Cystic Fibrosis
Conditions
Keywords
CFTR, ICM, NPD
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
Interventions
DRUGTreatment with cystic fibrosis transmembrane regulator (CFTR) modualtors Ivacaftor, Lumacaftor-Ivacaftor, Tezacaftor-Ivacaftor, Elexacaftor-Tezacaftor-Ivacaftor, Vanzacaftor-Tezacaftor-Deutivacaftor
observational
Sponsors
Charite University, Berlin, Germany
Hannover Medical School
Heidelberg University
University of Giessen
University of Luebeck
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Forced expiratory volume in 1 second (FEV1) | quaterly in the first year, yearly thereafter up to 5 years | 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 weeks, yearly thereafter up to 5 years | 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) | quaterly in the first year, yearly thereafter up to 5 years | Absolute change from baseline of the lung clearance index (LCI) |
| Lung magnetic resonance imaging (MRI) | 12, 52 weeks, yearly thereafter up to 5 years | 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 weeks, yearly thereafter up to 5 years | 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 weeks, yearly thereafter up to 5 years | Absolute change from baseline in fecal elastase-1 (FE-1) levels |
| Weight | quaterly in the first year, yearly thereafter up to 5 years | Absolute change from baseline in weight |
| Airway Microbiome | 4, 12, 52 weeks, yearly thereafter up to 5 years | Absolute change in shannon index representing the alpha-diversity in sputum samples |
| Sputum Elasticity | 4, 12, 52 weeks, yearly thereafter up to 5 years | Absolute change in the elastic modulus (G') in sputum samples measured with a rheometer |
| Sputum Viscocity | 4, 12, 52 weeks, yearly thereafter up to 5 years | Absolute change in the viscous modulus (G'') in sputum samples measured with a rheometer |
| Cystic Fibrosis Questionnaire-Revised (CFQ-R) | quarterly in the first year, yearly thereafter up to 5 years | The Cystic Fibrosis Questionnaire-Revised is a disease-specific health-related quality of life instrument for individuals with cystic fibrosis. Scores are standardized on a 0-100 scale. Minimum: 0; Maximum: 100. Higher scores indicate better health-related quality of life. Absolute change from baseline is calculated as follow-up score minus baseline score. |
| Patient Health Questionnaire-9 (PHQ-9) | quarterly in the first year, yearly thereafter up to 5 years | The Patient Health Questionnaire-9 is a 9-item self-report measure assessing depressive symptom severity over the past two weeks. Total score range: 0-27. Minimum: 0; Maximum: 27. Higher scores indicate more severe depressive symptoms. Absolute change from baseline is calculated as follow-up score minus baseline score. |
| Generalized Anxiety Disorder-7 (GAD-7) | quarterly in the first year, yearly thereafter up to 5 years | The Generalized Anxiety Disorder-7 is a 7-item self-report measure assessing anxiety symptom severity over the past two weeks. Total score range: 0-21. Minimum: 0; Maximum: 21. Higher scores indicate more severe anxiety symptoms. Absolute change from baseline is calculated as follow-up score minus baseline score. |
| Child Behavior Checklist for Ages 1½-5 (CBCL/1½-5) | quarterly in the first year, yearly thereafter up to 5 years | The Child Behavior Checklist for Ages 1½-5 is a parent-reported measure assessing emotional and behavioral problems in children aged 18 months to 5 years. The Total Problems raw score ranges from 0-198. Minimum: 0; Maximum: 198. Higher scores indicate more emotional and behavioral problems. Absolute change from baseline is calculated as follow-up score minus baseline score. |
| Child Behavior Checklist for Ages 6-18 (CBCL/6-18) | quarterly in the first year, yearly thereafter up to 5 years | The Child Behavior Checklist for Ages 6-18 is a parent-reported measure of emotional and behavioral problems. Raw total problem scores range from 0-226. Minimum: 0; Maximum: 226. Higher scores indicate more behavioral and emotional problems. Absolute change from baseline is calculated as follow-up score minus baseline score. |
| Youth Self-Report for Ages 11-18 (YSR/11-18) | quarterly in the first year, yearly thereafter up to 5 years | The Youth Self-Report for Ages 11-18 is a self-report measure of emotional and behavioral problems, corresponding to the Child Behavior Checklist. Raw total problem scores range from 0-224. Minimum: 0; Maximum: 224. Higher scores indicate more behavioral and emotional problems. Absolute change from baseline is calculated as follow-up score minus baseline score. |
| Strengths and Difficulties Questionnaire (SDQ) | quarterly in the first year, yearly thereafter up to 5 years | The Strengths and Difficulties Questionnaire is a behavioral screening questionnaire. The Total Difficulties Score ranges from 0-40. Minimum: 0; Maximum: 40. Higher scores indicate more emotional and behavioral difficulties. Absolute change from baseline is calculated as follow-up score minus baseline score. |
| 22-Item Sino-Nasal Outcome Test (SNOT-22) | quarterly in the first year, yearly thereafter up to 5 years | The 22-Item Sino-Nasal Outcome Test assesses symptom severity and health-related quality of life in sinonasal disease. The total score ranges from 0-110. Minimum: 0; Maximum: 110. Higher scores indicate more severe symptoms and poorer quality of life. Absolute change from baseline is calculated as follow-up score minus baseline score. |
Countries
Germany
Contacts
CONTACTSimon Y Graeber, MD
PRINCIPAL_INVESTIGATORMarcus A Mall, MD
Charite University, Berlin, Germany
PRINCIPAL_INVESTIGATORSimon Y Graeber, MD
Charite University, Berlin, Germany
Outcome results
None listed