NCT04485130: DISCO

DISulfiram for COvid-19 (DISCO) Trial

Terminated Phase 2 Results posted Last updated 13 September 2023

What this trial tests

Phase 2 trial testing Disulfiram in Covid19 in 11 participants. Terminated before completion.

Timeline

18 August 2021

Primary endpoint
28 February 2022

28 February 2022

Quick facts

Lead sponsor	University of California, San Francisco
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	sequential
Masking	quadruple
Primary purpose	treatment
Enrollment	11
Start date	18 August 2021
Primary completion	28 February 2022
Estimated completion	28 February 2022
Sites	2 locations across United States

Drugs / interventions tested

• Disulfiram (DISULFIRAM) — full drug profile →
• Placebo

Conditions studied

• Covid19 — all drugs for Covid19 →

Sponsor

University of California, San Francisco

Who can join

18 and older, any sex, with Covid19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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.). Primary · Day 0 and Day 31

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

Change in IL-6 (pg/mL) Day 0 to 31

Group	Value	95% CI
Cohort 1: Disulfiram 100 mg	-0.1186	-0.2012 – -0.0246
Cohort 1: Placebo	-0.0215	-0.1202 – -0.0178

Change in IL-1B (pg/mL) Day 0 to 31

Group	Value	95% CI
Cohort 1: Disulfiram 100 mg	-0.1402	-0.2583 – 0.0648
Cohort 1: Placebo	0.0268	-0.0438 – 0.0399

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. Secondary · Day 0 and Day 31

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

Group	Value	95% CI
Cohort 1: Disulfiram 1000 mg	-20.89	± 9.84
Cohort 1: Placebo	-20	± 13.53

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 Secondary · Day 0 and Day 31

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.

AE Grade 3 or Higher

Group	Value	95% CI
Cohort 1: Disulfiram 1000 mg	0
Cohort 1: Placebo	1

AE Grade 1 or 2

Group	Value	95% CI
Cohort 1: Disulfiram 1000 mg	4
Cohort 1: Placebo	1

Change in COVID-19 Symptom Severity Score as Assessed by a 5-point Adapted Somatic Symptom Severity Score (SSS-8) Secondary · Day 0 and Day 31

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.

Group	Value	95% CI
Cohort 1: Disulfiram	-2.60	-3.00 – 0.35
Cohort 1: Placebo	-2.14	-3.37 – -0.59

Adverse events — posted to ClinicalTrials.gov

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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1: Disulfiram

Serious: 0/7 (0%)

Deaths: 0/7

Cohort 1: Placebo

Serious: 1/4 (25%)

Deaths: 0/4

Cohort 2: Disulfiram

Serious: 0

Deaths: 0

Cohort 2: Placebo

Serious: 0

Deaths: 0

Serious adverse events (1 terms)

Reaction	System	Cohort 1: Disulfiram	Cohort 1: Placebo	Cohort 2: Disulfiram	Cohort 2: Placebo
Hospitalization	Respiratory, thoracic and mediastinal disorders	—	—	—	—

Other adverse events (5 terms — click to expand)

Reaction	System	Cohort 1: Disulfiram	Cohort 1: Placebo	Cohort 2: Disulfiram	Cohort 2: Placebo
Dehydration	Renal and urinary disorders	—	—	—	—
Black stool and post viral cough syndrome	Gastrointestinal disorders	—	—	—	—
GI (nausea/vomiting), fever, chills, congestion, sore throat, back pain, muscle ache, headache	General disorders	—	—	—	—
Smell and taste	General disorders	—	—	—	—
Smell/taste, gas, back pain	General disorders	—	—	—	—

Most-reported serious reactions: Hospitalization.

Data from ClinicalTrials.gov NCT04485130 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation.
   Junqueira C, Crespo Â, Ranjbar S, de Lacerda LB, et al · · 2022 · cited 496× · PMID 35385861 · DOI 10.1038/s41586-022-04702-4
2. Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases.
   Wigerblad G, Kaplan MJ. · · 2023 · cited 337× · PMID 36257987 · DOI 10.1038/s41577-022-00787-0
3. Neutrophil extracellular traps: from physiology to pathology.
   Hidalgo A, Libby P, Soehnlein O, Aramburu IV, et al · · 2022 · cited 270× · PMID 34648022 · DOI 10.1093/cvr/cvab329
4. Inflammasome activation at the crux of severe COVID-19.
   Vora SM, Lieberman J, Wu H. · · 2021 · cited 265× · PMID 34373622 · DOI 10.1038/s41577-021-00588-x
5. COVID-19: Characteristics and Therapeutics.
   Chilamakuri R, Agarwal S. · · 2021 · cited 192× · PMID 33494237 · DOI 10.3390/cells10020206
6. The role of inflammasomes in human diseases and their potential as therapeutic targets.
   Yao J, Sterling K, Wang Z, Zhang Y, et al · · 2024 · cited 135× · PMID 38177104 · DOI 10.1038/s41392-023-01687-y
7. Gasdermin D-mediated pyroptosis: mechanisms, diseases, and inhibitors.
   Dai Z, Liu WC, Chen XY, Wang X, et al · · 2023 · cited 120× · PMID 37275856 · DOI 10.3389/fimmu.2023.1178662
8. NETosis and Neutrophil Extracellular Traps in COVID-19: Immunothrombosis and Beyond.
   Zhu Y, Chen X, Liu X. · · 2022 · cited 119× · PMID 35309344 · DOI 10.3389/fimmu.2022.838011