Diagnosis of Tuberculosis in Swiss Children

NCT ID: NCT03044509

Last Updated: 2024-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

190 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-05-12

Study Completion Date

2028-12-31

Brief Summary

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1. The primary objective is to improve the sensitivity of novel immunodiagnostic tests for detection of TB disease in children.
2. The secondary objective is to determine biomarkers that discriminate children with TB infection and disease.

Detailed Description

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1. This will be done by measuring a variety of parameters in the blood samples and compare them with the current diagnostic gold standard for TB or for culture/NAAT non-confirmed TB cases a consensus case definition is used.

Currently available immunodiagnostic tests (IGRA/TST) will be compared to novel immunodiagnostic tests which will include:
* several novel, additional M. tuberculosis-specific Antigens
* cytokines that are highly expressed
2. Since there is no diagnostic gold standard for TB infection we will rely on a clinical composite reference standard for diagnosing TB infection. Biomarkers will be determined by:

* including M. tuberculosis-specific antigens that are specifically expressed in either TB infection or disease,
* measuring phenotypes and cytokine production of M. tuberculosis-specific cells.
* performing NMR Analysis with biofluids in order to identify metabolomic signatures in patients with TB disease and TB infection

Conditions

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Tuberculosis Mycobacterium Tuberculosis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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TB exposure

Secreted cytokine assay

Intervention Type DIAGNOSTIC_TEST

Blood collected in a sodium-heparin tube will be used for the assay using novel TB-specific antigens. After incubation the supernatant will be harvested and cryopreserved at -80 °C for further testing of cytokines. Cytokines will be measured using a bead-based multiplex assay reader (MAGPIX, Luminex Crop., Austin, USA).

Intracellular cytokine assay

Intervention Type DIAGNOSTIC_TEST

Blood will be stimulated with recombinant MTB-specific antigens, ESAT-6, CFP-10, positive control or left unstimulated. Following an initial duration of stimulation, Brefeldin-A will be added and the blood incubated for a further 5 hours. White cells will be fixed and cryopreserved at - 80°. Batched analysis within 6 months of cryopreservation will be done using multi-colour flow cytometry.

TB infection (latent TB)

Secreted cytokine assay

Intervention Type DIAGNOSTIC_TEST

Blood collected in a sodium-heparin tube will be used for the assay using novel TB-specific antigens. After incubation the supernatant will be harvested and cryopreserved at -80 °C for further testing of cytokines. Cytokines will be measured using a bead-based multiplex assay reader (MAGPIX, Luminex Crop., Austin, USA).

Intracellular cytokine assay

Intervention Type DIAGNOSTIC_TEST

Blood will be stimulated with recombinant MTB-specific antigens, ESAT-6, CFP-10, positive control or left unstimulated. Following an initial duration of stimulation, Brefeldin-A will be added and the blood incubated for a further 5 hours. White cells will be fixed and cryopreserved at - 80°. Batched analysis within 6 months of cryopreservation will be done using multi-colour flow cytometry.

TB disease (active TB)

Secreted cytokine assay

Intervention Type DIAGNOSTIC_TEST

Blood collected in a sodium-heparin tube will be used for the assay using novel TB-specific antigens. After incubation the supernatant will be harvested and cryopreserved at -80 °C for further testing of cytokines. Cytokines will be measured using a bead-based multiplex assay reader (MAGPIX, Luminex Crop., Austin, USA).

Intracellular cytokine assay

Intervention Type DIAGNOSTIC_TEST

Blood will be stimulated with recombinant MTB-specific antigens, ESAT-6, CFP-10, positive control or left unstimulated. Following an initial duration of stimulation, Brefeldin-A will be added and the blood incubated for a further 5 hours. White cells will be fixed and cryopreserved at - 80°. Batched analysis within 6 months of cryopreservation will be done using multi-colour flow cytometry.

Interventions

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Secreted cytokine assay

Blood collected in a sodium-heparin tube will be used for the assay using novel TB-specific antigens. After incubation the supernatant will be harvested and cryopreserved at -80 °C for further testing of cytokines. Cytokines will be measured using a bead-based multiplex assay reader (MAGPIX, Luminex Crop., Austin, USA).

Intervention Type DIAGNOSTIC_TEST

Intracellular cytokine assay

Blood will be stimulated with recombinant MTB-specific antigens, ESAT-6, CFP-10, positive control or left unstimulated. Following an initial duration of stimulation, Brefeldin-A will be added and the blood incubated for a further 5 hours. White cells will be fixed and cryopreserved at - 80°. Batched analysis within 6 months of cryopreservation will be done using multi-colour flow cytometry.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* all children / adolescents \< 18 years of age undergoing evaluation for TB exposure, infection or disease.

Exclusion Criteria

* children / adolescents with TB infection or disease who have already been started on anti-mycobacterial treatment, children who have been treated for TB previously.
Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ospedale Regionale Bellinzona e Valli

OTHER

Sponsor Role collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role collaborator

University of Lausanne Hospitals

OTHER

Sponsor Role collaborator

University Hospital, Geneva

OTHER

Sponsor Role collaborator

Luzerner Kantonsspital

OTHER

Sponsor Role collaborator

Cantonal Hospital of St. Gallen

OTHER

Sponsor Role collaborator

University Children's Hospital, Zurich

OTHER

Sponsor Role collaborator

Kantonsspital Aarau

OTHER

Sponsor Role collaborator

University Children's Hospital Basel

OTHER

Sponsor Role lead

Responsible Party

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Dr. Nicole Ritz, MD/PhD

PI

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Nicole Ritz, Prof Dr med

Role: PRINCIPAL_INVESTIGATOR

UKBB

Locations

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Kantonspital Aarau

Aarau, , Switzerland

Site Status RECRUITING

Nina Vaezipour

Basel, , Switzerland

Site Status RECRUITING

Ospedale Regionale di Bellinzona

Bellinzona, , Switzerland

Site Status RECRUITING

Inselspital Bern

Bern, , Switzerland

Site Status RECRUITING

Hôpital des enfants - HUG

Geneva, , Switzerland

Site Status RECRUITING

Kinserspital Luzern

Lucerne, , Switzerland

Site Status RECRUITING

Kinderspital St Gallen

Sankt Gallen, , Switzerland

Site Status RECRUITING

Kinderklinik Zürich

Zurich, , Switzerland

Site Status RECRUITING

Countries

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Switzerland

Central Contacts

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Nina Vaezipour, Dr med

Role: CONTACT

+41617042947

Nicole Ritz, Prof Dr med PhD

Role: CONTACT

+41617042947

Facility Contacts

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Florence Barbey, Dr med

Role: primary

+41628384192

Nina Vaezipour, Dr med

Role: primary

+41617042947

Lisa Kottanattu, Dr med

Role: primary

+41918118538

Andrea Duppenthaler, Dr. med.

Role: primary

+41316329414

Anne Mornand, Dr. med.

Role: primary

+41223724579

Michael Buettcher, Dr med

Role: primary

+41412056657

Jürg Barben, Prof Dr med

Role: primary

+41712437111

Christoph Berger, Prof Dr med

Role: primary

+41442667840

References

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Neudecker D, Fritschi N, Sutter T, Lu LL, Lu P, Tebruegge M, Santiago-Garcia B, Ritz N. Evaluation of serological assays for the diagnosis of childhood tuberculosis disease: a study protocol. BMC Infect Dis. 2024 May 10;24(1):481. doi: 10.1186/s12879-024-09359-0.

Reference Type DERIVED
PMID: 38730343 (View on PubMed)

Other Identifiers

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CITRUS

Identifier Type: -

Identifier Source: org_study_id

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