DISulfiram for COvid-19 (DISCO) Trial
Condition: Covid19
MeSH terms: COVID-19
Intervention: Disulfiram; Placebo
Intervention 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.; 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
Intervention MeSH terms: Disulfiram
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
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 .
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double blind
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Disulfiram; COVID-19; SARS-CoV-2

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to provide written informed consent, and

          -  Age >= 18 years, and

          -  SARS-CoV-2 positive PCR (nucleic acid) test within the preceding 7 days, and

          -  Not currently hospitalized, and

          -  Willing to abstain from any alcohol during the two week period in which disulfiram
             will be administered and during the two week period immediately after disulfiram
             administration.

          -  Both male and female subjects are eligible. Females of childbearing potential must
             have a negative pregnancy test at screening and agree to use a double-barrier method
             of contraception throughout the study period.

        Exclusion Criteria:

          -  Pregnant, breastfeeding, or unwilling to practice birth control during participation
             in the study

          -  Active malignancy requiring systemic chemotherapy or surgery in the preceding 3 months
             or for whom such therapies are expected in the subsequent 6 months

          -  Decompensated liver disease as defined by the presence of ascites, encephalopathy,
             esophageal or gastric varices, or persistent jaundice

          -  Serious illness requiring systemic treatment and/or hospitalization in the 3 months
             prior to study enrollment

          -  Concurrent treatment with immunomodulatory drugs, and/or exposure to any
             immunomodulatory drug in the 4 weeks prior to study enrollment (e.g. corticosteroid
             therapy equal to or exceeding a dose of 15 mg/day of prednisone for more than 10 days,
             IL-2, interferon-alpha, methotrexate, cancer chemotherapy). NOTE: use of inhaled or
             nasal steroid is not exclusionary.

          -  Serious medical or psychiatric illness that, in the opinion of the site investigator,
             would interfere with the ability to adhere to study requirements or to give informed
             consent.

          -  Current alcohol use disorder or hazardous alcohol use (>7 drinks per week for women or
             > 14 drinks per week for men) as determined by clinical evaluation.

          -  Current use of any drug formulation that contains alcohol or that might contain
             alcohol

          -  Current use of warfarin.

          -  Clinically active hepatitis determined by the study physician; ALT or AST > 3 x the
             upper limit of normal or total bilirubin outside the normal range.

          -  Allergy to rubber or thiuram derivatives