Lowering InterLeukin-1 Receptor Antagonist Concentrations After TB Treatment Onset (LILAC-TB)

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

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.

Study Overview

• Status: Unknown
• Conditions: Tuberculosis

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 Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Laurence Weiss, MD,PhD; Phone Number: 33 (1) 56 09 3297; Email: laurence.weiss@aphp.fr
• Study Contact Backup: Name: Polidy Pean, MD,PhD; Phone Number: 855 (0) 125 521 82; Email: polidy@pasteur-kh.org

Study Locations

• Cambodia
  • Phon Phen, Cambodia
    • Not yet recruiting
    • Institut Pasteur Cambodge
    • Contact: Polidy Pean, MD, PhD; Email: polidy@pasteur-kh.org
    • Contact: Laurence BORAND; Email: lborand@pasteur-kh.org
• Côte D'Ivoire
  • Abidjan, Côte D'Ivoire
    • Recruiting
    • CEPREF/Programme PACCI
    • Contact: Raoul Moh, MD,PhD; Phone Number: +225 07 82 83 79; Email: raoul.moh@pacci.ci
    • Contact: Alexandra Bitty-Anderson, MPH; Phone Number: +225 01 14 95 38; Email: alexandra.bitty@pacci.ci

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
TB HIV-negative; 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; 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?

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

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; European Georges Pompidou Hospital; Institut Pasteur, Cambodia
• Investigators: Principal Investigator: Laurence Weiss, MD,PhD, APHP Georges Pompidou European Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2020
• Primary Completion (Anticipated): March 1, 2021
• Study Completion (Anticipated): March 1, 2021

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 9, 2019
• First Posted (Actual): July 11, 2019

Study Record Updates

• Last Update Posted (Actual): February 6, 2020
• Last Update Submitted That Met QC Criteria: February 5, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: ANRS 12394 LILAC-TB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No