Tick-borne Encephalitis and Borrelial Antibodies in Serum

• ClinicalTrials.gov Identifier: NCT03956446
• Recruitment Status: Recruiting
• First Posted: May 20, 2019
• Last Update Posted: November 3, 2020
• Sponsor: University Medical Centre Ljubljana
• Collaborator: University of Ljubljana School of Medicine, Slovenia
• Information provided by (Responsible Party): Daša Stupica, University Medical Centre Ljubljana

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Tick Borne Encephalitis	Drug: Doxycycline; Drug: Symptomatic therapy; Other: Questionnaire	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Antibiotic Therapy for Patients With Tick-borne Encephalitis and Borrelial Antibodies in Serum
• Actual Study Start Date: September 1, 2014
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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.	Drug: Doxycycline; Beside symptomatic therapy, patients will receive oral Doxycycline 100 mg, Doxy® twice daily.; 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.; Other: Questionnaire; 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.	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.; Other: Questionnaire; 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.	Other: Questionnaire; Subjects will be asked to answer a questionnaire asking about the presence and frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.

Outcome Measures

Primary Outcome Measures :

1. Number of patients with objective manifestations of Lyme borreliosis [ Time Frame: one year ]
   At each visit physical examination will be performed and clinical signs indicating objective manifestations of Lyme borreliosis, such as erythema migrans, will be searched for.
2. Frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia [ Time Frame: one year ]

Eligibility Criteria

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

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.

Contacts and Locations

Contacts

Contact: Daša Stupica, MD PhD; +386 31 689324; dasa.stupica@kclj.si

Contact: Maša Velušček, MD; +38631332904; masa.veluscek@kclj.si

Locations

Slovenia

University Medical Center Ljubljana; Recruiting

Ljubljana, Slovenia

Contact: Daša Stupica, MD, PhD +386 31 689 324 dasa.stupica@kclj.si

Contact: Maša Velušček, MD +386 1 522 21 10 masa.veluscek@kclj.si

Sponsors and Collaborators

University Medical Centre Ljubljana

University of Ljubljana School of Medicine, Slovenia

Investigators

• Principal Investigator: Daša Stupica, MD PhD; University Medical Centre Ljubljana

More Information

• Responsible Party: Daša Stupica, Prinicipal Investigator, University Medical Centre Ljubljana
• ClinicalTrials.gov Identifier: NCT03956446
• Other Study ID Numbers: TBE-BB prospect
• First Posted: May 20, 2019
• Last Update Posted: November 3, 2020
• Last Verified: November 2020

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

Additional relevant MeSH terms:

Encephalitis, Tick-Borne; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Tick-Borne Diseases; Virus Diseases; RNA Virus Infections; Flavivirus Infections; Flaviviridae Infections; Doxycycline; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents