TuberculosisCITRUSNCT03044509
Diagnosis of Tuberculosis in Swiss Children
An observational study of Tuberculosis and Mycobacterium Tuberculosis, run by University Children's Hospital Basel at 8 sites in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Tuberculosis, Mycobacterium Tuberculosis
- What is being tested?
- Secreted cytokine assay and Intracellular cytokine assay
- How many people
- 190 participants
- Where
- 8 sitesSwitzerland
- Study dates
- 12 May 2017to Dec 2028
- How long will I take part?
- 2 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 17 years
- All sexes
- No healthy volunteers
- Child
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.
Who may be able to join
- all children / adolescents < 18 years of age undergoing evaluation for TB exposure, infection or disease.
Who cannot join
- children / adolescents with TB infection or disease who have already been started on anti-mycobacterial treatment, children who have been treated for TB previously.
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Switzerland8 sites, 8 recruiting
- Recruiting
Kantonspital Aarau
Aarau, 5001
Florence Barbey, Dr med, +41628384192, florence.barbey@ksa.ch
- Recruiting
Nina Vaezipour
Basel, 4056
Nina Vaezipour, Dr med, +41617042947, nina.vaezipour@ukbb.ch
Nicole Ritz, PD Dr med
- Recruiting
Ospedale Regionale di Bellinzona
Bellinzona, 6500
Lisa Kottanattu, Dr med, +41918118538, lisa.kottanattu@eoc.ch
- Recruiting
Inselspital Bern
Bern, 3010
Andrea Duppenthaler, Dr. med., +41316329414, andrea.duppenthaler@insel.ch
- Recruiting
Hôpital des enfants - HUG
Geneva, 1205
Anne Mornand, Dr. med., +41223724579, anne.mornand@hcuge.ch
Marie Rohr, Dr. med.
- Recruiting
Kinserspital Luzern
Lucerne, 6016
Michael Buettcher, Dr med, +41412056657, michael.buettcher@luks.ch
- Recruiting
Kinderspital St Gallen
Sankt Gallen, 9006
Jürg Barben, Prof Dr med, +41712437111, juerg.barben@kispisg.ch
Christian Kahlert, Dr med
- Recruiting
Kinderklinik Zürich
Zurich, 8032
Christoph Berger, Prof Dr med, +41442667840, christoph.berger@kispi.uzh.ch
Christa Relly, Dr med
About this study
Official title: Evaluation and Validation of Novel Immunodiagnostic Tests for Childhood Tuberculosis Infection and Disease in Switzerland. The CITRUS (ChIldhood TubeRcUlosis in Switzerland) Study.
- The primary objective is to improve the sensitivity of novel immunodiagnostic tests for detection of TB disease in children.
- The secondary objective is to determine biomarkers that discriminate children with TB infection and disease.
Read the detailed description
- 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
- 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
- Tuberculosis, Mycobacterium Tuberculosis
- Being tested
- Secreted cytokine assay, Intracellular cytokine assay
- Keywords
- Immunodiagnostics tests, TB exposure, Latent TB, TB disease, Biomarkers, Metabolomics, NMR
- Medical subject headings
- Tuberculosis, Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Secreted cytokine assayDiagnostic 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 assayDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| TB exposure | Not described Receives: Diagnostic Test: Secreted cytokine assay; Diagnostic Test: Intracellular cytokine assay | |
| TB infection (latent TB) | Not described Receives: Diagnostic Test: Secreted cytokine assay; Diagnostic Test: Intracellular cytokine assay | |
| TB disease (active TB) | Not described Receives: Diagnostic Test: Secreted cytokine assay; Diagnostic Test: Intracellular cytokine assay |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement of immunodiagnostic tests for TB in children.
Based on current evidence it is estimated that the sensitivity of the immunodiagnostic tests with regard to the identification of patients with TB infection or disease versus no TB is approximately 80 %. By applying a sample size approximation a minimum sample size of 126 patients with TB infection or disease (with a precision given by a 95 % confidence interval with a width of 20 %) will be needed to statistically show a significant result.
Measured: 27 months
Secondary outcomes (1)
Indicative markers identification for TB infection and disease distinction
A minimum sample size of 84 patients with TB infection is needed (with a precision given by a 95 % confidence interval with a width of 30 %). Among patients with TB infection or TB disease, a novel test is used to discriminate between these patient groups. It is estimated that the sensitivity of this test with regard to the identification of patients with TB infection (secondary outcome) is approximately 60 %.
