Cystic Fibrosis Transmembrane Regulator (CFTR) Biomarker Study to Evaluate the Rescue of Mutant CFTR in Patients With Cystic Fibrosis Treated With CFTR-modulators

Study Overview
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Brief Summary
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This observational study evaluates the effect of therapy with cystic fibrosis transmembrane regulator (CFTR) modulators on CFTR function measured by the CFTR biomarker intestinal current measurement (ICM), nasal potential difference (NPD) and sweat chloride in a post-approval setting in patients with cystic fibrosis (CF).

Detailed Description
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Cystic fibrosis transmembrane regulator (CFTR) biomarker (intestinal current measurement (ICM), nasal potential difference (NPD), sweat chloride) before the start of therapy and 12 and 52 weeks after initiation of therapy Clinical parameters (anthropometry, lung function, lung magnetic resonance imaging (MRI), lung computer tomography (CT)) before the start of therapy and after initiation of therapy Assessment of airway secretion specimens before the start of therapy and after initiation of therapy

Official Title
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CFTR Biomarker Studie Bei Patient*Innen Mit Mukoviszidose Und CFTR-Modulatortherapie

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Treatment with cystic fibrosis transmembrane regulator (CFTR) modualtors Ivacaftor, Lumacaftor-Ivacaftor, Tezacaftor-Ivacaftor, Elexacaftor-Tezacaftor-Ivacaftor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Decision for cystic fibrosis (CF) transmembrane regulator (CFTR)-modulator therapy by the patient and the caring CF physician Signed informed consent form (ICF) and, where appropriate, signed assent form. Exclusion Criteria: Ongoing participation in an investigational drug study (including studies investigating lumacaftor, tezacaftor or ivacaftor)

Ages Eligible for Study
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Minimum Age: 6 Months

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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Treatment with cystic fibrosis transmembrane regulator (CFTR) modualtors Ivacaftor, Lumacaftor-Ivacaftor, Tezacaftor-Ivacaftor, Elexacaftor-Tezacaftor-Ivacaftor|observational|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intestinal current measurement (ICM) | Absolute change from baseline of the chloride secretory ion current induced by cyclic adenosine monophosphate (cAMP) stimulation (forskolin/3-isobutyl-1-methylxanthine (IBMX)) in rectal tissue determined by intestinal current measurement (ICM) as a cystic fibrosis transmembrane conductance regulator (CFTR) biomarker | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced expiratory volume in 1 second (FEV1) | Absolute change from baseline in percent predicted forced expiratory volume in 1 second (FEV1) in spirometry | 12, 52, 104 weeks | 
| Nasal potential Difference (NPD) | Absolute change from baseline total chloride response (zero chloride and isoproterenol) in nasal potential Difference (NPD) as a cystic fibrosis transmembrane conductance regulator (CFTR) biomarker | 12 weeks | 
| Sweat chloride | Absolute change from baseline of the chloride concentration in Gibson-Cooke pilocarpine iontophoresis sweat test as a cystic fibrosis transmembrane conductance regulator (CFTR) biomarker | 12, 52, 104 weeks | 
| Lung clearance index (LCI) | Absolute change from baseline of the lung clearance index (LCI) | 12, 52, 104 weeks | 
| Lung magnetic resonance imaging (MRI) | Absolute change from baseline in lung magnetic resonance imaging (MRI) score (Heidelberg MRI score ranging from 0 to 72 with higher values associated with worsening of the outcome; Eichinger et al. Eur J Radiol 2012) | 12, 52, 104 weeks | 
| Lung computer tomography | Absolute change from baseline in lung computer tomography (CT) score (Brody score ranging from 0 to 40,5 with higher values associated with worsening of the outcome; Brody et al. J Thorac Imaging 2006) | 52, 104 weeks | 
| Paranasal sinus magnetic resonance imaging (MRI) | Absolute change from baseline in paranasal sinus magnetic resonance imaging (MRI) score (Sinunasal MRI score ranging from 0 to 68 with higher values associated with worsening of the outcome; Sommerburg et al. Ann Am Thorac Soc 2020) | 12, 52, 104 weeks | 
| Fecal elastase | Absolute change from baseline in fecal elastase-1 (FE-1) levels | 12, 52, 104 weeks | 
| Weight | Absolute change from baseline in weight | 12, 52, 104 weeks | 
| Airway Microbiome | Absolute change in shannon index representing the alpha-diversity in sputum samples | 4, 12, 52, 104 weeks | 
| Sputum Elasticity | Absolute change in the elastic modulus (G') in sputum samples measured with a rheometer | 4, 12, 52, 104 weeks | 
| Sputum Viscocity | Absolute change in the viscous modulus (G'') in sputum samples measured with a rheometer | 4, 12, 52, 104 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CFTR, ICM, NPD