Clinical trial NCT04271397: Immunological Biomarkers in Tuberculosis Management
Official title: Optimization of Tuberculosis Diagnosis and Management Using Four Immunological Biomarkers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tuberculosis
Tuberculosis Infection
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2020-02-17
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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

Primary outcomes:
measure: Concordance of the kinetics of biomarkers with the evolution of the disease
timeFrame: 6 months
Secondary outcomes:
measure: Analytical characteristics of a combination of 2 IGRAs (QuantiFERON-TB Gold Plus (QFT-P) and HBHA) in the diagnosis / prognosis of tuberculosis disease.
timeFrame: 6 months
measure: 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.
timeFrame: 6 months
measure: Evaluate the performance of a test based on the interpretation of a transcriptomic signature in plasma in the diagnosis / prognosis of TB.
timeFrame: 6 months
measure: Assess the performance of a test based on the interpretation of a protein signature in the diagnosis / prognosis of tuberculosis.
timeFrame: 6 months
measure: Determine the achievement of target concentrations of rifampicin
timeFrame: 6 months
measure: Establish the rate of metabolic self-induction of rifampicin
timeFrame: 6 months
Other outcomes:
Locations:
city: Lyon
country: France
facility: Service des Maladies Infectieuses - Hôpital de la Croix Rousse - Hospices Civils de Lyon
Study officials:
References:
citation: Bahuaud O, Genestet C, Hoffmann J, Dumitrescu O, Ader F. Opti-4TB: A protocol for a prospective cohort study evaluating the performance of new biomarkers for active tuberculosis outcome prediction. Front Med (Lausanne). 2022 Sep 14;9:998972. doi: 10.3389/fmed.2022.998972. eCollection 2022.