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Study of the Evolution of Olfactory Disorders in Patients With Persistent Loss of Smell Following COVID-19 (ETOC)

Primary Purpose

SARS-CoV-2 Acute Respiratory Disease

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Clinical examination
Blood collection
Olfactory evoked potentials
Brushing of olfactory slits
Neurological examination and neuropsychological assessment
Nasal endoscopy
Assessment of olfactory and taste functions
Sponsored by
Institut Pasteur
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for SARS-CoV-2 Acute Respiratory Disease focused on measuring Neuroinflammation, coronavirus, olfaction disorder, evoked potentials

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adults < 55 years
  • History of symptomatic COVID over 1 year +/- 4 months with a positive PCR diagnosis of SARS-CoV-2
  • Olfactory complaint
  • Able to understand simple questionnaires in French.
  • Subject covered by French Social Security (except for Aide Médicale d'Etat).

Exclusion Criteria:

  • Contraindication to nasal swabbing (for morphological reasons, haemostasis disorders, taking aspirin in the 15 days prior to swabbing or anticoagulants, contraindications to the use of a local anaesthetic such as a history of allergy to local anaesthetics or any other reasons judged by the clinical investigator)
  • To have been placed in the intensive care unit following COVID-19.
  • Known previous nasal-sinus pathology.
  • History of psychiatric pathology according to DSM IV criteria, ischaemic, neoplastic, inflammatory, infectious or neurodegenerative (meningitis, encephalopathy, encephalitis, stroke, neurodegenerative disease) known or suspected.
  • History of loss of sense of smell prior to COVID infection.
  • Patient affiliated to the Aide Médicale d'Etat.
  • Person deprived of liberty by judicial or administrative decision, or subject to legal protection.

Sites / Locations

  • Hôpital LariboisièreRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Study population

Arm Description

Adult subjects up to 55 years of age with persistent olfaction disorder after a symptomatic episode of COVID-19.

Outcomes

Primary Outcome Measures

Measurement of olfactory responses by PEO recording and by calculating the TDI score of the Sniffin'stick tests.
To characterise the evolution of the olfactory capacities of patients suffering from persistent odour disorders following SARS-CoV-2 infection over the course of a year.

Secondary Outcome Measures

Measurement of olfactory perception threshold, olfactory discrimination capacity and odour identification.
Describe the olfactory performance
To characterise the persistence of SARS-CoV-2 in the olfactory epithelium.
Characterisation of the presence of SARS-CoV-2 by PCR in the olfactory mucosa.
To characterise any damage to the olfactory nerve
Mapping analysis of the olfactory nerve of COVID-19 patients by MRI tractography technique.
To identify the presence of inflammatory markers in patients.
Measurement of cellular and inflammatory markers in the olfactory mucosa.
Detection and measurement of markers of neurological disorders in the blood.
To identify the neurological damage in patients.
Measurement of patients' cognitive performance by neuropsychological assessment (standardised tests).
To identify possible cognitive abnormalities in these patients with prolonged loss of smell.

Full Information

First Posted
November 23, 2021
Last Updated
October 10, 2023
Sponsor
Institut Pasteur
Collaborators
Hopital Lariboisière
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1. Study Identification

Unique Protocol Identification Number
NCT05133596
Brief Title
Study of the Evolution of Olfactory Disorders in Patients With Persistent Loss of Smell Following COVID-19
Acronym
ETOC
Official Title
Study of the Evolution of Olfactory Disorders in Patients With Persistent Loss of Smell Following COVID-19
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 20, 2022 (Actual)
Primary Completion Date
January 9, 2024 (Anticipated)
Study Completion Date
January 9, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Pasteur
Collaborators
Hopital Lariboisière

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The COVID-19 pandemic is a novel medical challenge, particularly because of the systemic nature of this disease. Indeed, COVID-19 affects several organs and systems at once. The brain is affected in several ways: direct infection of nerve cells by SARS-CoV-2, inflammation of the central nervous system, severe systemic inflammation damaging nerve cells, global cerebral ischaemia related to respiratory failure, thromboembolic events related to increased intravascular coagulation and severe psychological stress. As a result, COVID-19 sometimes manifests as neurological and neuropsychiatric symptoms such as dizziness, sleep disturbances, cognitive deficits, delirium, or severe depression. Sudden loss of smell is a common symptom associated with COVID-19 and SARS-CoV-2 infection of neurons in the olfactory system has been reported in both hamsters and humans. The vast majority of COVID-19 patients recover their olfactory function within a few weeks. However, a significant minority of infected individuals (1 in 5 cases) still suffers from olfactory disorders (anosmia, hyposmia and/or parosmia) several months after the primary infection. These olfactory disorders are frequently associated with depressive behaviour and cognitive complaints. In PET scans, it is even possible to correlate this cognitive dysfunction with hypometabolism of certain brain regions, including the olfactory gyrus. This project proposes, during one year, to evaluate and follow the evolution of the olfactory capacities of patients suffering from persistent smell disorder since one year (+/- 4 months) following COVID-19. The issue is to study the link between viral persistence in the olfactory sensory organ, chronic inflammation, and central damage to the olfactory system. The follow-up of the evolution of olfactory and neurocognitive capacities, in an integrative way by means of molecular, physiological and behavioural approaches, will inform us on the specificities of "COVID-long" and on the level of peripheral and/or central damage of the olfactory system.
Detailed Description
Prospective monocentric descriptive study. Evaluation of COVID-19 patients with persistent loss of smell during 2 visits at 1 year intervals (V1 and V2). V1 :The following examinations will be carried out specifically for the research. Clinical examination; Blood sampling; Recording of olfactory evoked potentials; Neurological examination and neuropsychological assessment; V2 : All examinations performed at V1 will be repeated at V2. If the following examinations are not carried out during care within 3 weeks of V2, they will be carried out as part of the research during this V2 visit. Nasal endoscopy ; Assessment of olfactory and gustatory functions. The following explorations will be carried out: Passing of two olfactory and gustatory scales; Olfactory and gustatory disorders will be quantified using two scales, the visual analogue scale VAS and the modified TSS; Sniffin Stick test. In addition, MRI data from clinical care will be collected.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
SARS-CoV-2 Acute Respiratory Disease
Keywords
Neuroinflammation, coronavirus, olfaction disorder, evoked potentials

