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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2012 by Institut National de la Santé Et de la Recherche Médicale, France
Sponsor:
Information provided by (Responsible Party):
Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier:
NCT01605565
First received: April 11, 2012
Last updated: May 21, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention
Cystic Fibrosis
Procedure: A nasal brushing

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Analyse Fonctionnelle Par Imagerie Dynamique de l'épithélium Respiratoire Chez Des Nourrissons Atteints de Mucoviscidose

Resource links provided by NLM:


Further study details as provided by Institut National de la Santé Et de la Recherche Médicale, France:

Primary Outcome Measures:
  • 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. [ Time Frame: no time frame ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 30
Study Start Date: November 2011
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: A nasal brushing
    A nasal brushing in every nostril
Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 6 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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,
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01605565

Contacts
Contact: Michel ABELY, Professor +333 326787007 mabely@chu-reims.fr

Locations
France
Chu Reims Recruiting
Reims, France, 51092
Contact: MICHEL ABELY, Professor    +333326787007    mabely@chu-reims.fr   
Principal Investigator: Michel ABELY, Professor         
Sponsors and Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
Principal Investigator: Michel ABELY, Professor CHU REIMS
  More Information

Publications:
Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier: NCT01605565     History of Changes
Other Study ID Numbers: C11-01, 2011-A00384-37
Study First Received: April 11, 2012
Last Updated: May 21, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on August 18, 2014