Lowering InterLeukin-1 Receptor Antagonist Concentrations After TB Treatment Onset

Study Overview
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Brief Summary
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Despite marked improvements in the diagnosis of tuberculosis there are difficulties in diagnosing and monitoring treatment outcome among TB patients. The use of immunological biomarkers alone or in combination with other clinical parameters could predict early the response to TB treatment. The aim of this study is to demonstrate that the IL-1 receptor antagonist (IL-1Ra) concentrations significantly decrease within two weeks following TB treatment initiation in adults with active documented TB.

Detailed Description
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The HIV/AIDS epidemic and Tuberculosis (TB) remain important challenges for global public health and are strongly linked. Despite marked improvements in the diagnosis of tuberculosis, there are difficulties in diagnosing and monitoring treatment outcome among TB patients. The use of immunological biomarkers alone or in combination with other clinical parameters could better predict the response to TB treatment. The aim of this study is to demonstrate that the IL-1 receptor antagonist (IL-1Ra) concentrations significantly decrease within two weeks following TB treatment initiation in adults with active documented TB. This is a proof-of-concept study, among 100 patients (50 HIV positive and 50 HIV negative) with documented active TB, in Cambodge and Côte d'Ivoire. Patients recruited for this study will receive the standard TB treatment per their respective national treatment guidelines. Plasma samples will be collected at baseline (initiation of TB treatment), weeks 1, 2, 4 and 8 to measure IL-1Ra, sCD163 and IP-10.

Official Title
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LILAC - TB : Lowering InterLeukin-1 Receptor Antagonist Concentrations After TB Treatment Onset : a Proof of Concept Study in Cambodia and Ivory Coast (ANRS 12394)

Conditions
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Tuberculosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Evidence of TB, with: positive Xpert MTB/RIF For HIV infected patients: ART-naïve Regardless of CD4 cell counts Written informed consent Willingness to be followed up in the study clinics for 6 months after inclusion Exclusion Criteria: Mycobacterium tuberculosis strain resistant to rifampin with Xpert MTB/RIF Ongoing TB treatment Overt evidence of other ongoing opportunistic infections Pregnant or breastfeeding women Karnofsky score ≤ 30 Person unable to understand the study Person currently participating in clinical trial Females on oestroprogestative and progestative hormonal contraception

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| TB HIV-negative<br>Patients will receive standard TB treatment and will be followed according to the national procedures. In addition, plasma samples will be collected at baseline, Week 1, Week 2, Week 4 and Week 8 to measure IL-1Ra, sCD163 and IP-10. Baseline will be the initiation of TB treatment. All participants will be followed 24 weeks. | |
| TB HIV-positive<br>Patients will receive standard TB treatment and will be followed according to the national procedures. In addition, plasma samples will be collected at baseline, Week 1, Week 2, Week 4 and Week 8 to measure IL-1Ra, sCD163 and IP-10. Baseline will be the initiation of TB treatment. All participants will be followed 24 weeks. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of the plasma concentration of IL-1Ra between baseline (initiation of TB treatment) and Week 2 | To measure plasma concentrations of IL - 1Ra among TB patients after two weeks of TB treatment | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of the plasma concentration of IL-1Ra between baseline (initation of TB treatment) and weeks 1, 2, 4 and 8 | To measure plasma concentrations of IL - 1Ra and assess the evolution of the concentration of IL-1Ra among TB patients at week 1, week 2, week 4 and week 8 after treatment initiation | 8 weeks | 
| Evolution of the concentration of sCD163 between baseline (initiation of TB treatment) and weeks 1, 2, 4 and 8 | To measure plasma concentrations of sCD163 and assess the evolution of the concentration of IL-1Ra among TB patients at week 1, week 2, week 4 and week 8 after treatment initiation | 8 weeks | 
| Evolution of the plasma concentration of IP-10 between baseline (initiation of TB treatment) and weeks 1, 2, 4 and 8 | To measure plasma concentrations of IP-10 and assess the evolution of the concentration of IL-1Ra among TB patients at week 1, week 2, week 4 and week 8 after treatment initiation | 8 weeks | 
| Impact of the occurrence of events on the evolution of biomarkers from baseline (initiation of TB treatment) to the end of treatment (Week 24) | Impact of the occurrence of the following events/situations on the evolution of biomarkers (IL-1Ra,sCD163 and IP-10) : intercurrent infection, TB-associated immune reconstitution inflammatory syndrome (IRIS), TB treatment outcome, MTb strains resistant to TB drugs. | 24 weeks |