<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/NCT04495816</url>
  </required_header>
  <id_info>
    <org_study_id>GCO 20-1132</org_study_id>
    <nct_id>NCT04495816</nct_id>
  </id_info>
  <brief_title>COVID-19 Anosmia Study</brief_title>
  <official_title>COVID-19 Anosmia Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Icahn School of Medicine at Mount Sinai</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Icahn School of Medicine at Mount Sinai</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      To capture the natural history of COVID-19 associated olfactory dysfunction as measured by&#xD;
      two patient reported outcome measures (SNOT-22, QOD-NS) and a 6-week BSIT with a comparison&#xD;
      to an intervention arm receiving daily omega-3 supplements.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Infection with the novel coronavirus (COVID-19) has been linked to new-onset olfactory&#xD;
      dysfunction, often as the only presenting symptom. In one multicenter European study, 85.6%&#xD;
      of patients with mild to moderate symptoms reported hyposmia or anosmia with early recovery&#xD;
      of olfactory function in just under half of patients. However, the pathogenesis and natural&#xD;
      history of COVID-19 related olfactory dysfunction is poorly understood.&#xD;
&#xD;
      Anosmia most commonly arises in association with sinonasal disease or post-infectious or&#xD;
      post-traumatic disorders. Notably, olfactory loss has been associated with impaired quality&#xD;
      of life, higher rates of depression, and even increased mortality risk. Spontaneous recovery&#xD;
      has been observed in patients with post- infectious olfactory dysfunction, typically over a&#xD;
      period of months to years, with an estimated one-third of patients demonstrating meaningful&#xD;
      improvement after one year.&#xD;
&#xD;
      Smell retraining therapy appears to be an effective therapeutic option for patients with&#xD;
      post-infectious olfactory dysfunction, particularly for patients who initiate treatment&#xD;
      within one year from onset of symptoms, but requires an intervention period of at least three&#xD;
      to four months. Various pharmacotherapies have been investigated in the treatment of&#xD;
      post-infectious anosmia but none have clearly demonstrated utility with the exception of a&#xD;
      possible benefit for nasal steroid irrigations in combination with smell retraining therapy.&#xD;
&#xD;
      More recently, omega-3 polyunsaturated fat supplementation has emerged as a promising&#xD;
      pharmacotherapy for olfactory dysfunction in patients without sinonasal disease. Omega-3&#xD;
      fatty acid deficient mice demonstrate evidence of olfactory dysfunction and mice receiving&#xD;
      omega-3 fatty acids have improved recovery after peripheral nerve injury, which has been&#xD;
      linked to neuroprotective effects mediated through anti-oxidant and anti-inflammatory&#xD;
      pathways. In humans, a large cross-sectional study found that older adults with higher&#xD;
      dietary fat intake had lower incidence of olfactory impairment. From a clinical perspective,&#xD;
      patients without sinonasal disease receiving postoperative omega-3 fatty acid supplementation&#xD;
      after endoscopic endonasal skull base surgery in a randomized control trial demonstrated a&#xD;
      significantly greater rate of return of normal olfactory dysfunction.&#xD;
&#xD;
      Little is known about either the natural history of olfactory dysfunction associated with&#xD;
      COVID-19 infection or about the therapeutic efficacy of omega-3 fatty acid supplementation in&#xD;
      patients with post-viral anosmia. The study team hopes to gain a better understanding of each&#xD;
      through a randomized double-blind placebo control study that assesses both objective and&#xD;
      subjective perception of olfactory dysfunction over a period of 6 weeks after infection.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 15, 2020</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Patients will be randomized into treatment and control groups. The treatment group will receive omega-3-fatty acid supplementation (1000 mg of omega-3 fatty acid blend including 683 mg Eicosapentaenoic Acid and 252 mg Docosahexaenoic Acid) to be taken twice daily for 6 weeks. The control arm will receive a placebo pill to be taken twice daily.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>The healthcare providers interacting with the patients, as well as the participants themselves, will not know which arm they have been assigned to. Only the research fellows will have access to the randomization scheme.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Brief Smell Identification Test (BSIT)</measure>
    <time_frame>Week 0 and Week 6</time_frame>
    <description>Change in BSIT. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Brief Smell Identification Test (BSIT) in Participants With Severe Olfactory Dysfunction</measure>
    <time_frame>Week 0 and Week 6</time_frame>
    <description>Mean change in BSIT in participants with severe olfactory dysfunction defined as BSIT ≤ 7. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Brief Smell Identification Test (BSIT) in Participants With Laboratory-Confirmed COVID-19 and Severe Olfactory Dysfunction</measure>
    <time_frame>Week 0 and Week 6</time_frame>
    <description>Mean change in BSIT in participants with laboratory-confirmed COVID-19. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Brief Smell Identification Test (BSIT) in Participants With Laboratory-Confirmed COVID-19</measure>
    <time_frame>Week 0 and Week 6</time_frame>
    <description>Mean change in BSIT in participants with severe olfactory dysfunction defined as BSIT ≤ 6. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Modified Brief Questionnaire of Olfactory Dysfunction (mQOD-NS)</measure>
    <time_frame>baseline, weeks 1, 2, 4 and 6 after softgel initiation</time_frame>
    <description>The modified Brief Questionnaire of Olfactory Dysfunction - Negative Statements (QOD-NS) survey is a 17-item instrument, each item graded on a scale from 0 to 3, with total scale range from 0 to 51. Higher score indicates better olfactory-specific quality of life (QOL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sinonasal Outcomes Test (SNOT-22)</measure>
    <time_frame>baseline, weeks 1, 2, 4 and 6 after softgel initiation</time_frame>
    <description>Sino-Nasal Outcome Test (SNOT-22) is a 22-item instrument, total scale range from 0 to 110, higher score indicates more severe QOL impact.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">139</enrollment>
  <condition>Anosmia</condition>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>Omega-3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1,000 mg of omega-3 fatty acid (2 softgels per day for 6 weeks)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo/Control</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>2 softgels per day for 6 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omega-3 Fatty Acid Supplement</intervention_name>
    <description>Participants randomized to this arm will be instructed to take two of the softgels they received per day for 6 weeks. They will receive softgels containing 1,000 mg of omega-3 fatty acid. 1000 mg of omega-3 fatty acid blend including 683 mg Eicosapentaenoic Acid and 252 mg Docosahexaenoic Acid</description>
    <arm_group_label>Omega-3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo/Control</intervention_name>
    <description>Patients randomized to this arm will also be instructed to take two of the softgels they received per day for 6 weeks. They will receive placebo softgels that are indistinguishable from those containing fish oil.</description>
    <arm_group_label>Placebo/Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults (18 years of age or older) with self-reported new-onset olfactory dysfunction&#xD;
&#xD;
          -  Positive COVID-19 diagnosis will be deemed eligible for inclusion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients &lt;18 years of age&#xD;
&#xD;
          -  Patients who are unable to provide informed consent&#xD;
&#xD;
          -  Patients without a positive COVID-19 PCR result obtained through nasopharyngeal swab -&#xD;
             Patients with a COVID-19 diagnosis but without self-reported anosmia&#xD;
&#xD;
          -  Patients with severe COVID-19 disease as defined by the Mouth Sinai Health System&#xD;
             Treatment Guidelines for SARS-COV-2 (requiring high flow nasal cannula,&#xD;
             non-rebreather, CPAP/BIPAP, or mechanical ventilation OR patients requiring pressor&#xD;
             medication OR patients with evidence of end organ damage)&#xD;
&#xD;
          -  Patients with pre-existing self-reported olfactory dysfunction&#xD;
&#xD;
          -  Patients with a history of chronic nasal/sinus infections (rhinosinusitis) or history&#xD;
             of endoscopic sinus surgery&#xD;
&#xD;
          -  Patients using nasal steroid sprays or irrigations for any reason&#xD;
&#xD;
          -  Patients who are prisoners of the state&#xD;
&#xD;
          -  Patients who have psychiatric or developmental disorder conditions that may impair&#xD;
             ability to provide informed consent&#xD;
&#xD;
          -  Patients will also be excluded if they have an allergy to fish or an omega-3&#xD;
