Cellular Markers in Treated or Untreated Non-tuberculous Mycobacterial Respiratory Infection in Patients With Cystic Fibrosis (MUCEM)

Cellular Markers During a Non-tuberculous Mycobacterial Respiratory Infection, Treated or Untreated, in Patients With Cystic Fibrosis

This study evaluates a diagnostic serological test for Non-Tuberculous Mycobacteria (NTM) infection in cystic fibrosis patients by measuring T cell response. It aims to highlight a dynamic response associated to the pathogen's presence. This multicenter case-control study involves two populations, providing a better understanding of the circulating T-IFNγ-MNT response in these patients.

Study Overview

• Status: Recruiting
• Conditions: Non-Tuberculous Mycobacterial Pneumonia
• Intervention / Treatment: Other: Scheduled visit (V1)

Detailed Description

Background: Evidence shows that Non-tuberculous Mycobacterial (NTM) infections have increased and are 1,000 to 8,000 times more frequent in patients with cystic fibrosis compared to the general population. The diagnosis is based on clinical, radiological, and microbiological criteria. Unfortunately, the first two criteria lack specificity, and microbiological detection of NTM is limited due to frequent sputum contamination by other pathogens in cystic fibrosis patients. Given these factors and the high incidence of NTM infections in this population, alternative diagnostic methods are necessary.

Aim: This study aims to validate an innovative diagnostic test based on the IGRA (Interferon-Gamma Release Assay) method, which measures T lymphocyte response to Interferon gamma (IFNγ). The test will be conducted on a subset of patients selected from the CIMeNT cohort (ID-RCB: 2017-A00025-48). This cohort consists of cystic fibrosis patients whose NTM infection prevalence has been previously assessed.

Method: This research is a multicenter case-control study. It includes two groups: a case group of patients with positive serological and/or microbiological responses indicating NTM infection, and a control group of patients without such responses. The test measures the host's immune response by evaluating circulating T cell activity. Specifically, it measures IFNγ release when T cells are in contact with NTM antigens. This method provides more informative diagnostics of NTM infection dynamics compared to serology or microbiology, which have known technical limitations.

The study involves a single visit, which is part of the routine care for cystic fibrosis patients. During this visit, a routine blood draw will be performed and an additional 7 ml tube will be collected.

• Study Type: Observational
• Enrollment (Estimated): 76

Contacts and Locations

• Study Contact: Name: Raphael CHIRON, MD; Phone Number: 0467336115; Email: r-chiron@chu-montpellier.fr
• Study Contact Backup: Name: Jean-Louis HERRMANN, Pr; Phone Number: 0147104470; Email: jean-louis.herrmann@aphp.fr

Study Locations

• France
  • Montpellier, France
    • Recruiting
    • CHU de Montpellier - Hôpital Arnaud de Villeneuve
    • Contact: Rapheal CHIRON, Hospital Praticien; Phone Number: 00334.67.33.61.15; Email: r.chiron@chu-montpelier.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with cystic fibrosis included in the CIMeNT study (N°ID RCB : 2017-A00025-48)

Description

Inclusion Criteria:

• Patient ≥18 years
• Patient previously included in the CIMeNT study
• Patient with a confirmed diagnosis of cystic fibrosis regardless of CFTR genotype
• Patient affiliated to the social security system
• Patient registered in the French Cystic Fibrosis Registry
• Adult patient capable of spontaneous expectoration or after induction

Exclusion Criteria:

• Lung transplant patients
• Person placed under judicial protection
• Pregnant and breastfeeding women

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case group MNT +; Cystic fibrosis patients with positive serology and positive culture	Other: Scheduled visit (V1); During the scheduled visit (V1), as part of routine care, a blood draw will be performed. On this occasion, an additional 7 ml tube will be collected to perform serology and culture. This will help define the group (NTM+ Cases/NTM- Controls) and measure cellular biomarkers.
Control group MNT -; Cystic fibrosis patients with negative serology and negative culture	Other: Scheduled visit (V1); During the scheduled visit (V1), as part of routine care, a blood draw will be performed. On this occasion, an additional 7 ml tube will be collected to perform serology and culture. This will help define the group (NTM+ Cases/NTM- Controls) and measure cellular biomarkers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of interferon-gamma release assay	Evaluation of T lymphocyte activation following mycobacterial antigen stimulation. The level of interferon gamma (IFN-γ) released is the measured marker of this activation, quantified in IU/ml. Sensitivity and specificity pairs will be calculated for each threshold value of the IFNγ rate in the T cell response test. A Receiver Operating Characteristic (ROC) curve will be plotted with its Area Under the Curve (AUC) and 95% confidence interval. For each threshold, sensitivity and specificity values will be computed, along with their 95% confidence intervals. The assessment aims to diagnose NTM in patients, as confirmed by serology and/or positive culture.	day 1 (V1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of T lymphocyte response	Measurement of IFN-γ release in response to T cell contact with NTM antigens, compared to clinical and radiological progression.	day 1 (V1)

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Hôpital Cochin; Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Raphael CHIRON, MD, Hôpital Arnaud de Villeneuve

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): September 17, 2026

Study Registration Dates

• First Submitted: September 16, 2024
• First Submitted That Met QC Criteria: September 16, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): July 10, 2025
• Last Update Submitted That Met QC Criteria: July 7, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; Diagnostic Test; Interferon gamma release assay
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Infections; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Fibrosis; Respiratory Tract Infections; Cystic Fibrosis
• Other Study ID Numbers: RECHMPL24_0124

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No