Immunological Biomarkers in Tuberculosis Management

Официальное название

Optimization of Tuberculosis Diagnosis and Management Using Four Immunological Biomarkers

Обзор

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.

Вмешательства

• Другое Multiple blood samples
  Patients 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.
• Другое Single blood sample
  Patients with Latent tuberculosis infection will have a single specific sample of 14 mL.

Первичные конечные точки

• Concordance of the kinetics of biomarkers with the evolution of the disease [Срок оценки: 6 months]

Вторичные конечные точки (6)

• Analytical characteristics of a combination of 2 IGRAs (QuantiFERON-TB Gold Plus (QFT-P) and HBHA) in the diagnosis / prognosis of tuberculosis disease. [Срок оценки: 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. [Срок оценки: 6 months]
• Evaluate the performance of a test based on the interpretation of a transcriptomic signature in plasma in the diagnosis / prognosis of TB. [Срок оценки: 6 months]
• Assess the performance of a test based on the interpretation of a protein signature in the diagnosis / prognosis of tuberculosis. [Срок оценки: 6 months]
• Determine the achievement of target concentrations of rifampicin [Срок оценки: 6 months]
• Establish the rate of metabolic self-induction of rifampicin [Срок оценки: 6 months]

Критерии участия

Критерии включения

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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Франция · 1 центр

• Service des Maladies Infectieuses - Hôpital de la Croix Rousse - Hospices Civils de Lyon — Lyon

Публикации

• Goutelle S, Bahuaud O, Genestet C, Millet A, Parant F, Dumitrescu O, Ader F; Lyon TB Study Group. Exposure to Rifampicin and its Metabolite 25-Deacetylrifampicin Rapidly Decreases During Tuberculosis Therapy. Clin Pharmacokinet. 2025 Mar;64(3):387-396. doi: 10.1007/s40262-025-01479-3. Epub 2025 Jan 27. PMID 39871048
• 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. PMID 36186786

Идентификаторы

NCT: NCT04271397 · 69HCL18_0757

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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