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Adult subjects up to 55 years of age with persistent olfaction disorder after a symptomatic episode of COVID-19.
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Study population
Arm Type
Experimental
Arm Description
Adult subjects up to 55 years of age with persistent olfaction disorder after a symptomatic episode of COVID-19.
Intervention Type
Other
Intervention Name(s)
Clinical examination
Intervention Description
The investigator will conduct a clinical examination to rule out other causes of olfactory impairment independent of COVID-19. The investigator will also collect the following information: socio-demographic data (age, sex, blood type, weight, height, etc.), history of olfaction disorder symptoms, past or current treatments received and tobacco/alcohol consumption.
Intervention Type
Other
Intervention Name(s)
Blood collection
Intervention Description
12ml-blood sample
Intervention Type
Other
Intervention Name(s)
Olfactory evoked potentials
Intervention Description
Olfactory evoked potentials will be recorded during olfactory tests.
Intervention Type
Other
Intervention Name(s)
Brushing of olfactory slits
Intervention Description
collection of olfactory slits cells.
Intervention Type
Other
Intervention Name(s)
Neurological examination and neuropsychological assessment
Intervention Description
MOCA, BREF CVLT WAIS IV, MEM III Right-side and left-side empan, Trail Making Test A and B (TMT), verbal fluency tests, PASAT, Attention Assessment Test Benton's Line Judgement, VOSP Assessment of psychological status, fatigue and screening for psychiatric comorbidities: depression & anxiety scales (HAD scale, mADRS depression scale, STAI anxiety scale), Fatigue Severity Scale.
Intervention Type
Other
Intervention Name(s)
Nasal endoscopy
Intervention Description
Nasal endoscopy
Intervention Type
Other
Intervention Name(s)
Assessment of olfactory and taste functions
Intervention Description
scales: VAS and TSS Sniffin Stick test
Primary Outcome Measure Information:
Title
Measurement of olfactory responses by PEO recording and by calculating the TDI score of the Sniffin'stick tests.
Description
To characterise the evolution of the olfactory capacities of patients suffering from persistent odour disorders following SARS-CoV-2 infection over the course of a year.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Measurement of olfactory perception threshold, olfactory discrimination capacity and odour identification.
Description
Describe the olfactory performance
Time Frame
24 months
Title
To characterise the persistence of SARS-CoV-2 in the olfactory epithelium.
Description
Characterisation of the presence of SARS-CoV-2 by PCR in the olfactory mucosa.
Time Frame
24 months
Title
To characterise any damage to the olfactory nerve
Description
Mapping analysis of the olfactory nerve of COVID-19 patients by MRI tractography technique.
Time Frame
24 months
Title
To identify the presence of inflammatory markers in patients.
Description
Measurement of cellular and inflammatory markers in the olfactory mucosa.
Time Frame
24 months
Title
Detection and measurement of markers of neurological disorders in the blood.
Description
To identify the neurological damage in patients.
Time Frame
24 months
Title
Measurement of patients' cognitive performance by neuropsychological assessment (standardised tests).
Description
To identify possible cognitive abnormalities in these patients with prolonged loss of smell.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adults < 55 years History of symptomatic COVID over 1 year +/- 4 months with a positive PCR diagnosis of SARS-CoV-2 Olfactory complaint Able to understand simple questionnaires in French. Subject covered by French Social Security (except for Aide Médicale d'Etat). Exclusion Criteria: Contraindication to nasal swabbing (for morphological reasons, haemostasis disorders, taking aspirin in the 15 days prior to swabbing or anticoagulants, contraindications to the use of a local anaesthetic such as a history of allergy to local anaesthetics or any other reasons judged by the clinical investigator) To have been placed in the intensive care unit following COVID-19. Known previous nasal-sinus pathology. History of psychiatric pathology according to DSM IV criteria, ischaemic, neoplastic, inflammatory, infectious or neurodegenerative (meningitis, encephalopathy, encephalitis, stroke, neurodegenerative disease) known or suspected. History of loss of sense of smell prior to COVID infection. Patient affiliated to the Aide Médicale d'Etat. Person deprived of liberty by judicial or administrative decision, or subject to legal protection.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pierre-Marie Lledo, Prof.
Phone
33 1 45688803
Email
pierre-marie.lledo@pasteur.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pierre-Marie Lledo, Prof.
Organizational Affiliation
Institut Pasteur
Official's Role
Study Director
Facility Information:
Facility Name
Hôpital Lariboisière
City
Paris
ZIP/Postal Code
75010
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charlotte Hautefort, MD
Phone
33 1 49959197
Email
charlotte.hautefort@aphp.fr

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of the Evolution of Olfactory Disorders in Patients With Persistent Loss of Smell Following COVID-19

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