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

NCT03891667 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 7755
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Approximately 10-20% of patients experience ongoing symptoms despite having received standard antibiotic therapy for Lyme disease. Possible explanations for persistent symptoms include persistent infection and/or post-infectious causes. Recent in vitro studies indicate that disulfiram is effective at killing both the actively replicating and the more quiescent persister forms of Borrelia burgdorferi, the microbe that causes Lyme Disease. In this study, the investigators are examining the safety of disulfiram among patients with post-treatment Lyme disease symptoms. The investigators are also conducting a preliminary investigation regarding the relative benefit of 4 vs 8 weeks of treatment with disulfiram.

Conditions

Fatigue; Quality of Life

Keywords

Lyme Disease; Post-treatment Lyme Disease Syndrome; Disulfiram; Chronic Lyme Disease

Outcome Measures

Primary Outcomes (2)

• Fatigue Severity Scale (FSS)

  This is a psychometrically validated self-report measure of fatigue. This measure consists of 11 items inquiring about the severity of fatigue in different situations during the past week. Scores for each item range from 1 to 7, where 1 indicates strong disagreement and 7 strong agreement. Higher scores indicate higher levels of fatigue. A responder on the FSS is an individual whose FSS total score has decreased by 0.7 its when compared baseline to week 10 (or last observation carried forward); 0.7 refers to the minimally clinical significant difference (MCID) in change over time. We report the number of participants who reached a meaningful reduction in fatigue (equal or more than MCID).

  Change will be assessed over a 10 week interval

• Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF)

  The Q-LES-Q - SF is a self-reported questionnaire, with 16 items evaluating overall enjoyment and satisfaction with physical health, mood, work, household and leisure activities, social and family relationships, daily functioning, sexual life, economic status, overall well-being and medications. Responses are scored on a 5-point scale, where higher scores indicate better enjoyment and satisfaction with life (possible range 14-70). Fourteen summated items create the total Q-LES-Q - SF score. Two last items, about medications and overall life satisfaction, are considered independently. Meaningful improvement on the Q-LES-Q to is a change score between baseline and week 10 (or last observation carried forward) of at least 6.8 points; 6.8 refers to the minimally clinical significant difference (MCID) where a score equal to or greater than 6.8 points represents an improved quality of file. We report # with meaningful improvement.

  Change will be assessed over a 10 week interval

Secondary Outcomes (4)

• The Short Form (36) Health Survey (SF-36) Physical Component Summary (PCS)

  Change will be assessed over a 10 week interval

• General Symptom Questionnaire (GSQ-30)- Assess Multisystemic Symptom Burden

  Change will be assessed over a 10 week interval

• Patient-Reported Outcomes Measurement Information System (PROMIS-29) Symptom Summary Score on Sleep Disturbance, Pain, Anxiety, Depression, and Low Energy/Fatigue (SPADE)

  Change will be assessed over a 10 week interval

• The Short Form (36) Health Survey (SF-36) Mental Component Summary (MCS)

  Change will be assessed over a 10 week interval

Study Arms (2)

8 Week Disulfiram

EXPERIMENTAL

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.

Drug: Disulfiram

4 Week Disulfiram

ACTIVE COMPARATOR

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.

Drug: Disulfiram

Interventions

Disulfiram DRUG

Patients will receive disulfiram for 4 weeks followed by placebo for 4 weeks or disulfiram for 8 weeks.

Also known as: Antabuse

4 Week Disulfiram; 8 Week Disulfiram

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of Lyme Disease diagnosis within the prior 16 years History of prior diagnosis of Lyme disease that met the Centers for Disease Control (CDC) surveillance criteria case definition
• For erythema migrans (EM) rash, this has to be health-care provider diagnosed;
• For later stages of Lyme disease, this requires a diagnosis of LD by a health-care provider and laboratory testing that confirms a positive result historically.
• History of treatment for Lyme disease that consists of at least 5 weeks of antibiotics (total adding all treatment courses) within the last 16 years.
• Partial Prior Response. History of at least partial response to prior antibiotic therapy for Lyme disease.
• Antibiotic-free interval. Willingness 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.
• Current moderate to severe fatigue. The following criteria need to be met:
• at least moderate intensity at study screening and at intake (a score of 4 or more on the Fatigue Severity Scale)
• triggered or perpetuated by Lyme disease and persisting for at least 6 months after treatment
• is not better attributed to another independent medical or psychiatric condition
• current episode of Lyme disease-related fatigue is relatively persistent and has not had an intervening interval of 8 months without fatigue since diagnosis of Lyme disease.
• Current post-Lyme symptoms impair the patient's quality of life
• Keeping other current treatments stable- Patients can stay on other non-antibiotic medications as long as these medications have been stable for the 3 months prior to study onset and the dosage regimen does not change during the course of this study (unless the latter is medically or psychiatrically indicated).
• Between the ages 18-65
• Ability to read and speak English

You may not qualify if:

