Tick-borne Encephalitis and Borrelial Antibodies in Serum

NCT ID: NCT03956446

Last Updated: 2025-03-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-01
• Study Completion Date: 2027-12-31

Brief Summary

In Slovenia, tick-borne encephalitis and Lyme borreliosis are both endemic diseases with high incidence rates and they are both transmitted by a bite of infected Ixodes ricinus tick. In clinical practice, tick-borne encephalitis is confirmed by demonstration of tick-borne encephalitis antibodies in serum of a patient with compatible clinical presentation and cerebrospinal pleocytosis. Patients with Lyme meningitis or meningoradiculitis also have cerebrospinal pleocytosis, however the presence of borrelial antibodies in serum does not attest Lyme neuroborreliosis. Patients with tick-borne encephalitis and positive borrelial antibodies in serum, but not fulfilling criteria for Lyme neuroborreliosis, are often being treated with antibiotics in several European countries due to the possibility of double infection. The investigators hypothesise that such patients do not benefit from antibiotics. Such an approach may appear safe regarding the possibility of borrelial infection, however it can also be associated with detrimental consequences such as antibiotic related adverse reactions, negative epidemiological impact on bacterial resistance, and intravenous catheter related complications.

Conditions

Tick Borne Encephalitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Doxycycline, Doxy®

Beside symptomatic therapy, patients will receive oral doxycycline 100 mg (Doxy®) twice daily. Patients will answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.

Group Type: ACTIVE_COMPARATOR

Doxycycline

Intervention Type: DRUG

Beside symptomatic therapy, patients will receive oral Doxycycline 100 mg, Doxy® twice daily.

Symptomatic therapy

Intervention Type: DRUG

Patients will receive symptomatic therapy with antipyretics, analgetics, antiemetics, and parenteral hydration: metamizole, Analgin®, paracetamol, Lekadol®, thiethylperazine, Kytril®, saline. Questionnaire Subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.

Questionnaire

Intervention Type: OTHER

Subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.

No antibiotics

Patients will receive symptomatic therapy (paracetamol, Lekadol®, granisetron, Kytril®, metamizol, Analgin®, parenteral hydration with saline). Patients will answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.

Group Type: OTHER

Symptomatic therapy

Intervention Type: DRUG

Patients will receive symptomatic therapy with antipyretics, analgetics, antiemetics, and parenteral hydration: metamizole, Analgin®, paracetamol, Lekadol®, thiethylperazine, Kytril®, saline. Questionnaire Subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.

Questionnaire

Intervention Type: OTHER

Subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.

Healthy controls

Patients will be asked to refer a spouse to serve as a control. If unmarried they will be asked to refer a family member or a friend of +/- 5 years to serve as a control. Control subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.

Group Type: OTHER

Questionnaire

Intervention Type: OTHER

Subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.

Interventions

Doxycycline

Beside symptomatic therapy, patients will receive oral Doxycycline 100 mg, Doxy® twice daily.

Intervention Type: DRUG

Symptomatic therapy

Patients will receive symptomatic therapy with antipyretics, analgetics, antiemetics, and parenteral hydration: metamizole, Analgin®, paracetamol, Lekadol®, thiethylperazine, Kytril®, saline. Questionnaire Subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.

Intervention Type: DRUG

Questionnaire

Subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 18 years or older
• clinical picture compatible with tick-borne encephalitis,
• clear cerebrospinal fluid,
• cerebrospinal pleocytosis (leucocytes in cerebrospinal fluid >5 x 106/)L,
• positive serum immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against tick-borne encephalitis virus,
• positive serum IgG antibodies against Lyme borreliae.

Exclusion Criteria

• isolation of B.burgdorferi sensu lato from cerebrospinal fluid,
• positive intrathecal borrelial antibody production index,
• seroconversion of borrelial IgG antibodies,
• presence of erythema migrans and/or borrelial lymphocytoma in the last month,
• Bannwarth syndrome.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Ljubljana School of Medicine, Slovenia

OTHER

Sponsor Role: collaborator

University Medical Centre Ljubljana

OTHER

Sponsor Role: lead

Responsible Party

Daša Stupica

Prinicipal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daša Stupica, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Centre Ljubljana

Locations

University Medical Center Ljubljana

Ljubljana, , Slovenia

Site Status: RECRUITING

Countries

Slovenia

Central Contacts

Daša Stupica, MD PhD

Role: CONTACT

dasa.stupica@kclj.si

+386 31 689324

Maša Velušček, MD

Role: CONTACT

masa.veluscek@kclj.si

+38631332904

Facility Contacts

Daša Stupica, MD, PhD

Role: primary

dasa.stupica@kclj.si

+386 31 689 324

Maša Velušček, MD

Role: backup

masa.veluscek@kclj.si

+386 1 522 21 10

Other Identifiers

TBE-BB prospect

Identifier Type: -

Identifier Source: org_study_id