AzTrials
AzTrials

Covid19Phase 2DISCONCT04485130

DISulfiram for COvid-19 (DISCO) Trial

A Phase 2 study testing Disulfiram in people with Covid19, run by University of California, San Francisco at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Covid19
What is being tested?
Disulfiram
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
11 participants
Where
2 sitesUnited States
Study dates
18 Aug 2021to 28 Feb 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 11Show fewer
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of California San Francisco, Fresno

    Fresno, California, 93701

  • San Francisco General Hospital

    San Francisco, California, 94110

Other trials in United States

About this study

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

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.

Read the detailed description

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).

Conditions
Covid19
Being tested
Disulfiram, Placebo
Keywords
Disulfiram, COVID-19, SARS-CoV-2
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DisulfiramDrug

    Also called Antabuse

    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.

  • PlaceboDrug

    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

Study groups in NCT04485130
Study groupRoleWhat they receive
DisulfiramExperimentalThis 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.
Receives: Drug: Disulfiram
PlaceboPlacebo comparatorThis 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.).

    Change in plasma inflammatory biomarker levels (e.g., IL-6, IL-1b) at days 5, 15, and 31.

    Measured: Day 0 and Day 31

Secondary outcomes (3)

  1. 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.

    Change in copies of SARS-CoV-2 PCR virus per mL between Baseline and Day 31.

    Measured: Day 0 and Day 31

  2. Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

    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.

    Measured: Day 0 and Day 31

  3. Change in COVID-19 Symptom Severity Score as Assessed by a 5-point Adapted Somatic Symptom Severity Score (SSS-8)

    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.

    Measured: Day 0 and Day 31

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jul 2020
  2. Study start18 Aug 2021
  3. Primary completion28 Feb 2022
  4. Study completion28 Feb 2022

Why it stopped: Low COVID case numbers, competing COVID treatments available

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
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 blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04485130
Sponsor's protocol ID
DSF151837
Acronym
DISCO
Status last verified
Aug 2023
First submitted
22 Jul 2020
Last updated
13 Sep 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Planned sharing of de-identified individual participant data for the purposes of collaboration and meta-analyses.

Publications

  • 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.

    PubMed 30137649

  • 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.

    PubMed 26614966

  • 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.

    PubMed 32272481

  • 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.

    PubMed 29289665

  • 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.

    PubMed 32367036

  • 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.

    PubMed 32364011

  • Saifi MA, Shaikh AS, Kaki VR, Godugu C. Disulfiram prevents collagen crosslinking and inhibits renal fibrosis by inhibiting lysyl oxidase enzymes. J Cell Physiol. 2022 May;237(5):2516-2527. doi: 10.1002/jcp.30717. Epub 2022 Mar 13.

    PubMed 35285015

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Disulfiram in people with Covid19, run by University of California, San Francisco at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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.). (time frame: Day 0 and Day 31). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04485130, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in