Performance Evaluation of the DualDur In Vitro Diagnostic System in the Diagnosis of Lyme Borreliosis

Study Overview
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Brief Summary
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The clinical data from the clinical trial will be used to assess the performance, sensitivity and specificity of the experimental DualDur In Vitro Diagnostic System.

Detailed Description
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The clinical data from the clinical trial will be used to assess the performance, sensitivity and specificity of the experimental DualDur In Vitro Diagnostic System. The sensitivity of the DualDur in Vitro Diagnostic System will be examined in subjects whose physician indicates drug therapy for Lyme borreliosis (positive arm). The specificity of the DualDur in Vitro Diagnostic System will be examined in healthy volunteers declared Lyme borreliosis negative by their physician and all the standard laboratory tests prove that they are free of Lyme borreliosis (negative arm). The diagnostic system developed by Lyme Diagnostics Ltd. is planned for application in the diagnosis during the entire life cycle of Lyme borreliosis.

Official Title
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Multicentre Clinical Trial to Assess the Performance of the DualDur In Vitro Diagnostic System in the Diagnosis of Lyme Borreliosis From Blood Samples of Subjects Who Are Either Pharmacotherapy-naive or Treatment-experienced and Their Physician Indicates Drug Therapy for Lyme Borreliosis

Conditions
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Lyme Borreliosis

Intervention / Treatment
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* Diagnostic Test: DualDur dark-field microscopic test
* Diagnostic Test: DualDur dark-field automatic microscopic test
* Diagnostic Test: Western blot IgM and IgG
* Diagnostic Test: Bózsik Western blot IgM and IgG
* Diagnostic Test: enzyme-linked immunosorbent assay (ELISA) IgM and IgG
* Diagnostic Test: DualDur Polymerase chain reaction


Participation Criteria
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Eligibility Criteria
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I. Positive trial arm I.1. Inclusion Criteria: Man or female subjects over 18 years of age Treatment-naive or treatment-experienced subjects with Lyme borreliosis, whose physician indicates drug therapy for Lyme borreliosis. Subjects capable of reading, understanding, and observing the requirements of the clinical trial, who sign the Patient Information Leaflet and Informed Consent Form approved by the Competent Authority and the Ethics Committee. I. 2. Exclusion Criteria: Man or female subjects over 80 years of age Pregnancy, breastfeeding History of any complication related to previous blood sampling Coagulation and/or bleeding disorders Anticoagulant therapy Acute, life-threatening condition Participation in another clinical trial The patient is under antibiotic therapy, or received such treatment in the preceding 3 months The patient is currently taking or has taken in the preceding 6 months dietary supplements of herbal origin, or medicinal herbs as first-line or add-on treatments for Lyme borreliosis In the event the patient has previously been treated for Lyme borreliosis, then this treatment took place less than 6 months before blood sampling. In the preceding 6 months, the patient used an electronic device operating along the principle of electromagnetic (i.e. electric or magnetic) fields - such as bioresonance, pulsed magnetic field, etc. - as add-on treatment for Lyme borreliosis. II. Negative trial arm II.1. Inclusion Criteria: Man or female subjects over 18 years of age Asymptomatic healthy volunteer subjects without acute or chronic symptoms of Lyme borreliosis, who are free of Lyme borreliosis by the indication of all standard laboratory tests, and who are willing to take part in a comprehensive medical examination and related blood sampling. Subjects capable of reading, understanding, and observing the requirements of the trial, who sign the Patient Information Leaflet and Informed Consent Form approved by the Competent Authority and the Ethics Committee. II. 2. Exclusion Criteria: Man or female subjects over 80 years of age Pregnancy, breastfeeding History of any complication related to previous blood sampling Coagulation and/or bleeding disorders Anticoagulant therapy Participation in another clinical trial Lyme borreliosis diagnosed previously, at any time during the life of the subject The subject has received any treatment for Lyme borreliosis (medicinal products, dietary supplements, medicinal plants, electronic devices, etc.) during his/her life The patient is under antibiotic therapy, or received such treatment in the preceding 3 months The occupation of the subject is either a forester or a hunter

