Study of Lyme Neuroborreliosis

Study of Lyme Neuroborreliosis: Epidemiology, Manifestations, Diagnostics and Treatment

The main purpose of this study is to determine whether four weeks treatment with oral doxycycline is as equally effective as three weeks treatment with intravenous ceftriaxone in patients with Lyme neuroborreliosis. The other purpose is to improve laboratory diagnostics of Lyme neuroborreliosis and further define the manifestations and epidemiology of the disease in Finland.

Study Overview

• Status: Completed
• Conditions: Lyme Neuroborreliosis
• Intervention / Treatment: Drug: Ceftriaxone; Drug: Doxycycline

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 4

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland, 00029
    • Helsinki University Hospital
  • Turku, Finland, 20521
    • Turku University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria for definite Lyme neuroborreliosis (Criteria 1-3 or 1 and 4 fulfilled):

1. Neurological symptoms suggestive of LNB without other obvious reasons
2. CSF pleocytosis (>4 leukocytes per mikrol)
3. Intrathecal production of B. burgdorferi specific antibodies
4. Detection of B. burgdorferi DNA in central spinal fluid

Inclusion Cirteria for possible LNB (criteria 1 and 2 or 3 fullfilled):

1. Neurological symptoms suggestive of LNB wihtout other obvious reasons
2. Production of B. burgdorferi spesific antibodies in serum
3. Erythema migrans during the previous three months

Exclusion Criteria:

• pregnancy and breastfeeding
• women planning to get pregnant in two months
• age under 18
• handicapped persons
• prisoners
• use of any antibiotics two weeks before study treatments begins
• allergy for tetracyclines or cephalosporins

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ceftriaxone; Treatment of intravenous ceftriaxone (2 g/day), three weeks	Drug: Ceftriaxone; 2 g intravenous once a day, three weeks
Experimental: Doxycycline; Treatment with oral doxycycline (200mg / day), four weeks	Drug: Doxycycline; Doxycycline: 100mg tablet two times per day, four weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The improvement of the clinical condition during the study.	The clinical condition of participants will be evaluated with visual analogue scale (from 0 to 10, 0=best) by the participants. The VAS scores are collected before the treatment with antibiotics, and 4 months and 12 months after the treatment.	12 months
The clinical condition evaluated by the participants after 12 months from the treatment	The clinical condition is evaluated with VAS by the participants.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Central spinal fluid (CSF) pleocytosis	The decline in CSF leukocyte count between the patients in doxycycline and ceftriaxone groups	3 weeks
CSF protein concentration	The decline in CSF protein concentration between the patients in doxycycline and ceftriaxone groups.	3 weeks
CSF lactate level	The decline in CSF lactate level between the patients in doxycycline and ceftriaxone groups.	3 weeks
CSF CXCL13 concentration	The decline in CSF CXCL13 concentration wetween the patients in doxycycline and ceftriaxone groups	3 weeks

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Investigators: Principal Investigator: Jukka Hytönen, University of Turku; Principal Investigator: Elisa Kortela, HYKS; Principal Investigator: Mari Kanerva, HYKS; Principal Investigator: Laura Airas, TYKS

Publications and helpful links

General Publications

• Kortela E, Kanerva MJ, Puustinen J, Hurme S, Airas L, Lauhio A, Hohenthal U, Jalava-Karvinen P, Nieminen T, Finnila T, Haggblom T, Pietikainen A, Koivisto M, Vilhonen J, Marttila-Vaara M, Hytonen J, Oksi J. Oral Doxycycline Compared to Intravenous Ceftriaxone in the Treatment of Lyme Neuroborreliosis: A Multicenter, Equivalence, Randomized, Open-label Trial. Clin Infect Dis. 2021 Apr 26;72(8):1323-1331. doi: 10.1093/cid/ciaa217.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2012
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: July 3, 2012
• First Submitted That Met QC Criteria: July 6, 2012
• First Posted (Estimate): July 9, 2012

Study Record Updates

• Last Update Posted (Actual): May 13, 2019
• Last Update Submitted That Met QC Criteria: May 9, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: ceftriaxone; doxycycline
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Vector Borne Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Central Nervous System Bacterial Infections; Tick-Borne Diseases; Borrelia Infections; Spirochaetales Infections; Lyme Disease; Lyme Neuroborreliosis; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Ceftriaxone; Doxycycline
• Other Study ID Numbers: T1/2012