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

• ClinicalTrials.gov Identifier: NCT03873974
• Recruitment Status: Completed
• First Posted: March 14, 2019
• Last Update Posted: March 2, 2020
• Sponsor: Lyme Diagnostics Ltd.
• Collaborator: Pharmahungary Group
• Information provided by (Responsible Party): Lyme Diagnostics Ltd.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Lyme Borreliosis	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 Design

• Study Type: Observational
• Actual Enrollment: 400 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: 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
• Actual Study Start Date: July 2, 2019
• Actual Primary Completion Date: November 25, 2019
• Actual Study Completion Date: December 4, 2019

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :

1. Primary endpoint, 1 (sensitivity of the experimental DualDur in Vitro Diagnostic System) [ Time Frame: Laboratory samples evaluated within 72-144 hours of sampling. ]
   The sensitivity of the experimental DualDur in Vitro Diagnostic System in the positive arm, based on medical diagnosis
2. Primary endpoint, 2 (specificity of the experimental DualDur In Vitro Diagnostic System) [ Time Frame: Laboratory samples evaluated within 72-144 hours of sampling. ]
   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

Secondary Outcome Measures :

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

Other Outcome Measures:

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

Biospecimen Retention:   None Retained

Blood samples will be collected from patients and healthy volunteers.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• 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.

Criteria

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

Contacts and Locations

Locations

Austria

MedUni Vienna,University Hospital Internal Medicine I, Clinical Dept. for Infections

Wien, Austria, 1090

Czechia

FORBELI s.r.o.

Prague, Czechia, 160 00

Neurologická ambulance

Praha 6, Czechia, 160 00

Germany

Praxis Dr.med. Reinhardt

Pforzheim, Germany, 5172

Hungary

Istenhegyi Géndiagnosztika Magánorvosi Rendelő Ltd.

Budapest, Hungary, 1125

Poland

St. Luke's Clinic

Gdańsk, Poland, 80-557

Centrum Dr. Ozimek

Warsaw, Poland, 00-001

Slovakia

Borélia centrum Bratislava, BCB Clinic

Bratislava, Slovakia, 821 02

Sponsors and Collaborators

Lyme Diagnostics Ltd.

Pharmahungary Group

Investigators

• Study Director: Bela P. Bozsik, MD; Lyme Diagnostics Ltd.

More Information

Additional Information:

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. 

• Responsible Party: Lyme Diagnostics Ltd.
• ClinicalTrials.gov Identifier: NCT03873974
• Other Study ID Numbers: LymeDD_CIP
• First Posted: March 14, 2019
• Last Update Posted: March 2, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: To be decided later.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lyme Diagnostics Ltd.:

Lyme Borreliosis; Lyme disease; In Vitro Diagnostics System; Dark Field Microscopy

Additional relevant MeSH terms:

Borrelia Infections; Lyme Disease; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Tick-Borne Diseases; Vector Borne Diseases; Immunoglobulin G; Immunoglobulin M; Immunologic Factors; Physiological Effects of Drugs