Borrelia B-cell Diagnostics (BRILLIANT)

April 27, 2026 updated by: University Children's Hospital, Zurich

Extensive Investigation of Immune Responses Against Borrelia Burgdorferi to Improve Diagnosis of Lyme Disease in Children: an Observational Study (BRILLIANT Study)

The investigators propose a single center, prospective observational study in children with Lyme disease (LD), the Borrelia B-cell diagnostics (BRILLIANT) study, to assess the immune response against Borrelia burgdorferi (Bb) with the following main objectives:

  1. Development of Bb-specific ASC ELISpot as a new test method for diagnosis of early LD.

    There is an urgent unmet clinical need for a better diagnostic tool for early LD, as the current standard two-tier testing has low sensitivity in recently infected patients and may show false positive results in recovered patients due to long-term persistence of antibodies against Bb. The measurement of Bb-specific ASC with the ELISpot assay my has the potential to overcome these issues and to improve diagnosis in early LD.

  2. Extensive analysis of the immune response in LD. The immune response in LD is not well understood. Large-scale studies assessing the detailed immune cell subsets/phenotypes present in blood, CSF, or synovial fluid of LD patients with respective manifestations are lacking.
  3. Isolation and characterization of causative Bb species. Existing literature suggests that Bb genospecies and/or genotypes may determine virulence and manifestations, but large-scale studies assessing Bb genospecies/genotypes in different manifestation of LD are lacking.
  4. Collection of clinical data about symptoms, severity, routine laboratory and diagnostic test results, treatment, and outcome of LD.
  5. Biobanking samples for analysis in the future.

Project population

Inclusion criteria: Children, 0-17 years of age, at University Children's Hospital Zurich:

  • LD differential diagnosis cohort: Patients presenting at the ED with differential diagnosis of LD according to the treating physician.
  • Control cohort: Previously healthy patients (HC) with routine blood investigations presenting at the ED or PID outpatient department

Exclusion criteria: Primary or secondary immunodeficiency.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Background:

Lyme disease (LD) is the most common tick born disease in Europe. It is caused by an infection with several genospecies of the spirochaetal bacteria Borrelia burgdorferi (Bb).

Although classical disease manifestations are well-known, the clinical presentation in children is often variable and inconclusive, which results in delayed diagnosis and treatment.

Methods/design:

The investigators are conducting an observational cohort study in children with LD. Study site is the University Children's Hospital Zurich. 502 patients will be enrolled. Children from 0-17 years of age presenting with signs and symptoms suspicious for LD are included in the study. Previously healthy children with routine blood investigation are enrolled as healthy controls. Patients will be excluded in cases of primary or secondary immunodeficiency.

Clinical and routine laboratory data regarding course and outcome, as well as venous blood samples are collected at first hospital contact and follow up visits (FUP). FUPs are scheduled at 28 days, 3 months and 6 months after hospital admission. Cerebrospinal fluid (CSF) and synovial fluid (SF) will be collected for the study only if sampling is indicated due to diagnostic or therapeutic reasons.

Primary objectives are to assess Bb-specific ASCs in blood using ELISpot assay, in order to develop new diagnostic tool for early LD. In addition, the investigators will examine immune response in patients with various LD manifestations using flow cytometry, ELISA assay, and ELISpot assay. Finally, the investigators will perform whole genome sequencing of causative Bb-species isolated from patients to investigate potential differences in virulence and associations with clinical presentations.

Discussion:

This single-centre, observational cohort study will improve the understanding of immunological response in LD in children. It will also provide new information about the virulence of distinct LD causing Bb-genospecies and will test a new approach in the diagnosis of early LD.

Study Type

Observational

Enrollment (Estimated)

502

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Children from 0-17 years of age presenting with signs and symptoms suspicious for LD are included in the study. Previously healthy children with routine blood investigation are enrolled as healthy controls.

Description

Inclusion Criteria:

  • Patients presenting at the ED with differential diagnosis of LD according to the treating physician

Exclusion Criteria:

  • Patients will be excluded in cases of primary or secondary immunodeficiency

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
LD_Diff_Diag
LD differential diagnosis cohort: Patients presenting at the ED with differential diagnosis of LD according to the treating physician
Procedure: venous blood puncture

Venous blood puncture performed at first hospital contact, and at 28 days, 3 month, and 6 months after hospital admission.

Lumbar puncture and joint puncture for the study will be performed if it is indicated due to diagnostic or therapeutic reasons.

Other Names:
  • lumbar puncture
  • joint puncture
Heathy_Control
Previously healthy patients (HC) with routine blood investigations presenting at the ED or PID outpatient department
Procedure: venous blood puncture

Venous blood puncture performed at first hospital contact, and at 28 days, 3 month, and 6 months after hospital admission.

