Disulfiram: A Test of Symptom Reduction Among Patients With Previously Treated Lyme Disease

Overseen By Shannon Delaney, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Research Foundation for Mental Hygiene, Inc.

Must not be taking: Warfarin, Metronidazole, Phenytoin, others

Disqualifiers: Cardiovascular disease, Seizure disorder, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

11 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You will need to stop taking any antibiotics for at least 3 months before and during the study. However, you can continue taking other non-antibiotic medications as long as they have been stable for 3 months before the study and do not change during the study, unless medically necessary.

What evidence supports the effectiveness of the drug Disulfiram?

Disulfiram has shown effectiveness in reducing rehospitalization rates and hospitalization duration in alcoholism treatment. Additionally, it has demonstrated potential anticancer activity, particularly in suppressing liver metastases from ocular melanoma, and has antibacterial properties against certain bacteria. ^{1 2 3 4 5}

Is Disulfiram generally safe for humans?

The safety of Disulfiram, also known as Antabuse, has been studied, and it is known to have some serious side effects. These can include liver damage and severe reactions if alcohol is consumed while taking the drug. It's important to discuss potential risks with a healthcare provider before starting treatment. ^{6 7 8 9 10}

How does the drug Disulfiram differ from other treatments?

Disulfiram is unique because it not only helps with alcohol dependence but also shows potential as an antibacterial agent, particularly against Gram-positive bacteria, and can enhance the effectiveness of certain antibiotics. This dual action is not typical of standard treatments for alcohol dependence. ^{1 2 11 12 13}

What is the purpose of this trial?

This trial tests disulfiram, a drug usually used to help people stop drinking alcohol, for treating long-lasting Lyme disease symptoms. It focuses on patients who still have symptoms after standard antibiotics. Disulfiram can kill both active and dormant Lyme bacteria. The study will check the safety and effectiveness of different treatment periods.

Research Team

Brian A Fallon, MD

Principal Investigator

Columbia University

Eligibility Criteria

Inclusion Criteria

The subject is willing to be off of other antibiotics during the course of this study and for at least 3 months prior to study randomization and during the 14 weeks of this study.

I have had a current episode of Lyme disease-related fatigue that has been relatively persistent and has not had an intervening interval of 8 months without fatigue since my diagnosis of Lyme disease.

The text above is a summary of the history of Lyme Disease diagnosis

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive disulfiram for either 4 or 8 weeks, with a fixed-flexible dosing schedule

8 weeks

Weekly visits for dose adjustment and monitoring

Placebo

Participants in the 4-week disulfiram group receive placebo for 4 weeks

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person) at weeks 10 and 14

Treatment Details

Interventions

• Disulfiram

Participant Groups

Group I: 8 Week Disulfiram Experimental Treatment 1 Intervention

Patients in this group receive disulfiram for 8 weeks. The dosing schedule is fixed-flexible, starting at 250 mg every other day at week 1, 250 mg daily for week 2, 250 mg alternating with 500 mg for week 3, and 500 mg daily for week 4 to week 8. Dose increases are based on clinical judgment guided by patient tolerance, response, body weight, and side effects.

Group II: 4 Week Disulfiram Active Control 1 Intervention

Patients in this group receive disulfiram for 4 weeks followed by placebo capsules for 4 weeks. The dosing schedule is fixed-flexible, starting at 250 mg every other day at week 1, 250 mg daily for week 2, 250 mg alternating with 500 mg during week 3, and 500 mg daily during week 4. Placebo capsules are given during weeks 5-8. Dose increases are based on clinical judgment guided by patient tolerance, response, body weight, and side effects.

Disulfiram is already approved in United States, European Union for the following indications:

Approved in United States as Antabuse for:

• Alcohol dependence

Approved in European Union as Antabuse for:

• Alcohol dependence

Who Is Running the Clinical Trial?

Research Foundation for Mental Hygiene, Inc.

