Clinical trial NCT03044509: Diagnosis of Tuberculosis in Swiss Children
Official title: Evaluation and Validation of Novel Immunodiagnostic Tests for Childhood Tuberculosis Infection and Disease in Switzerland. The CITRUS (ChIldhood TubeRcUlosis in Switzerland) Study.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Tuberculosis
Mycobacterium Tuberculosis
Keywords: Immunodiagnostics tests
TB exposure
Latent TB
TB disease
Biomarkers
Metabolomics
NMR
Lead sponsor: University Children's Hospital Basel
Sponsor class: OTHER
Collaborators: name: Ospedale Regionale Bellinzona e Valli
name: Insel Gruppe AG, University Hospital Bern
name: University of Lausanne Hospitals
name: University Hospital, Geneva
name: Luzerner Kantonsspital
name: Cantonal Hospital of St. Gallen
name: University Children's Hospital, Zurich
name: Kantonsspital Aarau
First posted: 2017-02-07
Enrollment: 190
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: It will be a national multicentre study in Switzerland. Children will be recruited within SwissPedNet, the Swiss Research Network of Clinical Paediatric Hubs, which includes five University Children's Hospitals (Basel, Bern, Geneva, Lausanne and Zürich) and four cantonal A-clinics (Aarau, Bellinzona, Luzern and St. Gallen). Currently approximately 20-30 children with TB disease are notified in Switzerland each year. For TB infection in children there are no data available in Switzerland. However, data from the "Lungenliga Schweiz" show that in 2014, at least 232 children were examined for a TB contact investigation (correspondence with Jean-Pierre Zellweger and Jean-Marie Egger, Lungenliga Schweiz 13.08.2015). Of these 13 % (i.e. around 30 children) are categorized as TB infection per year.

Brief summary: 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: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Improvement of immunodiagnostic tests for TB in children.
timeFrame: 27 months
Secondary outcomes:
measure: Indicative markers identification for TB infection and disease distinction
timeFrame: 27 months
Other outcomes:
Locations:
city: Aarau
country: Switzerland
facility: Kantonspital Aarau
city: Basel
country: Switzerland
facility: Nina Vaezipour
city: Bellinzona
country: Switzerland
facility: Ospedale Regionale di Bellinzona
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Genève
country: Switzerland
facility: Hôpital des enfants - HUG
city: Luzern
country: Switzerland
facility: Kinserspital Luzern
city: St. Gallen
country: Switzerland
facility: Kinderspital St Gallen
city: Zürich
country: Switzerland
facility: Kinderklinik Zürich
Study officials:
affiliation: UKBB
name: Nicole Ritz, Prof Dr med
role: PRINCIPAL_INVESTIGATOR
References: