<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04427332</url>
  </required_header>
  <id_info>
    <org_study_id>COVID-19 ORL</org_study_id>
    <nct_id>NCT04427332</nct_id>
  </id_info>
  <brief_title>Smell and Taste Disorders in COVID-19 Patients</brief_title>
  <acronym>COVID-19 ORL</acronym>
  <official_title>Smell and Taste Disorders in COVID-19 Patients: Prospective Observational Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Milano Bicocca</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Milano Bicocca</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective monocentric observational study with the aim of investigating the&#xD;
      demographic and clinical factors related to the smell and taste disorders in patients with&#xD;
      Severe Acute Respiratory Syndrome - Coronavirus - 2 (Sars-Cov-2) infection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND:&#xD;
&#xD;
      Preliminary observational data collected by Otorhinolaryngologist at the San Gerardo Hospital&#xD;
      in Monza and by literature evidenced that numerous patients suffering from Sars-CoV-2&#xD;
      infection had smell and taste disorders. The are many data in the literature but few&#xD;
      validated studies are available. Furthermore, it is not yet known in these patients what&#xD;
      factors are related to the presence of olfactory and gustatory symptoms.&#xD;
&#xD;
      The aim of the study is to identify the demographic and clinical factors related to the smell&#xD;
      and taste disorders in patients with Sars-CoV-2 infection, to evaluate the evolution of&#xD;
      symptoms with a follow-up and to evaluate which factors influence the improvement of that&#xD;
      symptoms.&#xD;
&#xD;
      STUDY DESIGN:&#xD;
&#xD;
      The study will include patients diagnosed with Sars-CoV-2 infection who have been&#xD;
      hospitalized in the COVID wards of the San Gerardo Hospital in Monza and non-hospitalized&#xD;
      patients but that get access to the &quot;nasopharyngeal swabs&quot; service of the hospital for the&#xD;
      detection of the Sars-CoV-2 virus.&#xD;
&#xD;
      The study includes 3 timepoints. After acquiring informed consent, patient will be contacted&#xD;
      on the phone and he will be asked to answer a multiple or short-answer questionnaire (T0)&#xD;
      aimed at collecting demographic and clinical data, in particular relating to the smell and&#xD;
      taste disorders, which will take place approximately 24 hours after running the swab.&#xD;
      Follow-up period will follow, which will require patients to be contacted and invited by the&#xD;
      Investigator to repeat the telephone questionnaire respectively 1 month (T1) and 3 months&#xD;
      (T2) from the first compilation (T0).&#xD;
&#xD;
      The following information will be collected and recorded on a paper CRF:&#xD;
&#xD;
        -  registry collection (date of birth, gender at birth)&#xD;
&#xD;
        -  origin of the subjects: hospitalized, not hospitalized&#xD;
&#xD;
        -  pathological, pharmacological history, allergies, smoking, flu vaccination&#xD;
&#xD;
        -  date of onset of COVID19 symptoms&#xD;
&#xD;
        -  smell and taste symptoms and temporal correlation with systemic symptoms (fever,&#xD;
           dyspnoea, headache, rhinitis, gastrointestinal symptoms, arthralgias, skin&#xD;
           manifestations)&#xD;
&#xD;
        -  date of regression of the smell and taste symptoms&#xD;
&#xD;
      STATISCAL ANALYSIS:&#xD;
&#xD;
      A logistic regression model is used to identify what the clinical and demographic factors&#xD;
      associated with the onset of the disease of interest are.&#xD;
&#xD;
      The composite endpoint consisting of the presence of smell and / or taste disorders vs the&#xD;
      absence of both pathologies will be used as a variable. The secondary analyzes will concern&#xD;
      only the subjects who have declared that they have had the disease in the study and, through&#xD;
      a logistic or ordinal regression model, we will try to identify which factors are associated&#xD;
      with the positive evolution of the disease at T3 compared to T0.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 11, 2020</start_date>
  <completion_date type="Actual">October 16, 2020</completion_date>
  <primary_completion_date type="Actual">October 16, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Identification of demographic and clinical factors in covid19 patients.</measure>
    <time_frame>Until patient discharge from the hospital (approximately four months)</time_frame>
    <description>Identify the demographic and clinical factors related to the sense of smell and taste in patients with Sars-CoV-2 infection included in the study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Description of the disturbances of smell and taste</measure>
    <time_frame>Until patient discharge from the hospital (approximately four months)</time_frame>
    <description>Description in patients with Sars-CoV-2 infection the evolution of the symptoms (disturbances of smell and taste) understood as partial or total regression by 1-month and 3-month follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Description of factors that influence smell and taste</measure>
    <time_frame>Until patient discharge from the hospital (approximately four months).</time_frame>
    <description>Define which factors (demographic and clinical) influence the improvement of the sense of smell and taste</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">376</enrollment>
  <condition>covid19</condition>
  <arm_group>
    <arm_group_label>Covid19 infection related patients</arm_group_label>
    <description>All subjects that had access to the &quot;nasopharyngeal swabs&quot; service of the hospital for the detection of the Sars-CoV-2 virus, both hospitalized and discharged from the hospital and not hospitalized, from mid-May to the end of June 2020, will be consecutively enrolled. It is assumed that 500 people will be recruited.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Investigation of smell and taste disorders</intervention_name>
    <description>The study consists of an epidemiological investigation by means of a prospective observational study with the aim of investigating the demographic and clinical factors related to the sense of smell and taste in patients with Sars Cov 2 infection.</description>
    <arm_group_label>Covid19 infection related patients</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        All subjects belonging to the nasopharyngeal swabs service for the detection of the&#xD;
        Sars-CoV-2 virus, both discharged from the hospital and not hospitalized, who will meet the&#xD;
        inclusion / exclusion criteria, from mid-May until the end of June 2020 will be&#xD;
        consecutively enrolled. It is assumed to recruit about 500 subjects.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The study should include patients diagnosed of Sars-Cov-2 infection carried out at the&#xD;
             San Gerardo Hospital of Monza:&#xD;
&#xD;
               -  discharged from the COVID + wards of the San Gerardo Hospital in Monza&#xD;
&#xD;
               -  not hospitalized subjected to nasopharyngeal swab for Sars-Cov-2 at the San&#xD;
                  Gerardo Hospital in Monza:&#xD;
&#xD;
          2. Patients older than or equal to 18 years.&#xD;
&#xD;
          3. The informed consent that will be freely granted and acquired before the start of the&#xD;
             study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients without ascertained diagnosis of Sars-Cov-2 infection carried out at San&#xD;
             Gerardo Hospital in Monza;&#xD;
&#xD;
          2. Patients with previous or current documented rhinosinusal pathologies, previous&#xD;
             rhinosinusal surgery, previous cranio-facial trauma, previous neurosurgical and&#xD;
             maxillofacial surgery interventions conditioning neurological or sensorineural&#xD;
             deficits at the rhinosinusal level, neuropsychiatric pathologies.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>ASST Monza-Ospedale San Gerardo</name>
      <address>
        <city>Monza</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Baig AM. Neurological manifestations in COVID-19 caused by SARS-CoV-2. CNS Neurosci Ther. 2020 May;26(5):499-501. doi: 10.1111/cns.13372. Epub 2020 Apr 7. No abstract available.</citation>
    <PMID>32266761</PMID>
  </reference>
  <reference>
    <citation>Hummel T, Whitcroft KL, Andrews P, Altundag A, Cinghi C, Costanzo RM, Damm M, Frasnelli J, Gudziol H, Gupta N, Haehne A, Holbrook E, Hong SC, Hornung D, Huttenbrink KB, Kamel R, Kobayashi M, Konstantinidis I, Landis BN, Leopold DA, Macchi A, Miwa T, Moesges R, Mullol J, Mueller CA, Ottaviano G, Passali GC, Philpott C, Pinto JM, Ramakrishnan VJ, Rombaux P, Roth Y, Schlosser RA, Shu B, Soler G, Stjarne P, Stuck BA, Vodicka J, Welge-Luessen A. Position paper on olfactory dysfunction. Rhinol Suppl. 2017 Mar;54(26):1-30. doi: 10.4193/Rhino16.248.</citation>
    <PMID>29528615</PMID>
  </reference>
  <reference>
    <citation>Fonteyn S, Huart C, Deggouj N, Collet S, Eloy P, Rombaux P. Non-sinonasal-related olfactory dysfunction: A cohort of 496 patients. Eur Ann Otorhinolaryngol Head Neck Dis. 2014 Apr;131(2):87-91. doi: 10.1016/j.anorl.2013.03.006. Epub 2014 Mar 26.</citation>
    <PMID>24679542</PMID>
  </reference>
  <reference>
    <citation>Klopfenstein T, Kadiane-Oussou NJ, Toko L, Royer PY, Lepiller Q, Gendrin V, Zayet S. Features of anosmia in COVID-19. Med Mal Infect. 2020 Aug;50(5):436-439. doi: 10.1016/j.medmal.2020.04.006. Epub 2020 Apr 17.</citation>
    <PMID>32305563</PMID>
  </reference>
  <reference>
    <citation>Nordin S, Bramerson A. Complaints of olfactory disorders: epidemiology, assessment and clinical implications. Curr Opin Allergy Clin Immunol. 2008 Feb;8(1):10-5. doi: 10.1097/ACI.0b013e3282f3f473.</citation>
    <PMID>18188011</PMID>
  </reference>
  <reference>
    <citation>Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020 Jun;92(6):552-555. doi: 10.1002/jmv.25728. Epub 2020 Mar 11.</citation>
    <PMID>32104915</PMID>
  </reference>
  <reference>
    <citation>Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X, Li Y, Hu B. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 Jun 1;77(6):683-690. doi: 10.1001/jamaneurol.2020.1127.</citation>
    <PMID>32275288</PMID>
  </reference>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>January 26, 2021</last_update_submitted>
  <last_update_submitted_qc>January 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Coronavirus</keyword>
  <keyword>sars-covid-2</keyword>
  <keyword>coronavirus infection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Taste Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04427332
org study id: COVID-19 ORL
nct id: NCT04427332
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a prospective monocentric observational study with the aim of investigating the
      demographic and clinical factors related to the smell and taste disorders in patients with
      Severe Acute Respiratory Syndrome - Coronavirus - 2 (Sars-Cov-2) infection.
BACKGROUND:

