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

March 8, 2019 updated by: Isabelle Sermet-Gaudelus, Institut National de la Santé Et de la Recherche Médicale, France

Evaluation of the Primary Human Nasal Epithelial Cell Culture Model in the Context of 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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Actual)

112

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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 compatibel with Cystic Fibrosis

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
cystic fibrosis patients
Cystic fibrosis patients carrying to 2 CFTR mutations undergoing cell sampling
Procedure: cell sampling
nasal brushing to collect cells
healthy heterozygotes
healthy heterozygotes carrying 1 CFTR mutations undergoing cell sampling
Procedure: cell sampling
nasal brushing to collect cells
healthy control
subject with no evidence of any symptoms compatible with Cystic Fibrosis undergoing cell sampling
Procedure: cell sampling
nasal brushing to collect cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
1 day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Collaborators

ABCF2

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 1, 2010

Primary Completion (ACTUAL)

March 3, 2016

Study Completion (ACTUAL)

March 3, 2016

Study Registration Dates

First Submitted

August 28, 2018

First Submitted That Met QC Criteria

August 28, 2018

First Posted (ACTUAL)

August 29, 2018

Study Record Updates

Last Update Posted (ACTUAL)

March 12, 2019

Last Update Submitted That Met QC Criteria

March 8, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010-05-03 A3

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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