Doxycycline Boosted Therapy in Lyme Borreliosis: DoBo Study. (DoBo)

A Monocenter, Randomized, Double Blind Pilot Study Comparing Doxycycline in Combination With Hydroxychloroquine Treatment Versus Doxycycline Monotherapy in Patients With Long-Term Complaints Attributed to Lyme Borreliosis.

The goal of this clinical trial is to learn if hydroxychloroquine works to treat long-term complaints attributed to Lyme borreliosis in adults. The main questions it aims to answer are:

Does addition of hydroxychloroquine reduce physical complaints? Researchers will compare hydroxychloroquine to a placebo (a look-alike substance that contains no drug) to see if hydroxychloroquine works to treat Lyme borreliosis.

Participants will:

Take hydroxychloroquine or a placebo two times a day during 28 days. Visit the clinic 4 times in one year for checkups and tests.

Study Overview

• Status: Not yet recruiting
• Conditions: Lyme Borreliosis, Nervous System
• Intervention / Treatment: Drug: Hydroxychloroquin; Drug: Doxycycline; Drug: Placebo

Detailed Description

Rationale Assess other strategies for Lyme patients with vexing symptoms.

Objective Provide initial insights as to whether addition of hydroxychloroquine results in reduction of physical complaints and assessing safety and tolerability of hydroxychloroquine in these patients.

Main trial endpoints The primary endpoint is health-related quality of life, as measured by the global score of the 36-item Short-form General Health Survey (SF-36) at EOT (week 4).

Secondary trial endpoints Secondary endpoints are improvement on subscales of SF-36 (pain and physical function) at week 4, safety at week 4 and 12 and global physical health composite score of the 36-item Short-form General Health Survey (SF-36) at week 52. Of note, there are no biochemical or microbiological test available to assess cure.

Trial design This is a monocentre, randomized, double blind pilot study. Treatment last one month, with a follow up at week 52. In total the subject are participating for one year.

Trial population Patients with possible persisting B. burgdorferi s.l. infection or probable or possible post Lyme treatment Lyme borreliosis syndrome (PTLBS) will be recruited. Patients who will start antibiotic treatment can be included.

Interventions The intervention group will be treated with 28 days Doxycycline 2 x 100 mg (standard of care) combined with hydroxychloroquine 2 x 200 mg (two time a day one tablet). The control arm receives 28 days Doxycycline 2 x 100 mg (standard of care) combined with placebo 2 x 1 tablet.

Ethical considerations relating to the clinical trial including the expected benefit to the individual subject or group of patients represented by the trial subjects as well as the nature and extent of burden and risks The combination of doxycycline en hydroxychloroquine is based on expected synergy and probably enhancement of effective therapy. Its combination has been used for years in malaria and Q-fever. Its pro- and con's are well known.

The use of doxycycline and hydroxychloroquine is not associated with increased health risk.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hadewych ter Hofstede, Dr.; Phone Number: +3124361819; Email: hadewych.terhofstede@radboudumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who are 18 years of age or older
• Patients with probable or possible signs and symptoms attributed to Lyme borreliosis
• Patients with probable or possible post Lyme treatment Lyme borreliosis syndrome (PTLBS)
• Males or non-pregnant females (who must agree to use barrier methods of contraception during the study therapy period, women of childbearing age must have a negative urine pregnancy or serum test at baseline).

Exclusion Criteria:

• Known contra-indication for used study medication.
• Women who are pregnant or lactating

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
Experimental: Doxycycline in combination with Hydroxychloroquine; Doxycycline (standard of care) in combination with Hydroxychloroquine 2 x 200 mg (two times a day one tablet).	Drug: Hydroxychloroquin; Added to the standard of care for Lyme Disease; Other Names: Plaquenil; Drug: Doxycycline; Standard of care
Placebo Comparator: Doxycycline in combination with placebo; Doxycycline (standard of care) in combination with Placebo (two times a day one tablet).	Drug: Doxycycline; Standard of care; Drug: Placebo; Standard of care in combination with placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-related quality of life.	Global physical health composite score of the 36-item Short-form General Health Survey (SF-36). Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100. Higher scores indicating better health and lower scores indicating worse health or disability	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of the study medication	ATL (U/L), creat (μmol/L) and adverse events	Week 4 and week 12
Tolerability of the study medication	Improvement on subscales of SF-36 questionnaire (Pain and physical function). Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100. higher scores indicating better health and lower scores indicating worse health or disability.	Week 4 and week 12
Health-related quality of life	Global physical health composite score of the 36-item Short-form General Health Survey (SF-36). Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100. Higher scores indicating better health and lower scores indicating worse health or disability	Week 52

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Ministerie van Volksgezondheid, Welzijn en Sport
• Investigators: Principal Investigator: Hadewych Ter Hofstede, Dr., Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: September 17, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 17, 2025

Study Record Updates

• Last Update Posted (Actual): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Hydroxychloroquine
• Additional Relevant MeSH Terms: Vector Borne Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Borrelia Infections; Spirochaetales Infections; Tick-Borne Diseases; Central Nervous System Infections; Central Nervous System Bacterial Infections; Lyme Disease; Lyme Neuroborreliosis; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Naphthacenes; Tetracyclines; Quinolines; Aminoquinolines; Chloroquine; Hydroxychloroquine; Doxycycline
• Other Study ID Numbers: DoBo; 2025-523078-18-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No