Surrogate Markers of Response to New Therapies in Cystic Fibrosis Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine which biological marker, or association of biological markers, best predict clinical response of cystic fibrosis patients to CFTR modulators.

Detailed Description
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This study is based upon the hypothesis that clinical response of cystic fibrosis patients to CFTR modulators is correlated to in vitro responses to these drugs of epithelial cells derived from the patients, as assessed by CFTR-dependent Chloride secretion. Epithelial cells will be derived either from nasal or rectal epithelia, and consist both of cultured cells and organoids. The drugs tested will be Ivacaftor, or Lumacaftor/Ivacaftor, according to patient's treatment. Results of these assays will be compared with response to treatment at 6 and 12 months, assessed by clinical response and in vivo assay of CFTR function.

Official Title
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Personalized Therapy of Cystic Fibrosis: Set-up of Response Markers

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Procedure: Nasal swab; rectal biopsy.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cystic fibrosis patients treated by CFTR modulators (Ivacaftor or the association Ivacaftor-Lumacaftor) Cystic fibrosis patients non treated by CFTR modulators Patients in whom cystic fibrosis diagnosis has been suspected, but excluded by physiological and genetic investigations Exclusion Criteria: pregnant or lactating women contraindication to nasal swab contraindication to rectal biopsy
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cystic fibrosis, treated<br>Cystic fibrosis patients treated either by Ivacaftor or by the association Ivacaftor-Lumacaftor | Procedure: Nasal swab; rectal biopsy.<br>* Nasal epithelial cells will be obtained by nasal swabs from patients of the three arms; intestinal epithelial cells will be obtained, by rectal biopsy, only from patients treated by CFTR modulators.<br>|
| Other: Cystic fibrosis, non treated<br>Cystic fibrosis patients, non treated by a CFTR modulator | Procedure: Nasal swab; rectal biopsy.<br>* Nasal epithelial cells will be obtained by nasal swabs from patients of the three arms; intestinal epithelial cells will be obtained, by rectal biopsy, only from patients treated by CFTR modulators.<br>|
| Other: Non-Cystic fibrosis<br>Patients in whom cystic fibrosis diagnosis has been suspected, but excluded by physiological and genetic investigations | Procedure: Nasal swab; rectal biopsy.<br>* Nasal epithelial cells will be obtained by nasal swabs from patients of the three arms; intestinal epithelial cells will be obtained, by rectal biopsy, only from patients treated by CFTR modulators.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between biological markers and clinical and physiological outcome |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between biological markers and clinical and physiological outcome |  | 12 months |