Lumbar puncture and joint puncture for the study will be performed if it is indicated due to diagnostic or therapeutic reasons.

Other Names:
  • lumbar puncture
  • joint puncture

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Bb-specific ASCs per 10^6 PBMCs
Time Frame: 10/2023 - 10/2026

Method:

Quantification of Bb-specific ASCs (IgM, IgG, IgA) per 10^6 PBMCs using ELISpot assay

Time: 0 d (hospital admission), (1-14 d), 28 d, 3 m, and 6 m (after hospital admission)
10/2023 - 10/2026

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of percentage and median fluorescence intensity (MFI) of immune cell subsets in blood, CSF and SF
Time Frame: 10/2023 - 10/2028

Method:

Measuring percentage and MFI of innate and adaptive immune cell subsets using established panels for flow cytometry

  • innate immune cells: DC, GC, Nk-cells
  • adaptive immune cells: Tc-cells and Th-cell subsets (Th1, Th2, Th17, Treg), B-cells

Time: 0 d (hospital admission), (1-14 d), 28 d, 3 m, and 6 m (after hospital admission)
10/2023 - 10/2028
Concentration of serum antibody levels (IU/mL)
Time Frame: 10/2023 - 10/2028

Method:

Measuring total serum IgM, IgG, IgA antibody levels using Enzyme-linked immunosorbant assay (ELISA)

Time: 0 d (hospital admission), (1-14 d), 28 d, 3 m, and 6 m (after hospital admission)
10/2023 - 10/2028
Number of Bb-specific T cells per 10^6 PBMCs
Time Frame: 10/2023 - 10/2028

Method:

Quantification of Bb-specific INF-gamma-secreting T cells per 10^6 PBMCs using INF-gamma ELISpot assay.

Time: 0 d (hospital admission), (1-14 d), 28 d, 3 m, and 6 m (after hospital admission)
10/2023 - 10/2028
Concentration of plasma and CSF cytokine/chemokine levels (pg/mL)
Time Frame: 10/2023 - 10/2028

Method:

Analysis of plasma and CSF cytokine/chemokine profiles using Multiplex Bead Array Kits

  • pro-inflammatory cytokines: interferon gamma (IFN-γ), Tumor necrosis factor A (TNF-α), IL-1, IL-17, IL-6 and IL-8
  • anti-inflammatory cytokines: IL-10 and IL-13
  • chemokines: Stromal cell-derived factor 1 (CXCL12), B cell-attracting chemokine 1 (CXCL13), IFN-γ inducible protein (IP-10/CXCL-10)

Time: 0 d (hospital admission), (1-14 d), 28 d, 3 m, and 6 m (after hospital admission)
10/2023 - 10/2028
Portion of Bb positive LD patients by culture/PCR, identification of Bb species in LD patients
Time Frame: 10/2023 - 10/2028

Method:

Bb culture and PCR out of blood, CSF and SF samples

Identification of Bb genospecies using PCR and whole genome sequencing (WGS)

- Expected Bb genospecies: Bb sensu stricto, B. garinii, B. afzelii, B. spielmanii, B. mayonii

Time: 0 d (hospital admission), (1-14 d), 28 d, 3 m, and 6 m (after hospital admission)
10/2023 - 10/2028

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Children's Hospital, Zurich

Collaborators

University of Zurich

Investigators

  • Principal Investigator: Patrick M Meyer Sauteur, MD PhD, Division of infectious diseases Univesity Children's Hospital Zurich
  • Study Director: Christoph Berger, MD, Division of infectious diseases Univesity Children's Hospital Zurich

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 2, 2024

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

November 1, 2028

Study Registration Dates

First Submitted

September 13, 2023

First Submitted That Met QC Criteria

September 13, 2023

First Posted (Actual)

September 21, 2023

Study Record Updates

Last Update Posted (Actual)

April 28, 2026

Last Update Submitted That Met QC Criteria

April 27, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-00528

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be handled with uttermost discretion and is only accessible to authorized personnel who require the data to fulfil their duties within the scope of the research. On the CRFs and other project specific documents, participants are only identified by a unique participant number. Biological material will be stored in coded manner with unique participant numbers in restricted areas at the Children's Research Center and the IMM. Collaborators will not be granted access to the key or any personal patient information.

IPD Sharing Time Frame

Project data are stored for at least 15 years. Biological data will be collected for 5 years with a start in 2023 until 2028 and destroyed after 10 years of study closure.

IPD Sharing Access Criteria

Access is authorized to personnel who require the data to fulfil their duties within the scope of the research.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe