Neuroborreliosis, Borrelia Burgdorferi
Conditions
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.
Interventions
DRUGDoxycycline
DRUGPlacebo
Sponsors
Sorlandet Hospital HF
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Doxycycline for 6 Weeks Doxycycline 200 mg once daily for six weeks
Doxycycline | 61 |
| Doxycycline for 2 Weeks + Placebo Doxycycline 200 mg once daily for two weeks + placebo for four weeks.
Doxycycline
Placebo | 60 |
| Total | 121 |
Baseline characteristics
| Characteristic | Doxycycline for 6 Weeks | Doxycycline for 2 Weeks + Placebo | Total |
|---|---|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 15 | 58 years STANDARD_DEVIATION 12 | 56 years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 61 Participants | 60 Participants | 121 Participants |
| Region of Enrollment Norway | 61 Participants | 60 Participants | 121 Participants |
| Sex: Female, Male Female | 29 Participants | 25 Participants | 54 Participants |
| Sex: Female, Male Male | 32 Participants | 35 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 61 | 0 / 60 |
| other Total, other adverse events | 0 / 61 | 0 / 60 |
| serious Total, serious adverse events | 0 / 61 | 0 / 60 |
Outcome results
Primary
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.
Time frame: Six months after end of treatment.
Population: Intention to treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Doxycycline for 6 Weeks | Difference in Composite Clinical Score From Inclusion to Six Months After Ended Treatment | 6.4 units on a scale |
| Doxycycline for 2 Weeks + Placebo | Difference in Composite Clinical Score From Inclusion to Six Months After Ended Treatment | 6.4 units on a scale |