Modulate-CF: Cystic Fibrosis Transmembrane Regulator (CFTR) Biomarker Study to Evaluate the Rescue of Mutant CFTR in Patients With Cystic Fibrosis Treated With CFTR-modulators
Study Details
Study Description
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).
Condition or Disease | Intervention/Treatment | Phase |
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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 Design
Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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
- 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)
- 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)
- 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)
- 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)
- 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
- Airway Microbiome [4, 12, 52, 104 weeks]
Absolute change in shannon index representing the alpha-diversity in sputum samples
- Sputum Elasticity [4, 12, 52, 104 weeks]
Absolute change in the elastic modulus (G') in sputum samples measured with a rheometer
- Sputum Viscocity [4, 12, 52, 104 weeks]
Absolute change in the viscous modulus (G'') in sputum samples measured with a rheometer
Eligibility Criteria
Criteria
Inclusion Criteria:
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Decision for cystic fibrosis (CF) transmembrane regulator (CFTR)-modulator therapy by the patient and the caring CF physician
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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)
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Charité - Universitätsmedizin Berlin | Berlin | Germany | 13353 | |
2 | Justus-Liebig-University Giessen | Gießen | Germany | ||
3 | Hannover Medical School | Hanover | Germany | ||
4 | University of Heidelberg | Heidelberg | Germany |
Sponsors and Collaborators
- Charite University, Berlin, Germany
- Hannover Medical School
- Heidelberg University
- University of Giessen
Investigators
- Principal Investigator: Simon Y Graeber, MD, Charite University, Berlin, Germany
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 20012746