Primary Nasal Cell Culture as a Tool for Personalized Therapy in Cystic Fibrosis

characterization of CFTR function and expression in nasal primary cells collected from patients with cystic fibrosis in comparison to their parents, healthy heterozygotes and healthy controls

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Key information

Conditions

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

Sex eligibility

All sexes

Study type

Observational

About this study

3 groups of subjects are enrolled CF subjects according to their genotypes (aiming to enroll patients carrying 2 CF causing mutations with no CFTR expression/function, and patients carrying at least 1 mutation with residual function, such R117H) Parents or siblings of the CF subjects, as healthy hétérozygotes healthy controls All these subjects experience nasal brushings. From these nasal brushings,nasal cells are expanded, and cultured in air liquid interface to obtain polarized epithelium. This epithelium is then studied in Ussing chamber experiments to characterize the level of cAMP dependant Chloride transport and Sodium reabsorption. Apical expression of CFTR is assessed by immunofluorescence.

Results will allow to define the variability of CFTR function and expression criteria in subjects with the same genotype. Such data are crucial for interpretation of the effect of CFTR modulators.

Who can participate

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

patients with Cystic Fibrosis with 2 mutations in CFTR
healthy heterozygotes with 1 mutation in CFTR
healthy subjects with no familial history of Cystic Fibrosis and no symptoms suggesting Cystic Fibrosis

Exclusion criteria

smoking

Treatment and study plan

cell sampling

Procedure

nasal brushing to collect cells

Primary outcomes

variation in the short-circuit-current (Isc) after Forskolin (Forskolin)/IBMx and VX-770 (∆IscFsk/IBMx+VX-770)

Time frame: 1 day

The short-circuit-current (Isc) was measured under voltage clamp conditions. Inhibitors and activators were added after stabilization of baseline Isc. The sum of the change after Forskolin (Forskolin)/IBMx and VX-770 (∆IscFsk/IBMx+VX-770) served as an index of CFTR function.

Secondary outcomes

percentage of cells displaying apical staining

Time frame: 1 day

CFTR immuno-detection was performed as previously described 31. Apical CFTR staining was assessed semi quantitatively as the percentage of cells displaying apical staining multiplied by the average corrected apical fluorescence 32.

Sponsors and collaborators

Lead sponsor

Institut National de la Santé Et de la Recherche Médicale, France

Other Gov

Collaborators

ABCF2

Registry information

Official study title

Evaluation of the Primary Human Nasal Epithelial Cell Culture Model in the Context of Personalized Therapy in Cystic Fibrosis

Acronym: Epiithelix

Important dates

Study start: 2010
Primary completion: 2016
Study completion: 2016
First posted: Aug 29, 2018
Registry last updated: Mar 12, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed