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

Cystic Fibrosis Clinical Trial

— Modulate-CF  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04732910
• Other study ID #: 20012746
• Status: Recruiting
• Start date: July 1, 2018
• Est. completion date: December 31, 2027

Study information

• Verified date: March 2024
• Source: Charite University, Berlin, Germany
• Contact: Simon Y Graeber, MD
• Phone: +4930 450 566 587
• Email: simon.graeber[@]charite.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2027
• Est. primary completion date: March 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months and older

Eligibility

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)

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

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

Locations

Country	Name	City	State
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Justus-Liebig-University Giessen	Gießen
Germany	Hannover Medical School	Hanover
Germany	University of Heidelberg	Heidelberg

Sponsors (4)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Hannover Medical School, Heidelberg University, University of Giessen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Lung clearance index (LCI)	Absolute change from baseline of the lung clearance index (LCI)	12, 52, 104 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	Fecal elastase	Absolute change from baseline in fecal elastase-1 (FE-1) levels	12, 52, 104 weeks
Secondary	Weight	Absolute change from baseline in weight	12, 52, 104 weeks
Secondary	Airway Microbiome	Absolute change in shannon index representing the alpha-diversity in sputum samples	4, 12, 52, 104 weeks
Secondary	Sputum Elasticity	Absolute change in the elastic modulus (G') in sputum samples measured with a rheometer	4, 12, 52, 104 weeks
Secondary	Sputum Viscocity	Absolute change in the viscous modulus (G'') in sputum samples measured with a rheometer	4, 12, 52, 104 weeks