Functional Analysis by Dynamic Imaging of the Respiratory Epithelium in Infants With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

Analyse Fonctionnelle Par Imagerie Dynamique de l'épithélium Respiratoire Chez Des Nourrissons Atteints de Mucoviscidose

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01605565
• Other study ID #: C11-01
• Secondary ID: 2011-A00384-37
• Status: Recruiting
• Phase: N/A
• First received: April 11, 2012
• Last updated: May 21, 2012
• Start date: November 2011
• Est. completion date: November 2014

Study information

• Verified date: May 2012
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: Michel ABELY, Professor
• Phone: +333 326787007
• Email: mabely[@]chu-reims.fr
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

Cystic fibrosis (CF) is characterized by airway inflammation and infection leading to progressive destruction of lungs. One of the most important abnormalities in CF is an abnormal processing of the mutated CFTR protein through the endoplasmic reticulum that causes abnormal location or even absence of the protein at the apical plasma membrane of airway epithelial cells. This abnormality results in a marked dehydration of the airway surface fluid, decreased mucus transport and airway obstruction. Nevertheless, the events that occur very early during the progression of the disease at the airway level in infants are not known. At cellular level, it has also been reported that the CFTR expression and localization could be related to the differentiation state of the airway epithelium. Furthermore, it has been reported that gap junctions could be involved in dysregulate inflammation process. In CF infants, many answers are still lacking. For a better understanding of the early stages of cystic fibrosis, it is of major interest to study respiratory epithelial cells obtained as early as possible. In 15 CF infants and 15 control infants, a nasal brushing will be performed by means of a soft sterile cytology brush. Samples will be used for cytological and functional studies: ciliary beating frequency, cAMP-dependent chloride efflux, potassium efflux, tight and gap junctions functionalities. These studies will be done in basal conditions and will be repeated after activation of the nasal epithelial cells by the bacteria, such as Staphylococcus aureus, which can be found very early in the course of CF disease.

Description:

Cystic fibrosis (CF) is characterized by airway inflammation and infection leading to progressive destruction of lungs. One of the most important abnormalities in CF is an abnormal processing of the mutated CFTR protein through the endoplasmic reticulum that causes abnormal location or even absence of the protein at the apical plasma membrane of airway epithelial cells. This abnormality results in a marked dehydration of the airway surface fluid, decreased mucus transport and airway obstruction. Nevertheless, the events that occur very early during the progression of the disease at the airway level in infants are not known. At cellular level, it has also been reported that the CFTR expression and localization could be related to the differentiation state of the airway epithelium. Furthermore, it has been reported that gap junctions could be involved in dysregulate inflammation process. In CF infants, many answers are still lacking.

Is inflammation present before infection? Is native epithelium of CF infants more sensitive than controls? Could the investigators analyse the localisation and functionality of CFTR, tight and gap junctions in respiratory epithelial cells in CF infants? Could the activation of the epithelial cells by bacteria alter their functional properties? For a better understanding of the early stages of cystic fibrosis, it is of major interest to study respiratory epithelial cells obtained as early as possible. Although bronchoalveolar lavage has been proposed for this purpose, nasal brushing, which is a much less invasive technique, has seldom been used in CF infants. the investigators have shown that, by means of a simple nasal brushing technique easily performed and well tolerated, it is feasible, in infants, to harvest native respiratory cell sheets in order to analyse the airway epithelium functionality. In 15 CF infants and 15 control infants, a nasal brushing will be performed by means of a soft sterile cytology brush. Samples will be used for cytological and functional studies: ciliary beating frequency, cAMP-dependent chloride efflux, potassium efflux, tight and gap junctions functionalities. These studies will be done in basal conditions and will be repeated after activation of the nasal epithelial cells by the bacteria, such as Staphylococcus aureus, which can be found very early in the course of CF disease.

the investigators believe that the present study could help to understand the pathophysiology on the very early stages of CF disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: November 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 6 Months

Eligibility

Inclusion Criteria:

• Cystic fibrosis

Exclusion Criteria:

• > 6 months old

• Other respiratory disease

• Other allergic disease

• Other infectious disease: fever (> 38° C), respiratory distress

• Altered general health state, rash,

Study Design

Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Procedure:
• A nasal brushing
A nasal brushing in every nostril

Locations

Country	Name	City	State
France	Chu Reims	Reims

Sponsors (1)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

References & Publications (1)

Mosler K, Coraux C, Fragaki K, Zahm JM, Bajolet O, Bessaci-Kabouya K, Puchelle E, Abély M, Mauran P. Feasibility of nasal epithelial brushing for the study of airway epithelial functions in CF infants. J Cyst Fibros. 2008 Jan;7(1):44-53. Epub 2007 Jun 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The main objective is to analyze the functionality of the respiratory epithelium in CF infant using a nasal brushing technique: ciliary beating frequency, cAMP-dependent chloride efflux, potassium efflux, tight and gap junctions functionalities.	In 15 CF infants and 15 control infants, a nasal brushing will be performed by means of a soft sterile cytology brush. Samples will be used for cytological and functional studies: ciliary beating frequency, cAMP-dependent chloride efflux, potassium efflux, tight and gap junctions functionalities.	no time frame	No