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Negative trial arm<br>Venous blood samples will be taken for central laboratory analysis with: DualDur dark-field microscopic test DualDur dark-field automatic microscopic test Western blot IgM and IgG Bózsik Western blot IgM and IgG Enzyme-Linked Immunosorbent Assay (ELISA) IgM and IgG DualDur Polymerase chain reaction | Diagnostic Test: DualDur dark-field microscopic test<br>* Morphologically identify the presence of Borrelia burgdorferi sensu lato bacteria (in a broader sense) which are present in the body fluid, hence to verify Borreliosis. Manual evaluation.<br>Diagnostic Test: DualDur dark-field automatic microscopic test<br>* Morphologically identify the presence of Borrelia burgdorferi sensu lato bacteria (in a broader sense) which are present in the body fluid, hence to verify Borreliosis. Software evaluation.<br>Diagnostic Test: Western blot IgM and IgG<br>* Borrelia qualitative in vitro test in order to detect and reliably identify IgG and IgM antibodies against Borrelia burgdorferi from human serum or plasma.<br>Diagnostic Test: Bózsik Western blot IgM and IgG<br>* Borrelia qualitative in vitro test in order to detect and reliably identify IgG and IgM antibodies against Borrelia burgdorferi from human serum or plasma.<br>Diagnostic Test: enzyme-linked immunosorbent assay (ELISA) IgM and IgG<br>* Standard ELISA test for Lyme borreliosis.<br>Diagnostic Test: DualDur Polymerase chain reaction<br>* DualDur PCR test for Lyme borreliosis.<br>|
| Positive trial arm<br>Venous blood samples will be taken for central laboratory analysis with: DualDur dark-field microscopic test DualDur dark-field automatic microscopic test Western blot IgM and IgG Bózsik Western blot IgM and IgG Enzyme-Linked Immunosorbent Assay (ELISA) IgM and IgG DualDur Polymerase chain reaction | Diagnostic Test: DualDur dark-field microscopic test<br>* Morphologically identify the presence of Borrelia burgdorferi sensu lato bacteria (in a broader sense) which are present in the body fluid, hence to verify Borreliosis. Manual evaluation.<br>Diagnostic Test: DualDur dark-field automatic microscopic test<br>* Morphologically identify the presence of Borrelia burgdorferi sensu lato bacteria (in a broader sense) which are present in the body fluid, hence to verify Borreliosis. Software evaluation.<br>Diagnostic Test: Western blot IgM and IgG<br>* Borrelia qualitative in vitro test in order to detect and reliably identify IgG and IgM antibodies against Borrelia burgdorferi from human serum or plasma.<br>Diagnostic Test: Bózsik Western blot IgM and IgG<br>* Borrelia qualitative in vitro test in order to detect and reliably identify IgG and IgM antibodies against Borrelia burgdorferi from human serum or plasma.<br>Diagnostic Test: enzyme-linked immunosorbent assay (ELISA) IgM and IgG<br>* Standard ELISA test for Lyme borreliosis.<br>Diagnostic Test: DualDur Polymerase chain reaction<br>* DualDur PCR test for Lyme borreliosis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint, 1 (sensitivity of the experimental DualDur in Vitro Diagnostic System) | The sensitivity of the experimental DualDur in Vitro Diagnostic System in the positive arm, based on medical diagnosis | Laboratory samples evaluated within 72-144 hours of sampling. | 
| Primary endpoint, 2 (specificity of the experimental DualDur In Vitro Diagnostic System) | The specificity of the experimental DualDur In Vitro Diagnostic System in the negative arm, based on medical diagnosis and all the standard laboratory test results | Laboratory samples evaluated within 72-144 hours of sampling. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary endpoint, 1 (sensitivity of the experimental DualDur in Vitro Diagnostic System) | 1. The sensitivity of the experimental DualDur in Vitro Diagnostic System, based on medical diagnosis (Lyme borreliosis positive) and direct/indirect diagnostic methods. | Laboratory samples evaluated within 72-144 hours of sampling. | 
| Secondary endpoint, 2 (Pairwise comparison of the sensitivity of the experimental DualDur in Vitro Diagnostic System and of the direct/indirect diagnostic methods) | Pairwise comparison of the sensitivity of the experimental DualDur in Vitro Diagnostic System and of the direct/indirect diagnostic methods | Laboratory samples evaluated within 72-144 hours of sampling. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lyme Borreliosis, Lyme disease, In Vitro Diagnostics System, Dark Field Microscopy