Olfactory Disfunction and Co-ultraPEALut

Study Overview
=================
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.

Detailed 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

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

Conditions
-----------------
Anosmia, Covid19, Hyposmia, Parosmia, Treatment Compliance

Intervention / Treatment
-----------------
* Combination Product: co-ultraPEALut
* Procedure: Olfactory Rehab
* Drug: PEA-LUT 1 sachet
* Drug: PEA-LUT 2 sachet day


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-blinded randomized clinical trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Rehabilitation therapy only (control group)<br>Olfactory training / stimulation through Sniffin' Sticks, administered twice every day (10 minutes session) | Procedure: Olfactory Rehab<br>* Olfactory Rehabilitation10 minutes twice a day for all the observation period<br>|
| Active Comparator: Rehabilitation and treatment with PEA-LUT<br>Olfactory training / stimulation through Sniffin' Sticks, plus daily treatment with PEA/Luteolin oral supplement | Combination Product: co-ultraPEALut<br>* Olfactory rehab 10 minutes twice a day for all the observation period + co-ultraPEALut (700 PEA + 70 Luteolin) 1 dose daily.<br>|
| Active Comparator: Treatment with PEA-LUT one sachet daily<br>Patients in this group only used a single dose of PEA-LUT | Drug: PEA-LUT 1 sachet<br>* Only 1 sachet day of PEA-LUT no olfactory training<br>|
| Active Comparator: Treatment with PEA-LUT two sachet daily<br>Patients in this group only used two doses of PEA-LUT | Drug: PEA-LUT 2 sachet day<br>* 2 sachets day of PEA-LUT no olfactory training<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | 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: 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parosmia after treatment | Prevalence of anosmia among the groups in the recovery | 60 days (T2) and 90 days (T3) |