Clinical trial NCT04015713: Lowering InterLeukin-1 Receptor Antagonist Concentrations After TB Treatment Onset
Official title: LILAC - TB : Lowering InterLeukin-1 Receptor Antagonist Concentrations After TB Treatment Onset : a Proof of Concept Study in Cambodia and Ivory Coast (ANRS 12394)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Tuberculosis
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Institut Pasteur, Cambodia
name: Institut National de la Santé Et de la Recherche Médicale, France
name: European Georges Pompidou Hospital
First posted: 2019-07-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: * 100 patients with documented active TB, 50 in Cambodia and 50 in Côte d'Ivoire
* 60 patients HIV-infected and 40 patients HIV negative

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Evolution of the plasma concentration of IL-1Ra between baseline (initiation of TB treatment) and Week 2
timeFrame: 2 weeks
Secondary outcomes:
measure: Evolution of the plasma concentration of IL-1Ra between baseline (initation of TB treatment) and weeks 1, 2, 4 and 8
timeFrame: 8 weeks
measure: Evolution of the concentration of sCD163 between baseline (initiation of TB treatment) and weeks 1, 2, 4 and 8
timeFrame: 8 weeks
measure: Evolution of the plasma concentration of IP-10 between baseline (initiation of TB treatment) and weeks 1, 2, 4 and 8
timeFrame: 8 weeks
measure: Impact of the occurrence of events on the evolution of biomarkers from baseline (initiation of TB treatment) to the end of treatment (Week 24)
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Phon Phen
country: Cambodia
facility: Institut Pasteur Cambodge
city: Abidjan
country: Côte D'Ivoire
facility: CEPREF/Programme PACCI
Study officials:
affiliation: APHP Georges Pompidou European Hospital
name: Laurence Weiss, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: