TuberculosisOPTI-4TBNCT04271397
Immunological Biomarkers in Tuberculosis Management
A study testing Multiple blood samples and Single blood sample in people with Tuberculosis and Tuberculosis Infection, run by Hospices Civils de Lyon at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, Tuberculosis Infection
- What is being tested?
- Multiple blood samples and Single blood sample
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- 30 Sep 2019to 10 Oct 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Service des Maladies Infectieuses - Hôpital de la Croix Rousse - Hospices Civils de Lyon
Lyon, 69004
Florence ADER, M.D., Ph.D., 04 72 07 11 07 ext. +33, florence.ader@chu-lyon.fr
Oana DUMITRESCU, M.D., PhD, 04 72 07 11 07 ext. +33, oana.dumitrescu@chu-lyon.fr
About this study
Official title: 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.
- Conditions
- Tuberculosis, Tuberculosis Infection
- Being tested
- Multiple blood samples, Single blood sample
- Medical subject headings
- Tuberculosis, Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multiple blood samplesOther
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 sampleOther
Patients with Latent tuberculosis infection will have a single specific sample of 14 mL.
| Study group | Role | What they receive |
|---|---|---|
| Active tuberculosis | Other | Not described Receives: Other: Multiple blood samples |
| Latent tuberculosis infection | Other | Not described Receives: Other: Single blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- 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).
Measured: 6 months
Secondary outcomes (6)
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.
Measured: 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.
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.
Measured: 6 months
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.
Measured: 6 months
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.
Measured: 6 months
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).
Measured: 6 months
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).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2020
- Study start30 Sep 2019
- Primary completion10 Sep 2026 (estimated)
- Study completion10 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04271397
- Sponsor's protocol ID
- 69HCL18_0757
- Acronym
- OPTI-4TB
- Status last verified
- Aug 2024
- First submitted
- 23 Dec 2019
- Last updated
- 12 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39871048Bahuaud 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.
PubMed 36186786
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimization of Tuberculosis Diagnosis and Management Using Four Immunological Biomarkers
- ClinicalTrials.gov ID
- NCT04271397
- Acronym / sponsor ID
- OPTI-4TB / 69HCL18_0757
- Conditions
- Tuberculosis, Tuberculosis Infection
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 30 Sep 2019 (actual)
- Primary completion
- 10 Sep 2026 (estimated)
- Study completion
- 10 Oct 2026 (estimated)
- First posted
- 17 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active tuberculosis | Other | Other: Multiple blood samples |
| Latent tuberculosis infection | Other | Other: Single blood sample |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (14 listed)
- Malignant solid tumor
- Malignant hemopathy
- Solid organ transplantation or hematopoietic stem cell transplantation
- Immunosuppressive treatments (i.e. biologics, calcineurin inhibitors, corticosteroids)
- Auto-inflammatory disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multiple blood samplesPatients 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 | Active tuberculosis |
| Single blood samplePatients with Latent tuberculosis infection will have a single specific sample of 14 mL. | Other | Latent tuberculosis infection |
Primary outcome
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 secondary outcomes
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
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
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
Assess the performance of a test based on the interpretation of a protein signature in the diagnosis / prognosis of tuberculosis.
Time frame: 6 months
Determine the achievement of target concentrations of rifampicin
Time frame: 6 months
Establish the rate of metabolic self-induction of rifampicin
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2024.
- Derived from this study: PubMed 39871048Goutelle 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.
- Derived from this study: PubMed 36186786Bahuaud 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Multiple blood samples and Single blood sample in people with Tuberculosis and Tuberculosis Infection, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Florence ADER, M.D., Ph.D (04 72 07 11 07 ext. +33, florence.ader@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concordance of the kinetics of biomarkers with the evolution of the disease (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04271397, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2024.