             supplement, or do not eat fish or fish- containing substances for any reason&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alfred-Marc Iloreta, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Vaira LA, Salzano G, Deiana G, De Riu G. Anosmia and Ageusia: Common Findings in COVID-19 Patients. Laryngoscope. 2020 Jul;130(7):1787. doi: 10.1002/lary.28692. Epub 2020 Apr 15.</citation>
    <PMID>32237238</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>Hendriks AP. Olfactory dysfunction. Rhinology. 1988 Dec;26(4):229-51.</citation>
    <PMID>3070710</PMID>
  </reference>
  <reference>
    <citation>Eliezer M, Hautefort C, Hamel AL, Verillaud B, Herman P, Houdart E, Eloit C. Sudden and Complete Olfactory Loss of Function as a Possible Symptom of COVID-19. JAMA Otolaryngol Head Neck Surg. 2020 Jul 1;146(7):674-675. doi: 10.1001/jamaoto.2020.0832. No abstract available.</citation>
    <PMID>32267483</PMID>
  </reference>
  <reference>
    <citation>Croy I, Nordin S, Hummel T. Olfactory disorders and quality of life--an updated review. Chem Senses. 2014 Mar;39(3):185-94. doi: 10.1093/chemse/bjt072. Epub 2014 Jan 15.</citation>
    <PMID>24429163</PMID>
  </reference>
  <reference>
    <citation>Reden J, Herting B, Lill K, Kern R, Hummel T. Treatment of postinfectious olfactory disorders with minocycline: a double-blind, placebo-controlled study. Laryngoscope. 2011 Mar;121(3):679-82. doi: 10.1002/lary.21401. Epub 2011 Feb 1.</citation>
    <PMID>21287560</PMID>
  </reference>
  <reference>
    <citation>Vukkadala N, Qian ZJ, Holsinger FC, Patel ZM, Rosenthal E. COVID-19 and the Otolaryngologist: Preliminary Evidence-Based Review. Laryngoscope. 2020 Nov;130(11):2537-2543. doi: 10.1002/lary.28672. Epub 2020 Apr 24.</citation>
    <PMID>32219846</PMID>
  </reference>
  <reference>
    <citation>Ekstrom I, Sjolund S, Nordin S, Nordin Adolfsson A, Adolfsson R, Nilsson LG, Larsson M, Olofsson JK. Smell Loss Predicts Mortality Risk Regardless of Dementia Conversion. J Am Geriatr Soc. 2017 Jun;65(6):1238-1243. doi: 10.1111/jgs.14770. Epub 2017 Mar 22.</citation>
    <PMID>28326534</PMID>
  </reference>
  <reference>
    <citation>Sorokowska A, Drechsler E, Karwowski M, Hummel T. Effects of olfactory training: a meta-analysis. Rhinology. 2017 Mar 1;55(1):17-26. doi: 10.4193/Rhino16.195.</citation>
    <PMID>28040824</PMID>
  </reference>
  <reference>
    <citation>Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D, Blecic S, El Afia F, Distinguin L, Chekkoury-Idrissi Y, Hans S, Delgado IL, Calvo-Henriquez C, Lavigne P, Falanga C, Barillari MR, Cammaroto G, Khalife M, Leich P, Souchay C, Rossi C, Journe F, Hsieh J, Edjlali M, Carlier R, Ris L, Lovato A, De Filippis C, Coppee F, Fakhry N, Ayad T, Saussez S. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020 Aug;277(8):2251-2261. doi: 10.1007/s00405-020-05965-1. Epub 2020 Apr 6.</citation>
    <PMID>32253535</PMID>
  </reference>
  <reference>
    <citation>Cavazzana A, Larsson M, Munch M, Hahner A, Hummel T. Postinfectious olfactory loss: A retrospective study on 791 patients. Laryngoscope. 2018 Jan;128(1):10-15. doi: 10.1002/lary.26606. Epub 2017 May 29.</citation>
    <PMID>28556265</PMID>
  </reference>
  <reference>
    <citation>Pekala K, Chandra RK, Turner JH. Efficacy of olfactory training in patients with olfactory loss: a systematic review and meta-analysis. Int Forum Allergy Rhinol. 2016 Mar;6(3):299-307. doi: 10.1002/alr.21669. Epub 2015 Dec 1.</citation>
    <PMID>26624966</PMID>
  </reference>
  <reference>
    <citation>Boesveldt S, Postma EM, Boak D, Welge-Luessen A, Schopf V, Mainland JD, Martens J, Ngai J, Duffy VB. Anosmia-A Clinical Review. Chem Senses. 2017 Sep 1;42(7):513-523. doi: 10.1093/chemse/bjx025. Erratum In: Chem Senses. 2017 Sep 1;42(7):607.</citation>
    <PMID>28531300</PMID>
  </reference>
  <reference>
    <citation>Reden J, Mueller A, Mueller C, Konstantinidis I, Frasnelli J, Landis BN, Hummel T. Recovery of olfactory function following closed head injury or infections of the upper respiratory tract. Arch Otolaryngol Head Neck Surg. 2006 Mar;132(3):265-9. doi: 10.1001/archotol.132.3.265.</citation>
    <PMID>16549746</PMID>
  </reference>
  <reference>
    <citation>Damm M, Pikart LK, Reimann H, Burkert S, Goktas O, Haxel B, Frey S, Charalampakis I, Beule A, Renner B, Hummel T, Huttenbrink KB. Olfactory training is helpful in postinfectious olfactory loss: a randomized, controlled, multicenter study. Laryngoscope. 2014 Apr;124(4):826-31. doi: 10.1002/lary.24340. Epub 2013 Sep 19.</citation>
    <PMID>23929687</PMID>
  </reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2020</study_first_posted>
  <results_first_submitted>September 15, 2022</results_first_submitted>
  <results_first_submitted_qc>January 11, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">January 31, 2023</results_first_posted>
  <last_update_submitted>January 11, 2023</last_update_submitted>
  <last_update_submitted_qc>January 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Icahn School of Medicine at Mount Sinai</investigator_affiliation>
    <investigator_full_name>Alfred-Marc Iloreta</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Novel Coronavirus</keyword>
  <keyword>Anosmia</keyword>
  <keyword>Smell Loss</keyword>
  <keyword>Parosmia</keyword>
  <keyword>Fish Oil Supplement</keyword>
  <keyword>Omega-3 Fatty Acid Supplements</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Anosmia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 18, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT04495816/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 18, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT04495816/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants with laboratory-confirmed or clinically-suspected COVID-19 infection and self-reported new-onset OD from August 2020 to November 2021 were prospectively recruited from otolaryngology and primary care practices across a large metropolitan health system as well as through a web-based symptom-tracking application and self-referral, resulting in a cohort of individuals from throughout the United States.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Omega-3</title>
          <description>2,000mg daily of O3FA supplementation in the form of 2 capsules of Nature Made® Ultra Omega-3 Fish Oil 1400mg, each of which contains 1000 mg of O3FAs</description>
        </group>
        <group group_id="P2">
          <title>Placebo/Control</title>
          <description>received a placebo pill of identical size and shape to be taken twice daily.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="70"/>
                <participants group_id="P2" count="69"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="57"/>
                <participants group_id="P2" count="60"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Omega-3</title>
          <description>2,000mg daily of O3FA supplementation in the form of 2 capsules of Nature Made® Ultra Omega-3 Fish Oil 1400mg, each of which contains 1000 mg of O3FAs</description>
        </group>
        <group group_id="B2">
          <title>Placebo/Control</title>
          <description>received a placebo pill of identical size and shape to be taken twice daily.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="57"/>
            <count group_id="B2" value="60"/>
            <count group_id="B3" value="117"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41.5" spread="14.6"/>
                    <measurement group_id="B2" value="40.7" spread="12.7"/>
                    <measurement group_id="B3" value="41.1" spread="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="46"/>
                    <measurement group_id="B3" value="92"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Type of Olfactory Dysfunction</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Anosmia</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="92"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hyposmia</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Parosmia</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hyposmia &amp; Parosmia</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Anosmia Severity (Worst)</title>
          <description>Full range from 1-100, with higher score indicating more severe</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="91.9" spread="16.9"/>
                    <measurement group_id="B2" value="96.0" spread="8.54"/>
                    <measurement group_id="B3" value="93.9" spread="13.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Anosmia Severity (Current)</title>
          <description>Full range from 1-100, with higher score indicating more severe</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="68.1" spread="27.7"/>
                    <measurement group_id="B2" value="73.2" spread="22.2"/>
                    <measurement group_id="B3" value="70.8" spread="25.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Comorbidities, n (%)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Ageusia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>History of Facial Trauma</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chronic Rhinosinusitis</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Allergic Rhinitis</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neurodegenerative Disease</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Duration of Olfactory Dysfunction Prior to Trial Start</title>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="196" spread="105"/>
