Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06045416
Other study ID # 2023-00528
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date April 2, 2024
Est. completion date November 1, 2028

Study information

Verified date December 2023
Source University Children's Hospital, Zurich
Contact Patrick M Meyer Sauteur, MD PhD
Phone 0041 44 266 78 96
Email patrick.meyersauteur@kispi.uzh.ch
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical Trial Summary

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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 502
Est. completion date November 1, 2028
Est. primary completion date November 1, 2026
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 1 Month to 17 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

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.

Locations

Country Name City State
Switzerland Chidren's Hospital Zurich Zürich

Sponsors (2)

Lead Sponsor Collaborator
University Children's Hospital, Zurich Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Bb-specific ASCs per 10^6 PBMCs 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 Measurement of percentage and median fluorescence intensity (MFI) of immune cell subsets in blood, CSF and SF 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
Secondary Concentration of serum antibody levels (IU/mL) 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
Secondary Number of Bb-specific T cells per 10^6 PBMCs 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
Secondary Concentration of plasma and CSF cytokine/chemokine levels (pg/mL) Method:
Analysis of plasma and CSF cytokine/chemokine profiles using Multiplex Bead Array Kits
pro-inflammatory cytokines: interferon gamma (IFN-?), Tumor necrosis factor A (TNF-a), 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-? 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
Secondary Portion of Bb positive LD patients by culture/PCR, identification of Bb species in LD patients 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
See also
  Status Clinical Trial Phase
Completed NCT01207739 - Persistent Lyme Empiric Antibiotic Study Europe Phase 4
Terminated NCT04577053 - PEMF Therapy to Treat Lingering Symptoms of Lyme Disease After Treatment With Antibiotics N/A
Completed NCT04867473 - Feasibility of Teleyoga for Treatment of Lyme Disease N/A
Recruiting NCT04038346 - Symptomatic Management of Lyme Arthritis Phase 3
Completed NCT01143558 - Searching for Persistence of Infection in Lyme Disease Early Phase 1
Withdrawn NCT04318925 - Evaluation and Follow-up of People With Tick-borne Diseases
Terminated NCT03581279 - Detection of Borrelia Bacteria in Early Stage Lyme Borreliosis Using the T2Lyme Panel N/A
Enrolling by invitation NCT05041595 - Lyme Disease Diagnostic Assay - Collection of Whole Blood
Recruiting NCT03981874 - Peripheral Facial Paralysis Sequelae in Lyme Disease Among Children N/A
Recruiting NCT03963635 - Novel Diagnostics for Early Lyme Disease
Terminated NCT03084614 - CD8 Reactivity to Microorganisms in Blood and Breast Milk
Recruiting NCT04835792 - Biomarker Study of Previously Treated Lyme Disease Volunteers in Comparison to Healthy Volunteers
Recruiting NCT06397794 - Navigating Pregnancy and Parenthood With Lyme Disease
Recruiting NCT04148222 - A Non-Interventional Pilot Study to Explore the Role of Gut Flora in Lyme Disease
Terminated NCT03201042 - Lyme Test Indication Combinations (LyTIC) Study
Completed NCT01368341 - Comparing 3 Antibiotic Regimes for Erythema Migrans in General Practice Phase 4
Terminated NCT00958139 - Passive Prophylaxis of Lyme Disease Using Permethrin Treated Clothes Phase 3
Recruiting NCT00001539 - A Comprehensive Clinical, Microbiological and Immunological Assessment of Patients With Suspected Post Treatment Lyme Disease Syndrome and Selected Control Populations
Recruiting NCT03501407 - Understanding Tick-borne Diseases
Completed NCT04422314 - ImmuneSense Lyme Study