Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Francisco, California
Dates
study started
estimated completion
Principal Investigator
by Sulggi A Lee, MD PhD
Photo of Sulggi A Lee
Sulggi A Lee

Description

Summary

Disulfiram 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 test disulfiram 2000 mg/day for 3 consecutive days (doses shown to be well tolerated and safe in a recent phase 2b trial) in 60 symptomatic COVID PCR+ individuals in a randomized (1:1) clinical trial evaluating the effect on COVID symptoms severity, SARS-CoV-2 viral load, and biomarkers of inflammation over 31 days.

Official Title

Virologic and Immunologic Response to Disulfiram in Early Symptomatic COVID+ Outpatients

Details

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. This is a randomized, placebo-controlled assessment of disulfiram in people with early mild-to-moderate symptomatic COVID-19. Disulfiram 2 grams or a placebo will be administered orally once daily for 3 consecutive days. Sixty (N=30 mild, N= moderate/severe) symptomatic COVID PCR+ participants will be randomized (1:1) to receive active drug versus placebo. Subsequent stratified analyses will be performed based on upper limit of normal hs-CRP, ferritin, D-dimer levels. 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).

Keywords

Covid19 Disulfiram COVID-19 SARS-CoV-2

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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.

You CAN'T join if...

  • 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

Location

  • San Francisco General Hospital
    San Francisco California 94110 United States

Lead Scientist at UCSF

  • Sulggi A Lee, MD PhD
    Sulggi Lee, MD PhD, is an Associate Professor of Medicine in Residence at the University of California, San Francisco (UCSF) and a faculty member in the Division of HIV, Infectious Diseases, and Global Medicine at the Zuckerberg San Francisco General Hospital.

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT04485130
Phase
Phase 2
Study Type
Interventional
Last Updated