                    <measurement group_id="B2" value="204" spread="95.6"/>
                    <measurement group_id="B3" value="200" spread="99.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Therapies Used Prior to Trial Start</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Smell Training</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal Saline Spray or Irrigation</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Intranasal Corticosteroid Spray or Irrigation</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Oral Corticosteroids</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Concomitant Therapies Used During the Trial, n (%) ***</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Smell Training</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal Saline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Intranasal Corticosteroid Spray or Irrigation</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Oral Corticosteroids</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="57"/>
                    <count group_id="B2" value="60"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Brief Smell Identification Test (BSIT)</title>
        <description>Change in BSIT. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.</description>
        <time_frame>Week 0 and Week 6</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>2,000mg daily of O3FA supplementation in the form of 2 capsules of Nature Made® Ultra Omega-3 Fish Oil 1400mg, each of which contains 1000 mg of O3FAs</description>
          </group>
          <group group_id="O2">
            <title>Placebo/Control</title>
            <description>received a placebo pill of identical size and shape to be taken twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Brief Smell Identification Test (BSIT)</title>
          <description>Change in BSIT. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="60"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.77" spread="1.94"/>
                    <measurement group_id="O2" value="7.20" spread="1.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.89" spread="2.00"/>
                    <measurement group_id="O2" value="7.88" spread="2.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.12" spread="1.99"/>
                    <measurement group_id="O2" value="0.68" spread="1.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Brief Smell Identification Test (BSIT) in Participants With Severe Olfactory Dysfunction</title>
        <description>Mean change in BSIT in participants with severe olfactory dysfunction defined as BSIT ≤ 7. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.</description>
        <time_frame>Week 0 and Week 6</time_frame>
        <population>Participants with severe olfactory dysfunction defined as BSIT ≤ 7</population>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>2,000mg daily of O3FA supplementation in the form of 2 capsules of Nature Made® Ultra Omega-3 Fish Oil 1400mg, each of which contains 1000 mg of O3FAs</description>
          </group>
          <group group_id="O2">
            <title>Placebo/Control</title>
            <description>received a placebo pill of identical size and shape to be taken twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Brief Smell Identification Test (BSIT) in Participants With Severe Olfactory Dysfunction</title>
          <description>Mean change in BSIT in participants with severe olfactory dysfunction defined as BSIT ≤ 7. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.</description>
          <population>Participants with severe olfactory dysfunction defined as BSIT ≤ 7</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.30" spread="1.77"/>
                    <measurement group_id="O2" value="1.63" spread="1.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Brief Smell Identification Test (BSIT) in Participants With Laboratory-Confirmed COVID-19 and Severe Olfactory Dysfunction</title>
        <description>Mean change in BSIT in participants with laboratory-confirmed COVID-19. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.</description>
        <time_frame>Week 0 and Week 6</time_frame>
        <population>Participants with Laboratory-Confirmed COVID-19</population>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>2,000mg daily of O3FA supplementation in the form of 2 capsules of Nature Made® Ultra Omega-3 Fish Oil 1400mg, each of which contains 1000 mg of O3FAs</description>
          </group>
          <group group_id="O2">
            <title>Placebo/Control</title>
            <description>received a placebo pill of identical size and shape to be taken twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Brief Smell Identification Test (BSIT) in Participants With Laboratory-Confirmed COVID-19 and Severe Olfactory Dysfunction</title>
          <description>Mean change in BSIT in participants with laboratory-confirmed COVID-19. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.</description>
          <population>Participants with Laboratory-Confirmed COVID-19</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.18" spread="1.88"/>
                    <measurement group_id="O2" value="0.61" spread="1.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Brief Smell Identification Test (BSIT) in Participants With Laboratory-Confirmed COVID-19</title>
        <description>Mean change in BSIT in participants with severe olfactory dysfunction defined as BSIT ≤ 6. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.</description>
        <time_frame>Week 0 and Week 6</time_frame>
        <population>Data not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>2,000mg daily of O3FA supplementation in the form of 2 capsules of Nature Made® Ultra Omega-3 Fish Oil 1400mg, each of which contains 1000 mg of O3FAs</description>
          </group>
          <group group_id="O2">
            <title>Placebo/Control</title>
            <description>received a placebo pill of identical size and shape to be taken twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Brief Smell Identification Test (BSIT) in Participants With Laboratory-Confirmed COVID-19</title>
          <description>Mean change in BSIT in participants with severe olfactory dysfunction defined as BSIT ≤ 6. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.</description>
          <population>Data not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Modified Brief Questionnaire of Olfactory Dysfunction (mQOD-NS)</title>
        <description>The modified Brief Questionnaire of Olfactory Dysfunction - Negative Statements (QOD-NS) survey is a 17-item instrument, each item graded on a scale from 0 to 3, with total scale range from 0 to 51. Higher score indicates better olfactory-specific quality of life (QOL).</description>
        <time_frame>baseline, weeks 1, 2, 4 and 6 after softgel initiation</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>2,000mg daily of O3FA supplementation in the form of 2 capsules of Nature Made® Ultra Omega-3 Fish Oil 1400mg, each of which contains 1000 mg of O3FAs</description>
          </group>
          <group group_id="O2">
            <title>Placebo/Control</title>
            <description>received a placebo pill of identical size and shape to be taken twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Modified Brief Questionnaire of Olfactory Dysfunction (mQOD-NS)</title>
          <description>The modified Brief Questionnaire of Olfactory Dysfunction - Negative Statements (QOD-NS) survey is a 17-item instrument, each item graded on a scale from 0 to 3, with total scale range from 0 to 51. Higher score indicates better olfactory-specific quality of life (QOL).</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="60"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.29" spread="4.46"/>
                    <measurement group_id="O2" value="13.73" spread="4.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.41" spread="4.42"/>
                    <measurement group_id="O2" value="12.54" spread="4.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.46" spread="4.81"/>
                    <measurement group_id="O2" value="12.76" spread="4.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.17" spread="5.15"/>
                    <measurement group_id="O2" value="12.95" spread="4.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.19" spread="4.58"/>
                    <measurement group_id="O2" value="12.33" spread="4.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Sinonasal Outcomes Test (SNOT-22)</title>
        <description>Sino-Nasal Outcome Test (SNOT-22) is a 22-item instrument, total scale range from 0 to 110, higher score indicates more severe QOL impact.</description>
        <time_frame>baseline, weeks 1, 2, 4 and 6 after softgel initiation</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Omega-3</title>
            <description>2,000mg daily of O3FA supplementation in the form of 2 capsules of Nature Made® Ultra Omega-3 Fish Oil 1400mg, each of which contains 1000 mg of O3FAs</description>
          </group>
          <group group_id="O2">
            <title>Placebo/Control</title>
            <description>received a placebo pill of identical size and shape to be taken twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Sinonasal Outcomes Test (SNOT-22)</title>
          <description>Sino-Nasal Outcome Test (SNOT-22) is a 22-item instrument, total scale range from 0 to 110, higher score indicates more severe QOL impact.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="60"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.35" spread="13.23"/>
                    <measurement group_id="O2" value="25.75" spread="12.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.23" spread="13.60"/>
                    <measurement group_id="O2" value="24.54" spread="12.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.41" spread="14.33"/>
                    <measurement group_id="O2" value="22.90" spread="12.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.79" spread="13.56"/>
                    <measurement group_id="O2" value="23.47" spread="13.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.91" spread="13.05"/>
                    <measurement group_id="O2" value="22.41" spread="13.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Omega-3</title>
          <description>2,000mg daily of O3FA supplementation in the form of 2 capsules of Nature Made® Ultra Omega-3 Fish Oil 1400mg, each of which contains 1000 mg of O3FAs</description>
        </group>
        <group group_id="E2">
          <title>Placebo/Control</title>
          <description>received a placebo pill of identical size and shape to be taken twice daily.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>worsening of gastroesophageal reflux symptoms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>unable to swallow the capsules</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Unrelated upcoming surgery</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. David Lerner</name_or_title>
      <organization>Icahn School of Medicine at Mount Sinai</organization>
      <phone>212-241-9410</phone>
      <email>david.lerner2@mountsinai.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04495816
org study id: GCO 20-1132
nct id: NCT04495816
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
To capture the natural history of COVID-19 associated olfactory dysfunction as measured by
      two patient reported outcome measures (SNOT-22, QOD-NS) and a 6-week BSIT with a comparison
      to an intervention arm receiving daily omega-3 supplements.
Infection with the novel coronavirus (COVID-19) has been linked to new-onset olfactory
      dysfunction, often as the only presenting symptom. In one multicenter European study, 85.6%
      of patients with mild to moderate symptoms reported hyposmia or anosmia with early recovery
      of olfactory function in just under half of patients. However, the pathogenesis and natural
      history of COVID-19 related olfactory dysfunction is poorly understood.

      Anosmia most commonly arises in association with sinonasal disease or post-infectious or
      post-traumatic disorders. Notably, olfactory loss has been associated with impaired quality
      of life, higher rates of depression, and even increased mortality risk. Spontaneous recovery
      has been observed in patients with post- infectious olfactory dysfunction, typically over a
      period of months to years, with an estimated one-third of patients demonstrating meaningful
      improvement after one year.

      Smell retraining therapy appears to be an effective therapeutic option for patients with
      post-infectious olfactory dysfunction, particularly for patients who initiate treatment
      within one year from onset of symptoms, but requires an intervention period of at least three
      to four months. Various pharmacotherapies have been investigated in the treatment of
      post-infectious anosmia but none have clearly demonstrated utility with the exception of a
      possible benefit for nasal steroid irrigations in combination with smell retraining therapy.

      More recently, omega-3 polyunsaturated fat supplementation has emerged as a promising
      pharmacotherapy for olfactory dysfunction in patients without sinonasal disease. Omega-3
      fatty acid deficient mice demonstrate evidence of olfactory dysfunction and mice receiving
      omega-3 fatty acids have improved recovery after peripheral nerve injury, which has been
      linked to neuroprotective effects mediated through anti-oxidant and anti-inflammatory
      pathways. In humans, a large cross-sectional study found that older adults with higher
      dietary fat intake had lower incidence of olfactory impairment. From a clinical perspective,
      patients without sinonasal disease receiving postoperative omega-3 fatty acid supplementation
      after endoscopic endonasal skull base surgery in a randomized control trial demonstrated a
      significantly greater rate of return of normal olfactory dysfunction.

