Impaired Secretory IgA and Mucosal Immunity in Cystic Fibrosis

NCT02308267 | Unknown

• 1 other identifier: Forton2015
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This project entitled "Impaired secretory IgA and mucosal immunity in cystic fibrosis" is a research program which aims to determine, owing to national (KULeuven) and international (Descartes university Paris, university of Torino) collaborations for expertise and access to human material, whether a defect exists for the production of IgA antibodies in the lung from patients with this serious genetic disease. These antibodies line and protect normally the airways, and are secreted through a specific epithelial receptor called pIgR (polymeric immunoglobulin receptor); its expression and regulation will be studied in lung tissue and in cell cultures of the lung epithelium from these patients. The link between the putative IgA defect and chronic bacterial infection with Pseudomonas aeruginosa, which often complicates the evolution of the disease, will also be evaluated ex vivo and in vivo, in an animal model of lung infection.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Mucosal immunity

Outcome Measures

Primary Outcomes (1)

• Evaluation of pIgR & IgA expression in bronchial tissue from CF patients, as compared to controls.

  3 years

Secondary Outcomes (1)

• Evaluation of S-IgA antibodies to respiratory bacteria in CF airways

  3 years

Study Arms (2)

Cystic fibrosis

Cystic fibrosis patients More than 18 years old DF508/DF508 mutation colonized or not with Pseudomonas aeruginosa

Other: Lung explants; Other: Sputum, nasal fluid and serum; Procedure: Bronchoscopy

Controls

Controls patients More than 18 years old Without CF Smokers or nonsmokers

Other: Lung explants; Other: Sputum, nasal fluid and serum; Procedure: Bronchoscopy

Interventions

Lung explants OTHER

Lung explants from end-stage CF, which were obtained for a reason independent from the study in the Paris (Prof Burgel) and Leuven (Prof Dupont) centres will be analysed for pIgR and IgA expression as well as for Pseudomonas aeruginosa colonization. Some lung explants from control patients will also be obtained from the Leuven centre.

Controls; Cystic fibrosis

Sputum, nasal fluid and serum OTHER

Sputum, nasal (fluid) and serum samples from CF patients and controls patients will be collected (Leuven, Paris, Torino, Verona and Saint-Luc Brussels) for S-IgA and microbiological assays. Spontaneous sputum will be collected, while nasal fluid will be sampled through nasal lavage. Control subjects will consist of COPD patients and healthy subjects (smokers or not).

Controls; Cystic fibrosis

Bronchoscopy PROCEDURE

Endobronchial biopsies (EBB) and broncho-alveolar lavage (BAL) will be sampled at the KULeuven centre (Prof Dupont) in some CF patients (homozygous for the DF508 mutation) and colonized or not with Pseudomonas aeruginosa and who must have a general anaesthesia for a reason independent from the study. In these patients, a bronchial endoscopy will be performed during narcosis to take EBB (n=8) and BAL (2x50mL). If possible, nasal and rectal biopsies will also be performed in some patients. Samples will be assessed for pIgR and IgA expression and for primary broncho-epithelial cultures (carried out at the UCL centre, Pr Pilette). Control subjects will be patients without CF and without evidence of lung disease and who are undergoing narcosis for an independent reason at the KULeuven centre.

Controls; Cystic fibrosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

CF patients followed in a CF center (UCL, KUL, Hôpital Cochin, Torino university) Controls patients (healthy volunteers for sputum or patients undergoing lung surgery for another reason).

You may qualify if:

• CF: adult CF patients (from age 18) with a classical clinical phenotype related to DF508/DF508 mutation, and colonized or not with Pseudomonas aeruginosa

You may not qualify if:

• \<18 years
• other chronic lung diseases except COPD as a specific control subgroup

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead

Study Sites (1)

StLuc

Brussels, 1200, Belgium

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

1. Lung explants from end-stage CF and control patients, which were obtained for a reason independent from the study. 2. Sputum, nasal (fluid) and serum samples from CF patients and controls patients (COPD patients and healthy subjects) will be collected for S-IgA and microbiological assays. Spontaneous sputum will be collected, while nasal fluid will be sampled through nasal lavage. 3. Endobronchial biopsies and broncho-alveolar lavage will be sampled in some CF patients who must have a general anaesthesia for a reason independent from the study. If possible, nasal and rectal biopsies will also be performed. Control subjects will be patients without evidence of lung disease and who are undergoing narcosis for an independent reason.

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Bronchoscopy

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures

Study Officials

• Charles Pilette, MD, PhD

  Cliniques universitaires Saint-Luc- Université Catholique de Louvain

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charles Pilette, MD, PhD

CONTACT

+32 2 764 28 32; charles.pilette@uclouvain.be

Sophie Gohy, MD, PhD

CONTACT

+ 32 2 764 28 32; sophie.gohy@uclouvain.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2014
• First Posted: December 4, 2014
• Study Start: November 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: February 25, 2016

Record last verified: 2016-02

Locations

BE (1)