Lowering InterLeukin-1 Receptor Antagonist Concentrations After TB Treatment Onset

• Conditions: Tuberculosis

• Registration Number: NCT04015713
• Lead Sponsor: ANRS, Emerging Infectious Diseases

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.

Study Timeline

• Study First Submitted: 2019-07-02
• Study First Submitted QC: 2019-07-09
• Study First Posted: 2019-07-11
• Study Start: 2020-01-21
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-05
• Last Update Posted: 2020-02-06
• Primary Completion: 2021-03
• Study Completion: 2021-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Impact of the occurrence of events on the evolution of biomarkers from baseline (initiation of TB treatment) to the end of treatment (Week 24)	24 weeks	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.
Evolution of the plasma concentration of IL-1Ra between baseline (initation of TB treatment) and weeks 1, 2, 4 and 8	8 weeks	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
Evolution of the concentration of sCD163 between baseline (initiation of TB treatment) and weeks 1, 2, 4 and 8	8 weeks	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
Evolution of the plasma concentration of IP-10 between baseline (initiation of TB treatment) and weeks 1, 2, 4 and 8	8 weeks	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

Trial Locations

Locations (2)

Institut Pasteur Cambodge; 🇰🇭 Phon Phen, Cambodia

CEPREF/Programme PACCI; 🇨🇮 Abidjan, Côte D'Ivoire