Immunological Biomarkers in Tuberculosis Management
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorHospices Civils de Lyon
About this trial
Tuberculosis (TB) is the leading cause of death by infectious disease in the world, responsible for 1.6 million deaths in 2017. The treatment of active TB requires at least a 6-month combined antibiotic regimen and can cause heavy side effects. As a consequence, treatment adherence is not optimal, particularly in primary care settings. Rapid and reliable monitoring of anti-TB treatment adherence and efficacy is critical to provide adequate patient care and curb relapse episodes and acquired drug resistance.
Investigators propose to evaluate the performance in terms of diagnosis accuracy and outcome prediction of four new biomarkers of active TB: 1) a double IGRA (Interferon Gamma Release Assay) including QuantiFERON-Gold Plus® and HBHA; 2) a whole blood transcriptomic analysis of mRNA (messenger Ribonucleic acid) expression of a panel of 150 genes; 3) a whole blood proteomic analysis; 4) an ex vivo immunophenotyping using flow and mass cytometry to characterize the lymphocyte populations.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients having given written consent
Patients accepting a follow up ≥ 6 months
Proven active tuberculosis (positive direct examination and/or PCR)
Latent tuberculosis infection assessed by positive IGRA
Disqualifiers
Malignant solid tumor
Malignant hemopathy
Solid organ transplantation or hematopoietic stem cell transplantation
Immunosuppressive treatments (i.e. biologics, calcineurin inhibitors, corticosteroids)
Trial design
Design model
Parallel
Treatments tested in this trial
Multiple blood samples
Other interventionPatients with active tuberculosis will have 5 research-specific blood samples: V1, (baseline) immediately before initiating anti-tuberculosis treatment, then 4 samples during anti-tuberculosis treatment and follow-up, i.e. at 48 hours (V2), 15 days (V3), 2 months (V4) and 6 months (V5) after initiation of treatment. The total volume of each sample will be 20 mL for a total of 100 mL.
Single blood sample
Other interventionPatients with Latent tuberculosis infection will have a single specific sample of 14 mL.
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: Active tuberculosisOther 1 intervention
Group B: Latent tuberculosis infectionOther 1 intervention
Trial outcomes
Primary outcomes
1
Concordance of the kinetics of biomarkers with the evolution of the disease
It is a composite outcome. Evolution of the disease is defined by clinical status, radiological computed tomography evolution and negation of the mycobacterial culture of routine respiratory samples. The biomarkers assessed are: 1\) a combination of IGRAs test (QuantiFERON-Gold Plus and HBHA); 2) a transcriptomic signature; 3) a protein signature; 4) a phenotypic signature (by implementing an immunomonitoring approach).
Time frame
6 monthsSecondary outcomes
1
Analytical characteristics of a combination of 2 IGRAs (QuantiFERON-TB Gold Plus (QFT-P) and HBHA) in the diagnosis / prognosis of tuberculosis disease.
Measurement of gamma interferon responses induced by different conditions of ex-vivo stimulation of the blood sample by specific Mtb peptides. This biomarker will be confronted with the evolution of the evolution of the disease as defined in the primary outcome measure.
Time frame
6 months2
Performance of an immunomonitoring test by mass or flow cytometry in the diagnosis / prognosis of tuberculosis by measuring the dynamics of the blood population of T lymphocytes over time.
Qualitative and quantitative monitoring of the different subpopulations of immune cells (CD4 + T cells, CD8 +(cluster of differentiation 8) T cells, MAIT, Th1, Th2, Th1, Tfh, Treg, naive, effector and memory cells) during anti-tuberculosis treatment will be carried out. The analytical characteristics (sensitivity, specificity, VPN and VPP) of this immunomonitoring tool will be determined by comparing the abundance of different cellular phenotypes with the evolution of the disease as defined in the primary outcome measure.
Time frame
6 months3
Evaluate the performance of a test based on the interpretation of a transcriptomic signature in plasma in the diagnosis / prognosis of TB.
A transcriptomic signature in plasma is a set of genes involved in the immune response specifically deregulated during the different stages of infection and disease progression. This assessment will be made from blood samples. The transcriptomic signature composed of 16 genes will be evaluated during the anti-tuberculosis treatment and confronted with the evolution of the disease as defined in the primary outcome measure.
Time frame
6 months4
Assess the performance of a test based on the interpretation of a protein signature in the diagnosis / prognosis of tuberculosis.
A protein signature is composed of cytokines and chemokines, also deregulated during the various stages of infection and progression of the disease. This assessment will be made from blood samples. The protein signature composed of cytokines / chemokines of interest (ie IP-10, TNF-a (tumor necrosis factor - a), IL-1(interleukin - 1), IL-18, IL-12, CCL4, IL-2, IFN-g (interferon - g),…) will be evaluated during the anti-tuberculosis treatment and confronted with the evolution of the disease as defined in the primary outcome measure.
Time frame
6 monthsSponsors and contacts
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Source ClinicalTrials.gov