Clinical trial NCT03891667
Conditions: Fatigue Quality of Life
Keywords: Lyme Disease Post-treatment Lyme Disease Syndrome Disulfiram Chronic Lyme Disease
Sponsor: Research Foundation for Mental Hygiene, Inc.
Start date: 2019-07-31; Completion date: 2022-03-31
Enrollment: 11 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Detailed description:
Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common tick-borne illness in the United States. Typically, after being bitten by an infected tick, patients will notice an expanding rash and flu-like symptoms. Most patients recover fully after initial treatment with antibiotics such as doxycycline or amoxicillin. Some patients, however, do not recover fully or their symptoms return within a few months after having completed antibiotic treatment. Common persistent symptoms include fatigue, joint pain, muscle pain, numbness, tingling, burning pains, and changes in mood, memory or mental clarity. These symptoms can last months to years after treatment and, when accompanied by functional impairment, are collectively referred to by the academic community as "Post Treatment Lyme Disease Syndrome (PTLDS)". Patients however typically refer to this constellation of persistent symptoms as "Chronic Lyme Disease".

There are several possible explanations for why patients may have persistent symptoms, including persistent infection and post-infectious changes triggered by the prior infection.

Scientists recently discovered that disulfiram is effective in the lab setting at killing the microbes that cause Lyme disease. Disulfiram is more commonly known as "Antabuse". It is an FDA-approved compound used to assist alcoholics in resisting alcohol consumption. Most remarkable is that disulfiram was effective at killing not only the actively replicating Lyme bacteria (ie, the ones that are typically killed by several antibiotics) but also the relatively dormant or quiescent Lyme bacteria (these are called "drug-tolerant persisters") - these latter spirochetes are the ones that may account for the development of chronic Lyme disease symptoms.

This initial pilot study will focus on patients with persistent symptoms despite having received the standard antibiotic therapy (or more) for Lyme disease. Because no one has yet studied the safety of disulfiram for patients with a history of Lyme disease and because the investigators do not know the optimal treatment duration for disulfiram, the initial effort will have the primary aims of assessing safety and determining whether a longer course of daily treatment is more effective than a shorter course of daily treatment.

The investigators propose therefore a small 14-week randomized placebo-controlled pilot study enrolling 24 patients with persistent symptoms despite prior antibiotic treatment for Lyme disease (known as Post-treatment Lyme Disease Syndrome). Among the 24 disulfiram-treated patients, half will get 8 weeks of disulfiram and the other half will get a shorter duration of disulfiram for 4 weeks followed by 4 weeks of matching placebo. After week 8, patients will be off pills for 2 weeks for the primary week 10 evaluation and then for another 4 weeks for the week 14 follow-up evaluation. This will be a double-blinded study; neither physician nor patient will know which treatment group the patient is assigned to.

With this initial study, the investigators will be able to evaluate the side effects, tolerability and initial signs of the effectiveness of disulfiram in reducing symptoms among the 24 patients assessed. The results of this study will guide the investigators regarding whether a larger definitive randomized trial should be conducted and which treatment schedule is optimal.

Arms: arm 1: 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. arm 2: 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.
Interventions: intervention 1: Disulfiram
Intervention descriptions: intervention 1: Patients will receive disulfiram for 4 weeks followed by placebo for 4 weeks or disulfiram for 8 weeks.

Protocol documents:
Prot_SAP_000.pdf: 
Signed copy on file at IRB 
 
             v. 4/19/13 
                                          NEW YORK STATE PSYCHIATRIC INSTITUTE         
INSTITUTIONAL REVIEW BOARD 
MEMORANDUM 
 
 
 
 
 
 
 
 
 
March 14, 2023 
TO: 
 
Dr. Brian Fallon 
 
FROM: 
Dr. Agnes Whitaker, Co-Chair, IRB  
Dr. Richard Foltin, Interim Co-Chair, IRB 
 
 
SUBJECT: 
APPROVAL NOTICE:  CONTINUATION     
 
 
Expedited per 45CFR46.110(b)(1)(f)(8)(c) 
 
Your protocol #7755 entitled  Disulfiram ("Antabuse"): A Test of Symptom Reduction Among 
Patients with Previously Treated Lyme (version date 03-14-2023) and Consent Forms have been 
approved by the New York State Psychiatric Institute - Columbia University Department of 
Psychiatry Institutional Review Board from March 25, 2023 to March 24, 2024.   
 
Consent requirements: 
   
  X Not applicable: (DATA BEING ANALYZED) 
    
   Signature by the person(s) obtaining consent is required to document the consent process. 
 
   Documentation of an independent assessment of the participant’s capacity to consent is also required. 
 
       
    Approved for recruitment of subjects who lack capacity to consent:   No      Yes    
 
 
    Field Monitoring Requirements:  Routine      Special:                                    
 
√   Only copies of consent documents that are currently approved and stamped by the IRB 
may be used to obtain consent for participation in this study. 
√  A progress report and application for continuing review is required 2 months prior to the  
expiration date of IRB approval. 
√  Changes to this research may be not be initiated without the review and approval of the  
IRB except when necessary to eliminate immediate hazards to participants.  
√  All serious and/or unanticipated problems involving risks to subjects or others must be 
reported immediately to the IRB.  Please refer to the PI-IRB website at http://irb.nyspi.org 
for Adverse Event Reporting Procedures and additional reporting requirements.  
 
 
 
 
 
AHW/RWF/Scr 


Protocol Summary Form
7755
Fallon, Brian
1
Protocol Title:
Disulfiram ("Antabuse"): A Test of Symptom 
Reduction Among Patients with Previously Treated 
Lyme
Protocol Number:
7755
First Approval:
04/02/2019
Expiration Date:
03/24/2024
Version Date:
03/14/2023
Research Area:  
Anxiety, Mood, Eating & Related Disorders
Division:  
Anxiety/PTSD/OCD
Contact Principal Investigator:
Brian Fallon, MD
Email: baf1@columbia.edu
Telephone: 646-774-8052
Research Chief:
Helen Simpson, MD
Cover Sheet
Choose ONE option from the following that is applicable to your study
If you are creating a new protocol, select "I am submitting a new protocol." As 5 Year Renewals are 
no longer required, this option remains for historical purposes.
I am submitting an annual continuation without modifications 
Department & Unaffiliated Personnel
Department
What Department does the PI belong to?
Mood, Anxiety, Eating, and Related Disorders
Within the department, what Center or group are you affiliated with, if any? 
Lyme Disease Research Center
Unaffiliated Personnel
List investigators, if any, who will be participating in this protocol but are not affiliated with New 
York State Psychiatric Institute or Columbia University. Provide: Full Name, Degrees and Affiliation.
Alessandra Luchini, PhD Professor in the School of Systems Biology Center for Applied Proteomics and 
Molecular Medicine George Mason University Kim Lewis, PhD University Distinguished Professor 


Protocol Summary Form
7755
Fallon, Brian
2
Director, Antimicrobial Discovery Center Northeastern University 
Application for Continuation of Research
Status
Current Status of Study: 
All research interventions were completed. Only data analysis is ongoing.
Summary of Experiences to Date
Please provide a summary of scientific progress of the study and the experience of research 
participants, to date. This requirement is designed to allow for the investigator and the IRB to 
reassess the study’s risks and benefits in terms of developments in the field, changing practice 
patterns, and new IRB policies and procedures.
We are submitting this protocol for annual continuation. The research enrollment is complete, and all 
subjects have completed all research-related activity. Ongoing activity in this protocol is limited to analysis 
of previously collected data. 
Funding
Have there been any changes in funding status since the prior approval? 
No
Have the principal investigator and other investigators made all required disclosures of financial 
interest in the study sponsor/product?
Yes
Summary
Have there been any study findings, recent literature, or untoward events occuring here or at other 
sites in the past year which might affect the analysis of the safety, risks or benefits of study 
participation? 
No
Have there been any serious adverse events (serious and/or unanticipated problems involving risks to 
subjects or others at this site which occured in the past year)? 
No
Have all study staff with a significant role in the design or implementation of the human subject 
components of this study received required training in human research subject protections?
Yes
Is the study covered by a certificate of confidentiality? 
No
Overall Progress


Protocol Summary Form
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Fallon, Brian
3
Approved sample size
24
Total number of participants enrolled to date
11
Number of participants who have completed the study to date 
10
Have there been any significant deviations from the anticipated study recruitment, retention or 
completion estimates? 
Yes
Describe actions taken or planned to address these problems. 
The study enrollment was stopped in 2021 for the following reasons: a) the treatment drop-out rate in our 
study due to adverse events has been higher than expected; b) funding for this project is nearly complete; c) 
our pilot study has provided useful information about the relative safety of lower doses of disulfiram and the 
possibility of benefit with treatment; and d) based on the literature, disulfiram is a drug with uncommon but 
serious risk of toxicity.
Comments / additional information 
Sample Demographics
Select the # of samples applicable
Specify population
Patients with Post-Treatment Lyme Disease Syndrome
Total number of participants enrolled from this population to date 
11
Gender, Racial and Ethnic Breakdown 
Sex: Female (6, 54.0%) Male (5, 46.0%) Racial Background: American Indian or Alaska Native (0, 0.0%) 
Asian (0, 0.0%) Native Hawaiian or Other Pacific Islander (0, 0.0%) Black or African American (1, 9.0%) 
White (10, 91.0%) More Than One Race (0, 0.0%) Other: (0, 0.0%) Ethnic Background: Hispanic or Latino 
(2, 18.0%) Not Hispanic or Latino (9, 82.0%)
Summary of Current Year's Enrollment and Drop-out 
Number of participants who signed consent in the past year
0
Number of participants currently enrolled
0
Did the investigator withdraw participants from the study? 
No
Did participants decide to discontinue study involvement? 
No


Protocol Summary Form
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Fallon, Brian
4
Procedures
To create the protocol summary form, first indicate if this research will include any of the following 
procedures 
   Collection of Biological Specimens
   Internet-based Data Collection or Transmission
   Medication Trial
   Medication-Free Period or Treatment Washout
   Neuropsychological Evaluation
   Off-label Use of Drug or Device
   Psychiatric Assessment
   Use of Placebo or Sham Treatment
Population
Indicate which of the following populations will be included in this research
   Medically Ill Subjects
   Adults
   Adults over 50


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Fallon, Brian
Page 1 of 43
Department & Unaffiliated Personnel
Department
Unaffiliated Personnel
Protocol Title:
Disulfiram ("Antabuse"): A Test of 
Symptom Reduction Among Patients with 
Previously Treated Lyme
Protocol Number:
7755
First Approval:
04/02/2019
Expiration Date:
03/24/2023
Version Date:
03/21/2022
Contact Principal Investigator:
Brian Fallon, MD
Email: baf1@columbia.edu 
Telephone: 646-774-8052
Research Chief:
Helen Simpson, MD
Cover Sheet
Choose ONE option from the following that is applicable to your study
If you are creating a new protocol, select "I am submitting a new protocol." As 5 Year Renewals are no 
longer required, this option remains for historical purposes.
I am submitting an annual continuation with modifications
What Department does the PI belong to? 
Mood, Anxiety, Eating, and Related Disorders
Within the department, what Center or group are you affiliated with, if any? 
Lyme Disease Research Center
List investigators, if any, who will be participating in this protocol but are not affiliated with New York 
State Psychiatric Institute or Columbia University. Provide: Full Name, Degrees and Affiliation.
Alessandra Luchini, PhD
Professor in the School of Systems Biology


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Fallon, Brian
Page 2 of 43
Amendment
Application for Continuation of Research
Status
Center for Applied Proteomics and Molecular Medicine 
George Mason University
Kim Lewis, PhD
University Distinguished Professor 
Director, Antimicrobial Discovery Center 
Northeastern University
Describe the change(s) being made
We are making one addition and one modification to the Disulfiram protocol
1. Addition:
We request permission to add to the protocol a new staff member, Dr. Kristen Kendrick.
Dr. Kristen Kendrick, a Family Medicine Physician, is a new clinician for the study. Dr. Kendrick, DO, has 
completed the CITI training (basic course and a course on Good Clinical Practices).
Dr. Kendrick sees study participants for clinical evaluations under the supervision of Dr. Fallon.
2. Modification:
Under the protocol section entitled “Unaffiliated Personnel”, we are removing Dr. Charles Brown and Dr. 
Edward Dennis; neither has had involvement in this project. I am replacing their names with Dr. Kim Lewis 
at Northeastern University and Dr. Alessandra Luchini at George Mason University; Dr. Lewis is a 
microbiome collaborator and Dr. Luchini is a proteomic collaborator.
Provide the rationale for the change(s)
Dr. Kristen Kendrick as a Family Medicine physician working with Dr. Fallon has knowledge of medicine 
broadly and knowledge of Lyme disease specifically. She joined our team in August 2021.
Dr. Charles Brown and Dr. Edward Dennis are not participating in this study. However, both Dr. Kim 
Lewis and Dr. Alessandra Luchini are collaborating with Dr. Fallon in aspects of this study. Dr. Kim Lewis 
will analyze the fecal matter change during the course of treatment with disulfiram in our study participants 
and Dr. Luchini will analyze the urine for proteomic markers of tick-borne infection. The collection of fecal 
matter and urine for these studies has been in the protocol and consent forms from the start of this study.
Comment on the extent to which the proposed change(s) alter or affect risks/benefits to subjects 
These changes do not alter or affect the risks/benefits to subjects.
Comment on if the proposed change(s) require a modification to the Consent Form (CF) 
The consent form does not need to be modified.


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Fallon, Brian
Page 3 of 43
Current Status of Study:
All research interventions were completed. Only data analysis is ongoing.
 Summary of Experiences to Date
Please provide a summary of scientific progress of the study and the experience of research participants, to 
date. This requirement is designed to allow for the investigator and the IRB to reassess the study’s risks and 
benefits in terms of developments in the field, changing practice patterns, and new IRB policies and 
procedures.
Over the last year:
4 new participants entered treatment in the study in 2021. The last person to sign study consent for this 
study signed on 7.18.2021
Of these 4 new completers, 0 signed the fully on-site consent, 1 signed the fully remote consent, and 3 
signed the hybrid consent.
No individuals are currently enrolled.
Summary of study from onset to present:
Since study onset, we have had a total of 11 patients sign consent who were randomized to study drug. Of 
these 11, 10 started medication; 1 was randomized to study drug but did not start medication due to onset of 
COVID-19. He would not be considered a completer as he didn’t start study drug.
Of these 10 who started study medication, all 10 have completed the study.
3 of the 10 completed the full 8 weeks of study medication without complications.
1 of the 10 withdrew on his own after 4 weeks as he didn’t want to risk placebo randomization in the latter 4 
weeks of the study.
1 of the 10 were withdrawn by us due to the onset of COVID-19 – she had completed 2 weeks of study 
medication.
3 of the 10 were withdrawn from the study by the PI due to mildly-moderately elevated liver function tests 
which resolved after termination of study medication; only one in this latter group had symptoms associated 
with the elevated LFTs (abdominal pain) which led to a short-term hospitalization for evaluation (previously 
reported to the IRB as a SAE - possibly related to a disulfiram reaction due to inadvertent alcohol 
consumption in food).
1 of the 10 withdrew on her own due to headaches and 10 days after ending disulfiram treatment, she had 
an episode of throat tightness that led her to an ER evaluation for a possible emerging allergic
reaction (reported to the IRB in 2019, but not likely to be due to disulfiram).
1 of the 10 was withdrawn by the PI due a slightly elevated serum creatinine (1.5) at wk 2. Although there 
was no history of kidney disease, the patient did have slightly elevated creatinine prior to study entry 
(1.3/1.4) considered normal by his PCP. For the patient’s safety, the PI withdrew him from the study 
because he also had a marginally low glomerular filtration rate (58) at week 2; the patient was 
recommended to have a full kidney function work-up and this information was conveyed to his PCP. (In a 
subsequent call to us 1 month later, he indicated his PCP reviewed his labs and viewed him as healthy from 
a renal perspective.)
Among all 11 who signed consent and were randomized to study drug, 7 signed the fully on-site consent, 1


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Page 4 of 43
signed the fully remote consent, and 3 signed the hybrid consent.
Decisions on the study:
We have decided to end enrollment this study at this point for four reasons: a) the treatment drop-out rate in 
our study thus far due to adverse events has been higher than expected; b) funding for this project is nearly 
complete; c) our pilot study has provided useful information about the relative safety of lower doses of 
disulfiram and the possibility of benefit with treatment; and d) based on the literature, disulfiram is a drug 
with uncommon but serious risk of toxicity. We are pleased to see that 60% of participants were 
“responders” on the primary outcome fatigue measure at the primary endpoint and that 50% of participants 
reported sustained improvement 4 weeks later.
Note: In the 2021 ACAR, we indicated that there were 6 individuals in total who enrolled and started on 
study medication and in this 2022 ACAR we indicate that there were 10 individuals in total who enrolled 
and started on study medication (4 of whom were added since the prior ACAR.) Using the definition of 
enrollment (eligible and randomized to study medication), we have had 11 enrolled in the study to date. The 
prior ACAR indicated 9 had been “enrolled”; the definition of “enrolled” was overly broad – we report here 
in this ACAR only those who were eligible and randomized to study medication (as per pharmacy 
confirmation). Using a definition of “completer” as individuals who were randomized, started study 
medication and either completed the full study or were withdrawn by us or dropped out for other reasons, 
we had 10 who completed the study. Dr. Fallon has personally reviewed all data for the preparation of this 
2022 ACAR (both our research data and pharmacy data) and certifies these numbers are correct.
 Funding
Have there been any changes in funding status since the prior approval? 
Yes
Have the principal investigator and other investigators made all required disclosures of financial interest in 
the study sponsor/product?
Yes
Is the previous funding completed? 
Yes
Has new funding been obtained? 
No
 Summary
Have there been any study findings, recent literature, or untoward events occuring here or at other sites in 
the past year which might affect the analysis of the safety, risks or benefits of study participation?
Yes
Please indicate how the new information affects the study's risk/benefit analysis and comment on whether 
consent form changes are necessary.
1. Our study findings this past year:
a. Safety: The pattern of elevated liver function tests associated with disulfiram treatment observed in 2 of 
the first 6 patients continued this past year in that 1 of the 4 also developed asymptomatic elevated LFTs


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which resolved after study medication discontinuation; he had been on 250mg qd of disulfiram for 6 weeks.
b. Benefit: Of the 4 newly treated participants this year, 3 met criteria for meaningful improvement on the 
primary outcome Fatigue Severity Scale, including the individual whose study med treatment was stopped 
after 6 weeks.
2. Our study findings to date:
a. Safety overall: Disulfiram in our small study has been associated with more adverse events than we had 
anticipated. All participants recovered. One participant had a serious adverse event requiring hospitalization 
related to abdominal pain and elevated LFTs (and recovered); one had discontinued disulfiram due to 
headaches (which she had prior to study medication) but then had an ER evaluation for a possible emerging 
allergic reaction 10 days later; two others had asymptomatic elevations of LFTs that led to study medication 
discontinuation. In summary of the 10 study completers, 4 had adverse events that required study 
medication discontinuation.
b. Safety of dosing: Of the 2 of the 10 participants who had reached 500 mg qd of study medication, both 
had elevated LFTs that required study discontinuation. Lower doses appeared better tolerated.
c. Benefit: Of the 10 study completers (using last observation for dropouts), 6 met criteria for meaningful 
improvement on the Fatigue severity scale at the primary outcome of week 10 and 5 continued to show 
meaningful improvement in fatigue at the week 14 follow-up rating. A 60% responder rate at week 10 and 
50% at week 14 is of interest (NB: improvement on other clinical measures as well), but it is also hard to 
interpret given the lack of a placebo-control group.
3. A recent article. A retrospective review from a private practice clinician’s office evaluated 3 years of 
clinical experience with disulfiram among patients with persistent Lyme disease symptoms (Gao et al., 
Antibiotics, Dec 2020). 71 patients were included, treated over a 3 year interval. No standardized clinical 
ratings were used during the evaluation and treatment; the report was based on clinical impressions in the 
chart notes. 62 of 67 (92%) endorsed a “net benefit of the treatment”. Individuals who had received one to 
two courses of higher dose therapy (4-5+ mg/kg/day) were more likely to have an “enduring remission” than 
the group at lower doses (36.4% vs 0%); the high dose group corresponds to a dose of 272-340+/day for a 
150 lb person or 360-450+/day for a 200 lb person. Side effects were dose related. Common side effects in 
the higher dose group included: fatigue (67%); psychiatric symptoms (49%); paresthesias (27%), and mild 
to moderate elevation of liver enzymes (15%). The article indicates that paresthesias resolved in all but 1 
case, in which mild residuum remained. Psychiatric symptoms included “emotional instability ranging from 
hypomania to anxiety and/or depression”. The authors stated that adverse events thought to be due to 
disulfiram resolved in nearly all individuals; no serious adverse events were reported.
Comment: As no rating scales were used in this clinical series to monitor adverse effects, it is hard to know 
which symptoms were Lyme disease related and present prior to disulfiram treatment vs adverse effects due 
to disulfiram. Fatigue, paresthesias, and psychiatric symptoms are common among patients with post- 
treatment Lyme disease. The absence of serious adverse events is encouraging. Our disulfiram study 
excludes individuals with a history of psychosis or bipolar disorder; it is unclear if the same was true in this 
clinician’s practice. Nevertheless, disulfiram can induce mania, psychosis, or other psychiatric disorders due 
its inhibition of dopamine beta-hydroxylase, resulting in an excess of dopamine. Disulfiram is known to 
have side effects that are dose-related, consistent with the above results. The rate of paresthesias are high, 
but these are also common post-treatment Lyme symptoms; given the absence of peripheral neuropathy 
assessments before and after treatment, it is hard to interpret this finding. Our study consent form lists these 
risks; our study results (though sample size is small) will add clarification on the side effect profile.


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4. A recent case report. A troubling case report by Frankl et. al. (Mayo Clin Proceedings July 2021) 
described a middle-aged man being treated with minocycline (100 bid), disulfiram (375 mg), and tinidazole 
(500 bid) for “chronic Lyme disease” who developed mental status changes and lethargy and was 
hospitalized; according to his wife, he took his medications at higher doses than prescribed and had been on 
disulfiram for 8 months. Brain MRI showed T2 hyperintensities in bilateral thalami and diffusion restriction 
in the posterior putamen. Axonal neuropathy was documented 8 months earlier shortly after he started 
disulfiram. The patient went into respiratory failure, suffered hospital acquired infections, and died 2.5 
months later.
Comment: This case report documents the recognized potential neurotoxicity of disulfiram, especially in 
combination with other medication and at higher doses. When disulfiram is taken with nitroimidazoles (such 
as tinidazole or metronidazole), psychosis and confusion have been reported. It is likely that taking both 
disulfiram and tinidazole together had an additive toxic effect, as both have been associated with CNS 
hyperintensities. (Concurrent antibiotic therapy is an exclusion for entry in our study). One prior case of 
extremely high dose disulfiram (1 gm of implanted disulfiram) (Peddawad, Neurology 2018) led to a 
fulminant encephalopathy. In the Frankl case report, this man’s wife reported he took higher doses of his 
medication than prescribed; it is unknown how much he had been taking prior to his hospital evaluation, but 
a very high dose of disulfiram (>500 mg) may have led to this bad outcome.
5. Disulfiram and immune function. Other recent literature has explored the potential benefits of 
disulfiram on immune function, including reduction of the damaging effects of inflammation. A recent 
article by Schwartz et al in the Journal of Clinical Insight (March 2022) reported that disulfiram protected 
rodents from immune-mediated lung injury, presumably by its ability to block the formation of neutrophil 
extracellular traps (NETS). In SARS-CoV-2-infected golden hamsters, disulfiram reduced NETs and 
perivascular fibrosis in the lungs, and it downregulated innate immune and complement/coagulation 
pathways, suggesting that it could be beneficial for patients with COVID-19. There are currently 2 human 
clinical trials listed on clinicaltrials.gov examining disulfiram as a treatment for COVID-19 based on its 
anti-inflammatory and anti-viral properties.
Have there been any serious adverse events (serious and/or unanticipated problems involving risks to 
subjects or others at this site which occured in the past year)?
No
Have all study staff with a significant role in the design or implementation of the human subject components 
of this study received required training in human research subject protections?
Yes
Is the study covered by a certificate of confidentiality? 
No
 Overall Progress
Approved sample size 
24
Total number of participants enrolled to date 
11
Number of participants who have completed the study to date 
10


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Have there been any significant deviations from the anticipated study recruitment, retention or completion 
estimates?
Yes
Describe actions taken or planned to address these problems.
Our anticipated study completion date was March 2022. The study enrollment was drastically impacted by 
the pause of the study at onset due to the COVID-19 pandemic, by the need to schedule the baseline visit far 
enough away from COVID-19 vaccine shots to be able to distinguish adverse events from COVID-19 
vaccine reactions vs study medication, by participant reluctance to enroll prior to major holidays (i.e., 
unwilling to avoid alcohol use), by delay in obtaining disulfiram due to supply-chain shortages, and by the 
difficulty potential participants had in finding local physicians willing to assist in the fully remote version of 
the study.
Hybrid option approval by the IRB since the last ACAR: The IRB approved a “hybrid” option for study 
participation. This hybrid option allows for telehealth except for two visits (one at the start of the study and 
the other two weeks after stopping study medication) that require the participant to come in person for a 
physical exam. New consent forms and procedures were created to accommodate this hybrid participation. 
Comments / additional information
 Sample Demographics
Specify population
Patients with Post-Treatment Lyme Disease Syndrome
Total number of participants enrolled from this population to date 
11
Gender, Racial and Ethnic Breakdown 
Sex:
Female (6, 54.0%)
Male (5, 46.0%)
Racial Background:
American Indian or Alaska Native (0, 0.0%) 
Asian (0, 0.0%)
Native Hawaiian or Other Pacific Islander (0, 0.0%) 
Black or African American (1, 9.0%)
White (10, 91.0%)
More Than One Race (0, 0.0%)
Other: (0, 0.0%)
Ethnic Background:
Hispanic or Latino (2, 18.0%)
Not Hispanic or Latino (9, 82.0%)


