Effects of Doxycycline on Persistent Symptoms Post-neuroborreliosis

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

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.

Study Overview

• Status: Completed
• Conditions: Fatigue; Paresis; Cognitive Dysfunction; Paresthesia; Radicular Pain
• Intervention / Treatment: Drug: Doxycycline; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Östergötland
    • Linköping, Östergötland, Sweden, 58185
      • Clinic for Infectious Diseases, University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Doxycycline; Treatment with Capsule Doxycycline 200 mg, once daily, for 21 days.	Drug: Doxycycline; Doxycycline, 100 mg, 2 capsules once daily, 24 hour time interval, 21 days.; Other Names: Vibramycin; Tetracycline; Doxyferm
Placebo Comparator: Sugar pill; Capsule Placebo, 200 mg, once daily, for 21 days.	Drug: Placebo; Placebo, 100 mg, 2 capsules once daily, 24 hour dosage interval, 21 days.; Other Names: Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Improvement in persistent symptoms	12 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Linkoeping University
• Investigators: Principal Investigator: Pia Forsberg, MD, Department of Infectious Diseases, Faculty of Health Sciences, Linköping university, Sweden

Publications and helpful links

General Publications

• Sjowall J, Ledel A, Ernerudh J, Ekerfelt C, Forsberg P. Doxycycline-mediated effects on persistent symptoms and systemic cytokine responses post-neuroborreliosis: a randomized, prospective, cross-over study. BMC Infect Dis. 2012 Aug 10;12:186. doi: 10.1186/1471-2334-12-186.

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: September 17, 2010
• First Submitted That Met QC Criteria: September 17, 2010
• First Posted (Estimate): September 20, 2010

Study Record Updates

• Last Update Posted (Estimate): September 20, 2010
• Last Update Submitted That Met QC Criteria: September 17, 2010
• Last Verified: February 1, 2005

More Information

Terms related to this study

• Keywords: Placebo; Doxycycline; Neuroborreliosis; Persistent symptoms
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurocognitive Disorders; Cognition Disorders; Sensation Disorders; Somatosensory Disorders; Cognitive Dysfunction; Paresis; Paresthesia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline; Tetracycline
• Other Study ID Numbers: 151:2004/25331