<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/NCT04485130</url>
  </required_header>
  <id_info>
    <org_study_id>DSF151837</org_study_id>
    <nct_id>NCT04485130</nct_id>
  </id_info>
  <brief_title>DISulfiram for COvid-19 (DISCO) Trial</brief_title>
  <acronym>DISCO</acronym>
  <official_title>DISulfiram for COvid-19 (DISCO) Trial: A Phase 2 Double-Blind, Randomized Placebo-Controlled Trial of Disulfiram Compared to Standard Care in Patients With Symptomatic COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Disulfiram (DSF) a safe, easily dosed, FDA-approved drug for the treatment of alcohol&#xD;
      dependence has been identified to be a potential therapeutic target for SARS-CoV-2 infection.&#xD;
      Disulfiram may have both antiviral (inhibiting viral replication via blocking the Mpro&#xD;
      protease and zinc ejection) and anti-inflammatory effects (via inhibition of NF-kB-induced&#xD;
      and NLRP inflammasome-induced cytokine release) on SARS-CoV-2. We will study oral disulfiram&#xD;
      given for 5 consecutive days (1000 mg/day in cohort 1; 2000 mg/day in cohort 2) in 60&#xD;
      symptomatic COVID+ individuals in a randomized (2:1) randomized, double blind&#xD;
      placebo-controlled trial evaluating disulfiram's effect on COVID-19 symptom severity,&#xD;
      SARS-CoV-2 viral load, and biomarkers of inflammation and pyroptosis (aberrant&#xD;
      pro-inflammatory cell death) over 31 days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The identification of a safe, effective treatment for individuals with early mild-to-moderate&#xD;
      symptomatic COVID-19 that prevent progression to more severe disease would have immediate&#xD;
      public health implications. A hallmark of severe COVID-19 disease is immune system&#xD;
      dysregulation called cytokine storm. Multiple studies have reported that patients with severe&#xD;
      disease demonstrate elevated levels of pro-inflammatory cytokines early in disease, and&#xD;
      elevated IL-6 plasma concentrations are predictive of poor clinical outcomes in COVID-19.&#xD;
      Disulfiram, an FDA-approved drug for the treatment of alcohol dependence disorder is an&#xD;
      appealing therapeutic option for COVID-19. It has a good safety profile, easy dosing&#xD;
      schedule, and recent data suggesting multiple mechanisms by which disulfiram may act on&#xD;
      COVID-19 (both as a direct antiviral agent as well as indirect effects on reducing&#xD;
      inflammation). In addition disulfiram has been studied extensively with detailed available&#xD;
      pharmacokinetic data; disulfiram has a short half-life ~7.5 hours with &gt;90% of drug&#xD;
      eliminated within 3 days post-dose, allowing quick reversal of any potential adverse effects.&#xD;
      We will perform a phase 2 randomized (2:1), double blind placebo-controlled assessment of&#xD;
      disulfiram in people with early mild-to-moderate symptomatic COVID-19. A total of 60&#xD;
      symptomatic COVID+ individuals will enrolled to receive active drug versus placebo (with&#xD;
      equal distribution of mild or moderate/severe within each dosing cohort and within each&#xD;
      randomization arm). For cohort 1, N=20 will receive DSF 1000 mg/N=10 placebo, and for cohort&#xD;
      2, N=20 will receive DSF 2000 mg/N=10 placebo. Drug/placebo will be administered using strict&#xD;
      infection control protocols designed to support the study of people with acute COVID-19&#xD;
      infection per the Center for Diseases Control (CDC) guidelines&#xD;
      (https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-in-home-patients.html).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low COVID case numbers, competing COVID treatments available&#xD;
  </why_stopped>
  <start_date type="Actual">August 18, 2021</start_date>
  <completion_date type="Actual">February 28, 2022</completion_date>
  <primary_completion_date type="Actual">February 28, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>This is a dose escalation double blind randomized (2:1) placebo-controlled trial of disulfiram given as 1000 mg/day x 5 consecutive days (Cohort 1: N=20 drug/N=10 placebo) or 2000 mg/day x 5 consecutive days (Cohort 2: N=20 drug/N=10 placebo) among 60 acute symptomatic lab-confirmed (&lt;7 days) COVID+ individuals .</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Immunologic Impact of 5 Days of Disulfiram, as Measured by the Fold-change in Plasma Levels of Pro-inflammatory Cytokines (e.g, Interleukin 6, Interleukin 1-beta, Etc.).</measure>
    <time_frame>Day 0 and Day 31</time_frame>
    <description>Change in plasma inflammatory biomarker levels (e.g., IL-6, IL-1b) at days 5, 15, and 31.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Virologic Impact of 5 Days of Disulfiram, as Measured by the Change in Copies of SARS-CoV-2 Virus Per mL Between Baseline and Day 31.</measure>
    <time_frame>Day 0 and Day 31</time_frame>
    <description>Change in copies of SARS-CoV-2 PCR virus per mL between Baseline and Day 31.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0</measure>
    <time_frame>Day 0 and Day 31</time_frame>
    <description>The safety and tolerability of a 5 day course of disulfiram. The number of adverse events and their grade will be determined for each participant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in COVID-19 Symptom Severity Score as Assessed by a 5-point Adapted Somatic Symptom Severity Score (SSS-8)</measure>
    <time_frame>Day 0 and Day 31</time_frame>
    <description>The severity of COVID-19 symptoms will be recorded on a 5-point symptom severity scale at each visit for each participant. A question about how much the symptoms bother the participants will be asked. The participant will rank 1 as &quot;not at all,&quot; 2 as &quot;a little bit,&quot; 3 as &quot;somewhat,&quot; 4 as &quot;quite a bit&quot; and 5 as &quot;very much.&quot; Higher values represent worse outcomes. Scales are combined to compute a total score at Day 0 and Day 31. A change of the median is reported.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>Disulfiram</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This study will provide disulfiram. Participants in Cohort 1 receiving disulfiram will take 2 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days. Participants in Cohort 2 receiving placebo will take 4 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>This study will provide placebo comparator for disulfiram. Participants in Cohort 1 receiving placebo will take 2 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days. Participants in Cohort 2 receiving placebo will take 4 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Disulfiram</intervention_name>
    <description>This study will provide disulfiram. Participants in Cohort 1 receiving disulfiram will take 2 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days. Participants in Cohort 2 receiving placebo will take 4 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
    <arm_group_label>Disulfiram</arm_group_label>
    <other_name>Antabuse</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>This study will provide placebo. Participants in Cohort 1 receiving placebo will take 2 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days. Participants in Cohort 2 receiving placebo will take 4 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing and able to provide written informed consent, and&#xD;
&#xD;
          -  Age &gt;= 18 years, and&#xD;
&#xD;
          -  SARS-CoV-2 positive PCR (nucleic acid) test within the preceding 7 days, and&#xD;
&#xD;
          -  Not currently hospitalized, and&#xD;
&#xD;
          -  Willing to abstain from any alcohol during the two week period in which disulfiram&#xD;
             will be administered and during the two week period immediately after disulfiram&#xD;
             administration.&#xD;
&#xD;
          -  Both male and female subjects are eligible. Females of childbearing potential must&#xD;
             have a negative pregnancy test at screening and agree to use a double-barrier method&#xD;
             of contraception throughout the study period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant, breastfeeding, or unwilling to practice birth control during participation&#xD;
             in the study&#xD;
&#xD;
          -  Active malignancy requiring systemic chemotherapy or surgery in the preceding 3 months&#xD;
             or for whom such therapies are expected in the subsequent 6 months&#xD;
&#xD;
          -  Decompensated liver disease as defined by the presence of ascites, encephalopathy,&#xD;
             esophageal or gastric varices, or persistent jaundice&#xD;
&#xD;
          -  Serious illness requiring systemic treatment and/or hospitalization in the 3 months&#xD;
             prior to study enrollment&#xD;
&#xD;
          -  Concurrent treatment with immunomodulatory drugs, and/or exposure to any&#xD;
             immunomodulatory drug in the 4 weeks prior to study enrollment (e.g. corticosteroid&#xD;
             therapy equal to or exceeding a dose of 15 mg/day of prednisone for more than 10 days,&#xD;
             IL-2, interferon-alpha, methotrexate, cancer chemotherapy). NOTE: use of inhaled or&#xD;
             nasal steroid is not exclusionary.&#xD;
&#xD;
          -  Serious medical or psychiatric illness that, in the opinion of the site investigator,&#xD;
             would interfere with the ability to adhere to study requirements or to give informed&#xD;
             consent.&#xD;
&#xD;
          -  Current alcohol use disorder or hazardous alcohol use (&gt;7 drinks per week for women or&#xD;
             &gt; 14 drinks per week for men) as determined by clinical evaluation.&#xD;
&#xD;
          -  Current use of any drug formulation that contains alcohol or that might contain&#xD;
             alcohol&#xD;
&#xD;
          -  Current use of warfarin.&#xD;
&#xD;
          -  Clinically active hepatitis determined by the study physician; ALT or AST &gt; 3 x the&#xD;
             upper limit of normal or total bilirubin outside the normal range.&#xD;
&#xD;
          -  Allergy to rubber or thiuram derivatives&#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>Sulggi A Lee, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California San Francisco, Fresno</name>
      <address>
        <city>Fresno</city>
        <state>California</state>
        <zip>93701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Francisco General Hospital</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Lee SA, Elliott JH, McMahon J, Hartogenesis W, Bumpus NN, Lifson JD, Gorelick RJ, Bacchetti P, Deeks SG, Lewin SR, Savic RM. Population Pharmacokinetics and Pharmacodynamics of Disulfiram on Inducing Latent HIV-1 Transcription in a Phase IIb Trial. Clin Pharmacol Ther. 2019 Mar;105(3):692-702. doi: 10.1002/cpt.1220. Epub 2018 Oct 9.</citation>
    <PMID>30137649</PMID>
  </reference>
  <reference>
    <citation>Elliott JH, McMahon JH, Chang CC, Lee SA, Hartogensis W, Bumpus N, Savic R, Roney J, Hoh R, Solomon A, Piatak M, Gorelick RJ, Lifson J, Bacchetti P, Deeks SG, Lewin SR. Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV. 2015 Dec;2(12):e520-9. doi: 10.1016/S2352-3018(15)00226-X. Epub 2015 Nov 17.</citation>
    <PMID>26614966</PMID>
  </reference>
  <reference>
    <citation>Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, Zhang B, Li X, Zhang L, Peng C, Duan Y, Yu J, Wang L, Yang K, Liu F, Jiang R, Yang X, You T, Liu X, Yang X, Bai F, Liu H, Liu X, Guddat LW, Xu W, Xiao G, Qin C, Shi Z, Jiang H, Rao Z, Yang H. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020 Jun;582(7811):289-293. doi: 10.1038/s41586-020-2223-y. Epub 2020 Apr 9.</citation>
    <PMID>32272481</PMID>
  </reference>
  <reference>
    <citation>Lin MH, Moses DC, Hsieh CH, Cheng SC, Chen YH, Sun CY, Chou CY. Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes. Antiviral Res. 2018 Feb;150:155-163. doi: 10.1016/j.antiviral.2017.12.015. Epub 2017 Dec 28.</citation>
    <PMID>29289665</PMID>
  </reference>
  <reference>
    <citation>Hu JJ, Liu X, Xia S, Zhang Z, Zhang Y, Zhao J, Ruan J, Luo X, Lou X, Bai Y, Wang J, Hollingsworth LR, Magupalli VG, Zhao L, Luo HR, Kim J, Lieberman J, Wu H. FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation. Nat Immunol. 2020 Jul;21(7):736-745. doi: 10.1038/s41590-020-0669-6. Epub 2020 May 4.</citation>
    <PMID>32367036</PMID>
  </reference>
  <reference>
    <citation>Lobo-Galo N, Terrazas-Lopez M, Martinez-Martinez A, Diaz-Sanchez AG. FDA-approved thiol-reacting drugs that potentially bind into the SARS-CoV-2 main protease, essential for viral replication. J Biomol Struct Dyn. 2021 Jun;39(9):3419-3427. doi: 10.1080/07391102.2020.1764393. Epub 2020 May 14.</citation>
    <PMID>32364011</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <results_first_submitted>June 1, 2023</results_first_submitted>
  <results_first_submitted_qc>August 30, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">September 13, 2023</results_first_posted>
  <last_update_submitted>August 30, 2023</last_update_submitted>
  <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Francisco</investigator_affiliation>
    <investigator_full_name>Sulggi A. Lee, MD, PhD</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Disulfiram</keyword>
  <keyword>COVID-19</keyword>
  <keyword>SARS-CoV-2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Disulfiram</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Planned sharing of de-identified individual participant data for the purposes of collaboration and meta-analyses.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>After publication of study results</ipd_time_frame>
    <ipd_access_criteria>De-identified data</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 8, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/30/NCT04485130/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 7, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/30/NCT04485130/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1 - Disulfiram 1000 mg</title>
          <description>Participants in Cohort 1 receiving disulfiram will take 2 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
        </group>
        <group group_id="P2">
          <title>Cohort 1: Placebo</title>
          <description>This study will provide placebo comparator for disulfiram. Participants in Cohort 1 receiving placebo will take 2 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
        </group>
        <group group_id="P3">
          <title>Cohort 2: Disulfiram 2000 mg</title>
          <description>Participants in Cohort 2 receiving placebo will take 4 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
        </group>
        <group group_id="P4">
          <title>Cohort 2: Placebo</title>
          <description>Participants in Cohort 2 receiving placebo will take 4 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The trial stopped early so we were unable to enroll for Cohort 2.</population>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1: Disulfiram 1000 mg</title>
          <description>This study will provide disulfiram. Participants in Cohort 1 receiving disulfiram will take 2 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
        </group>
        <group group_id="B2">
          <title>Cohort 1: Placebo</title>
          <description>This study will provide placebo comparator for disulfiram. Participants in Cohort 1 receiving placebo will take 2 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
        </group>
        <group group_id="B3">
          <title>Cohort 2: Disulfiram 2000 mg</title>
          <description>Participants in Cohort 2 receiving placebo will take 4 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
        </group>
        <group group_id="B4">
          <title>Cohort 2: Placebo</title>
          <description>Participants in Cohort 2 receiving placebo will take 4 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
        </group>
        <group group_id="B5">
          <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="7"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="0"/>
            <count group_id="B4" value="0"/>
            <count group_id="B5" value="11"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38" spread="12.5"/>
                    <measurement group_id="B2" value="43.5" spread="8"/>
                    <measurement group_id="B5" value="40" spread="11"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B5" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B5" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B5" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B5" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25.6" spread="5.5"/>
                    <measurement group_id="B2" value="33.3" spread="2.2"/>
                    <measurement group_id="B5" value="28.4" spread="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Immunologic Impact of 5 Days of Disulfiram, as Measured by the Fold-change in Plasma Levels of Pro-inflammatory Cytokines (e.g, Interleukin 6, Interleukin 1-beta, Etc.).</title>
        <description>Change in plasma inflammatory biomarker levels (e.g., IL-6, IL-1b) at days 5, 15, and 31.</description>
        <time_frame>Day 0 and Day 31</time_frame>
        <population>The trial stopped early so we were unable to enroll for Cohort 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Disulfiram 100 mg</title>
            <description>This study will provide disulfiram. Participants in Cohort 1 receiving disulfiram will take 2 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: Placebo</title>
            <description>This study will provide placebo comparator for disulfiram. Participants in Cohort 1 receiving placebo will take 2 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 2: Disulfiram 2000 mg</title>
            <description>Participants in Cohort 2 receiving placebo will take 4 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 2: Placebo</title>
            <description>Participants in Cohort 2 receiving placebo will take 4 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
        </group_list>
        <measure>
          <title>Immunologic Impact of 5 Days of Disulfiram, as Measured by the Fold-change in Plasma Levels of Pro-inflammatory Cytokines (e.g, Interleukin 6, Interleukin 1-beta, Etc.).</title>
          <description>Change in plasma inflammatory biomarker levels (e.g., IL-6, IL-1b) at days 5, 15, and 31.</description>
          <population>The trial stopped early so we were unable to enroll for Cohort 2.</population>
          <units>fold change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change in IL-6 (pg/mL) Day 0 to 31</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1186" lower_limit="-0.2012" upper_limit="-0.0246"/>
                    <measurement group_id="O2" value="-0.0215" lower_limit="-0.1202" upper_limit="-0.0178"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change in IL-1B (pg/mL) Day 0 to 31</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1402" lower_limit="-0.2583" upper_limit="0.0648"/>
                    <measurement group_id="O2" value="0.0268" lower_limit="-0.0438" upper_limit="0.0399"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Virologic Impact of 5 Days of Disulfiram, as Measured by the Change in Copies of SARS-CoV-2 Virus Per mL Between Baseline and Day 31.</title>
        <description>Change in copies of SARS-CoV-2 PCR virus per mL between Baseline and Day 31.</description>
        <time_frame>Day 0 and Day 31</time_frame>
        <population>The trial stopped early so we were unable to enroll for Cohort 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Disulfiram 1000 mg</title>
            <description>This study will provide disulfiram. Participants in Cohort 1 receiving disulfiram will take 2 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: Placebo</title>