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Page 8 of 43
Procedures
Population
Summary of Current Year's Enrollment and Drop-out
Number of participants who signed consent in the past year 
6
Did the investigator withdraw participants from the study? 
Yes
Circumstances of withdrawal:
Two of six participants who signed consent during 2021 were deemed not eligible for the study.
A participant who enrolled in the study was withdrawn by the PI due a slightly elevated serum creatinine 
(1.5) and slightly decreased GFR (glomerular filtration rate) at week 2. Although there was no history of 
kidney disease, the patient did have slightly elevated creatinine prior to study entry (1.3/1.4) that he reported 
was considered normal by his PCP. For the patient’s safety, the PI withdrew him from the study because he 
also had a marginally low glomerular filtration rate (58) at week 2; the patient was recommended to have a 
full kidney function work-up and this information was conveyed to his PCP. (In a subsequent call to us 1 
month later, this participant indicated his PCP had reviewed his labs and viewed him as healthy from a renal 
perspective.)
Did participants decide to discontinue study involvement? 
No
To create the protocol summary form, first indicate if this research will include any of the following 
procedures
  Collection of Biological Specimens
 Internet-based Data Collection or Transmission 
 Medication Trial
 Neuropsychological Evaluation 
 Off-label Use of Drug or Device 
 Psychiatric Assessment
  Use of Placebo or Sham Treatment
Indicate which of the following populations will be included in this research
 Medically Ill Subjects 
 Adults
 Adults over 50


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Fallon, Brian
Page 9 of 43
Funding Source #1
Funding Source #2
Research Support/Funding
Will an existing internal account be used to support the project? 
No
Is the project externally funded or is external funding planned? 
Yes
Select the number of external sources of funding that will be applicable to this study 
2
Is the PI of the grant/contract the same as the PI of the IRB protocol? 
Yes
Select one of the following
The grant/contract is currently funded 
Source of Funding
Foundation 
Sponsor 
FDC
Select one of the following 
Single Site
Business Office 
CU
Does the grant/contract involve a subcontract? 
No
Is the PI of the grant/contract the same as the PI of the IRB protocol? 
Yes
Select one of the following
The grant/contract is currently funded 
Source of Funding
Foundation 
Sponsor 
Anonymous Donor
Select one of the following 
Single Site
Business Office 
RFMH
Does the grant/contract involve a subcontract? 
No


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Hospitals,clinics and other healthcare facilities
Lay Summary of Proposed Research
Study Location
Indicate if the research is/will be conducted at any of the following
 NYSPI
This protocol describes research conducted by the PI at other facilities/locations 
Yes
  Hospital, clinics and other healthcare facilities
Select from the list
or type in location(s)..
Some aspects of data collection for participants who choose to participate in the study remotely will be 
conducted in the offices of collaborating consulting physicians. Participants who participate remotely or via 
the hybrid protocol will also have some data collection conducted at Quest Diagnostics testing centers.
Lay Summary of Proposed Research
Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common tick-borne illness in the 
United States. Typically, after being bitten by an infected tick, patients will notice an expanding rash and 
flu-like symptoms. Most patients recover fully after initial treatment with antibiotics such as doxycycline or 
amoxicillin. Some patients, however, do not recover fully or their symptoms return within a few months 
after having completed antibiotic treatment. Common persistent symptoms include fatigue, joint pain, 
muscle pain, numbness, tingling, burning pains, and changes in mood, memory or mental clarity. These 
symptoms can last months to years after treatment and, when accompanied by functional impairment, are
collectively referred to by the academic community as “Post Treatment Lyme Disease Syndrome (PTLDS)”. 
Patients however typically refer to this constellation of persistent symptoms as “Chronic Lyme Disease”.
One of the potential explanations for persistent symptoms is that some patients may have persistent 
infection. Some scientists and medical doctors suggest that persistent infection with the agent of Lyme 
disease could be treated more effectively with other medications or combinations of medications.
Scientists recently discovered that disulfiram is very effective in the lab setting at killing the microbes that 
cause Lyme disease. Disulfiram is more commonly known as “Antabuse”. It is an FDA-approved compound 
used to assist alcoholics in resisting alcohol consumption. Most remarkable is that disulfiram was effective 
at killing not only the actively replicating Lyme bacteria (ie, the ones that are typically killed by several 
antibiotics) but also the relatively dormant or quiescent Lyme bacteria (these are called “drug-tolerant 
persisters”) – these latter spirochetes are the ones that may account for the development of chronic Lyme 
disease symptoms.
Our initial pilot study will focus on patients with persistent symptoms despite having received the standard 
antibiotic therapy (or more) for Lyme disease. Because no one has yet studied the safety of disulfiram for


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patients with a history of Lyme disease and because we do not know the optimal treatment duration for 
disulfiram, our initial effort will have the primary aims of assessing safety and determining whether a longer 
course of daily treatment is more effective than a shorter course of daily treatment.
We propose therefore a small 14-week randomized placebo-controlled pilot study enrolling 24 patients with 
persistent symptoms despite prior antibiotic treatment for Lyme disease (known as Post-treatment Lyme 
Disease Syndrome or "chronic Lyme"). Among the 24 disulfiram-treated patients, half will get 54 days of 
disulfiram treatment over the course of 8 weeks and the other half will get a shorter duration of disulfiram 
for 26 days given over the course of 4 weeks. After week 8, patients will be off pills for 2 weeks for the 
primary week 10 evaluation and then for another 4 weeks for the week 14 follow-up evaluation. This will be 
a double-blinded study; neither clinician nor patient will know which treatment group the patient is assigned 
to.
With this initial study, we will be able to evaluate the side effects, tolerability and initial signs of 
effectiveness of disulfiram in reducing symptoms among the 24 patients assessed. The results of this study 
will guide us regarding the safety of disulfiram among patients with Lyme disease and whether a definitive 
randomized trial should be conducted; it will also inform us regarding which treatment schedule is optimal.
Background, Significance and Rationale
Background, Significance and Rationale
About 10-20% of patients treated with standard antibiotic therapy suffer from persistent relapsing-remitting 
symptoms. Persistent infection may account for the persistent symptoms in some of these patients, as 
persistent infection after antibiotic treatment has been well-documented in several animal models of Lyme 
disease. Clearly, a more effective antibiotic is needed
A recent laboratory-based research study discovered that disulfiram, an FDA-approved compound used to 
assist alcoholics in resisting alcohol consumption, was one of the more potent compounds in killing Borrelia 
burgdorferi (Bb - the microbe that causes Lyme disease) (Potheni 2016; Lewis 2017). Disulfiram was shown 
to be more effective than 1,000s of other FDA-approved compounds that were tested, even when compared 
to standard antibiotics for Lyme disease such as doxycycline and amoxicillin. Disulfiram administered for 
just 2 days was shown to be effective at inhibiting the growth of not only the actively replicating Borrelia 
(ie, the ones that are typically killed by several antibiotics) but also the relatively dormant Borrelia (these 
are called “drug- tolerant persisters”) – these latter spirochetes have been hypothesized as one possible 
cause for the development of chronic or relapsing symptoms. Other reports indicate that the metabolites of 
disulfiram inhibit the growth of a number of other bacterial species as well, including Pseudomonas 
aeruginosa and Staph aureus (Zaldivar-Machorro 2011, Long 2017). In addition to its ability to eradicate 
drug-tolerant persister Borrelia, disulfiram has the advantage of excellent tissue penetration – it crosses the 
blood-brain barrier easily. Because of excellent tissue penetration, it may be a more effective agent than 
many other antibiotics in killing Borrelia spirochetes in humans.


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As a next step in assessing disulfiram, disulfiram was studied in a mouse model of Lyme disease; disulfiram 
was given for 5 days to 13 infected mice and found to be ineffective at eradicating Borrelia spirochetes in 
this mouse model. Dr. Kim Lewis, the lead investigator on these laboratory and mouse model studies, 
considers it reasonable that disulfiram may still work in the human as "the metabolic rate of the mouse is 
10x faster than the human." Dr. Lewis is Director of the Drug Discovery Center at Northeastern University 
and University Professor of Biochemistry. His hypothesis is that the rapid metabolism of the mouse 
denatured the disulfiram to such an extent that the blood concentration was too low to be effective. A 
second hypothesis for the failure of disulfiram in the mouse model is that the duration of treatment may 
have been too short. To our knowledge, all published studies investigating antibiotic efficacy in the mouse 
model have used between 10 and 30 days of antimicrobial treatment; the Lewis lab mouse study only used 5 
days of disulfiram.
Most recently, an internal medicine colleague of ours in private practice has given disulfiram to 3 of his 
chronically ill patients and reported remarkable improvement. To report these results, he has submitted a 
manuscript to a peer-reviewed journal for consideration of publication. He had previously treated these 
patients for years with various courses of antibiotics for Lyme disease without much success. In the past 2 
years, each was taken off standard antibiotics and then given disulfiram, reaching a 500 mg/day dose for 6- 
12 weeks; the improvement was remarkable, far beyond what had been achieved with many courses of 
antibiotic therapy previously.
Given the report from this physician and given that disulfiram has impressive tissue penetration and has 
been shown in the laboratory setting to be highly effective in killing Borrelia spirochetes, it is our intent to 
conduct a preliminary study to assess safety and to conduct a duration of treatment study to assess whether 
disulfiram leads to improvement in some of the core symptoms of post-treatment Lyme disease.
Significance
Disulfiram is a well-known drug in psychiatry. Not without side effects or risk, it is nevertheless considered 
to be a useful treatment option for patients wishing to maintain alcohol abstinence. The only treatment 
approach that has been studied for patients with PTLS is repeated antibiotic therapy with IV ceftriaxone 
(with or without doxycycline) (Klempner 2001; Krupp 2003; Fallon 2008); this treatment option is not 
widely recommended given that the IV route requiring a PICC or Mid-line is associated with serious risk 
(sepsis, thrombi) and given that the results of the clinical trials have been equivocal, with some showing 
benefit and others no benefit.
If this pilot study indicates that disulfiram is well-tolerated among patients with post-treatment Lyme 
disease and if the dose-finding study suggests disulfiram is effective, we will then conduct a placebo- 
controlled study to confirms efficacy. If the next study after that shows that disulfiram is even better than 
standard antibiotic treatment in leading to sustained improvement, then this would be a major treatment 
advance for patients with post-treatment Lyme disease. Given that disulfiram is not a "broad-spectrum 
antibiotic" it would be expected to have a smaller impact on the gut microbiome than standard antibiotic 
therapy which would make it much more appealing to patients and to infectious disease doctors; (we will 
assess gut microbiome changes in this study with the different dosing duration of disulfiram).
Rationale


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We have chosen not to start by conducting a larger efficacy study comparing disulfiram to placebo for two 
reasons: a) we would like to assess how well disulfiram is tolerated; b) we would like preliminary data to 
determine the magnitude of effect and to test out our different primary and secondary outcome measures; c) 
we are uncertain as to the optimal duration (26 days vs 54 days). A shorter duration of exposure to 
disulfiram would be expected to reduce the risk to the patient of disulfiram treatment.
For this study, we will consider a negative finding in each active treatment group to be a result at 10 weeks 
indicating that 30% or fewer patients are rated as responders on either of the primary outcome measures of 
fatigue (FSS-9) or quality of life experience (Q-LES-Q). Secondary outcome measures include functional 
status (PROMIS-29 and SF-36), general symptoms (GSQ-30), pain (from PROMIS 29 domain), cognitive 
symptoms (computer battery), and mood (BDI, STAI).
If one of the two active treatment regimens offers more promise than the other and if the percentage of 
responders is greater than the anticipated 20-30% responder rate typically seen with placebo, we would then 
choose that option for the next larger and definitive placebo-controlled study. The sample size in this study 
is likely too small to show statistically significant differences between the groups.
This initial duration-finding study focuses on patients with persistent symptoms despite having received the 
standard antibiotic therapy for Lyme disease. While it would be reasonable from a scientific perspective to 
examine whether this particular treatment would be effective at the time of early Lyme disease, it would be 
considered unethical without additional data to experiment on patients by randomizing them to something 
other than what is already known to be helpful for most patients with early Lyme disease (e.g., about 80% of 
patients respond well to doxycycline or amoxicillin treatment of the Lyme rash).
For our proposed initial study, therefore, our focus of attention will be on patients who have already tried 
the standard course of treatment but who relapsed or not responded adequately; these patients are urgently in 
need of a cure for their disabling relapsing symptoms. Currently there is no evidence-based treatment for 
these patients.
Specific Aims and Hypotheses
Specific Aims and Hypotheses
Specific Aims and Hypotheses Specific Aims and Hypotheses
There are two primary aims. First, we will assess the safety and side effect profile of disulfiram among 
patients with post-treatment Lyme symptoms. Second, we will investigate whether treatment with disulfiram 
results in a meaningful reduction in fatigue and improvement in the quality of life among patients with Post- 
treatment Lyme Disease. Fatigue will be assessed by the Fatigue Severity Scale (FSS) and quality of life 
will be assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).


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There are several secondary goals.
1. We will examine whether there is a difference in the proportion of responders on the fatigue scale among 
the 2 different dosing regimens (54 days over 8 weeks vs. 26 days over 4 weeks followed by placebo). We 
will assess both the percentage of responders and magnitude of the effect.
2. We will examine whether there is an improvement on the secondary outcome measures.
3. We will examine the side effect profile and drop-out rate associated with different treatment schedules of 
disulfiram.
4. We will examine whether there are other self-report measures that are more sensitive in documenting 
change over time than the FSS and the Q-LES-Q. These other measures, for example, include the PROMIS 
29 v2.0 profile questionnaire, the SF-36, and the General Symptom Questionnaire (GSQ-30).
5. We will examine whether tests of sensory function, autonomic function, and cognitive function change 
with treatment.
6. We will examine whether the urine antigen marker of Borrelia burgdorferi (as assessed by the Ceres 
Nanoscience Urine Nanotrap assay) is present at baseline and not present after treatment.
7. We will collect biological samples for future precision medicine studies to be stored in our repository.
8. We will collect fecal samples to be probed by investigators interested in studying microbiome changes in 
response to disulfiram.
9. We will also monitor patients' activity via the data generated by Fitbit- The rationale for the Fitbit is that 
our primary outcome is fatigue. People who are less fatigued may be engaging in more activity, such as 
doing more steps during the day. Moreover, activity monitoring using a device such as a Fitbit is being 
increasingly used in research studies as a measure of the change in response to treatment.
REMOTE PARTICIPATION CONSIDERATIONS:
Due to the challenges imposed with remote data collection, we will not address research aims addressing 
sensory and autonomic function (aim 5), or collection of biological specimens for our repository (aim
7). Capacity to address these aims is dependent on final numbers of in-person vs. remote study participation. 
In light of the current COVID-19 pandemic, no in-person procedures will be conducted at NYSPI and we 
are unable to estimate future in-person enrollments at this time.
Description of Subject Population
 Sample #1
Specify subject population
Patients with Post-Treatment Lyme Disease Syndrome 
Number of completers required to accomplish study aims 
20
Projected number of subjects who will be enrolled to obtain required number of completers 
24
Age range of subject population


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18-65
Gender, Racial and Ethnic Breakdown
Based on prior studies of individuals with Lyme disease, we anticipate the following gender and 
racial/ethnic group representation:
Gender: 60% women, 40% men
Racial/ethnic: 90% Caucasian; 10% other
(The racial/ethnic mix reflects the demographics of heavily Lyme endemic areas which tend to be rural or 
suburban areas as opposed to urban cities)
Description of subject population
All participants will have a history of prior Lyme disease, a history of symptoms that persist or relapse after 
antibiotic therapy, at least moderate fatigue at enrollment (>4 on the Fatigue Severity Scale), and a history 
of having received more than the recommended duration of antibiotic therapy for Lyme disease based on the 
Lyme Disease Treatment Guidelines (IDSA, 2006).
In order to maximize the likelihood of response, in our enrollment, we seek to enroll a majority of patients 
(at least half) who have received at least 8 weeks but no more than 6 months total of prior antibiotic therapy. 
If completing our enrollment numbers of patients with PTLS using this criterion proves infeasible then we 
will allow the other half of patients in this study to have had more than 6 months but no more than 24 
months of prior antibiotic therapy for this bout of Lyme disease.
Recruitment Procedures
Describe settings where recruitment will occur
Recruitment will primarily occur at the NYS Psychiatric Institute, with initial screening conducted remotely 
by a research assistant.
Because doctors will have heard about our study (see below), patients may initially be told about the study 
by a health care provider.
How and by whom will subjects be approached and/or recruited? 
A research assistant will be specifically assigned to this study.
She (or he) will reach out to all PTLS patients who have contacted us and/or responded to our mailers or 
posters. She will then conduct an initial telephone screening during which she will inform the individual 
about the study and answer questions. Eligible patients will be invited for the initial visit to confirm 
eligibility and obtain consent. If the participant is participating remotely or via the hybrid protocol, this


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initial visit will be completed remotely. RAs will use a telephone screening form when talking to patients 
interested in the study (see uploaded document).
How will the study be advertised/publicized?
1. Our Lyme Center website and the Columbia Recruit Me website.
2. We will be mailing flyers to physicians who are known to treat many patients with Lyme disease to 
inform them about our study. Physicians can post these flyers in their office and can share the information 
about our study with potentially eligible patients and give our contact information to those who are 
interested.
3. Patients on our mailing list will be contacted by mail and email.
4. Patients from past studies who gave consent to be contacted if new studies emerged will be informed of 
this study.
Do you have ads/recruitment material requiring review at this time? 
Yes
Does this study involve a clinical trial? 
Yes
Please provide the NCT Registration Number 
NCT03891667
Concurrent Research Studies
Will subjects in this study participate in or be recruited from other studies? 
Yes
Describe concurrent research involvement
If a patient who is enrolled in our Lyme Diagnostic Study (IRB# 6805) is identified as having persistent 
post-treatment Lyme symptoms that have lasted more than six months, he/she will be informed about this 
study.
Inclusion/Exclusion Criteria
Name the subject group/sub sample
Patients with Post-Treatment Lyme Disease Symptoms
Create or insert table to describe the inclusion criteria and methods to ascertain them
1. History of Lyme Disease diagnosis meeting CDC surveillance case criteria within the prior 16 years 
This requires:
-For erythema migrans (EM) rash, this has to be health-care provider diagnosed


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-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.
Ascertainment: photo of rash, provider's note, or a provider’s note years later reporting the initial Lyme 
disease, and/or positive lab test results.
2. History of treatment for Lyme disease within the last 16 years
-Documentation of prior antibiotic treatment for Lyme Disease of at least 5 weeks within the last 16 years; 
this meets or exceeds the Infectious Diseases Society of America (IDSA) recommended standards.
(We aim to recruit as many patients who have received between 5 weeks and 6 months of prior antibiotic 
therapy for this episode of illness; for this study, at least half of the sample will need to meet this criterion. 
Duration of prior treatment for the remaining portion of the study sample will have no upper limit for this 
episode of illness).
Ascertainment: Self-Report of patient and provision of at least one piece of external confirmatory 
historical documentation; for example, a provider’s note years later reporting the initial or later 
Lyme treatment or pharmacy record.
3. Partial Prior Response. History of at least partial response to prior antibiotic therapy for Lyme disease. 
Ascertainment: self-report
4. Antibiotic-free interval:
a) If antibiotics known to be effective for Lyme disease has been taken for 5 days or more in the recent past, 
the participant must agree to delay entering this study for at least 8 weeks prior to study randomization;
b) If antibiotics not effective against Lyme disease have been prescribed for other purposes, the participant 
must agree to wait 2 weeks before study randomization,
c) All participants must agree to be off antibiotics during the course of the study, regardless of length of 
antibiotic treatment.
Ascertainment: Self-report
Additionally, study clinician will confirm with the patients that the decision to stop antibiotics should only 
be made after the patient has consulted with their prescribing physician.
5. Current moderate to severe fatigue. The following criteria need to be met:
a) at least moderate intensity at study screening and at intake (a score of 4 or more on the Fatigue Severity 
Scale)
b) triggered or perpetuated by Lyme disease and persisting for at least 6 months after treatment
c) is not better attributed to another independent medical or psychiatric condition
d) 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.
6. Current post-Lyme symptoms impairs the patient’s quality of life (self-report)


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7. 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).
8. Between the ages 18-65 (Patient Report)
9. Ability to read and speak English (Patient Report)
10. Willingness to wear an activity monitor (e.g., Fitbit which we will provide) (Patient Report) 
Create or insert table to describe the exclusion criteria and methods to ascertain them
1. History of cardiovascular disease (e.g., coronary artery disease or heart failure). Ascertainment: Patient 
Report, EKG at Intake.
a) Remote and hybrid participants: Results provided of an abnormal EKG done within 6 months prior 
to starting the study or failure to provide an EKG done within 6 months prior to starting the study.
2. History of seizure disorder, abnormal EEGs, traumatic brain injury, renal disease (e.g. nephritis), 
diabetes mellitus, hypothyroidism and/or psychosis. History of active liver disease, including chronic active 
hepatitis, viral hepatitis (hepatitis B, C and CMV), cholestatic jaundice of any etiology, cirrhosis, toxic
hepatitis, or cholestatic hepatitis or jaundice with bilirubin greater than 2.0 X upper institutional limit. Given 
that disulfiram may exacerbate these pre-existing conditions, patients with these conditions will be 
excluded. Also excluded will be individuals with a documented history of large fiber neuropathy based on 
EMG and/or Nerve Conduction Studies. Ascertainment: self-report, MINI and LFTs (AST & ALT) & 
Bilirubin not greater than 2 times upper limit at intake.
3. History of Substance Use Disorder (e.g., alcohol abuse, multi-drug dependence) within the past 2 years 
Ascertainment: self-report and MINI interview
4. 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
Ascertainment: alcohol use questions in the screening questionnaire (self-report).
5. Evidence of current active tick-borne illness other than Lyme disease Ascertainment: self-report and 
review of provided medical records
(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)
6. 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. 
(Patient Report and Urinalysis).


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7. Inability to confirm abstinence from cannabis or CBD or THC-containing products 
Ascertainment: urinalysis at intake and at weeks 2 and 6 and patient report.
8. Women who are breastfeeding, pregnant, or at risk of becoming pregnant during the course of the study. 
Ascertainment: a) current pregnancy will be assessed by self-report and by a pregnancy test given to all 
women post-menarche and pre-menopausal onsite or for remote patients, at their initial testing visit); b) 
breastfeeding will be assessed by self-report; and c) if pregnancy is a risk, patients will be excluded if they 
plan to become pregnant during the course of this study or indicate an unwillingness to use an effective birth 
control method – these include double barrier methods (condom plus spermicide, or diaphragm plus 
spermicide), birth control, and abstinence.
9. Patients who are taking or plan to take warfarin, metronidazole, paraldehyde, phenytoin, theophylline, 
oral anticoagulants, or isoniazid (Patient report)
10. A concurrent or recent illness that may better account for current fatigue (Review of history)
11. Unwillingness to not take any new non-emergency medications during the course of this study without 
first reviewing with the study research physician (Patient Report)
12. History of rubber-contact dermatitis or allergy to disulfiram or thiuram derivatives (patient report)
13. Prior history of serious adverse reaction to disulfiram (Patient Report)
14. Cognitive Impairment for patients over 60.
Patient's with scores of less than 24 on the Mini-Mental Status Exam will not be eligible for this study.
15. Suicidal acts in the last 6 months (Screening Form) or current suicidal thoughts with intent or plan 
(assessed at intake by the study clinician and by the MINI). History of bipolar disorder (MINI).
16. Remote participants only: Unwillingness to provide a local physician who will provide secondary 
monitoring and collaborate to complete physical exams as part of study (patient report, screening form)
17. Remote and hybrid participants: Unwillingness to attend all required safety testing at his/her local 
Quest testing center (patient report, screening form).
Inclusion/Exclusion Criteria #2
Name the subject group/sub sample 
Highly Probable
Create or insert table to describe the inclusion criteria and methods to ascertain them
1. Meets criteria for any one of the 4 follow categories of Highly Probable past Lyme Disease:


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a. Health-care provider diagnosed Lyme disease in an individual exposed to a Lyme endemic 
area for which the HCP started antibiotic treatment for typical acute or disseminated Lyme 
disease (e.g., erythema migrans rash, arthritis, neurologic signs, or carditis)
or
b. EM rash after exposure to a Lyme endemic area that by history was not typical but highly 
suggestive and led a HCP to prescribe antibiotics for probable Lyme disease infection.
or
c. Multi-system symptoms (not better explained by another diagnosis) after exposure to a Lyme 
endemic area and current or past positive IgG Western blot or Lyme C6 ELISA or a Lyme 
PCR. Documentation of blood test is required.
or
d. A history of an acute viral-like illness after exposure to a Lyme endemic area followed 
within 16 weeks of symptom onset by a positive Lyme test that led the clinician to prescribe 
antibiotic treatment. (This criterion is partly based on the results from Steere and Sikand 
(NEJM 2003) in which they found that 18% of patients will present with only viral like 
symptoms (e.g., headache, arthralgia, fever) and none of the typical signs (ie, not showing signs 
such as EM rash or arthritis or facial palsy).
Ascertainment: photo of rash, provider's note, a provider’s note years later reporting the initial Lyme 
disease, and/or positive lab test results (including the Lyme C6 Peptide ELISA), documentation of prior 
treatment for Lyme disease based on subsequent clinical notes, pharmacy records, and/or other sources.
2. History of treatment for Lyme disease within the last 16 years
-Documentation of prior antibiotic treatment for Lyme Disease of at least 5 weeks within the last 16 years; 
this meets or exceeds the Infectious Diseases Society of America (IDSA) recommended standards.
(We aim to recruit as many patients who have received between 5 weeks and 6 months of prior antibiotic 
therapy for this episode of illness; for this study, at least half of the sample will need to meet this criterion. 
Duration of prior treatment for the remaining portion of the study sample will have no upper limit for this 
episode of illness).
Ascertainment: Self-Report of patient and provision of at least one piece of external confirmatory 
historical documentation; for example, a provider’s note years later reporting the initial or later Lyme 
treatment or pharmacy record.
3. Partial Prior Response. History of at least partial response to prior antibiotic therapy for Lyme disease. 
Ascertainment: self-report
4. Antibiotic-free interval:
a) If antibiotics known to be effective for Lyme disease has been taken for 5 days or more in the recent past, 
the participant must agree to delay entering this study for at least 8 weeks prior to study randomization;


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b) If antibiotics not effective against Lyme disease have been prescribed for other purposes, the participant 
must agree to wait 2 weeks before study randomization,
c) All participants must agree to be off antibiotics during the course of the study, regardless of length of 
antibiotic treatment.
Additionally, study clinician will confirm with the patients that the decision to stop antibiotics should only 
be made after the patient has consulted with their prescribing physician.
5. Current moderate to severe fatigue - The following criteria need to be met:
a) at least moderate intensity at study screening and at intake (a score of 4 or more on the Fatigue Severity 
Scale)
b) triggered or perpetuated by Lyme disease and persisting for at least 6 months after treatment
c) is not better attributed to another independent medical or psychiatric condition
d) 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.
6. Current post-Lyme symptoms impairs the patient’s quality of life 
Ascertainment: self-report
7. 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).
8. Between the ages 18-65 (Patient Report)
9. Ability to read and speak English (Patient Report)
10. Willingness to wear an activity monitor (e.g., Fitbit which we will provide) (Patient Report) 
Create or insert table to describe the exclusion criteria and methods to ascertain them
1. History of cardiovascular disease (e.g., coronary artery disease or heart failure). Ascertainment: Patient 
Report, EKG at Intake.
a) Remote and hybrid participants: Results provided of an abnormal EKG done within 6 months prior 
to starting the study or failure to provide an EKG done within 6 months prior to starting the study.
2. History of seizure disorder, abnormal EEGs, traumatic brain injury, renal disease (e.g. nephritis), diabetes 
mellitus, hypothyroidism and/or psychosis. History of active liver disease, including chronic active hepatitis, 
viral hepatitis (hepatitis B, C and CMV), cholestatic jaundice of any etiology, cirrhosis, toxic hepatitis, or 
cholestatic hepatitis or jaundice with bilirubin greater than 2.0 X upper institutional limit. Given that 
disulfiram may exacerbate these pre-existing conditions, patients with these conditions will be excluded. 
Also excluded will be individuals with a documented history of large fiber neuropathy based on EMG 
and/or Nerve Conduction Studies. Ascertainment: self-report, MINI and LFTs (AST & ALT) & Bilirubin 
not greater than 2 times upper limit at intake.


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3. History of Substance Use Disorder (e.g., alcohol abuse, multi-drug dependence) within the past 2 years 
Ascertainment: self-report and MINI interview
4. 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
Ascertainment: alcohol use questions in the screening questionnaire (self-report).
5. Evidence of current active tick-borne illness other than Lyme disease Ascertainment: self-report and 
review of provided medical records
(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)
6. 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. 
(Patient Report and Urinalysis).
7. Inability to confirm abstinence from cannabis or CBD or THC-containing products 
Ascertainment: urinalysis at intake and at weeks 2 and 6 and patient report.
8. Women who are breastfeeding, pregnant, or at risk of becoming pregnant during the course of the study. 
Ascertainment: a) current pregnancy will be assessed by self-report and by a pregnancy test given to all 
women post-menarche and pre-menopausal onsite or for remote patients, at their initial testing site visit); b) 
breastfeeding will be assessed by self-report; and c) if pregnancy is a risk, patients will be excluded if they 
plan to become pregnant during the course of this study or indicate an unwillingness to use an effective birth 
control method – these include double barrier methods (condom plus spermicide, or diaphragm plus 
spermicide), birth control, and abstinence.
9. Patients who are taking or plan to take warfarin, metronidazole, paraldehyde, phenytoin, theophylline, 
oral anticoagulants, or isoniazid (Patient report)
10. A concurrent or recent illness that may better account for current fatigue (Review of history)
11. Unwillingness to not take any new non-emergency medications during the course of this study without 
first reviewing with the study research physician (Patient Report)
12. History of rubber-contact dermatitis or allergy to disulfiram or thiuram derivatives (patient report)
13. Prior history of serious adverse reaction to disulfiram (Patient Report)
14. Cognitive Impairment for patients over 60.
Patient's with scores of less than 24 on the Mini-Mental Status Exam will not be eligible for this study.


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15. Suicidal acts in the last 6 months (Screening Form) or current suicidal thoughts with intent or plan 
(assessed at intake by the study clinician and by the MINI). History of bipolar disorder (MINI).
16. Remote participants only: Unwillingness to provide a local physician who will provide secondary 
monitoring and collaborate to complete physical exams as part of study (patient report, screening form)
17. Remote and hybrid participants: Unwillingness to attend all required safety testing at his/her local 
Quest testing center (patient report, screening form).
Waiver of Consent/Authorization
Indicate if you are requesting any of the following consent waivers
Waiver of consent for use of records that include protected health information (a HIPAA waiver of 
Authorization)
No
Waiver or alteration of consent 
No
Waiver of documentation of consent 
No
Waiver of parental consent 
No
Consent Procedures
Is eligibility screening for this study conducted under a different IRB protocol? 
No
Describe procedures used to obtain consent during the screening process
A research assistant will review with the potential study participant his/her history as it pertains to the 
specific inclusion/exclusion criteria of the study. During the phone screening, the study will be explained to 
the potentially eligible participants. The potential study participant will be informed that cannabis and/or 
alcohol use is strictly prohibited throughout the duration of this study. Those who are interested in the 
remote or hybrid study protocols will be notified that the consent forms will be provided prior to his/her 
initial telehealth study evaluation and will be reviewed with the study clinician and signed at the time of the 
initial evaluation. Those who are interested in the in-person study will be notified that the formal written 
consent will be provided for his/her review at the time of the in-person evaluation at the NYS psychiatric 
Institute.
Describe Study Consent Procedures
During the initial in-person or telehealth evaluation, the nature of the research protocol, including potential 
risks and benefits, will be explained verbally to all potential subjects by an experienced member of the study 
team who is knowledgeable about all aspects of the study. All remote and hybrid participants will receive 
the consent forms via email before or at the start of their initial telehealth evaluation.


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The clinicians conducting the consent procedure will have a frank discussion with the potential participant 
about the serious risks associated with the use of cannabis and/or alcohol while taking disulfiram. This 
discussion will be documented, including the participant's plan for not using these substances during the 
duration of the study.
For individuals who are interested in completing the study remotely or via the hybrid protocol, the clinician 
obtaining consent will have a frank discussion regarding the risks of travel during COVID-19 when 
attending the Quest lab visits, NYSPI, and/or their local clinician's office. Discussion points will include 
maintaining social distance, avoiding crowds, and wearing masks in public spaces. They will be encouraged 
to stay informed about public health recommendations and guidelines regarding
COVID-19, such as those issued by the Centers for Disease Control (CDC.gov) and local government 
guidelines and directives. Prospective participants will be advised that if they have any questions or 
concerns regarding their safety, they will be able to reschedule appointments. The clinician will also discuss 
the use of technology HIPAA-compliant platforms, and review any concerns the participant has including 
access to private space and accessible technology and internet connectivity.
Participants will be asked to read the study Consent Form and HIPPA Form. The person obtaining consent 
will answer any questions the subject may have. Once he/she feels confident the subject understands the 
study description, he/she will obtain informed consent from the subject by having him/her sign the consent 
form. Remote participants will sign and return the consent forms by scanning and returning them via a 
secure platform. Participants will be verbally reminded of the key points of the consent form and procedures 
of the study at the beginning of each study visit.
Indicate which of the following are employed as a part of screening or main study consent procedures
 Consent Form
Persons designated to discuss and document consent
Select the names of persons designated to obtain consent/assent 
Delaney, Shannon, MD
Fallon, Brian, MD 
McClellan, Denise
Type in the name(s) not found in the above list
Study Procedures
Describe the procedures required for this study 
Screening/Intake Procedures
Telephone Screen- (30 mins)
Attached screening form will be completed over the phone by an RA. This will be used to collect basic


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information about Lyme exposure and history of Lyme-like symptoms and treatment and of substance abuse 
history. Potentially eligible individuals will be invited to participate in the research study with the option for 
in-person, remote, or hybrid participation. If during the screening process, an individual should disclose a 
history of suicidal acts in the last 6 months, the study RA will inform the study clinician. The study clinician 
will then contact the person who had been screened to assess the patient and to make recommendations 
regarding additional psychiatric assessment or care as deemed advisable by the study clinician. Given that a 
history of suicidal acts is an exclusion item for eligibility, the clinician will inform the participant that the 
best clinical option is personalized treatment with a local mental health care provider as he/she would not be 
eligible for this study.
Participants who have been deemed eligible to participate in the remote or hybrid protocols after the 
screening process will be scheduled for their telehealth visits (described below). Once the intake has been 
scheduled, the RA will send a Medical History Form to the participants via email. In-person participants 
will be requested to bring the completed form to their intake visit. Remote and hybrid participants will be 
asked to return the completed forms via a secure method before their intake visit. The form will not only 
help in reviewing eligibility one final time, but will also help the study clinician organize their clinical notes 
while reducing the assessment time for the clinician and the participant alike. This form will be included in 
the participants' clinical folder. In the event, the participant is deemed ineligible the form will be returned to 
them.
IN-PERSON INTAKE AND STUDY VISITS- (please see attached document for visit breakdown)
Informed Consent and HIPPA Forms
On the intake day of the study, the nature of the research evaluation protocol, including potential risks and 
benefits, will be explained verbally to all potential subjects by an experienced member of the study team 
who is knowledgeable about all aspects of the evaluation process. Participants will be asked to also read the 
study Consent and HIPPA Forms. The person obtaining consent will answer any questions the subject may 
have. Once he/she feels confident the subject understands the evaluation description, he/she will obtain 
informed consent from the subject by having him/her sign the consent form. Participants will be verbally 
reminded of the key points of the consent form and procedures of the evaluation at the beginning of each 
study visit.
The study clinician will have a detailed and frank discussion about participants’ cannabis and alcohol use 
and the risks of using these substances while taking disulfiram. The study clinician will also inquire if the 
patient is either vegan or lactose intolerant. If the patient reports being either of the two, then the pharmacy 
will be informed about the specific dietary restriction immediately following the intake visit. Documentation 
of this discussion and participants plan for not using these substances will be made in the consent procedure 
note.
Physical examination, sensory testing and collection of biological samples
A medical history and physical examination will be conducted, including sensory testing (pain, sound, 
vibration, sweat gland function). The Neuropathy Total Symptom Scale- 6 and the Total Neuropathy Scale 
will be administered by the clinician during the neurologic assessment at intake and at week 8. EKG will be 
conducted by one of the study RAs and read by one of the study clinicians in order to confirm the 
participants’ inclusion/exclusion criteria during the intake visit.


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The following tests will be performed during the study:
• CBC, Chemistry Screen, TFT (Tests performed at Nathan Klein Clinic- CBC and Chem screen with LFTS 
will be conducted at intake, baseline, wk 1 (post tx), 2, 4, 6, 8, and 10, study while TFTs will be done only 
at intake, Tox Screen will be done at Intake and Wks 2 and 6)
• Lyme, Babesia Microti (Tests performed only at intake)
• Lyme Urine Proteome Test (Test performed by the Center for Applied Proteomics and Molecular 
Medicine at George Mason University.- done at intake and Week 10)
• Fecal matter samples collected at intake, week 4, week 8 and at week 10 will be sent to our collaborator 
Dr. Kim Lewis at Northeastern University
• All females who are post-menarche and pre-menopausal will be required to take a urine pregnancy test at 
the time of the intake (Test performed at NYSPI)
• EKG (Test performed at NYSPI- done at intake)
• Storage for biorepository for analysis at the end of the study. This will include Blood (serum, plasma, 
whole blood) and urine collected at baseline, week 4, week 8, and week 10). (More information is provided 
in the blood and other biological samples subsection)
While some of these samples will be sent to known collaborators, others will be stored in anticipation of 
future collaborations. The known collaborators for stored samples include samples to: a) the Center for 
Applied Proteomics at George Mason University; b) Dr. Armin Alaedini at Columbia for inflammatory and 
immune markers; c) Dr. Rafal Tokarz at Columbia for coinfection markers; and d) Drs. Charlie Brown 
(University of Missouri) and Dr. Edward Dennis at (UCSD) for lipidomic markers.
REMOTE INTAKE AND STUDY VISITS- (please see attached study overview visit checklist document 
for visit breakdown)
Informed Consent and HIPPA Forms
On the day of the intake visit, the nature of the research evaluation protocol, including potential risks and 
benefits, will be explained verbally via a secure telehealth platform to all potential subjects by an 
experienced member of the study team who is knowledgeable about all aspects of the evaluation
process. Participants will be asked to also read the study Consent and HIPPA Forms. The person obtaining 
consent will answer any questions the subject may have. Once he/she feels confident the subject understands 
the evaluation description, he/she will obtain informed consent from the subject by having him/her sign the 
consent form and scanning and returning them via a secure platform. Participants will be verbally reminded 
of the key points of the consent form and procedures of the evaluation at the beginning of each study visit.
The study clinician will have a detailed and frank discussion about participants’ cannabis and alcohol use 
and the risks of using these substances while taking disulfiram. The study clinician will also inquire if the 
patient is either vegan or lactose intolerant. If the patient reports being either of the two, then the pharmacy 
will be informed about the specific dietary restriction immediately following the intake visit. Documentation 
of this discussion and participants plan for not using these substances will be made in the consent procedure 
note.
Physical examination


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A medical history will be conducted via telehealth by a study clinician and a physical examination will be 
conducted by each participant's local physician. The Neuropathy Total Symptom Scale- 6 and the Total 
Neuropathy Scale will be administered by the local clinician during the neurologic assessment at intake and 
at week 8. The results of these assessments and any visit notes will be securely faxed from the local 
physician's office to the study clinician.
Remote participants will be required to visit their local Quest Diagnostic testing site for the following tests 
that will be performed during the study:
• CBC, Chemistry Screen, TFT (Tests performed at Quest Diagnostic- CBC and Chem screen with LFTS 
will be conducted at intake, Weeks 2, 4, 6, and 10, study while TFTs will be done only at intake, Tox Screen 
will be done at Intake and Week 6)
• Lyme, Babesia Microti (Tests performed only at intake)
• Lyme Urine Proteome Test (Test performed by the Center for Applied Proteomics and Molecular 
Medicine at George Mason University.- samples collected at home and sent to collaborating lab at intake 
and Week 10)
• Fecal matter samples collected at home at intake, week 4, week 8 and at week 10 will be sent to our 
collaborator Dr. Kim Lewis at Northeastern University
• All females who are post-menarche and pre-menopausal will be required to take a urine pregnancy test at 
the time of the intake (Test performed at Quest Diagnostic)
The results of these laboratory tests will be accessible to the study clinicians via a HIPPA compliant, secure 
EHR portal provided by Quest Diagnostics.
HYBRID INTAKE, BASELINE, AND STUDY VISITS- (please see attached study overview visit 
checklist document for visit breakdown)
Informed Consent and HIPPA Forms
On the day of the intake visit, the nature of the research evaluation protocol, including potential risks and 
benefits, will be explained verbally via a secure telehealth platform to all potential subjects by an 
experienced member of the study team who is knowledgeable about all aspects of the evaluation process. 
Participants will be asked to also read the study Consent and HIPPA Forms. The person obtaining consent 
will answer any questions the subject may have. Once he/she feels confident the subject understands the 
evaluation description, he/she will obtain informed consent from the subject by having him/her sign the 
consent form and scanning and returning them via a secure platform. Participants will be verbally reminded 
of the key points of the consent form and procedures of the evaluation at the beginning of each study visit.
The study clinician will have a detailed and frank discussion about participants’ cannabis and alcohol use 
and the risks of using these substances while taking disulfiram. The study clinician will also inquire if the 
patient is either vegan or lactose intolerant. If the patient reports being either of the two, then the pharmacy 
will be informed about the specific dietary restriction immediately following the intake visit. Documentation 
of this discussion and participants plan for not using these substances will be made in the consent procedure 
note.
Physical examination


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A medical history and physical examination will be conducted at the baseline visit prior to initiation of the 
study medication. The Neuropathy Total Symptom Scale- 6 and the Total Neuropathy Scale will be 
administered by the clinician during the neurologic assessment at baseline and at week 10.
Hybrid participants will be required to visit their local Quest Diagnostic testing site for the following tests 
that will be performed during the study:
• CBC, Chemistry Screen, TFT (Tests performed at Quest Diagnostic- CBC and Chem screen with LFTS 
will be conducted at intake, Weeks 2, 4, 6, and 10, study while TFTs will be done only at intake, Tox Screen 
will be done at Intake and Week 6)
• Lyme, Babesia Microti (Tests performed only at intake)
• Lyme Urine Proteome Test (Test performed by the Center for Applied Proteomics and Molecular 
Medicine at George Mason University.- samples collected at home and sent to collaborating lab at intake 
and Week 10)
• Fecal matter samples collected at home at intake, week 4, week 8 and at week 10 will be sent to our 
collaborator Dr. Kim Lewis at Northeastern University
• All females who are post-menarche and pre-menopausal will be required to take a urine pregnancy test at 
the time of the intake (Test performed at Quest Diagnostic)
• Storage for biorepository for analysis at the end of the study. This will include Blood (serum, plasma, 
whole blood) and urine collected at baseline and week 10). (More information is provided in the blood and 
other biological samples subsection)
The results of laboratory tests done through Quest will be accessible to the study clinicians via a HIPPA 
compliant, secure EHR portal provided by Quest Diagnostics.
While some of these samples will be sent to known collaborators, others will be stored in anticipation of 
future collaborations. The known collaborators for stored samples include samples to: a) the Center for 
Applied Proteomics at George Mason University; b) Dr. Armin Alaedini at Columbia for inflammatory and 
immune markers; c) Dr. Rafal Tokarz at Columbia for coinfection markers; and d) Drs. Charlie Brown 
(University of Missouri) and Dr. Edward Dennis at (UCSD) for lipidomic markers.
All Participants (Remote, Hybrid and In-Person) will also complete the following as part of study 
visits:
Medical history and psychiatric diagnostic Interview MINI
At intake, all subjects will undergo structured diagnostic interviews in-person or via telehealth, which 
include questions about their current and psychiatric history using MINI. A medical history will be obtained 
at intake using the Self-Administered Comorbidity Questionnaire (SCQ) and by the study clinician during 
the clinician interview.
Self-report questionnaires
Participants will have in-person or telehealth assessments at baseline and at weeks 1, 2, 4, 6, 8, 10. 
Participants will complete self-report questionnaires every 2 weeks at each assessment throughout the study 
and at Week 14.


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These self-report questionnaires and research data will be collected electronically via REDCap (Research 
Electronic Data Capture), hosted by New York State Psychiatric Institute. REDCap is a secure web 
application for building and managing online surveys and databases that complies with HIPAA 
requirements for a secure database.
For in-person participants who opt to complete paper versions of the questionnaires, this data will be stored 
in locked files and will be kept confidential to the extent permitted by law. Research binders will be 
available only to research staff and Federal, State and Institutional personnel as part of routine audits. Paper 
versions of self-report questionnaires will be labeled with a research number assigned to the patient, not the 
patient’s name.
Wearing of activity monitor
All participants will be provided with an activity monitor (e.g., Fitbit) to keep track of sleep and of the 
number of steps taken each day. Participants will wear this device for 2 weeks prior to randomization and 
throughout the 14 weeks of the study. We will also inform the participants that they will need to share the 
data from their devices periodically during their study visits.
Phone-calls at end of Weeks 3, 5,7, 9 and 12 (10-20 mins)
The follow-up phone calls will be done by one of the study clinicians and will focus on inquiring about the 
following-
• If the participant is experiencing side-effects related to disulfiram
• If the participant is adhering to the study treatment
• If the participant has used any kind of substance like alcohol, cannabis etc.
• If the participant has started any new medications
Treatment Phase 
Patients will be randomly assigned to one of two groups.
Both groups (the 4 week duration and the 8 week duration groups) will share the same protocol for the first 
4 weeks as follows:
Week 1
Disulfiram 250 every other day 
Week 2
Disulfiram 250 daily.
Week 3
Disulfiram 250 alternating with 500
Week 4
Disulfiram 500 daily.
Week 5-8 Continue with 500 daily (2 pills daily of disulfiram or placebo) or lower if needed based on side 
effects. (Note: the last 4 weeks of the study are double-blind)
(The long duration group will increase to two pills daily (500 mg) or the highest dosing regimen they can 
tolerate without significant side effects, while the short duration group during the last 4 weeks of the 
treatment period will be given placebo pills).


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In-person patients will be seen in the clinic at least every 2 weeks to week 10 and at week -14 for a follow- 
up. Remote and Hybrid patients will be seen in via scheduled telehealth sessions at least every 2 weeks up to 
week 10 and at week -14 for follow-up. Additionally, when not seen in person or via telehealth, patients will 
be followed up weekly over the phone to week 12.
Remote and Hybrid patients will be sent a digital blood pressure cuff prior to the Intake visit for safety- 
related monitoring. At each telehealth evaluation, the participant will be asked to take and report pulse and 
blood pressure to the NYSPI clinician. These blood pressure values will be documented by the NYSPI 
clinician to allow for the observation of any critical changes throughout treatment.
In-person and hybrid patients will be asked to take their first dose of medication during the baseline visit 
and will be monitored on site at NYSPI for 1/2 hour to ensure that they are not experiencing any serious 
side-effects of the medication. If during this time, the patient experiences signs of a mild allergic reaction, 
the patient will be given 50 mg of diphenydramine orally; observation will continue until the patient is free 
of allergic symptoms for at least 1/2 hour. Should the patient experience signs of an emerging, more severe 
allergic reaction, a medical emergency will be called (x5555) and the patient will be transferred to the ER if 
needed (e.g., symptoms are consistent with anaphylaxis). Some hybrid patients will receive their second 4 
weeks of treatment in the mail directly from the NYS Psychiatric Institute's Pharmacy. Some hybrid 
patients will receive both the first month and second month of treatment at their initial study visit in 
medication vials labeled "Bottle 1" and Bottle 2". The study clinician will initiate treatment with the 
patients at that appointment with "Bottle 1". They will also provide clear instructions not to open or 
use "Bottle 2" until instructed to do so after week 4.
Remote patients will receive their medication in the mail directly from the NYS Psychiatric Institute's 
Pharmacy. The NYSPI pharmacist will send the medication directly to the participant with detailed 
instructions that they are not to begin taking the medication until they meet with the study clinician at their 
baseline telehealth visit. At the baseline telehealth visit, the study clinician will ask patients to open the 
sealed packaging enclosing their medication. Subsequently, they will be asked to take their first dose of 
medication and will be monitored via telehealth for 1/2 hour to ensure that they are not experiencing any 
serious side-effects of the medication. If during this time, the patient experiences signs of a mild allergic 
reaction, the patient will be instructed to take 50 mg of diphenydramine orally; observation will continue 
until the patient is free of allergic symptoms for at least 1/2 hour. Should the patient experience signs of an 
emerging more severe allergic reaction, the patient will be instructed to visit their local physician or ER if 
needed (e.g., symptoms are consistent with anaphylaxis). As part of the consent process, the participant has 
agreed that a family member or friend will be present when taking the initial study medication. The family 
member or friend provides an additional layer of safety (on top of the NYSPI clinician monitoring remotely) 
should the participant start to experience an initial adverse reaction (e.g., an allergic reaction).
To monitor adherence to treatment, all patients will be given a pill log to document the pill taking.
While all patients will be started on the schedule of dose escalation as stated above and our study aims for 
patients to keep this schedule, if an individual patient has trouble tolerating disulfiram the clinician can 
adjust the dose based on patient tolerance.
Assessment of Outcome


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The outcome will be assessed across groups and within groups. Data will be evaluated both as categorical 
and continuous measures. A reduction from baseline on the FSS of >0.7 points is considered clinically 
meaningful.
Assessment of Outcome among individuals with early discontinuation 
Should a patient need to be discontinued from the study before week 10, he/she will be asked to return to 
NYSPI or to complete a telehealth evaluation and an assessment with their local physician (if participating 
remotely) to complete the major week 8/10 assessments so that his/her progress can continued to be 
evaluated by the study clinician. Since we do not know the optimal duration of disulfiram (ie, shorter 
courses may be effective) and because improvement may occur during the weeks after discontinuation, we 
will ask patients to return at week 10 (or to complete telehealth and local evaluations) but also to complete 
self-reports assessments and telephone follow-up at home at weeks 2, 6, 8, and 14.
Should a patient who drops from treatment early plan to start a new treatment that might impact clinical 
ratings, we will ask the patient to complete the full set of week 10 assessments early so that these can be 
used in the final data analysis; that patient will then be discontinued from both the treatment and assessment 
phase of the study. The patient will also be asked to return all study medication which we will then return to 
the NYSPI pharmacy.
During COVID-19 pandemic: I attest to follow the COVID-19 Safety Guidelines for Columbia Psychiatry 
and NYSPI Re-Entry outlined in the NYSPI Director’s June 1st memo, which
include but are not limited to:
• Infection Control/PPE – Guidelines
• Research participants will only come on-site if absolutely necessary for 
study procedures.
• No volunteers/externs on-site during Stage 1.
• Clinical research teams will screen their participants for COVID symptoms 
(night before and day of onsite visit, documenting this in the chart), and 
escort them in and out of the building.
• COVID/COVID-like symptoms in participants will be reported to the IRB 
via PRISM as an SAE.
You can upload charts or diagrams if any
Criteria for Early Discontinuation
Criteria for Early Discontinuation
Patients will be monitored for global clinical change (CGI Change - clinician rating) and for side-effects of 
the medications (Saftee) during the clinic visits or telehealth visits and weekly phone check-ups.


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• A patient will be discontinued from treatment early if he/she shows signs of liver toxicity on laboratory 
tests; an abnormal finding (e.g., Moderate or Severe ALT elevation > 2x ULN or AlkPhos > 1.5x ULN or 
Bili > 1.5x ULN) will lead to a discontinuation of the treatment, repeat of the lab test with close monitoring 
of the patient, and a referral for the patient to see their internist for further liver monitoring. If patients 
experience any mild ALT elevation or Alk Phos elevation (e.g., ALT >ULN but <2x ULN or ALK Phos
>ULN <1.5x ULN), then the study clinician will keep their disulfiram dose the same and repeat testing in 2 
weeks as long as their TB remains <1.5 ULN. Patients will be advised to immediately notify their study 
clinician of any early symptoms of hepatitis, such as fatigue, weakness, malaise, anorexia, nausea, vomiting, 
jaundice or dark urine; this will lead to a medical evaluation to rule out liver involvement.
• Patients will also be discontinued from the treatment component of the study early if they experience any 
new onset adverse neurological reactions thought to be due to the study treatment and which persists for at 
least 1 week (e.g., polyneuritis, peripheral neuropathy).
Clinically, early discontinuation from treatment will occur if:
a. a patient's self-report on the CGI Global Change scale indicates a score of "very much worse" for 2 
consecutive weeks or "much worse" for 4 consecutive weeks.
b. a patient's score on the BDI item 9 suicide item is 2 or higher for 2 consecutive assessments. A BDI item 
9 score of 2 or 3 will lead to an evaluation by a psychiatrist and closer monitoring which will include a 
reassessment one week later. If the worsening suicidal ideation continues, the patient will be withdrawn 
from the study and appropriate clinical care will be arranged.
Blood and other Biological Samples
Please create or insert a table describing the proposed collection of blood or other biological specimens
IN-PERSON PARTICIPANT SPECIMEN COLLECTION:
The following will be drawn or collected for in-person participants:
Intake
CBC, Chemistry Screen, TFT (Tests performed at NKI)
1. CBC- 1 4cc EDTA
2. TFTs and Chemistry Screen- 2, 8cc Red Top
3. Tox Screen and Pregnancy Test- 50 cc Urine
Lyme and Babesia test (Tests performed at MDL)
1. 2, 8.5cc Serum Tube
Stool collection kit is given to patient at intake visit. Patient is to collect stool sample at home and send to 
Dr. Lewis' lab at Northeastern- kits prior to the Baseline visit.
Baseline/Wk0


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Lyme Proteome Test (Test performed at George Mason University)
1. 80cc Urine Sample
Storage for Biorepository-
1. 2, 8 cc Red top Serum Tube- stored in .25cc aliquots
2. 1, 8cc EDTA Plasma-tube - stored in .5cc aliquots
3. 1, 4cc EDTA Whole Blood - stored in .5cc aliquots
CBC, Chemistry Screen, LFT (Tests performed at NKI)
1. CBC- 1 4cc EDTA
2. TFTs and Chemistry Screen- 2, 8cc Red Top
Weeks 1, 2, 4, 6, 8 
CBC and Chem screen (including LFTs). Urine Tox Screen at Wks 2 and Wk 6
Week 4 & 8
Storage for Biorepository-
1. 1, Serum from one 8cc Red Top Tube
2. 1, Plasma from one 6cc EDTA Plasma Tube
3. 50cc Urine Sample
Stool sample (collected at home and sent to Dr. Lewis' lab at Northeastern)
Week 10
CBC and Chem screen (including LFTs)
1. CBC- 1 4cc EDTA
2. TFTs and Chemistry Screen- 2 8cc Red Top
Lyme Proteome Test (Test performed at George Mason University)
1. 80cc Urine Sample
Storage for Biorepository-
1. 2, 8 cc Red Top Serum Tube- stored in .25cc aliquots
2. 1, 8cc EDTA Plasma-tube - stored in .5cc aliquots
3. 1, 4cc EDTA Whole Blood - stored in .5cc aliquots
Stool sample (collected at home and sent to Dr. Lewis' lab at Northeastern)
REMOTE PARTICIPANT SPECIMEN COLLECTION:
The following will be drawn or collected for remote participants:
Intake
CBC, Chemistry Screen, TFT (Tests performed at Quest Diagnostics)
1. CBC- 1 4cc EDTA
2. TFTs and Chemistry Screen- 2, 8cc Red Top


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3. Tox Screen and Pregnancy Test- 50 cc Urine
Lyme and Babesia test (Tests performed at MDL)
1. 2, 8.5cc Serum Tube
Stool collection kit is mailed to patient after intake telehealth visit. Patient is to collect stool sample at home 
and send to Dr. Lewis' lab at Northeastern prior to the Baseline visit.
Baseline/Wk0
Lyme Proteome Test (Test performed at George Mason University)
1. 80cc Urine Sample (Participants will be mailed a urine collection kit. Urine sample is to be collected at 
home and sent to George Mason University collaborators)
Weeks 2, 4, & 6
CBC and Chem screen (including LFTs). Urine Tox Screen at Wk 6 only (Tests performed at Quest 
Diagnostics)
Week 4 & 8
Stool sample (collected at home and sent to Dr. Lewis' lab at Northeastern)
Week 10
CBC and Chem screen (including LFTs) - (Tests performed at Quest Diagnostics)
1. CBC- 1 4cc EDTA
2. TFTs and Chemistry Screen- 2 8cc Red Top
Lyme Proteome Test (Test performed at George Mason University)
1. 80cc Urine Sample (Urine sample is to be collected at home and sent to George Mason University 
collaborators)
Stool sample (collected at home and sent to Dr. Lewis' lab at Northeastern)
HYBRID PARTICIPANT SPECIMEN COLLECTION:
The following will be drawn or collected for remote participants:
Intake
CBC, Chemistry Screen, TFT (Tests performed at Quest Diagnostics)
1. CBC- 1 4cc EDTA
2. TFTs and Chemistry Screen- 2, 8cc Red Top
3. Tox Screen and Pregnancy Test- 50 cc Urine
Lyme and Babesia test (Tests performed at MDL)
1. 2, 8.5cc Serum Tube


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Stool collection kit is mailed to patient after intake telehealth visit. Patient is to collect stool sample at home 
and send to Dr. Lewis' lab at Northeastern prior to the Baseline visit.
Baseline/Wk0 
Storage for Biorepository- Collected at NYSPI
1. 2, 8 cc Red top Serum Tube- stored in .25cc aliquots
2. 1, 8cc EDTA Plasma-tube - stored in .5cc aliquots
3. 1, 4cc EDTA Whole Blood - stored in .5cc aliquots
Lyme Proteome Test (test performed at George Mason University)
1. 80cc Urine Sample - collected at NYSPI
Weeks 2, 4, & 6
CBC and Chem screen (including LFTs). Urine Tox Screen at Wk 6 only (Tests performed at Quest 
Diagnostics).
Stool sample at Wk 4 only (collected at home and sent to Dr. Lewis' lab at Northeastern)
Week 8
Stool sample (collected at home and sent to Dr. Lewis' lab at Northeastern)
Week 10
CBC and Chem screen (including LFTs) - (Tests performed at Quest Diagnostics)
1. CBC- 1 4cc EDTA
2. TFTs and Chemistry Screen- 2 8cc Red Top
Storage for Biorepository-
1. 2, 8 cc Red Top Serum Tube- stored in .25cc aliquots
2. 1, 8cc EDTA Plasma-tube - stored in .5cc aliquots
3. 1, 4cc EDTA Whole Blood - stored in .5cc aliquots
Lyme Proteome Test (Test performed at George Mason University)
1. 80cc Urine Sample - collected at NYSPI
Stool sample (collected at home and sent to Dr. Lewis' lab at Northeastern)
Assessment Instruments
Create a table or give a brief description of the instruments that will be used for assessment 
Participants will complete the following questionnaires. Detailed information on what intervals these


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questionnaires will be completed is attached below.
Overall Multi-Domain Assessment:
1. Promis 29
2. Patient-rated Clinical Global Improvement
Somatic Symptoms
1. General System Questionnaire- 30 items
2. VAS - for "Fatigue"
3. Fatigue Severity Scale
Psychopathology:
1. Depression: Beck Depression Inventory II; (and PROMIS module) 
2 Anxiety: STAI (and PROMIS module)
3. MINI-Neuropsychiatric Assessment
Cognition:
1. Keilp Cognitive Battery or Abbreviated Cognitive Battery for remote and hybrid participants
2. NeuroQoL-Short Form v2.0 Cognition
3. VAS- for "Brain Fog"
4. Mini Mental Status (for participants 60 and older)
Functional Status
1. SF-36
2. Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q SF)
Demographics & History
1. History of Medical and Tick-borne Illness, Medical Utilization
2. Demographics+ Identifying Information Form
3. Physical History Form x 2 (completed by the MD)
4. Stressful Life Events Scale
5. NTSS6, TSS
6. Cumulative Illness Rating Scale (CIRS)
Sensory and Neuro testing (These procedures will not be conducted at NYSPI at present due to COVID-19)
1. Sensitivity to sound, light, vibration, pressure (in-person only)
2. Heart rate variability (in-person only)
3. Sudomotor small fiber function (Sudoscan) (in-person only)
Side-effect Monitoring
1. SAFTEE


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Off label and investigational use of drugs/devices
Drug #1
Research Related Delay to Treatment
Please attach copies, unless standard instruments are used
Choose from the following that will be applicable to your study
 Drug
Select the number of drugs used in this study 
1
Name of the drug 
Disulfiram
Manufacturer and other information
Disulfiram is FDA approved to help individuals wishing to abstain from alcohol. 
There are several manufacturers of disulfiram.
Approval Status 
IND is approved 
IND#
142979
Who holds the IND/IND sponsor? 
IND is held by PI/CU Investigator 
Fallon, Brian, MD
Will research procedures result in a delay to treatment? 
Yes
Maximum duration of delay to any treatment
We are asking patients not to start any new treatments during the course of this study and for 3 months 
prior. Therefore, the delay in starting any new treatment will be approximately 6.5 months.
Treatment is provided to all the participants. However, the participants who are randomized to the shorter 
dose regimen will receive 26 days of treatment compared to the participants who will get treatment for 54 
days.
Maximum duration of delay to standard care or treatment of known efficacy
There is no treatment of known efficacy for patients with post-treatment Lyme disease. 
Treatment to be provided at the end of the study


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Patients will be offered the option of 3 months of symptom-based clinical treatment at the end of the study. 
The clinician visits at PI will be free. Patients will be given scripts of medication if needed, the cost of 
which will be covered by them or their insurance carrier.
Clinical Treatment Alternatives
Clinical treatment alternatives
The treatment of post-treatment Lyme disease symptoms is a matter of considerable uncertainty. Some 
health care providers offer repeated courses of antibiotics while other health care providers offer symptom- 
based therapies. Unfortunately too few studies have been conducted among patients with post-treatment 
Lyme disease to recommend specific treatments.
Risks/Discomforts/Inconveniences
Risks that could be encountered during the study period 
Treatment with Disulfiram
1. Disulfiram-alcohol reaction. If patients consume alcohol or alcohol-containing products while on 
disulfiram, the patient may experience diaphoresis, palpitations, facial flushing, nausea, vertigo, 
hypotension, and tachycardia.
2. Disulfiram-related adverse effects.
a) Less serious side effects include headache, sleepiness, fatigue, and a metallic taste in the mouth.
b) More serious and rare side effects have been reported affect the following systems.
i. Dermatologic. Rare reports exist of exfoliative dermatitis, rash, and pruritis.
ii. Liver. Rare reports exist of hepatitis, hepatotoxicity, and hepatic failure; there have been cases of fatal 
fulminant hepatic failure despite discontinuation of medication (1 case in 30,000 patients treated per year) 
(Stokes, Abdifadid Stat Pearls Publishing, October 2017).
iii. Psychiatric. Rare reports exist of psychosis, confusional states, mutisim, head banging, memory 
impairment, and stupor.
iv. Neurologic. Neuropathy occurs in 1 case per 10,000 patients treated with disulfiram per year. Cases of 
seizures and optic neuritis attributed to disulfiram have been reported.
v. Cardiac. Cases of heart failure and death have been reported in patients with significant coronary artery 
disease or heart failure.


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vi. Genitourinary. Impotence has also been reported.
3. Disulfiram interaction with other medications.
a). Disulfiram and cannabis increases the risk of psychosis.
b) Disulfiram and metronidazole can lead to confusion or psychosis (hallucinations/delusions).
c). Interaction with compounds that use the P450 enzyme system for metabolism has been reported and is 
likely to occur. These include (but are not limited to): amitriptyline, imipramine, phenytoin, 
chlordiazepoxide, diazepam, omeprazole, and acetaminophen. Other drug-drug interactions have been 
reported as well.
4. Disulfiram may exacerbate certain conditions such as diabetes mellitus, hypothyroidism, seizure disorder, 
cerebral damage, cardiac, liver and renal disease.
Self -Report Questionnaires
Psychological distress at completing the self-report questionnaires.
Blood Draw
There is the risk of discomfort and a possible bruise at the site of the needle insertion. There is also a small 
risk of infection which can be treated if that occurs.
Sensory Testing (These procedures will not be conducted at NYSPI at present due to COVID-19.)
Some participants might find the sensory testing mildly unpleasant. There is no significant risk to subjects 
associated with this kind of testing. The experimenter can stop the task at any time if the participant 
experiences discomfort and wants to discontinue the task.
Remote and hybrid participation during COVID-19 pandemic:
There are some risks associated with travel during the COVID-19 pandemic for participants completing 
study procedures remotely or via the hybrid protocol. The number of laboratory assessments and in-person 
assessments has been reduced to minimize risk. Nonetheless, for safety-related reasons, it will still be 
necessary for participants to attend some assessments in-person.
Describe procedures for minimizing risks 
Treatment with Disulfiram
1. Disulfiram-alcohol reaction. Patients are required to be alcohol-free during this study and for at least 2 
weeks prior to starting the study and for 6 weeks after receiving the last dose of study medication (I.e from 
weeks 8-14). The consent form will describe this reaction so that patients will be aware of the typical 
symptom profile should he/she inadvertently consume an alcohol-containing product; this will also be 
described in detail to the patient by the study clinician. Patients will also be advised to check labels of all 
consumed products to ensure there is no alcohol within the food preparation (e.g., sauces, vinegar, cough 
medication).
2. Patients will be monitored for side-effects of the medication during the clinic visits and weekly phone 
check-ups. The number of pills taken (either 2 or 1 or none) each day can be adjusted based on tolerability


