Six Versus Two Weeks Treatment With Doxycycline in Lyme Neuroborreliosis

Phase 3

Completed

• Conditions: Neuroborreliosis, Borrelia Burgdorferi
• Interventions: Drug: Doxycycline; Drug: Placebo

• Registration Number: NCT02553473
• Lead Sponsor: Sorlandet Hospital HF

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-09-16
• Study First Submitted QC: 2015-09-16
• Study First Posted: 2015-09-17
• Study Start: 2015-10
• Primary Completion: 2020-01
• Study Completion: 2021-02
• Status Verified: 2021-06
• Results First Submitted: 2023-11-21
• Results First Submitted QC: 2024-01-02
• Last Update Submitted: 2024-01-02
• Results First Posted: 2024-01-23
• Last Update Posted: 2024-01-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 121

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Doxycycline for 6 weeks	Doxycycline	Doxycycline 200 mg once daily for six weeks
Doxycycline for 2 weeks + placebo	Placebo	Doxycycline 200 mg once daily for two weeks + placebo for four weeks.
Doxycycline for 2 weeks + placebo	Doxycycline	Doxycycline 200 mg once daily for two weeks + placebo for four weeks.

Primary Outcome Measures

Name	Time	Method
Difference in Composite Clinical Score From Inclusion to Six Months After Ended Treatment	Six months after end of 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.