Measured: 27 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2017 (estimated)
- Study start12 May 2017
- Primary completionDec 2026 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 190 participants (estimated)
- Target duration
- 2 Months
Sponsor and investigators
- Lead sponsor
- University Children's Hospital Basel
- Sponsor type
- University, hospital or other
- Collaborators
- Ospedale Regionale Bellinzona e Valli, Insel Gruppe AG, University Hospital Bern, University of Lausanne Hospitals, University Hospital, Geneva, Luzerner Kantonsspital, Cantonal Hospital of St. Gallen, University Children's Hospital, Zurich, Kantonsspital Aarau
- Responsible party
- Principal investigator, Dr. Nicole Ritz, MD/PhD, University Children's Hospital Basel
- Investigators
- Nicole Ritz, Prof Dr med, Principal investigator, UKBB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03044509
- Sponsor's protocol ID
- CITRUS
- Acronym
- CITRUS
- Status last verified
- Sep 2024
- First submitted
- 3 Feb 2017
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 38730343
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation and Validation of Novel Immunodiagnostic Tests for Childhood Tuberculosis Infection and Disease in Switzerland. The CITRUS (ChIldhood TubeRcUlosis in Switzerland) Study.
- ClinicalTrials.gov ID
- NCT03044509
- Acronym / sponsor ID
- CITRUS / CITRUS
- Conditions
- Tuberculosis, Mycobacterium Tuberculosis
- Keywords
- Immunodiagnostics tests, TB exposure, Latent TB, TB disease, Biomarkers, Metabolomics, NMR
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 190 participants (estimated)
- Lead sponsor
- University Children's Hospital BaselUniversity, hospital or other
- Collaborators
- Ospedale Regionale Bellinzona e Valli, Insel Gruppe AG, University Hospital Bern, University of Lausanne Hospitals, University Hospital, Geneva, Luzerner Kantonsspital, Cantonal Hospital of St. Gallen, University Children's Hospital, Zurich, Kantonsspital Aarau
- Study start
- 12 May 2017 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 7 Feb 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- The primary objective is to improve the sensitivity of novel immunodiagnostic tests for detection of TB disease in children.
- The secondary objective is to determine biomarkers that discriminate children with TB infection and disease.
Detailed description
- 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
- 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
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Months
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| TB exposure | – | Diagnostic Test: Secreted cytokine assay, Diagnostic Test: Intracellular cytokine assay |
| TB infection (latent TB) | – | Diagnostic Test: Secreted cytokine assay, Diagnostic Test: Intracellular cytokine assay |
| TB disease (active TB) | – | Diagnostic Test: Secreted cytokine assay, Diagnostic Test: Intracellular cytokine assay |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- 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.
Key inclusion criteria (1 listed)
- all children / adolescents < 18 years of age undergoing evaluation for TB exposure, infection or disease.
Key exclusion criteria (1 listed)
- children / adolescents with TB infection or disease who have already been started on anti-mycobacterial treatment, children who have been treated for TB previously.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Secreted cytokine assayBlood 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). | Diagnostic test | TB disease (active TB), TB exposure, TB infection (latent TB) |
| Intracellular cytokine assayBlood 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. | Diagnostic test | TB disease (active TB), TB exposure, TB infection (latent TB) |
Primary outcome
Improvement of immunodiagnostic tests for TB in children.
Time frame: 27 months
Based on current evidence it is estimated that the sensitivity of the immunodiagnostic tests with regard to the identification of patients with TB infection or disease versus no TB is approximately 80 %. By applying a sample size approximation a minimum sample size of 126 patients with TB infection or disease (with a precision given by a 95 % confidence interval with a width of 20 %) will be needed to statistically show a significant result.
1 secondary outcome
Indicative markers identification for TB infection and disease distinction
Time frame: 27 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Derived from this study: PubMed 38730343Neudecker 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nicole Ritz, Prof Dr med principal investigator
UKBB
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis and Mycobacterium Tuberculosis, run by University Children's Hospital Basel at 8 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nina Vaezipour, Dr med (+41617042947, nina.vaezipour@ukbb.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement of immunodiagnostic tests for TB in children. (time frame: 27 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03044509, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.