Disulfiram for 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called disulfiram to determine if it can reduce ongoing symptoms in individuals who have completed Lyme disease treatment but still experience issues like fatigue. Researchers aim to discover whether taking this drug for 4 weeks or 8 weeks proves more effective. Suitable candidates for this trial have received a Lyme disease diagnosis within the last 16 years, have already undergone antibiotic treatment, and continue to experience moderate to severe fatigue impacting daily life. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants an opportunity to contribute to early-stage research.

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.

Is there any evidence suggesting that disulfiram is likely to be safe for humans?

Research shows that disulfiram has long been used to help people stop drinking alcohol. Disulfiram can cause side effects, such as liver problems, and some individuals have experienced serious reactions. It is not suitable for everyone, particularly those with certain heart conditions.

In terms of safety, reported side effects include skin reactions and liver issues. Avoiding alcohol while taking disulfiram is crucial, even in small amounts, as it can cause unpleasant reactions.

This trial is in the early stages of testing disulfiram for Lyme disease symptoms, so not all safety details are known yet. However, since disulfiram is already used for alcohol dependence, some understanding of its safety exists. As individual responses vary, consulting a doctor is essential to determine if this treatment is appropriate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Lyme disease?

Researchers are excited about using disulfiram for Lyme disease because it offers a novel approach compared to standard treatments like antibiotics. Disulfiram, originally used for alcohol dependence, has a unique mechanism that may target the Lyme bacteria differently, potentially reducing symptoms that persist even after traditional antibiotic treatment. This approach could offer hope for patients who have limited options once antibiotics have been tried, providing a new avenue for symptom management and improved quality of life.

What evidence suggests that disulfiram might be an effective treatment for post-treatment Lyme disease symptoms?

Research has shown that disulfiram, a drug commonly used to treat alcohol dependence, can kill both active and dormant forms of the bacteria that cause Lyme disease. Recent lab studies suggest that disulfiram might help individuals who continue to feel sick even after taking standard antibiotics for Lyme disease. In this trial, participants will be assigned to one of two treatment arms: one group will receive disulfiram for 4 weeks followed by a placebo, while the other group will receive disulfiram for 8 weeks. However, since most evidence comes from lab studies, more research is needed to determine its effectiveness in people with Lyme disease symptoms. ^{5 6 7 8 9}

Who Is on the Research Team?

Brian A Fallon, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Disulfiram

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3919718/

Disulfiram Efficacy in the Treatment of Alcohol Dependence Based on results with open-label studies, disulfiram is a safe and efficacious treatment compared to other abstinence supportive pharmacological treatments.

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/adb.70035?af=R

Effectiveness of Disulfiram as Adjunct to Addiction‐ ... The literature presents evidence supporting the superior efficacy of disulfiram as an adjunct to addiction-focused therapy compared to other ...

3. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2811435

Pharmacotherapy for Alcohol Use Disorder: A Systematic ... Disulfiram has been FDA approved for alcohol use disorder since the 1950s. However, relatively limited evidence exists to support the efficacy ...

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK459340/

Disulfiram - StatPearls - NCBI Bookshelf - NIH Neurological adverse effects may occur as early as 10 days after initiation. Axonal polyneuropathy is a rare adverse effect.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1043661824003992

Efficacy of medications for the treatment of alcohol use ... At baseline, participants consumed on average approximately 12 DDD, and experienced 70 % DD, and 61 % HDD. Placebo halved or reduced these values to a third.

6. cdn.caymanchem.com cdn.caymanchem.com/cdn/msds/15303m.pdf

Safety Data Sheet Trade name: Disulfiram​​ Acute toxicity - oral 4 H302 Harmful if swallowed. Sensitization - skin 1 H317 May cause an allergic skin reaction.

7. medsafe.govt.nz medsafe.govt.nz/profs/datasheet/a/antabusetab.pdf

Antabuse Disulfiram treatment may cause drug-induced liver injury. Fatal cases have been reported (see section 4.8 Undesirable effects).

8. mayoclinic.org mayoclinic.org/drugs-supplements/disulfiram-oral-route/description/drg-20063488

Disulfiram (oral route) - Side effects & dosage Do not drink any alcohol, even small amounts, while you are taking this medicine and for 14 days after you stop taking it, because the alcohol ...

9. samhsa.gov samhsa.gov/substance-use/treatment/options/disulfiram

What is Disulfiram? Side Effects, Treatments & Use Disulfiram Safety Precautions. Patients should not take disulfiram if they have a history of: Severe heart disease or heart failure; Severe ...