• History of cardiovascular disease (e.g., coronary artery disease or heart failure).
• History of seizure disorder, abnormal EEGs, traumatic brain injury, renal disease (e.g. nephritis), liver disease (e.g., hepatitis, CIRRHOSIS), diabetes mellitus, hypothyroidism and/or psychosis. Patients with a history of large fiber neuropathy (EMG/NCS documented) will also be excluded.
• History of Substance Use Disorder (e.g., alcohol abuse, multi-drug dependence) within the past 2 years
• History in the last 6 months of heavy alcohol use which is defined as binge drinking more than 5 days in a one-month period. A binge-drinking episode refers to the consumption of 5 or more drinks for men or 4 or more drinks for women in a 2-hour period.
• Evidence of current active tick-borne illness other than Lyme disease. (Note: patients with evidence of positive antibodies for another TBI will be eligible unless there is evidence that this other TBI is currently active (eg., elevated LFTS (AST \& ALT not greater than 2 times upper limit), low platelets, low WBC, high fevers)
• Unwillingness to confirm that he/she will abstain from alcohol and products that may contain alcohol (including sauces, cough syrup, vinegar, backrub products, aftershave lotions) during the month prior to randomization, during the course of this study, and for 6 weeks after the last dose of study medication.
• Inability to confirm abstinence from cannabis or CBD or THC-containing products
• Women who are breastfeeding, pregnant, or at risk of becoming pregnant during the course of the study.
• Patients who are taking or plan to take warfarin, metronidazole, paraldehyde, phenytoin, theophylline, oral anticoagulants, or isoniazid
• A concurrent or recent illness that may better account for current fatigue
• Unwillingness to not take any new non-emergency medications during the course of this study without first reviewing with the study research physician
• History of rubber-contact dermatitis or allergy to disulfiram or thiuram derivatives
• Prior history of serious adverse reaction to disulfiram
• Cognitive Impairment for patients over 60.
• Suicidal acts in the last 6 months or current suicidal thoughts with intent or plan or history of bipolar disorder.

Sponsors & Collaborators

• Research Foundation for Mental Hygiene, Inc.: lead
• FDC Foundation: collaborator

Study Sites (1)

Lyme Research Center New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Related Publications (5)

• Long TE. Repurposing Thiram and Disulfiram as Antibacterial Agents for Multidrug-Resistant Staphylococcus aureus Infections. Antimicrob Agents Chemother. 2017 Aug 24;61(9):e00898-17. doi: 10.1128/AAC.00898-17. Print 2017 Sep.

  PMID: 28674046 BACKGROUND

• Pothineni VR, Wagh D, Babar MM, Inayathullah M, Solow-Cordero D, Kim KM, Samineni AV, Parekh MB, Tayebi L, Rajadas J. Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening. Drug Des Devel Ther. 2016 Apr 1;10:1307-22. doi: 10.2147/DDDT.S101486. eCollection 2016.

  PMID: 27103785 BACKGROUND

• Guerzoni S, Pellesi L, Pini LA, Caputo F. Drug-drug interactions in the treatment for alcohol use disorders: A comprehensive review. Pharmacol Res. 2018 Jul;133:65-76. doi: 10.1016/j.phrs.2018.04.024. Epub 2018 Apr 30.

  PMID: 29719204 BACKGROUND

• Liegner KB. Disulfiram (Tetraethylthiuram Disulfide) in the Treatment of Lyme Disease and Babesiosis: Report of Experience in Three Cases. Antibiotics (Basel). 2019 May 30;8(2):72. doi: 10.3390/antibiotics8020072.

  PMID: 31151194 BACKGROUND

• Kuvaldina M, Preston J, McClellan D, Pavlicova M, Brannagan TH, Fallon BA. A pilot study of disulfiram for individuals with persistent symptoms despite prior antibiotic treatment for Lyme disease. Front Med (Lausanne). 2025 Apr 2;12:1549324. doi: 10.3389/fmed.2025.1549324. eCollection 2025.

  PMID: 40265182 DERIVED

Related Links

• NIH website review of disulfiram's risk of liver toxicity

MeSH Terms

Conditions

Fatigue; Lyme Disease; Post-Lyme Disease Syndrome

Interventions

Disulfiram

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Borrelia Infections; Spirochaetales Infections; Tick-Borne Diseases; Vector Borne Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds

Limitations and Caveats

This study did not reach its goal of 24 participants largely due to the impact of the COVID-19 pandemic on the ability to recruit subjects. Our small sample limits the conclusions that can be drawn from this trial, but the findings will be helpful to inform future studies.

Results Point of Contact

• Title: Dr. Brian A. Fallon
• Organization: Lyme Research Center New York State Psychiatric Institute, New York, New York, United States, 10032

baf1@cumc.columbia.edu

646-774-8052

Study Officials

• Brian A Fallon, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This is a placebo-controlled study using matching capsules for disulfiram and placebo. Neither the participant, the care provider, nor the investigator will know the randomized assignment. The research pharmacy and a researcher not involved with this study will keep the code regarding group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Psychiatry

Model Details: Patients will be randomly assigned to one of two groups: Treatment Group I- patients will receive Disulfiram for 8 weeks Treatment Group 2 - patients will receive Disulfiram for 4 weeks followed by 4 weeks of placebo. The dosing follows a fixed-flexible schedule. Clinical judgment guides dosing increases, based on patient tolerance, side effects, and response. Week 1: 250 mg every other day. Week 2: 250 mg daily (or continuation of lower dose based on clinical judgment). Week 3: 250 mg alternating with 500 mg/daily (or continued lower dose based on clinical judgment) Week 4: 500 mg daily (or continued lower dose based on clinical judgment) Week 5-8: 500 mg/daily (or continued lower dose based on clinical judgment) : Primary outcome is at week 10. Patients will be reassessed at week 14.

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: March 27, 2019
• Study Start: July 31, 2019
• Primary Completion: November 26, 2021
• Study Completion: March 31, 2022
• Last Updated: January 9, 2025
• Results First Posted: June 5, 2023

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)