            <description>This study will provide placebo comparator for disulfiram. Participants in Cohort 1 receiving placebo will take 2 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 2: Disulfiram 2000 mg</title>
            <description>Participants in Cohort 2 receiving disulfiram will take 4 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 2: Placebo</title>
            <description>Participants in Cohort 2 receiving placebo will take 4 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
        </group_list>
        <measure>
          <title>Virologic Impact of 5 Days of Disulfiram, as Measured by the Change in Copies of SARS-CoV-2 Virus Per mL Between Baseline and Day 31.</title>
          <description>Change in copies of SARS-CoV-2 PCR virus per mL between Baseline and Day 31.</description>
          <population>The trial stopped early so we were unable to enroll for Cohort 2.</population>
          <units>copies/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.89" spread="9.84"/>
                    <measurement group_id="O2" value="-20" spread="13.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0</title>
        <description>The safety and tolerability of a 5 day course of disulfiram. The number of adverse events and their grade will be determined for each participant.</description>
        <time_frame>Day 0 and Day 31</time_frame>
        <population>The trial stopped early so we were unable to enroll for Cohort 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Disulfiram 1000 mg</title>
            <description>This study will provide disulfiram. Participants in Cohort 1 receiving disulfiram will take 2 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: Placebo</title>
            <description>This study will provide placebo comparator for disulfiram. Participants in Cohort 1 receiving placebo will take 2 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 2: Disulfiram 2000 mg</title>
            <description>Participants in Cohort 2 receiving disulfiram will take 4 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 2: Placebo</title>
            <description>Participants in Cohort 2 receiving placebo will take 4 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0</title>
          <description>The safety and tolerability of a 5 day course of disulfiram. The number of adverse events and their grade will be determined for each participant.</description>
          <population>The trial stopped early so we were unable to enroll for Cohort 2.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AE Grade 3 or Higher</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AE Grade 1 or 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in COVID-19 Symptom Severity Score as Assessed by a 5-point Adapted Somatic Symptom Severity Score (SSS-8)</title>
        <description>The severity of COVID-19 symptoms will be recorded on a 5-point symptom severity scale at each visit for each participant. A question about how much the symptoms bother the participants will be asked. The participant will rank 1 as &quot;not at all,&quot; 2 as &quot;a little bit,&quot; 3 as &quot;somewhat,&quot; 4 as &quot;quite a bit&quot; and 5 as &quot;very much.&quot; Higher values represent worse outcomes. Scales are combined to compute a total score at Day 0 and Day 31. A change of the median is reported.</description>
        <time_frame>Day 0 and Day 31</time_frame>
        <population>The trial stopped early so we were unable to enroll for Cohort 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Disulfiram</title>
            <description>This study will provide disulfiram. Participants in Cohort 1 receiving disulfiram will take 2 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1: Placebo</title>
            <description>This study will provide placebo comparator for disulfiram. Participants in Cohort 1 receiving placebo will take 2 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 2: Disulfiram</title>
            <description>Participants in Cohort 2 receiving placebo will take 4 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
          <group group_id="O4">
            <title>Cohort 2: Placebo</title>
            <description>Participants in Cohort 2 receiving placebo will take 4 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in COVID-19 Symptom Severity Score as Assessed by a 5-point Adapted Somatic Symptom Severity Score (SSS-8)</title>
          <description>The severity of COVID-19 symptoms will be recorded on a 5-point symptom severity scale at each visit for each participant. A question about how much the symptoms bother the participants will be asked. The participant will rank 1 as &quot;not at all,&quot; 2 as &quot;a little bit,&quot; 3 as &quot;somewhat,&quot; 4 as &quot;quite a bit&quot; and 5 as &quot;very much.&quot; Higher values represent worse outcomes. Scales are combined to compute a total score at Day 0 and Day 31. A change of the median is reported.</description>
          <population>The trial stopped early so we were unable to enroll for Cohort 2.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.60" lower_limit="-3.00" upper_limit="0.35"/>
                    <measurement group_id="O2" value="-2.14" lower_limit="-3.37" upper_limit="-0.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The total duration of the study was approximately 6 months from August 18, 2021 to February 28, 2022. Each participant was assessed for 31 days during the duration of their enrollment in the study. There was one serious adverse event that lasted 5 days from September 6, 2021 to September 11, 2021.</time_frame>
      <desc>Systematic assessment through detailed questionnaires and principal investigator physical exam assessment was conducted at each visit.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1: Disulfiram</title>
          <description>This study will provide disulfiram. Participants in Cohort 1 receiving disulfiram will take 2 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
        </group>
        <group group_id="E2">
          <title>Cohort 1: Placebo</title>
          <description>This study will provide placebo comparator for disulfiram. Participants in Cohort 1 receiving placebo will take 2 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
        </group>
        <group group_id="E3">
          <title>Cohort 2: Disulfiram</title>
          <description>Participants in Cohort 2 receiving placebo will take 4 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
        </group>
        <group group_id="E4">
          <title>Cohort 2: Placebo</title>
          <description>Participants in Cohort 2 receiving placebo will take 4 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hospitalization</sub_title>
                <description>Chest pain resulted in hospitalization for 5 days; no relationship to study drug and was resolved</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_at_risk="0"/>
                <counts group_id="E4" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>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="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Black stool and post viral cough syndrome</sub_title>
                <description>Mild severity of black stool and not related to study drug Moderate severity of post viral cough syndrome and not related to study drug</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_at_risk="0"/>
                <counts group_id="E4" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>GI (nausea/vomiting), fever, chills, congestion, sore throat, back pain, muscle ache, headache</sub_title>
                <description>All symptoms were mild severity and not related to study drug</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_at_risk="0"/>
                <counts group_id="E4" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Smell and taste</sub_title>
                <description>Mild severity lasting 11 days until resolved; not related to study drug</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_at_risk="0"/>
                <counts group_id="E4" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Smell/taste, gas, back pain</sub_title>
                <description>All mild severity; not related to study drug Back pain lasted 1 day until resolved</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_at_risk="0"/>
                <counts group_id="E4" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <description>dehydration for 1 day; not related to study drug and was resolved</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_at_risk="0"/>
                <counts group_id="E4" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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. Sulggi Lee</name_or_title>
      <organization>University of California, San Francisco</organization>
      <phone>415-735-5127</phone>
      <email>sulggi.lee@ucsf.edu</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/NCT04485130
org study id: DSF151837
nct id: NCT04485130
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Disulfiram (DSF) a safe, easily dosed, FDA-approved drug for the treatment of alcohol
      dependence has been identified to be a potential therapeutic target for SARS-CoV-2 infection.
      Disulfiram may have both antiviral (inhibiting viral replication via blocking the Mpro
      protease and zinc ejection) and anti-inflammatory effects (via inhibition of NF-kB-induced
      and NLRP inflammasome-induced cytokine release) on SARS-CoV-2. We will study oral disulfiram
      given for 5 consecutive days (1000 mg/day in cohort 1; 2000 mg/day in cohort 2) in 60
      symptomatic COVID+ individuals in a randomized (2:1) randomized, double blind
      placebo-controlled trial evaluating disulfiram's effect on COVID-19 symptom severity,
      SARS-CoV-2 viral load, and biomarkers of inflammation and pyroptosis (aberrant
      pro-inflammatory cell death) over 31 days.
