TerminatedNCT04485130DISCOUpdated Sep 13, 2023Results posted

DISulfiram for COvid-19 (DISCO) Trial

A Phase 2 interventional study of Disulfiram and Placebo in Covid19, sponsored by University of California, San Francisco. Terminated at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-09-13.

Sponsored by University of California, San Francisco · Phase 2, Interventional, and Treatment

Why this study was terminated

Low COVID case numbers, competing COVID treatments available

Phase: Phase 2
Study type: Interventional
Enrollment: 11
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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.

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 studied

Covid19

Browse trials for

COVID-19 7,640

Keywords

Disulfiram
COVID-19
SARS-CoV-2

In context

COVID-19

7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.

This study's enrollment of 11 is below the median of 100 across 4,099 interventional studies indexed under COVID-19.

Browse COVID-19 studies →

Lead sponsor

University of California, San Francisco is the lead sponsor of 2,133 studies on the registry; 376 are open to participants now.

Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 11 participants (actual)

Study arms

Experimental
Disulfiram
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.
Drug: Disulfiram
Placebo comparator
Placebo
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.
Drug: Placebo

Interventions

DrugDisulfiram
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.
Also known as: Antabuse
DrugPlacebo
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

What researchers measure

Primary outcomes

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.
Time frame: Day 0 and Day 31

Secondary outcomes

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.
Time frame: Day 0 and Day 31
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.
Time frame: Day 0 and Day 31
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.
Time frame: Day 0 and Day 31

Results

Posted Sep 13, 2023

Participant flow

Participant flow — Overall Study
Milestone	Cohort 1 - Disulfiram 1000 mg	Cohort 1: Placebo
Started	7	4
Completed	7	4
Not completed	0	0

Outcome measures

PrimaryImmunologic 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.

Time frame:: Day 0 and Day 31
Reported as:: Median · fold change

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.).
fold change	Cohort 1: Disulfiram 100 mg	Cohort 1: Placebo	Cohort 2: Disulfiram 2000 mg	Cohort 2: Placebo
Change in IL-6 (pg/mL) Day 0 to 31	-0.1186 (-0.2012 to -0.0246)	-0.0215 (-0.1202 to -0.0178)	—	—
Change in IL-1B (pg/mL) Day 0 to 31	-0.1402 (-0.2583 to 0.0648)	0.0268 (-0.0438 to 0.0399)	—	—

SecondaryVirologic 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.

Time frame:: Day 0 and Day 31
Reported as:: Mean · copies/mL

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.
copies/mL	Cohort 1: Disulfiram 1000 mg	Cohort 1: Placebo	Cohort 2: Disulfiram 2000 mg	Cohort 2: Placebo
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.	-20.89 ± 9.84	-20 ± 13.53	—	—

SecondaryNumber 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.

Time frame:: Day 0 and Day 31
Reported as:: Count of participants · Participants

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Participants	Cohort 1: Disulfiram 1000 mg	Cohort 1: Placebo	Cohort 2: Disulfiram 2000 mg	Cohort 2: Placebo
AE Grade 3 or Higher	0	1	—	—
AE Grade 1 or 2	4	1	—	—

SecondaryChange 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.

Time frame:: Day 0 and Day 31
Reported as:: Median · units on a scale

Change in COVID-19 Symptom Severity Score as Assessed by a 5-point Adapted Somatic Symptom Severity Score (SSS-8)
units on a scale	Cohort 1: Disulfiram	Cohort 1: Placebo	Cohort 2: Disulfiram	Cohort 2: Placebo
Change in COVID-19 Symptom Severity Score as Assessed by a 5-point Adapted Somatic Symptom Severity Score (SSS-8)	-2.60 (-3.00 to 0.35)	-2.14 (-3.37 to -0.59)	—	—

Adverse events

Collected over 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.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cohort 1: Disulfiram	0/7 (0%)	0/7 (0%)	4/7 (57.1%)
Cohort 1: Placebo	0/4 (0%)	1/4 (25%)	1/4 (25%)
Cohort 2: Disulfiram	—	—	—
Cohort 2: Placebo	—	—	—

Most frequent serious events

Most frequent serious events
Event	Cohort 1: Disulfiram	Cohort 1: Placebo	Cohort 2: Disulfiram	Cohort 2: Placebo
HospitalizationRespiratory, thoracic and mediastinal disorders	0/7	1/4	—	—

Most frequent other events

Most frequent other events
Event	Cohort 1: Disulfiram	Cohort 1: Placebo	Cohort 2: Disulfiram	Cohort 2: Placebo
Black stool and post viral cough syndromeGastrointestinal disorders	0/7	1/4	—	—
DehydrationRenal and urinary disorders	1/7	0/4	—	—
GI (nausea/vomiting), fever, chills, congestion, sore throat, back pain, muscle ache, headacheGeneral disorders	1/7	0/4	—	—
Smell and tasteGeneral disorders	1/7	0/4	—	—
Smell/taste, gas, back painGeneral disorders	1/7	0/4	—	—

Baseline characteristics

The trial stopped early so we were unable to enroll for Cohort 2.

Age, Categorical
Age, Categorical(Participants)	Cohort 1: Disulfiram 1000 mg	Cohort 1: Placebo	Total
<=18 years	0	0	0
Between 18 and 65 years	7	4	11
>=65 years	0	0	0

Age, Continuous
Age, Continuous(years)	Cohort 1: Disulfiram 1000 mg	Cohort 1: Placebo	Cohort 2: Disulfiram 2000 mg	Cohort 2: Placebo	Total
Mean	38 ± 12.5	43.5 ± 8	—	—	40 ± 11

Sex: Female, Male
Sex: Female, Male(Participants)	Cohort 1: Disulfiram 1000 mg	Cohort 1: Placebo	Cohort 2: Disulfiram 2000 mg	Cohort 2: Placebo	Total
Female	5	2	—	—	7
Male	2	2	—	—	4

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Cohort 1: Disulfiram 1000 mg	Cohort 1: Placebo	Cohort 2: Disulfiram 2000 mg	Cohort 2: Placebo	Total
Hispanic or Latino	3	1	—	—	4
Not Hispanic or Latino	4	3	—	—	7
Unknown or Not Reported	0	0	—	—	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Cohort 1: Disulfiram 1000 mg	Cohort 1: Placebo	Cohort 2: Disulfiram 2000 mg	Cohort 2: Placebo	Total
American Indian or Alaska Native	0	0	—	—	0
Asian	1	0	—	—	1
Native Hawaiian or Other Pacific Islander	0	0	—	—	0
Black or African American	1	0	—	—	1
White	5	4	—	—	9
More than one race	0	0	—	—	0
Unknown or Not Reported	0	0	—	—	0

Region of Enrollment
Region of Enrollment(participants)	Cohort 1: Disulfiram 1000 mg	Cohort 1: Placebo	Cohort 2: Disulfiram 2000 mg	Cohort 2: Placebo	Total
United States	7	4	—	—	11

BMI
BMI(kg/m^2)	Cohort 1: Disulfiram 1000 mg	Cohort 1: Placebo	Cohort 2: Disulfiram 2000 mg	Cohort 2: Placebo	Total
Mean	25.6 ± 5.5	33.3 ± 2.2	—	—	28.4 ± 5.9

Study locations

2 sites

University of California San Francisco, Fresno
Fresno, California 93701, United States
San Francisco General Hospital
San Francisco, California 94110, United States

References and documents

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 ↗

Study documents

Protocol and statistical analysis plan · Sep 8, 2021
Informed consent form · Oct 7, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Planned sharing of de-identified individual participant data for the purposes of collaboration and meta-analyses.

Supporting information: Study protocol, Sap, Icf, Csr, Analytic code

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 13, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04485130
Lead sponsor: University of California, San Francisco
Responsible party: Sulggi A. Lee, MD, PhD (Associate Professor of Medicine, University of California, San Francisco) — Principal investigator
First posted: Jul 24, 2020
Start date: Aug 18, 2021
Primary completion: Feb 28, 2022
Completion: Feb 28, 2022
Results posted: Sep 13, 2023
Last update: Sep 13, 2023

Study contacts

Sulggi A Lee, MD PhD

principal investigator · University of California, San Francisco

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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