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

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

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.

Study Overview

• Status: Completed
• Conditions: Lyme Borreliosis
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 400

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
    • MedUni Vienna,University Hospital Internal Medicine I, Clinical Dept. for Infections
• Czechia
  • Prague, Czechia, 160 00
    • Forbeli s.r.o.
  • Praha 6, Czechia, 160 00
    • Neurologicka ambulance
• Germany
  • Pforzheim, Germany, 5172
    • Praxis Dr.med. Reinhardt
• Hungary
  • Budapest, Hungary, 1125
    • Istenhegyi Géndiagnosztika Magánorvosi Rendelő Ltd.
• Poland
  • Gdańsk, Poland, 80-557
    • St. Luke's Clinic
  • Warsaw, Poland, 00-001
    • Centrum Dr. Ozimek
• Slovakia
  • Bratislava, Slovakia, 821 02
    • Borélia centrum Bratislava, BCB Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Positive trial arm: At least 18-year-old, treatment-naive or treatment-experienced men and women with Lyme borreliosis, whose physician indicates drug therapy for Lyme borreliosis. Furthermore, they consent to the collection and processing of their data during the clinical trial, and to blood sampling for the assessment of the DualDur IVD System, and to the diagnostic analyses of these samples in the central laboratory of the trial.

Negative trial arm: At least 18-year-old healthy volunteers without the symptoms of either acute or chronic Lyme borreliosis, who have not been treated for Lyme borreliosis, and all the standard laboratory tests prove that they are free of Lyme borreliosis.

Furthermore, they give their consent to blood sampling for the purposes of the clinical trial, to the collection and processing of their data, and to the analyses of their blood samples in the central laboratory of the trial.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Negative trial arm; 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; 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.; Diagnostic test: DualDur dark-field automatic microscopic test; 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.; Diagnostic test: Western blot IgM and IgG; Borrelia qualitative in vitro test in order to detect and reliably identify IgG and IgM antibodies against Borrelia burgdorferi from human serum or plasma.; Diagnostic test: Bózsik Western blot IgM and IgG; Borrelia qualitative in vitro test in order to detect and reliably identify IgG and IgM antibodies against Borrelia burgdorferi from human serum or plasma.; Diagnostic test: enzyme-linked immunosorbent assay (ELISA) IgM and IgG; Standard ELISA test for Lyme borreliosis.; Diagnostic test: DualDur Polymerase chain reaction; DualDur PCR test for Lyme borreliosis.
Positive trial arm; 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; 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.; Diagnostic test: DualDur dark-field automatic microscopic test; 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.; Diagnostic test: Western blot IgM and IgG; Borrelia qualitative in vitro test in order to detect and reliably identify IgG and IgM antibodies against Borrelia burgdorferi from human serum or plasma.; Diagnostic test: Bózsik Western blot IgM and IgG; Borrelia qualitative in vitro test in order to detect and reliably identify IgG and IgM antibodies against Borrelia burgdorferi from human serum or plasma.; Diagnostic test: enzyme-linked immunosorbent assay (ELISA) IgM and IgG; Standard ELISA test for Lyme borreliosis.; Diagnostic test: DualDur Polymerase chain reaction; DualDur PCR test for Lyme borreliosis.

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tertiary endpoint (Validation of the image evaluation)	Validation of the image evaluation software applied in the diagnosis of Lyme borreliosis by dark field microscopy.	Software evaluation done at planned study completion date, February 2020.

Collaborators and Investigators

• Sponsor: Lyme Diagnostics Ltd.
• Collaborators: Pharmahungary Group
• Investigators: Study Director: Bela P. Bozsik, MD, Lyme Diagnostics Ltd.

Publications and helpful links

Helpful Links

• Official website of study Sponsor, Lyme Diagnostics Ltd.
• Official website of central laboratory, Synlab Hungary Ltd.
• European Parliament Resolution of 15 November 2018 on Lyme disease (Borreliosis) (2018/2774(RSP)
• Official website of CRO, Pharmahungary Group.

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2019
• Primary Completion (Actual): November 25, 2019
• Study Completion (Actual): December 4, 2019

Study Registration Dates

• First Submitted: February 28, 2019
• First Submitted That Met QC Criteria: March 12, 2019
• First Posted (Actual): March 14, 2019

Study Record Updates

• Last Update Posted (Actual): March 2, 2020
• Last Update Submitted That Met QC Criteria: February 27, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Lyme disease; Lyme Borreliosis; In Vitro Diagnostics System; Dark Field Microscopy
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Tick-Borne Diseases; Spirochaetales Infections; Lyme Disease; Borrelia Infections; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulin G; Immunoglobulin M
• Other Study ID Numbers: LymeDD_CIP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: To be decided later.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No