      Little is known about either the natural history of olfactory dysfunction associated with
      COVID-19 infection or about the therapeutic efficacy of omega-3 fatty acid supplementation in
      patients with post-viral anosmia. The study team hopes to gain a better understanding of each
      through a randomized double-blind placebo control study that assesses both objective and
      subjective perception of olfactory dysfunction over a period of 6 weeks after infection.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients will be randomized into treatment and control groups. The treatment group will receive omega-3-fatty acid supplementation (1000 mg of omega-3 fatty acid blend including 683 mg Eicosapentaenoic Acid and 252 mg Docosahexaenoic Acid) to be taken twice daily for 6 weeks. The control arm will receive a placebo pill to be taken twice daily.
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: The healthcare providers interacting with the patients, as well as the participants themselves, will not know which arm they have been assigned to. Only the research fellows will have access to the randomization scheme.
measure: Change in Brief Smell Identification Test (BSIT)
time frame: Week 0 and Week 6
description: Change in BSIT. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.
measure: Change in Brief Smell Identification Test (BSIT) in Participants With Severe Olfactory Dysfunction
time frame: Week 0 and Week 6
description: Mean change in BSIT in participants with severe olfactory dysfunction defined as BSIT ≤ 7. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.
measure: Change in Brief Smell Identification Test (BSIT) in Participants With Laboratory-Confirmed COVID-19 and Severe Olfactory Dysfunction
time frame: Week 0 and Week 6
description: Mean change in BSIT in participants with laboratory-confirmed COVID-19. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.
measure: Change in Brief Smell Identification Test (BSIT) in Participants With Laboratory-Confirmed COVID-19
time frame: Week 0 and Week 6
description: Mean change in BSIT in participants with severe olfactory dysfunction defined as BSIT ≤ 6. Brief Smell Identification Test (BSIT) is a 12-item instrument, full range score from 0 to 12, higher score indicates better olfactory performances.
measure: Modified Brief Questionnaire of Olfactory Dysfunction (mQOD-NS)
time frame: baseline, weeks 1, 2, 4 and 6 after softgel initiation
description: The modified Brief Questionnaire of Olfactory Dysfunction - Negative Statements (QOD-NS) survey is a 17-item instrument, each item graded on a scale from 0 to 3, with total scale range from 0 to 51. Higher score indicates better olfactory-specific quality of life (QOL).
measure: Sinonasal Outcomes Test (SNOT-22)
time frame: baseline, weeks 1, 2, 4 and 6 after softgel initiation
description: Sino-Nasal Outcome Test (SNOT-22) is a 22-item instrument, total scale range from 0 to 110, higher score indicates more severe QOL impact.
arm group label: Omega-3
arm group type: Active Comparator
description: 1,000 mg of omega-3 fatty acid (2 softgels per day for 6 weeks)
arm group label: Placebo/Control
arm group type: Sham Comparator
description: 2 softgels per day for 6 weeks
intervention type: Drug
intervention name: Omega-3 Fatty Acid Supplement
description: Participants randomized to this arm will be instructed to take two of the softgels they received per day for 6 weeks. They will receive softgels containing 1,000 mg of omega-3 fatty acid. 1000 mg of omega-3 fatty acid blend including 683 mg Eicosapentaenoic Acid and 252 mg Docosahexaenoic Acid
arm group label: Omega-3
intervention type: Drug
intervention name: Placebo/Control
description: Patients randomized to this arm will also be instructed to take two of the softgels they received per day for 6 weeks. They will receive placebo softgels that are indistinguishable from those containing fish oil.
arm group label: Placebo/Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alfred-Marc Iloreta, MD
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
facility: 
country: United States
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PMID: 32237238
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PMID: 24679542
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PMID: 3070710
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PMID: 32267483
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PMID: 24429163
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PMID: 21287560
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PMID: 32219846
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PMID: 28326534
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PMID: 23929687
responsible party type: Principal Investigator
investigator affiliation: Icahn School of Medicine at Mount Sinai
investigator full name: Alfred-Marc Iloreta
investigator title: Assistant Professor
mesh term: COVID-19
mesh term: Anosmia
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 