Lead Sponsor

Trials

68

Recruited

21,100+

FDC Foundation

Collaborator

Trials

3

Recruited

10+

Findings from Research

Disulfiram (DSF) and its metabolite diethyldithiocarbamate (DDTC) were evaluated against 30 types of bacteria, with DDTC showing notable antibacterial activity specifically against Bacillus anthracis.

The study suggests that while DSF's metabolites do not significantly enhance its antibacterial properties, DDTC can boost the effectiveness of DSF, indicating its potential as an antibiotic adjuvant for treating resistant staph infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibacterial activity of disulfiram and its metabolites. Frazier, KR., Moore, JA., Long, TE.[2019]

In a double-blind trial involving 15 HIV-positive men, disulfiram was administered at doses of 100 mg or 400 mg daily for 4 weeks, but it did not show any significant effects on immune function or overall health.

Despite its potential as an immunomodulating agent, disulfiram did not improve immunological, hematological, or clinical outcomes in participants with low CD4 counts or impaired lymphocyte response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of immunomodulating effect of disulfiram on HIV positive patients. Hørding, M., Gøtzsche, PC., Bygbjerg, IC., et al.[2019]

Disulfiram, a drug traditionally used to treat alcoholism, has shown promising anticancer activity, particularly in suppressing liver metastases from ocular melanoma, making it a potential new treatment option.

This drug is not only inexpensive and widely available, but it also has a favorable safety profile compared to conventional cancer treatments, with negligible adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of proteasome inhibition in cancer. Can the old drug, disulfiram, have a bright new future as a novel proteasome inhibitor? Cvek, B., Dvorak, Z.[2015]

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

MetaADEDB 2.0 is an updated online database that now includes 744,709 drug-adverse drug event (ADE) associations, representing a 40% increase from its previous version, making it a more comprehensive resource for researchers.

The new version features a user-friendly web interface, enhancing accessibility for drug safety assessments and studies in drug discovery and development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MetaADEDB 2.0: a comprehensive database on adverse drug events. Yu, Z., Wu, Z., Li, W., et al.[2021]

Disulfiram (Antabuse) effectively inhibits the RNA-dependent DNA polymerase of Rous sarcoma virus, preventing it from causing malignant transformation in chick embryo cells, highlighting its potential anti-cancer properties.

Disulfiram induces the synthesis of specific proteins in normal cells and shows a greater impact on DNA synthesis compared to RNA and protein synthesis, suggesting it may influence cellular processes beyond its use in treating alcoholism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of antabuse (disulfiram) on Rous sarcoma virus and on eukaryotic cells. Levinson, W., Mikelens, P., Oppermann, H., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Antibacterial activity of disulfiram and its metabolites. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Disulfiram-based disulfides as narrow-spectrum antibacterial agents. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Lack of immunomodulating effect of disulfiram on HIV positive patients. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

A community program for control of alcoholism. [2013]

5. England pubmed.ncbi.nlm.nih.gov

The value of proteasome inhibition in cancer. Can the old drug, disulfiram, have a bright new future as a novel proteasome inhibitor? [2015]

6. United States pubmed.ncbi.nlm.nih.gov

ADVERPred-Web Service for Prediction of Adverse Effects of Drugs. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. [2023]

8. England pubmed.ncbi.nlm.nih.gov

MetaADEDB 2.0: a comprehensive database on adverse drug events. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Data-mining-based detection of adverse drug events. [2013]

10. Egypt pubmed.ncbi.nlm.nih.gov

Pantoprazole associated dyspepsia hypocalcemia and hyponatremia: A disproportionality analysis in FDA adverse event reporting system (FAERS) database. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of antabuse (disulfiram) on Rous sarcoma virus and on eukaryotic cells. [2019]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Determination of disulfiram and metabolites from biological fluids by high-performance liquid chromatography. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Pharmacological evaluation of disulfiram analogs as antimicrobial agents and their application as inhibitors of fosB-mediated fosfomycin resistance. [2022]