The identification of a safe, effective treatment for individuals with early mild-to-moderate
      symptomatic COVID-19 that prevent progression to more severe disease would have immediate
      public health implications. A hallmark of severe COVID-19 disease is immune system
      dysregulation called cytokine storm. Multiple studies have reported that patients with severe
      disease demonstrate elevated levels of pro-inflammatory cytokines early in disease, and
      elevated IL-6 plasma concentrations are predictive of poor clinical outcomes in COVID-19.
      Disulfiram, an FDA-approved drug for the treatment of alcohol dependence disorder is an
      appealing therapeutic option for COVID-19. It has a good safety profile, easy dosing
      schedule, and recent data suggesting multiple mechanisms by which disulfiram may act on
      COVID-19 (both as a direct antiviral agent as well as indirect effects on reducing
      inflammation). In addition disulfiram has been studied extensively with detailed available
      pharmacokinetic data; disulfiram has a short half-life ~7.5 hours with >90% of drug
      eliminated within 3 days post-dose, allowing quick reversal of any potential adverse effects.
      We will perform a phase 2 randomized (2:1), double blind placebo-controlled assessment of
      disulfiram in people with early mild-to-moderate symptomatic COVID-19. A total of 60
      symptomatic COVID+ individuals will enrolled to receive active drug versus placebo (with
      equal distribution of mild or moderate/severe within each dosing cohort and within each
      randomization arm). For cohort 1, N=20 will receive DSF 1000 mg/N=10 placebo, and for cohort
      2, N=20 will receive DSF 2000 mg/N=10 placebo. Drug/placebo will be administered using strict
      infection control protocols designed to support the study of people with acute COVID-19
      infection per the Center for Diseases Control (CDC) guidelines
      (https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-in-home-patients.html).
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: This is a dose escalation double blind randomized (2:1) placebo-controlled trial of disulfiram given as 1000 mg/day x 5 consecutive days (Cohort 1: N=20 drug/N=10 placebo) or 2000 mg/day x 5 consecutive days (Cohort 2: N=20 drug/N=10 placebo) among 60 acute symptomatic lab-confirmed (<7 days) COVID+ individuals .
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double blind
measure: Immunologic Impact of 5 Days of Disulfiram, as Measured by the Fold-change in Plasma Levels of Pro-inflammatory Cytokines (e.g, Interleukin 6, Interleukin 1-beta, Etc.).
time frame: Day 0 and Day 31
description: Change in plasma inflammatory biomarker levels (e.g., IL-6, IL-1b) at days 5, 15, and 31.
measure: Virologic Impact of 5 Days of Disulfiram, as Measured by the Change in Copies of SARS-CoV-2 Virus Per mL Between Baseline and Day 31.
time frame: Day 0 and Day 31
description: Change in copies of SARS-CoV-2 PCR virus per mL between Baseline and Day 31.
measure: Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
time frame: Day 0 and Day 31
description: The safety and tolerability of a 5 day course of disulfiram. The number of adverse events and their grade will be determined for each participant.
measure: Change in COVID-19 Symptom Severity Score as Assessed by a 5-point Adapted Somatic Symptom Severity Score (SSS-8)
time frame: Day 0 and Day 31
description: The severity of COVID-19 symptoms will be recorded on a 5-point symptom severity scale at each visit for each participant. A question about how much the symptoms bother the participants will be asked. The participant will rank 1 as "not at all," 2 as "a little bit," 3 as "somewhat," 4 as "quite a bit" and 5 as "very much." Higher values represent worse outcomes. Scales are combined to compute a total score at Day 0 and Day 31. A change of the median is reported.
arm group label: Disulfiram
arm group type: Experimental
description: This study will provide disulfiram. Participants in Cohort 1 receiving disulfiram will take 2 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days. Participants in Cohort 2 receiving placebo will take 4 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.
arm group label: Placebo
arm group type: Placebo Comparator
description: This study will provide placebo comparator for disulfiram. Participants in Cohort 1 receiving placebo will take 2 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days. Participants in Cohort 2 receiving placebo will take 4 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days.
intervention type: Drug
intervention name: Disulfiram
description: This study will provide disulfiram. Participants in Cohort 1 receiving disulfiram will take 2 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days. Participants in Cohort 2 receiving placebo will take 4 capsules of disulfiram (each capsule contains 500 mg DSF plus 27.75 mg microcrystalline cellulose powder) per day for a total of 5 consecutive days.
arm group label: Disulfiram
other name: Antabuse
intervention type: Drug
intervention name: Placebo
description: This study will provide placebo. Participants in Cohort 1 receiving placebo will take 2 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days. Participants in Cohort 2 receiving placebo will take 4 capsules of placebo (each capsule contains only microcrystalline cellulose powder) per day for a total of 5 consecutive days
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sulggi A Lee, MD PhD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
facility: 
country: United States
citation: Lee SA, Elliott JH, McMahon J, Hartogenesis W, Bumpus NN, Lifson JD, Gorelick RJ, Bacchetti P, Deeks SG, Lewin SR, Savic RM. Population Pharmacokinetics and Pharmacodynamics of Disulfiram on Inducing Latent HIV-1 Transcription in a Phase IIb Trial. Clin Pharmacol Ther. 2019 Mar;105(3):692-702. doi: 10.1002/cpt.1220. Epub 2018 Oct 9.
PMID: 30137649
citation: Elliott JH, McMahon JH, Chang CC, Lee SA, Hartogensis W, Bumpus N, Savic R, Roney J, Hoh R, Solomon A, Piatak M, Gorelick RJ, Lifson J, Bacchetti P, Deeks SG, Lewin SR. Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV. 2015 Dec;2(12):e520-9. doi: 10.1016/S2352-3018(15)00226-X. Epub 2015 Nov 17.
PMID: 26614966
citation: Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, Zhang B, Li X, Zhang L, Peng C, Duan Y, Yu J, Wang L, Yang K, Liu F, Jiang R, Yang X, You T, Liu X, Yang X, Bai F, Liu H, Liu X, Guddat LW, Xu W, Xiao G, Qin C, Shi Z, Jiang H, Rao Z, Yang H. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020 Jun;582(7811):289-293. doi: 10.1038/s41586-020-2223-y. Epub 2020 Apr 9.
PMID: 32272481
citation: Lin MH, Moses DC, Hsieh CH, Cheng SC, Chen YH, Sun CY, Chou CY. Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes. Antiviral Res. 2018 Feb;150:155-163. doi: 10.1016/j.antiviral.2017.12.015. Epub 2017 Dec 28.
PMID: 29289665
citation: Hu JJ, Liu X, Xia S, Zhang Z, Zhang Y, Zhao J, Ruan J, Luo X, Lou X, Bai Y, Wang J, Hollingsworth LR, Magupalli VG, Zhao L, Luo HR, Kim J, Lieberman J, Wu H. FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation. Nat Immunol. 2020 Jul;21(7):736-745. doi: 10.1038/s41590-020-0669-6. Epub 2020 May 4.
PMID: 32367036
citation: Lobo-Galo N, Terrazas-Lopez M, Martinez-Martinez A, Diaz-Sanchez AG. FDA-approved thiol-reacting drugs that potentially bind into the SARS-CoV-2 main protease, essential for viral replication. J Biomol Struct Dyn. 2021 Jun;39(9):3419-3427. doi: 10.1080/07391102.2020.1764393. Epub 2020 May 14.
PMID: 32364011
responsible party type: Principal Investigator
investigator affiliation: University of California, San Francisco
investigator full name: Sulggi A. Lee, MD, PhD
investigator title: Associate Professor of Medicine
mesh term: COVID-19
mesh term: Disulfiram
sharing ipd: Yes
ipd description: Planned sharing of de-identified individual participant data for the purposes of collaboration and meta-analyses.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: After publication of study results
ipd access criteria: De-identified data
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 