- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04271397
Immunological Biomarkers in Tuberculosis Management (OPTI-4TB)
Optimization of Tuberculosis Diagnosis and Management Using Four Immunological Biomarkers
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 Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Florence ADER, M.D., Ph.D
- Phone Number: +33 04 72 07 11 07
- Email: florence.ader@chu-lyon.fr
Study Contact Backup
- Name: Oana DUMITRESCU, M.D., PhD
- Phone Number: +33 04 72 07 11 07
- Email: oana.dumitrescu@chu-lyon.fr
Study Locations
-
-
-
Lyon, France, 69004
- Recruiting
- Service des Maladies Infectieuses - Hôpital de la Croix Rousse - Hospices Civils de Lyon
-
Contact:
- Oana DUMITRESCU, M.D., PhD
- Phone Number: +33 04 72 07 11 07
- Email: oana.dumitrescu@chu-lyon.fr
-
Contact:
- Florence ADER, M.D., Ph.D.
- Phone Number: +33 04 72 07 11 07
- Email: florence.ader@chu-lyon.fr
-
Principal Investigator:
- Florence ADER, M.D., Ph.D.
-
Sub-Investigator:
- Anne CONRAD, CCU-AH
-
Sub-Investigator:
- Thomas PERPOINT, PH
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: DIAGNOSTIC
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
OTHER: Active tuberculosis
|
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.
|
OTHER: Latent tuberculosis infection
|
Patients with Latent tuberculosis infection will have a single specific sample of 14 mL.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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). |
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Analytical characteristics of a combination of 2 IGRAs (QuantiFERON-TB Gold Plus (QFT-P) and HBHA) in the diagnosis / prognosis of tuberculosis disease.
Time Frame: 6 months
|
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
|
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.
Time Frame: 6 months
|
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
|
Evaluate the performance of a test based on the interpretation of a transcriptomic signature in plasma in the diagnosis / prognosis of TB.
Time Frame: 6 months
|
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
|
Assess the performance of a test based on the interpretation of a protein signature in the diagnosis / prognosis of tuberculosis.
Time Frame: 6 months
|
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
|
Determine the achievement of target concentrations of rifampicin
Time Frame: 6 months
|
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
|
Establish the rate of metabolic self-induction of rifampicin
Time Frame: 6 months
|
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
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 69HCL18_0757
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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