Optimization of Tuberculosis Diagnosis and Management Using Four Immunological Biomarkers
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Hospices Civils de Lyon
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Concordance of the kinetics of biomarkers with the evolution of the disease
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adult ≥ 18 year-old
- •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
Exclusion Criteria
- •Malignant solid tumor
- •Malignant hemopathy
- •Solid organ transplantation or hematopoietic stem cell transplantation
- •Immunosuppressive treatments (i.e. biologics, calcineurin inhibitors, corticosteroids)
- •Auto-inflammatory disease
- •Chronic liver diseases
- •Chronic infection with HIV, HCV (hepatitis C virus) or HBV (hepatitis B virus)
- •Antimycobacterial treatment initiated > 7 days
- •Pregnancy or breastfeeding
- •Refusal to participate to the study
- •Persons deprived of their liberty by judicial or administrative decision
- •Protected adults
- •Patients not affiliated to health-care social security
- •The homeless
Arms & Interventions
Latent tuberculosis infection
Intervention: Single blood sample (Other)
Active tuberculosis
Intervention: Multiple blood samples (Other)
Outcomes
Primary Outcomes
Concordance of the kinetics of biomarkers with the evolution of the disease
Time Frame: 6 months
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).
Secondary Outcomes
- Assess the performance of a test based on the interpretation of a protein signature in the diagnosis / prognosis of tuberculosis.(6 months)
- Analytical characteristics of a combination of 2 IGRAs (QuantiFERON-TB Gold Plus (QFT-P) and HBHA) in the diagnosis / prognosis of tuberculosis disease.(6 months)
- Determine the achievement of target concentrations of rifampicin(6 months)
- 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.(6 months)
- Evaluate the performance of a test based on the interpretation of a transcriptomic signature in plasma in the diagnosis / prognosis of TB.(6 months)
- Establish the rate of metabolic self-induction of rifampicin(6 months)