Immunological Biomarkers in Tuberculosis Management

Tuberculosis Clinical Trial

— OPTI-4TB  

Official title:

Optimization of Tuberculosis Diagnosis and Management Using Four Immunological Biomarkers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04271397
• Other study ID #: 69HCL18_0757
• Status: Recruiting
• Phase: N/A
• Start date: September 30, 2019
• Est. completion date: April 9, 2023

Study information

• Verified date: February 2020
• Source: Hospices Civils de Lyon
• Contact: Florence ADER, M.D., Ph.D
• Phone: 04 72 07 11 07
• Email: florence.ader[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: April 9, 2023
• Est. primary completion date: April 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Latent Tuberculosis
• Tuberculosis
• Tuberculosis Infection

Intervention

Other:
• 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.
• Single blood sample
Patients with Latent tuberculosis infection will have a single specific sample of 14 mL.

Locations

Country	Name	City	State
France	Service des Maladies Infectieuses - Hôpital de la Croix Rousse - Hospices Civils de Lyon	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	6 months
Secondary	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.	6 months
Secondary	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.	6 months
Secondary	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.	6 months
Secondary	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.	6 months
Secondary	Determine the achievement of target concentrations of rifampicin	To determine the achievement of target concentrations of rifampicin the pharmacokinetic profile of rifampicin will be evaluate by a combination of parameters such as the area under the curve, maximum and minimum concentration, clearance, volume of distribution, modeled from three concentration measurements at each visit. (V2, V3 and V4).	6 months
Secondary	Establish the rate of metabolic self-induction of rifampicin	To establish the rate of metabolic self-induction of rifampicin the pharmacokinetic profile of rifampicin will be evaluate by a combination of parameters such as the area under the curve, maximum and minimum concentration, clearance, volume of distribution, modeled from three concentration measurements at each visit. (V2, V3 and V4).	6 months