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

Completed

• Conditions: Cystic Fibrosis
• Interventions: Procedure: cell sampling

• Registration Number: NCT03652090
• Lead Sponsor: Institut National de la Santé Et de la Recherche Médicale, France

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2010-09-01
• Primary Completion: 2016-03-03
• Study Completion: 2016-03-03
• Study First Submitted: 2018-08-28
• Study First Submitted QC: 2018-08-28
• Study First Posted: 2018-08-29
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-08
• Last Update Posted: 2019-03-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 112

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
healthy heterozygotes	cell sampling	healthy heterozygotes carrying 1 CFTR mutations undergoing cell sampling
healthy control	cell sampling	subject with no evidence of any symptoms compatible with Cystic Fibrosis undergoing cell sampling
cystic fibrosis patients	cell sampling	Cystic fibrosis patients carrying to 2 CFTR mutations undergoing cell sampling

Primary Outcome Measures

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

Name	Time	Method
percentage of cells displaying apical staining	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.