Novel Diagnostics for Early Lyme Disease

Study Overview
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Brief Summary
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There are more than 300,000 new cases of Lyme disease every year in the US. Lyme disease is a dangerous bacterial infection transmitted by tick bites and it becomes increasingly severe as the infection progresses. Definitive diagnosis is based on serum-based tests that have fundamental limitations: 1) current tests cannot detect early infections so patients do not receive antibiotic therapy until the infection has progressed, and 2) there is no way to measure if antibiotic therapy has been successful. MicroB-plex will address these two unmet clinical needs by introducing a novel, blood-based diagnostic method that will enable clinicians to diagnose infections earlier and to monitor the success of their interventions.

Detailed Description
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Lyme disease is the most commonly reported arthropod-borne infection in the US with recent CDC estimates eclipsing 300,000 new cases in 2013. In addition to growing in frequency, the infections have a complex and increasingly severe course. Beginning with mild flu-like symptoms and frequently a signature bull's-eye rash, erythema migrans, Lyme disease can progress to severe articular, neurological and cardiac symptoms, most of which are preventable with early antibiotic therapy. Leading investigators have identified two major shortcomings to the current serology-based methods for the definitive diagnosis of Early Localized Lyme disease. First, the clinical sensitivity in the first four weeks is poor, under 50% at the time of symptom onset, so many patients remain undiagnosed or unconfirmed until the disease has had time to progress. Second, serum antibody levels remain elevated long after the infection has been resolved making the monitoring of therapeutic success or diagnosis of re-infection virtually impossible. MicroB-plex will address these shortcomings by using a novel sample matrix from circulating antibody secreting cells (ASC) for diagnosis of Lyme disease. This novel matrix is MENSA (medium enriched for newly synthesized antibody). In this study, MicroB-plex and its clinical collaborators will test whether MENSA is effective in early Lyme diagnostic (within the first 2 weeks) and if this new approach will track therapeutic success.

Official Title
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Novel Diagnostics for Early Lyme Disease

Conditions
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Lyme Disease

Intervention / Treatment
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* Diagnostic Test: MicroB-plex Lyme Immunoassay


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Human adults at least 21 years of age and no more than 80 years of age at the time of screening. Have the ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), and comply with the study protocol procedures (including required study visits). High clinical suspicion of acute Lyme disease, with symptoms seven days or less. Must have erythema migrans rash and physician diagnosis of early Lyme disease. Brief history and physical exam will be obtained during the study visit. Be willing to return to our clinic for up to nine visits and blood draws over a one-year period. People who do not have Lyme disease, but want to participate as healthy controls (one time visit) Exclusion Criteria: Have poor venous access. Have received any immunosuppressive therapy including biologics or recent course of steroids, or recent chemotherapy. Anti-TNF therapy (eg, adalimumab, etanercept, infliximab). Intravenous (IV) cyclophosphamide Interleukin-1 receptor antagonist (anakinra). Intravenous immunoglobulin (IVIG). High dose prednisone or equivalent (> 100 mg/day). Plasmapheresis. Any new immunosuppressive/immunomodulatory agent Any steroid injection (eg, intramuscular, intraarticular, or intravenous). On treatment for Lyme disease greater than seven days Recent chemotherapy History of solid organ transplant History of autoimmune disorders (SLE, Rheumatoid arthritis, Scleroderma, etc.) History of inflammatory muscle disease (polymyositis, dermatomyositis, etc.) History of inflammatory bowel disease (Crohn's disease, Ulcerative colitis, etc.) History of HIV infection Received a Lyme disease vaccine in the past History of prior Lyme disease infection in the past Have any condition that, in the opinion of the principal investigator, would significantly increase the risk for the subject.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lyme Infected<br>Subjects presenting with suspected Lyme Disease | Diagnostic Test: MicroB-plex Lyme Immunoassay<br>* Subject's blood and clinical data are collected to develop a diagnostic immunoassay<br>|
| Controls<br>Subjects with no known Lyme Disease, past or present | Diagnostic Test: MicroB-plex Lyme Immunoassay<br>* Subject's blood and clinical data are collected to develop a diagnostic immunoassay<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of EM positive patients who become MicroB-plex Lyme test positive prior to seroconversion | MicroB-plex Lyme Test, that measures anti-Lyme antibodies in MENSA, becomes positive prior to conventional Lyme immunoassays that measure antibodies in serum, resulting in earlier diagnosis | Within 14 days of enrollment | 
| Percentage of treated EM positive patients who become MicroB-plex Lyme test negative prior to their decline in serum | MicroB-plex Lyme Test, that measures anti-Lyme antibodies in MENSA, becomes negative with successful treatment, prior to a decline in serum antibody level in conventional immunoassays, providing an earlier measure of effective therapy | Up to one year from enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of treated EM positive patients who remain MicroB-plex Lyme test positive following treatment | MicroB-plex Lyme Test, that measures anti-Lyme antibodies in MENSA, remains positive with treatment failure | Up to one year from enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lyme Disease, Borrelia burgdorferi, Antibody Secreting Cells, Diagnostics, Early Diagnosis, Treatment Outcome, Health Volunteers, Adult