Disulfiram: A Test of Symptom Reduction Among Patients With Previously Treated Lyme Disease
Condition: Fatigue; Quality of Life
MeSH terms: Lyme Disease
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): Disulfiram
Intervention type(s): Drug
Intervention description(s): Patients will receive disulfiram for 4 weeks followed by placebo for 4 weeks or disulfiram for 8 weeks.
Other intervention name(s): Antabuse
Intervention MeSH terms: Disulfiram
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients will be randomly assigned to one of two groups:
Treatment Group I- patients will receive Disulfiram for 8 weeks
Treatment Group 2 - patients will receive Disulfiram for 4 weeks followed by 4 weeks of placebo.
The dosing follows a fixed-flexible schedule. Clinical judgment guides dosing increases, based on patient tolerance, side effects, and response.
Week 1: 250 mg every other day. Week 2: 250 mg daily (or continuation of lower dose based on clinical judgment).
Week 3: 250 mg alternating with 500 mg/daily (or continued lower dose based on clinical judgment) Week 4: 500 mg daily (or continued lower dose based on clinical judgment)
Week 5-8: 500 mg/daily (or continued lower dose based on clinical judgment) :
Primary outcome is at week 10. Patients will be reassessed at week 14.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Lyme Disease; Post-treatment Lyme Disease Syndrome; Disulfiram; Chronic Lyme Disease