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

Recruiting

• Conditions: Cystic Fibrosis

• Registration Number: NCT04732910
• Lead Sponsor: Charite University, Berlin, Germany

Brief Summary

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

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

Study Timeline

• Study Start: 2018-07-01
• Study First Submitted: 2021-01-25
• Study First Submitted QC: 2021-01-29
• Study First Posted: 2021-02-01
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-01
• Last Update Posted: 2024-03-04
• Primary Completion: 2027-03-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Intestinal current measurement (ICM)	12 weeks	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

Secondary Outcome Measures

Name	Time	Method
Sweat chloride	12, 52, 104 weeks	Absolute change from baseline of the chloride concentration in Gibson-Cooke pilocarpine iontophoresis sweat test as a cystic fibrosis transmembrane conductance regulator (CFTR) biomarker
Lung clearance index (LCI)	12, 52, 104 weeks	Absolute change from baseline of the lung clearance index (LCI)
Paranasal sinus magnetic resonance imaging (MRI)	12, 52, 104 weeks	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)
Sputum Elasticity	4, 12, 52, 104 weeks	Absolute change in the elastic modulus (G') in sputum samples measured with a rheometer
Nasal potential Difference (NPD)	12 weeks	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
Forced expiratory volume in 1 second (FEV1)	12, 52, 104 weeks	Absolute change from baseline in percent predicted forced expiratory volume in 1 second (FEV1) in spirometry
Lung magnetic resonance imaging (MRI)	12, 52, 104 weeks	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)
Airway Microbiome	4, 12, 52, 104 weeks	Absolute change in shannon index representing the alpha-diversity in sputum samples
Lung computer tomography	52, 104 weeks	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)
Fecal elastase	12, 52, 104 weeks	Absolute change from baseline in fecal elastase-1 (FE-1) levels
Weight	12, 52, 104 weeks	Absolute change from baseline in weight
Sputum Viscocity	4, 12, 52, 104 weeks	Absolute change in the viscous modulus (G'') in sputum samples measured with a rheometer

Trial Locations

Locations (4)

Charité - Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Justus-Liebig-University Giessen; 🇩🇪 Gießen, Germany

Hannover Medical School; 🇩🇪 Hanover, Germany

University of Heidelberg; 🇩🇪 Heidelberg, Germany