Effects of Doxycycline on Persistent Symptoms Post-neuroborreliosis

Study Overview
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Brief Summary
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The aim of this randomised, double-blind crossover study was to determine whether Doxycycline has an impact on the persistent symptoms post-neuroborreliosis, through alterations in the immune response and whether such an effect could influence the clinical outcome.

Detailed Description
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Persistent symptoms after treatment of neuroborreliosis (NB) are not uncommon. There is currently no evidence for improvement of symptoms after repeated or prolonged antibiotic treatment. However, clinical observations have indicated that some patients improve during treatment with doxycycline (DOX), but regain the symptoms some time after completed treatment. This may be due to an immunomodulatory effect of the drug. The aim of this randomised, double-blind crossover study was to determine whether DOX has an impact on the persistent symptoms through alterations in the immune response and whether such an effect can influence the clinical outcome. A total of 15 patients from South-East Sweden with previously adequately diagnosed NB with diverse persistent symptoms ≥6months after antibiotic treatment were randomised in a double-blind, crossover fashion to receive either DOX 200 mg or placebo (PBO) once daily for three weeks, followed by a wash-out period of six weeks and a further three-weeks treatment with either DOX 200 mg or PBO once daily for three weeks. The primary outcome measures were improvement of the persistent symptoms and physical and mental health, evaluated using the visual analogue scale (VAS), the 36-item Short-Form General Health Survey (SF-36) and through physical examination with special emphasis on neurologic status at the follow-up visits. Secondary outcome measures were changes in drug-induced antigen-stimulated and unstimulated cytokine responses.

Official Title
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Immunomodulatory and Clinical Effects of Doxycycline on Persistent Symptoms After Treatment of Neuroborreliosis: A Double-blind, Randomised, Crossover Study

Conditions
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Fatigue, Radicular Pain, Cognitive Dysfunction, Paresthesia, Paresis

Intervention / Treatment
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* Drug: Doxycycline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a history of adequately diagnosed and treated neuroborreliosis (presence of intrathecal borrelia-antibody production) persistence of symptoms (with debut in conjunction with neuroborreliosis) of typical character, such as headache, radiculitis, cognitive dysfunction, fatigue, mood disorders, paresthesia or paresis > 6 months post-treatment of neuroborreliosis Exclusion Criteria: systemic immunosuppression (treatment with corticosteroids, cytostatics etc) ongoing infection at inclusion allergy against doxycycline pregnancy breast feeding psychiatric disease multiple sclerosis rheumatoid arthritis diabetes mellitus type 1 or II inflammatory systemic diseases liver ohc kidney dysfunction treatment with didanosine, quinapril, antacids malignancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Doxycycline<br>Treatment with Capsule Doxycycline 200 mg, once daily, for 21 days. | Drug: Doxycycline<br>* Doxycycline, 100 mg, 2 capsules once daily, 24 hour time interval, 21 days.<br>* Other names: Tetracycline;|
| Placebo Comparator: Sugar pill<br>Capsule Placebo, 200 mg, once daily, for 21 days. | Drug: Placebo<br>* Placebo, 100 mg, 2 capsules once daily, 24 hour dosage interval, 21 days.<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in persistent symptoms |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in cytokine levels in plasma/serum in patients during treatment with DOX/PBO |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Persistent symptoms, Doxycycline, Placebo, Neuroborreliosis