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and clinician's judgment. Intolerable side effects or clinically severe worsening that is sustained for 2 
consecutive assessments will result in withdrawal from the study.
3. To reduce the risk of rare but serious adverse effects, patients will be excluded from enrollment in the 
study if there is:
a. Liver: evidence or history of liver disease or insufficiency
b. Psychiatric: a lifetime history of psychosis or of bipolar disorder or recent or current suicidality
c. Substance use: alcohol or substance abuse disorder within the past 2 years
d. Neurologic: a lifetime history of seizures or history of abnormal EEG
e. Cardiac: a current or lifetime history of coronary artery disease or heart failure.
As additional precaution against liver injury, patients will be monitored closely during the study, including 
blood tests at intake and after weeks 2, 4, 6, and 10. If the clinician notices mild ALT or Alk Phos elevation 
(e.g., ALT >ULN but <2x ULN or ALK Phos >ULN <1.5x ULN), then the patient will remain at the same 
dose and repeat testing in 2 weeks (as long as TB <1.5 ULN). If the clinician notices moderate or severe 
LFT elevation (e.g., ALT > 2x ULN or AlkPhos > 1.5x ULN or Bili > 1.5x ULN), then the patient
will discontinue disulfiram, be monitored closely, and referred to their internist for further liver 
monitoring. The clinician will also monitor the patient for signs of hepatitis, such as fatigue, weakness, 
anorexia, nausea, vomiting, jaundice, malaise, and dark urine.
Because disulfiram may exacerbate certain conditions, patients will be excluded from participation who 
have a diagnosis of diabetes mellitus, hypothyroidism, seizure disorder, cerebral damage, cardiac, liver or 
renal disease
4. Drug interactions:
a. Patients will be warned not to take metronidazole or paraldehyde; as the latter is not available in the 
United States, we anticipate this to be an unlikely risk.
b. Patients will be advised to review all new medications (prescribed or over the counter) with his/her 
research clinician to ensure lack of drug interactions.
Self- Report Questionnaires
Patients will be told that they can skip questions if they are too distressing to complete.
Blood Draw (These procedures will be minimally conducted as needed at NYSPI due to COVID-19.) 
Gloves will be used to reduce risk of infection and the skin is wiped with alcohol prior to the blood draw; if 
an infection occurs, it will be treated.
Sensory Testing (These procedures will not be conducted at NYSPI at present due to COVID-19.)
Some participants might find the sensory testing mildly unpleasant. There is no significant risk to subjects 
associated with this kind of testing. The experimenter can stop the task at any time if the participant 
experiences discomfort and wants to discontinue the task.
Remote and hybrid participation during COVID-19 pandemic:
The number of laboratory assessments and in-person assessments has been reduced to minimize risk. 
However, for safety-related reasons, participants will be required to attend some assessments in-person. To


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minimize risks associated with travel, the clinician obtaining consent will have a frank discussion regarding 
the risks of travel when attending the local physician's office, visits to NYSPI, and all Quest lab visits.
Discussion points will include maintaining social distance, wearing masks in public spaces, exercising 
caution when traveling in public, and following public health guidelines. Participants will be informed about 
implemented procedures at NYSPI to minimize COVID-19 exposure risk such as personal protective 
equipment (masks and face shields), frequent disinfecting of equipment, and social distancing when 
possible. Prospective participants will also be advised that if they have any concerns regarding their safety, 
they will be able to reschedule appointments.
Methods to Protect Confidentiality
Describe methods to protect confidentiality
New techniques and technologies are developed each year that when applied to blood samples can help 
facilitate new discoveries and biomarkers; that is one of the goals of Precision Medicine research. To enable 
us to take advantage of emerging technologies, we would like to keep participant samples for at least 10 
years or as long as they are deemed useful for research purposes. However, participants have the right to 
request that their samples be destroyed at any time.
All of the patient’s medical records, laboratory reports, and research data will be stored in locked files and 
will be kept confidential to the extent permitted by law. Medical records, laboratory reports, research 
binders, and medical charts will be available only to research staff, local consulting physicians, and Federal, 
State and Institutional personnel as part of routine audits. There are legal advocacy organizations that have 
the authority under State law to access otherwise confidential subject records, but they cannot re-disclose 
this information without the patient’s consent. Any research data transmitted or stored electronically will 
use a number assigned to the patient, not the patient’s name. As a part of our remote protocol, local 
physicians will fax all assessment results and notes to the study clinicians via a HIPPA compliant fax. Quest 
diagnostics, who will perform local laboratory tests, have provided access to a HIPPA compliant secure 
EHR portal. Study clinicians will access participant laboratory results via that secure portal.
All the shared samples will be assigned a unique subject ID and no PHI will be shared with the 
collaborators. Samples will be shared after obtaining a Material Transfer Agreement (MTA).
Will the study be conducted under a certificate of confidentiality?
No
Direct Benefits to Subjects
Direct Benefits to Subjects
There is no direct benefit to the participants expected from participation in this research study. It is hoped,


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however, that the knowledge gained from this study may lead to a significant public health benefit as we 
hope it will help establish the safety and suggest efficacy of disulfiram as a medication to treat chronic 
symptoms of Lyme disease. While we hypothesize that patients will experience a reduction in symptom 
burden as a result of participation in this study, we are not certain this will be the case. Therefore, at this 
point, we cannot state that there will be direct benefits to the subjects.
Compensation and/or Reimbursement
Will compensation or reimbursement for expenses be offered to subjects? 
Yes
Please describe and indicate total amount and schedule of payment(s).
Include justification for compensation amounts and indicate if there are bonus payments.
Participants who live outside the NYC metro area and choose to participate in-person will be reimbursed for 
reasonable travel expenses up to $100 per visit. The amount is considered proportionate to the costs of rail 
travel for participants that live along the Northeast corridor and/or cover costs incurred for paid parking. For 
participants traveling from interstate, the reimbursement may be used to subsidize the cost of 
accommodation for each visit. Remote participants will not receive reimbursement. During the COVID-19 
Pandemic, we will reimburse travel for participants within and outside the NYC metro area so that it may be 
more feasible for them to avoid public transportation. Hybrid participants will be reimbursed for reasonable 
travel expenses up to $200 per visit.
References
References
Long TE. Repurposing thiram and disulfiram as antibacterial agents for multi-drug resistant Staphylococcus 
aureus infections. Antimicrobial agents and chemotherapy. 2017 Jul 3:AAC-00898.
Pothineni VR, Wagh D, Babar MM, Inayathullah M, Solow-Cordero D, Kim, Samineni AV, Parekh MB, 
Tayebi L, Rajadas J. Identification of new drug candidates against Borrelia burgdorferi using high- 
throughput screening. Drug design, development and therapy. 2016;10:1307.
Mariangela Antonelli, Anna Ferrulli, Luisa Sestito, Gabriele A. Vassallo,
Claudia Tarli, Carolina Mosoni, Maria M. Rando, Antonio Mirijello, Antonio Gasbarrini & Giovanni 
Addolorato (2018) Alcohol addiction - the safety of available approved treatment options, Expert 
Opinion on Drug Safety, 17:2, 169-177
Simona G, Lanfranco P, Alberto PL, Fabio C. Drug-drug interactions in the treatment for alcohol use 
disorders: a comprehensive review. Pharmacological research. 2018 Apr 30.
Soyka M, Müller CA. Pharmacotherapy of alcoholism–an update on approved and off-label medications. 
Expert opinion on pharmacotherapy. 2017 Aug 13;18(12):1187-99.


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Stokes, Maranda, and Sara Abdijadid. "Disulfiram." (NCBI Bookshelf, StatPearls, 2017).
Uploads
Upload copy(ies) of unbolded Consent Form(s) 
Upload copy(ies) of bolded Consent Form(s)
Upload copy(ies) of recruitment materials/ads to be reviewed 
Disulfiram_Facebook_Ad_Text_approved_2019-06-26.pdf 
Email_template_to_clinicians_approved 2019-11-04.pdf 
Lyme_Clinical_Trial_flyer_(002).pdf
Upload evidence of FDA IND approval(s) 
FDA_IND_Letter_7766.pdf 
7755_'Form_of_Notice_by_IND.IDE_Holder_03292019.pdf 
Upload copy(ies) of the HIPAA form 
HIPPA_Disulfiram_03-11-2021.pdf
Upload any additional documents that may be related to this study 
7755_Request_for_Deidentified_Data_sharing_approved 2019-06-26.pdf 
FDC_Foundation_Nov_2018.pdf
Consent Procedure Note.pdf 
Disulfiram instructions_02.28.22.pdf
Disulfiram_Alcohol_Interaction_Information_Feb_2020.pdf 
DSFLocalProviderPhysicalNeuroExamFINAL2.25.2021. docx..pdf 
Hybrid Study Overview Visit Checklist.pdf 
Medical_History_Form_approved_2019-07-31.pdf
Revised Remote Disulfiram Screening Form_2020-09-18_JP.pdf 
Study Overview Visits Checklist_approved 2019-06-26.pdf 
Consulting_Agreement_10-13-20 (1).pdf
'Dr._Fallon's_General_Symptom_Questionnaire_30_item_3_04_16_version.pdf 
Amendment 3.16.22 Prot 7755_BAF_to_IRB_03.16.202 Amendment.pdf


 
Statistician 
Data preparation and analysis is performed by a research scientist for the 
team.  
Study 
Objectives 
A study is a preliminary investigation regarding the relative benefit of 4 vs 8 
weeks of treatment with disulfiram. With this initial study, the investigators 
will be able to evaluate the side effects, tolerability and initial signs of the 
effectiveness of disulfiram in reducing symptoms among the 24 patients 
assessed. The results of this study will guide the investigators regarding 
whether a larger definitive randomized trial should be conducted, and 
which treatment schedule is optimal. 
Primary 
endpoint 
Week 10 evaluation. 
Study Design 
 
A small 14-week randomized placebo-controlled pilot study enrolling 24 
patients with persistent symptoms despite prior antibiotic treatment for 
Lyme disease (known as Post-treatment Lyme Disease Syndrome). Among 
the 24 disulfiram-treated patients, half will get 8 weeks of disulfiram and 
the other half will get a shorter duration of disulfiram for 4 weeks followed 
by 4 weeks of matching placebo. After week 8, patients will be off pills for 2 
weeks for the primary week 10 evaluation and then for another 4 weeks for 
the week 14 follow-up evaluation. This will be a double-blinded study; 
neither physician nor patient will know which treatment group the patient 
is assigned to. For details see PSF.  
General Study 
Population 
See PSF respective section 
Inclusion-
Exclusion 
Criteria  
See PSF respective section 
Study 
Assessments 
See PSF respective section 
Sample size 
24 as of 04/02/2019. The study was terminated in 2022 with a sample size 
of 11.  
Randomization  This will be a double-blinded study; neither physician nor patient will know 
which treatment group the patient is assigned to. Randomization is 
performed at New York Psychiatric Institute pharmacy when medication is 
issued to an enrolled participant.  Randomization is performed in blocked of 
12. The study unblind will occur when the enrollment is completed, and all 
patients finish their follow-up assessments.  
Primary aim#1 
To assess the safety and side effect profile of disulfiram among patients 
with post treatment Lyme symptoms. This will be assessed by SAFTEE 
(systematically) as well as recording all unanticipated adverse 
events/serious adverse events. 
Primary aim #2 To investigate whether treatment with disulfiram results in a meaningful 
reduction in fatigue and improvement in the quality of life among patients 


with Post- treatment Lyme Disease. Fatigue will be assessed by the Fatigue 
Severity Scale (FSS) and quality of life will be assessed with the Quality-of-
Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).  
Secondary 
aims and 
Exploratory 
goals:  
1. We will examine whether there is a difference in the proportion of 
responders on the fatigue scale among the 2 different dosing regimens (54 
days over 8 weeks vs. 26 days over 4 weeks followed by placebo). We will 
assess both the percentage of responders and magnitude of the effect. 
2. We will examine whether there is an improvement on the secondary 
outcome measures. 
3. We will examine the side effect profile and drop-out rate associated with 
different treatment schedules of disulfiram. 
4. We will examine whether there are other self-report measures that are 
more sensitive in documenting change over time than the FSS and the Q-
LES-Q. These other measures, for example, include the PROMIS 29 v2.0 
profile questionnaire, the SF-36, and the General Symptom Questionnaire 
(GSQ-30). 
5. We will examine whether tests of sensory function, autonomic function, 
and cognitive function change with treatment. 
6. We will examine whether the urine antigen marker of Borrelia 
burgdorferi (as assessed by the Ceres Nanoscience Urine Nanotrap assay) is 
present at baseline and not present after treatment. 
7. We will collect biological samples for future precision medicine studies to 
be stored in our repository. 
8. We will collect fecal samples to be probed by investigators interested in 
studying microbiome changes in response to disulfiram. 
9. We will also monitor patients' activity via the data generated by Fitbit- 
The rationale for the Fitbit is that our primary outcome is fatigue. People 
who are less fatigued may be engaging in more activity, such as doing more 
steps during the day. Moreover, activity monitoring using a device such as a 
Fitbit is being increasingly used in research studies as a measure of the 
change in response to treatment.  
Timing of 
Analysis 
Analysis will be performed after  the study is unblinded.  
Analysis 
Population 
We conduct intent to treat analysis which covers all enrolled patients who 
received a study drug and who participated in at least one post-baseline 
assessment. 
Missing Data 
Missing data is treated as missing at random 
Interim 
Analyses and 
Data 
Monitoring 
There is no interim analysis for the protocol.  


Primary aim#1 
analysis 
Tables on all mortality rate, SAE and AE will be generated. To estimate 
safety, number of adverse events in active and sham treatment groups by 
the end of 10-week period will be computed and reported.  
Primary aim#2 
analysis 
To investigate whether treatment with disulfiram results in a meaningful 
reduction in fatigue and improvement in the quality of life, a change in 
scores between the baseline and week 10 will be computed. We will 
calculate a number of participants who’s change in score reached a minimal 
clinically significant difference (MCID) for each of the measures. MCID for 
Fatigue Severity Scale (FSS) and MCID for Quality-of-Life Enjoyment and 
Satisfaction Questionnaire (Q-LES-Q) is 6.8.  A Log Odds ratio for 8-week 
and 4-week group will be computed along with the 95% confidence interval 
for this ratio.  The 95% confidence interval provides considerably more 
information than testing a specific null hypothesis: it provides a range of 
plausible values for differences in these primary outcomes between 
treatment groups which can be used to inform research in larger studies.