      Preliminary observational data collected by Otorhinolaryngologist at the San Gerardo Hospital
      in Monza and by literature evidenced that numerous patients suffering from Sars-CoV-2
      infection had smell and taste disorders. The are many data in the literature but few
      validated studies are available. Furthermore, it is not yet known in these patients what
      factors are related to the presence of olfactory and gustatory symptoms.

      The aim of the study is to identify the demographic and clinical factors related to the smell
      and taste disorders in patients with Sars-CoV-2 infection, to evaluate the evolution of
      symptoms with a follow-up and to evaluate which factors influence the improvement of that
      symptoms.

      STUDY DESIGN:

      The study will include patients diagnosed with Sars-CoV-2 infection who have been
      hospitalized in the COVID wards of the San Gerardo Hospital in Monza and non-hospitalized
      patients but that get access to the "nasopharyngeal swabs" service of the hospital for the
      detection of the Sars-CoV-2 virus.

      The study includes 3 timepoints. After acquiring informed consent, patient will be contacted
      on the phone and he will be asked to answer a multiple or short-answer questionnaire (T0)
      aimed at collecting demographic and clinical data, in particular relating to the smell and
      taste disorders, which will take place approximately 24 hours after running the swab.
      Follow-up period will follow, which will require patients to be contacted and invited by the
      Investigator to repeat the telephone questionnaire respectively 1 month (T1) and 3 months
      (T2) from the first compilation (T0).

      The following information will be collected and recorded on a paper CRF:

        -  registry collection (date of birth, gender at birth)

        -  origin of the subjects: hospitalized, not hospitalized

        -  pathological, pharmacological history, allergies, smoking, flu vaccination

        -  date of onset of COVID19 symptoms

        -  smell and taste symptoms and temporal correlation with systemic symptoms (fever,
           dyspnoea, headache, rhinitis, gastrointestinal symptoms, arthralgias, skin
           manifestations)

        -  date of regression of the smell and taste symptoms

      STATISCAL ANALYSIS:

      A logistic regression model is used to identify what the clinical and demographic factors
      associated with the onset of the disease of interest are.

