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

Sponsor
Charite University, Berlin, Germany (Other)
Overall Status
Recruiting
CT.gov ID
NCT04732910
Collaborator
Hannover Medical School (Other), Heidelberg University (Other), University of Giessen (Other)
90
4
66
22.5
0.3

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

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

Study Type:
Observational
Anticipated Enrollment :
90 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
CFTR Biomarker Studie Bei Patient*Innen Mit Mukoviszidose Und CFTR-Modulatortherapie
Actual Study Start Date :
Jul 1, 2018
Anticipated Primary Completion Date :
Jan 31, 2023
Anticipated Study Completion Date :
Dec 31, 2023

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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

  2. 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

  3. 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

  4. Lung clearance index (LCI) [12, 52, 104 weeks]

    Absolute change from baseline of the lung clearance index (LCI)

  5. 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)

  6. 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)

  7. 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)

  8. Fecal elastase [12, 52, 104 weeks]

    Absolute change from baseline in fecal elastase-1 (FE-1) levels

  9. Weight [12, 52, 104 weeks]

    Absolute change from baseline in weight

  10. Airway Microbiome [4, 12, 52, 104 weeks]

    Absolute change in shannon index representing the alpha-diversity in sputum samples

  11. Sputum Elasticity [4, 12, 52, 104 weeks]

    Absolute change in the elastic modulus (G') in sputum samples measured with a rheometer

  12. Sputum Viscocity [4, 12, 52, 104 weeks]

    Absolute change in the viscous modulus (G'') in sputum samples measured with a rheometer

Eligibility Criteria

Criteria

Ages Eligible for Study:
6 Months and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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)

Contacts and Locations

Locations

Site City State Country Postal Code
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.
Responsible Party:
Simon Graeber, BIH Clinician Scientist, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT04732910
Other Study ID Numbers:
  • 20012746
First Posted:
Feb 1, 2021
Last Update Posted:
Apr 4, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Simon Graeber, BIH Clinician Scientist, Charite University, Berlin, Germany
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 4, 2022