Role of BARriers in IgG-Pathogen Interactions at the Mucosal Surface in Human Airways

NCT06670937 | Recruiting

• 1 other identifier: DR240158
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Context. Non cystic fibrosis bronchiectasis (NCFB) is a group of suppurative chronic airway diseases of multiple causes. Bronchiectasis is characterized by an abnormal, irreversible dilatation of the bronchi, airway obstruction, chronic cough, and sputum production. Inhaled polyclonal immunoglobulin G (IgG) is a new therapeutic approach for NCFB. Inhaled IgG is expected to have beneficial effects due to its ability to reduce the range of respiratory pathogens capable of infecting the respiratory tract, decrease the pulmonary load of existing bacterial populations, improve mucociliary clearance by restoring epithelial cell functions, and decrease lung inflammation. Pre-clinical data packages showed that IgG reduced the airway pathogen load and related cell damage after infection in rodents and non-human primates. The aim of this study is collect information on the impact of NFCB airway mucus on the biological barriers to locally delivered IgG. Study design. Thirty patients with stable NFCB will be recruited. The patients will provide induced sputum samples after inhaling isotonic saline. Induced sputum will be used for 1) identification of colonizing bacteriological, fungal and virological populations and 2) for in vitro pharmacological experiments. The main outcome is the quantification by whole-cell ELISA of binding to Pseudomonas aeruginosa by a polyclonal IgG in the presence of mucus derived from the sputum of NCFB patients. Secondary outcomes are (1) the measurement of proteolysis, by Western-Blot, of exogenous polyclonal IgG added in the mucus derived from sputum of NCFB patients. The results will be expressed as a percentage of integrity over the one obtained when the polyclonal IgG is added in saline solution and will be compared with in vitro results; (2) the measurement of mobility by Fluorescence Recovery After Photobleaching (FRAP) of exogenous fluorescently-labelled polyclonal IgG added in the mucus derived from sputum of NCFB patients. The results will include the determination of the t(1/2), mobile and immobile fractions over the one obtained when the polyclonal IgG is added in saline solution and will be compared with in vitro results; (3) impact of microbial airway colonization on IgG binding, proteolysis and Ig mobility. Samples with microbial colonization (either bacterial, viral or fungal) will be compared with uncolonized samples. This project will help in decision-making in the development of inhaled antibody therapeutics. Specifically, the study will provide information on the capacity of locally applied polyclonal IgG to diffuse through mucus and bind to pathogens.

Conditions

Bronchiectasis Adult

Keywords

induced sputum; IgG

Outcome Measures

Primary Outcomes (1)

• Binding of Pseduomonas aeruginosa by a polyclonal IgG preparation in the presence of airway mucus obtained from patients with non-cystic fibrosis bronchiectasis

  The main outcome is the quantification of polyclonal IgG binding to Pseudomonas aeruginosa in the presence of mucus derived from sputum of NCFB patients. Binding will be assessed by whole-cell ELISA. The results will be expressed as a percentage of binding over the one obtained when the polyclonal IgG is added in saline solution and will be compared with artificial mucus preparations in a range of viscosity similar to human airway mucus.

  From enrollment to 3 months

Secondary Outcomes (5)

• Proteolysis of exogenous polyclonal IgG

  From enrolment to 3 months

• Mobility of fluorescently labelled polyclonal IgG in mucus

  From enrollment to 3 months

• Impact of microbial airway colonization on IgG binding

  From enrollment to 3 months

• Impact of microbial airway colonization on proteolysis

  From enrollement to 3 months

• Impact of microbial airway colonization on Ig mobility

  From enrollement to 3 months

Other Outcomes (1)

• Comparaison between samples with microbial colonization (either bacterial, viral or fungal) and uncolonized samples.

  From enrollement to 3 months

Study Arms (1)

study group

EXPERIMENTAL

This is the single arm of this study. Patients with non-CF bronchiectasis will provide 1) an induced sputum sample after inhaling 15 ml of 0.9% NaCl solution and 2) a blood sample.

Other: Induced sputum; Other: Blood sample

Interventions

Induced sputum OTHER

Patients will provide 1) an induced sputum sample after inhaling 15 ml of 0.9% NaCl solution

study group

Blood sample OTHER

Patients will provide 2) a blood sample.

study group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Clinical diagnosis of NCFB
• Computed tomography (CT) evidence of bilateral bronchiectasis
• Consent for research use of data and material
• Ability to provide an induced sputum sample
• Stable clinical status over the last 4 weeks

You may not qualify if:

• Pulmonary disease other than NCFB (except asthma)
• Diagnosis of cystic fibrosis
• Diagnosis of primary ciliary dyskinesia
• Requirement for oxygen therapy at rest
• Diagnosis of IgG deficiency (total serum IgG \< 5.4 g/l)
• Treatment with a CFTR modulator drug in the last 6 months
• Unilateral bronchectasis
• CT evidence of interstitial lung disease with traction bronchectasis
• Refusal of the patient
• Acute exacerbation of NFCB in the last 4 weeks
• No sputum production
• Current treatment with systemic antibiotics (other than low dose azithromycin)
• Pregnancy or breastfeeding
• Subject under legal protection (e.g., guardianship, tutorship).
• Inability to produce a sputum sample

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (1)

CHRU de Tours

Tours, France, 37044, France

RECRUITING

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Laurent PLANTIER, MD

  CHRU de Tours

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laurent PLANTIER, MD, PhD

CONTACT

+33247476242; laurent.plantier@univ-tours.fr

Thomas Secher, PhD

CONTACT

+33247366050; thomas.secher@inserm.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study aims at collecting airway mucus from individuals with non cystic fibrosis bronchiectasis.

Study Record Dates

• First Submitted: October 30, 2024
• First Posted: November 1, 2024
• Study Start: December 16, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)