Six Versus Two Weeks Treatment With Doxycycline in Lyme Neuroborreliosis

Six Versus Two Weeks Treatment With Doxycycline in Lyme Neuroborreliosis; a Multicenter, Non-inferiority, Penta-blind, Randomized Trial

Comparison of Doxycycline 200 mg once daily for six weeks versus Doxycycline 200 mg once daily for two weeks + placebo for four weeks. Primary objective is to answer the question "is two weeks doxycycline treatment (currently suggested treatment) at least as effective as six weeks doxycycline treatment in Lyme Neuroborreliosis?".Key secondary objectives are to provide a better understanding of the pathogenesis and long-term complaints, and to search for new biomarkers in Lyme Neuroborreliosis (LNB) by collecting clinical data, blood, and cerebrospinal fluid (CSF) in a biobank for future research

Endpoints:

Primary endpoint: Improvement on a composite clinical score from inclusion to six months after ended treatment defined as clinical score at inclusion minus clinical score at six months.

Secondary endpoints: Improvement on a composite clinical score 12 months after ended treatment. Fatigue Severity Scale (FSS),Patient Health Questionnaire (PHQ-15), Short Form 36 (SF-36) and blood and CSF findings at inclusion, after 6 and 12 months.

The study design is a multicenter, non-inferiority, randomized, penta-blind, placebo-controlled trial. 120 patients will be included from approximately 8 Norwegian hospitals.

Main inclusion criteria are neurological symptoms suggestive of LNB without other obvious reasons, one or both of a) Cerebrospinal fluid pleocytosis (>5 leukocytes/mm3) b) intrathecal Bb antibody Production and signed informed consent. Safety assessments during the trial: Comparison of clinical outcome six months after end of treatment between the two treatment groups. Subjective experiences and blood tests including hematology and biochemistry for four weeks after ended treatment.

Study Overview

• Status: Completed
• Conditions: Neuroborreliosis, Borrelia Burgdorferi
• Intervention / Treatment: Drug: Placebo; Drug: Doxycycline

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Neurological symptoms suggestive of LNB without other obvious reasons and one or both of

   1. Cerebrospinal fluid pleocytosis ≥5 leukocytes pr mm3
   2. Intrathecal Bb antibody production
2. Signed informed consent

Exclusion Criteria:

• Age less than 18 years
• Pregnancy, breast-feeding
• Adverse reaction to tetracyclines
• Treatment with cephalosporin, penicillin, or tetracycline the last 14 days
• Serious liver or kidney disease that contraindicates use of doxycycline
• Lactose intolerance
• Need to use medications contraindicated according to Summary of Product Characteristics of the Investigational Medicinal Product

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Doxycycline for 6 weeks; Doxycycline 200 mg once daily for six weeks	Drug: Doxycycline
Placebo Comparator: Doxycycline for 2 weeks + placebo; Doxycycline 200 mg once daily for two weeks + placebo for four weeks.	Drug: Placebo; Drug: Doxycycline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Composite Clinical Score From Inclusion to Six Months After Ended Treatment	Clinical change on composite clinical score (CCS) defined as score at inclusion minus score at 6 months after treatment.CCS consisted of 32 variables,scored from 0 to 2 points.Minimum 0 points,maximum 64 points.High scale score indicated worse outcome. Variables scored:Malaise,Fatigue,Headache,Neck and/or back pain,Abdominal and/or breast pain,Arm pain,Leg pain,Generalised pain located to joints and/or muscles,Memory and/or concentration problems,Other,Facial palsy,Paresis of the eye muscles,Reduced hearing,Other cranial neuropathies,Cervical radicular sensory findings,Cervical radicular paresis,Thoracic radicular sensory findings,Lumbar radicular sensory findings,Lumbar radicular paresis,Non-radicular sensory findings,Non-radicular paresis,Other,Central findings in one extremity,Central findings in a hemi pattern,Central findings in both legs,Central findings in all extremities,Gait ataxia,Dysphasia/aphasia, Nystagmus,Involuntary movement including tremor,Cognitive impairment,Other.	Six months after end of treatment.

Collaborators and Investigators

• Sponsor: Sorlandet Hospital HF
• Investigators: Principal Investigator: Anne Marit Solheim, M.D, Sørlandet Hospital HF

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): February 1, 2021

Study Registration Dates

• First Submitted: September 16, 2015
• First Submitted That Met QC Criteria: September 16, 2015
• First Posted (Estimated): September 17, 2015

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: June 1, 2021

More Information

Terms related to this study

• 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; Doxycycline
• Other Study ID Numbers: 2015-001481-25