      The composite endpoint consisting of the presence of smell and / or taste disorders vs the
      absence of both pathologies will be used as a variable. The secondary analyzes will concern
      only the subjects who have declared that they have had the disease in the study and, through
      a logistic or ordinal regression model, we will try to identify which factors are associated
      with the positive evolution of the disease at T3 compared to T0.
observational model: Cohort
time perspective: Prospective
measure: Identification of demographic and clinical factors in covid19 patients.
time frame: Until patient discharge from the hospital (approximately four months)
description: Identify the demographic and clinical factors related to the sense of smell and taste in patients with Sars-CoV-2 infection included in the study.
measure: Description of the disturbances of smell and taste
time frame: Until patient discharge from the hospital (approximately four months)
description: Description in patients with Sars-CoV-2 infection the evolution of the symptoms (disturbances of smell and taste) understood as partial or total regression by 1-month and 3-month follow-up
measure: Description of factors that influence smell and taste
time frame: Until patient discharge from the hospital (approximately four months).
description: Define which factors (demographic and clinical) influence the improvement of the sense of smell and taste
arm group label: Covid19 infection related patients
description: All subjects that had access to the "nasopharyngeal swabs" service of the hospital for the detection of the Sars-CoV-2 virus, both hospitalized and discharged from the hospital and not hospitalized, from mid-May to the end of June 2020, will be consecutively enrolled. It is assumed that 500 people will be recruited.
intervention type: Other
intervention name: Investigation of smell and taste disorders
description: The study consists of an epidemiological investigation by means of a prospective observational study with the aim of investigating the demographic and clinical factors related to the sense of smell and taste in patients with Sars Cov 2 infection.
arm group label: Covid19 infection related patients
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Italy
citation: Baig AM. Neurological manifestations in COVID-19 caused by SARS-CoV-2. CNS Neurosci Ther. 2020 May;26(5):499-501. doi: 10.1111/cns.13372. Epub 2020 Apr 7. No abstract available.
PMID: 32266761
citation: Hummel T, Whitcroft KL, Andrews P, Altundag A, Cinghi C, Costanzo RM, Damm M, Frasnelli J, Gudziol H, Gupta N, Haehne A, Holbrook E, Hong SC, Hornung D, Huttenbrink KB, Kamel R, Kobayashi M, Konstantinidis I, Landis BN, Leopold DA, Macchi A, Miwa T, Moesges R, Mullol J, Mueller CA, Ottaviano G, Passali GC, Philpott C, Pinto JM, Ramakrishnan VJ, Rombaux P, Roth Y, Schlosser RA, Shu B, Soler G, Stjarne P, Stuck BA, Vodicka J, Welge-Luessen A. Position paper on olfactory dysfunction. Rhinol Suppl. 2017 Mar;54(26):1-30. doi: 10.4193/Rhino16.248.
PMID: 29528615
citation: Fonteyn S, Huart C, Deggouj N, Collet S, Eloy P, Rombaux P. Non-sinonasal-related olfactory dysfunction: A cohort of 496 patients. Eur Ann Otorhinolaryngol Head Neck Dis. 2014 Apr;131(2):87-91. doi: 10.1016/j.anorl.2013.03.006. Epub 2014 Mar 26.
PMID: 24679542
citation: Klopfenstein T, Kadiane-Oussou NJ, Toko L, Royer PY, Lepiller Q, Gendrin V, Zayet S. Features of anosmia in COVID-19. Med Mal Infect. 2020 Aug;50(5):436-439. doi: 10.1016/j.medmal.2020.04.006. Epub 2020 Apr 17.
PMID: 32305563
citation: Nordin S, Bramerson A. Complaints of olfactory disorders: epidemiology, assessment and clinical implications. Curr Opin Allergy Clin Immunol. 2008 Feb;8(1):10-5. doi: 10.1097/ACI.0b013e3282f3f473.
PMID: 18188011
citation: Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020 Jun;92(6):552-555. doi: 10.1002/jmv.25728. Epub 2020 Mar 11.
PMID: 32104915
citation: Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X, Li Y, Hu B. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 Jun 1;77(6):683-690. doi: 10.1001/jamaneurol.2020.1127.
PMID: 32275288
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Taste Disorders
sharing ipd: No