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| Name | Class |
|---|---|
| Hannover Medical School | OTHER |
| Heidelberg University | OTHER |
| University of Giessen | OTHER |
| University of Luebeck |
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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).
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
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Treatment with cystic fibrosis transmembrane regulator (CFTR) modualtors Ivacaftor, Lumacaftor-Ivacaftor, Tezacaftor-Ivacaftor, Elexacaftor-Tezacaftor-Ivacaftor, Vanzacaftor-Tezacaftor-Deutivacaftor | Drug | observational |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Forced expiratory volume in 1 second (FEV1) | Absolute change from baseline in percent predicted forced expiratory volume in 1 second (FEV1) in spirometry | quaterly in the first year, yearly thereafter up to 5 years |
| Nasal potential Difference (NPD) |
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Inclusion Criteria:
Exclusion Criteria:
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Cystic Fibrosis patients
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Simon Y Graeber, MD | Contact | +4930 450 566 587 | simon.graeber@charite.de |
| Name | Affiliation | Role |
|---|---|---|
| Marcus A Mall, MD | Charite University, Berlin, Germany | Principal Investigator |
| Simon Y Graeber, MD | Charite University, Berlin, Germany | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Charité - Universitätsmedizin Berlin | Recruiting | Berlin | State of Berlin | 13353 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38573129 | Derived | Dohna M, Voskrebenzev A, Klimes F, Kaireit TF, Glandorf J, Pallenberg ST, Ringshausen FC, Hansen G, Renz DM, Wacker F, Dittrich AM, Vogel-Claussen J. PREFUL MRI for Monitoring Perfusion and Ventilation Changes after Elexacaftor-Tezacaftor-Ivacaftor Therapy for Cystic Fibrosis: A Feasibility Study. Radiol Cardiothorac Imaging. 2024 Apr;6(2):e230104. doi: 10.1148/ryct.230104. | |
| 37414422 |
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| OTHER |
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Sputum, Blood
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 |
| 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 weeks, yearly thereafter up to 5 years |
| Lung clearance index (LCI) | Absolute change from baseline of the lung clearance index (LCI) | quaterly in the first year, yearly thereafter up to 5 years |
| 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 weeks, yearly thereafter up to 5 years |
| 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 |
| 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 weeks, yearly thereafter up to 5 years |
| Fecal elastase | Absolute change from baseline in fecal elastase-1 (FE-1) levels | 12, 52 weeks, yearly thereafter up to 5 years |
| Weight | Absolute change from baseline in weight | quaterly in the first year, yearly thereafter up to 5 years |
| Airway Microbiome | Absolute change in shannon index representing the alpha-diversity in sputum samples | 4, 12, 52 weeks, yearly thereafter up to 5 years |
| Sputum Elasticity | Absolute change in the elastic modulus (G') in sputum samples measured with a rheometer | 4, 12, 52 weeks, yearly thereafter up to 5 years |
| Sputum Viscocity | Absolute change in the viscous modulus (G'') in sputum samples measured with a rheometer | 4, 12, 52 weeks, yearly thereafter up to 5 years |
| Cystic Fibrosis Questionnaire-Revised (CFQ-R) | 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. | quarterly in the first year, yearly thereafter up to 5 years |
| Patient Health Questionnaire-9 (PHQ-9) | 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. | quarterly in the first year, yearly thereafter up to 5 years |
| Generalized Anxiety Disorder-7 (GAD-7) | 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. | quarterly in the first year, yearly thereafter up to 5 years |
| Child Behavior Checklist for Ages 1½-5 (CBCL/1½-5) | 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. | quarterly in the first year, yearly thereafter up to 5 years |
| Child Behavior Checklist for Ages 6-18 (CBCL/6-18) | 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. | quarterly in the first year, yearly thereafter up to 5 years |
| Youth Self-Report for Ages 11-18 (YSR/11-18) | 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. | quarterly in the first year, yearly thereafter up to 5 years |
| Strengths and Difficulties Questionnaire (SDQ) | 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. | quarterly in the first year, yearly thereafter up to 5 years |
| 22-Item Sino-Nasal Outcome Test (SNOT-22) | 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. | quarterly in the first year, yearly thereafter up to 5 years |
| Justus-Liebig-University Giessen | Recruiting | Giessen | Germany |
|
| Hannover Medical School | Recruiting | Hanover | Germany |
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| University of Heidelberg | Recruiting | Heidelberg | Germany |
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| Derived |
| Schaupp L, Addante A, Voller M, Fentker K, Kuppe A, Bardua M, Duerr J, Piehler L, Rohmel J, Thee S, Kirchner M, Ziehm M, Lauster D, Haag R, Gradzielski M, Stahl M, Mertins P, Boutin S, Graeber SY, Mall MA. Longitudinal effects of elexacaftor/tezacaftor/ivacaftor on sputum viscoelastic properties, airway infection and inflammation in patients with cystic fibrosis. Eur Respir J. 2023 Aug 3;62(2):2202153. doi: 10.1183/13993003.02153-2022. Print 2023 Aug. |
| 35536314 | Derived | Graeber SY, Renz DM, Stahl M, Pallenberg ST, Sommerburg O, Naehrlich L, Berges J, Dohna M, Ringshausen FC, Doellinger F, Vitzthum C, Rohmel J, Allomba C, Hammerling S, Barth S, Ruckes-Nilges C, Wielputz MO, Hansen G, Vogel-Claussen J, Tummler B, Mall MA, Dittrich AM. Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Patients with Cystic Fibrosis and One or Two F508del Alleles. Am J Respir Crit Care Med. 2022 Aug 1;206(3):311-320. doi: 10.1164/rccm.202201-0219OC. |
| 34936849 | Derived | Graeber SY, Vitzthum C, Pallenberg ST, Naehrlich L, Stahl M, Rohrbach A, Drescher M, Minso R, Ringshausen FC, Rueckes-Nilges C, Klajda J, Berges J, Yu Y, Scheuermann H, Hirtz S, Sommerburg O, Dittrich AM, Tummler B, Mall MA. Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on CFTR Function in Patients with Cystic Fibrosis and One or Two F508del Alleles. Am J Respir Crit Care Med. 2022 Mar 1;205(5):540-549. doi: 10.1164/rccm.202110-2249OC. |
| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
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| ID | Term |
|---|---|
| D013812 | Therapeutics |
| C000599212 | lumacaftor, ivacaftor drug combination |
| C000654124 | tezacaftor, ivacaftor drug combination |
| C000706587 | elexacaftor, ivacaftor, tezacaftor drug combination |
| C000731138 | deutivacaftor, tezacaftor , vanzacaftor |
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