|---|---|
| C000610984 | co-ultraPEALut |
Not provided
Not provided
Not provided
| OTHER |
| Policlinico Universitario, Catania | OTHER |
| Azienda Ospedaliero-Universitaria Careggi | OTHER |
| Azienda Ospedaliero Universitaria di Sassari | OTHER |
| Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo | OTHER |
| Ospedale Universitario di Genova, Italy | UNKNOWN |
| Istituto per la Sicurezza Sociale (ISS) della Repubblica di San Marino | UNKNOWN |
| Ospedale Bufalini di Cesena, Italy | UNKNOWN |
Single-blinded randomized clinical trial
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The investor will assign patients to one of the groups before Sniff test evaluation at T0
| Olfactory Rehab | Procedure | Olfactory Rehabilitation10 minutes twice a day for all the observation period |
|
| PEA-LUT 1 sachet | Drug | Only 1 sachet day of PEA-LUT no olfactory training |
|
| PEA-LUT 2 sachet day | Drug | 2 sachets day of PEA-LUT no olfactory training |
|
| 32614399 | 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. |
| 32662745 | 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. |
| 32930820 | 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. |
| 32444492 | 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. |
| 33378608 | 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. |
| 33415060 | 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. |
| 23813098 | 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. |
| 32314810 | 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. |
| 28336953 | 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. |
| 28731190 | 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. |
| 36062970 | Derived | 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. |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D010342 | Patient Acceptance of Health Care |
| D000074822 | Treatment Adherence and Compliance |
| D015438 | Health Behavior |
| D001519 | Behavior |