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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-A00309-42 | Other Identifier | ANSM, French national agency for drug safety |
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| Name | Class |
|---|---|
| Association Mucoviscidose-ABCF2 | OTHER |
| Vaincre la Mucoviscidose | OTHER |
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The purpose of this study is to determine which biological marker, or association of biological markers, best predict clinical response of cystic fibrosis patients to CFTR modulators.
This study is based upon the hypothesis that clinical response of cystic fibrosis patients to CFTR modulators is correlated to in vitro responses to these drugs of epithelial cells derived from the patients, as assessed by CFTR-dependent Chloride secretion. Epithelial cells will be derived either from nasal or rectal epithelia, and consist both of cultured cells and organoids. The drugs tested will be Ivacaftor, or Lumacaftor/Ivacaftor, according to patient's treatment. Results of these assays will be compared with response to treatment at 6 and 12 months, assessed by clinical response and in vivo assay of CFTR function.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cystic fibrosis, treated | Other | Cystic fibrosis patients treated either by Ivacaftor or by the association Ivacaftor-Lumacaftor |
|
| Cystic fibrosis, non treated | Other | Cystic fibrosis patients, non treated by a CFTR modulator |
|
| Non-Cystic fibrosis | Other | Patients in whom cystic fibrosis diagnosis has been suspected, but excluded by physiological and genetic investigations |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nasal swab; rectal biopsy. | Procedure | Nasal epithelial cells will be obtained by nasal swabs from patients of the three arms; intestinal epithelial cells will be obtained, by rectal biopsy, only from patients treated by CFTR modulators. |
| Measure | Description | Time Frame |
|---|---|---|
| Forced Expiratory Volume in 1 second | Respiratory Function test | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Forced Vital Capacity | Respiratory Function test | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months |
| Forced Expiratory Flow 25-75 | Respiratory Function test |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Isabelle Sermet, MD, PhD | Contact | 33 1 44 49 48 87 | isabelle.sermet@aphp.fr | |
| Jean-Louis Pérignon, MD, PhD | Contact | jean-louis.perignon@aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Aleksander Edelman, phD | APHP | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Necker Hospital | Recruiting | Paris | 75014 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22047557 | Background | Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Drevinek P, Griese M, McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe SM, Dong Q, Rodriguez S, Yen K, Ordonez C, Elborn JS; VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011 Nov 3;365(18):1663-72. doi: 10.1056/NEJMoa1105185. | |
| 26568242 |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| initiation, 7 days, 1 month, 6 months, 1 year and every 6 months |
| Residual Volume | Respiratory Function test | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months |
| elastase in sputum | elastase activity in UI/g of sputum | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months |
| calprotectin in sputum | calprotectin in µg/g of sputum | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months |
| IL-8 in sputum | IL-8 in µg/g of sputum | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months |
| Calprotectin in blood | calprotectin in µg/ml of blood | initiation, 1 month, 3 Months, 6 months and every 6 months |
| IL-8 in blood | IL-8 in µg/ml of blood | initiation, 1 month, 3 Months, 6 months and every 6 months |
| tumor necrosis factor in sputum | tumor necrosis factor in µg/g of sputum | initiation, 1 month, 3 Months, 6 months and every 6 months |
| liver function test in blood | serum glutamate oxaloacetate transaminase in ui/ml | initiation, 1 month, 3 Months, 6 months and every 6 months |
| liver function test/SGPT in blood | serum glutamate pyruvate transaminase in ui/ml | initiation, 1 month, 3 Months, 6 months and every 6 months |
| liver function test/bilirubin in blood | Bilirubin in mg/ml | initiation, 1 month, 3 Months, 6 months and every 6 months |
| liver function test, gammaGT in blood | GammaGT in UI/ml | initiation, 1 month, 3 Months, 6 months and every 6 months |
| creatine phosphokinase in blood | CPK in mg/ml | initiation, 1 month, 3 Months, 6 months and every 6 months |
| Amylase in blood | amylase in mg/ml | initiation, 1 month, 3 Months, 6 months and every 6 months |
| Impedancemetry | ambulatory measurement of body composition | initiation , 1 month, 3 Months, 6 months and every 6 months |
| Dynamometry | ambulatory measurement of quadriceps strength | initiation , 1 month, 3 Months, 6 months and every 6 months |
| Sweat test | chloride concentration in sweat | initiation ,1 month |
| proteomics of sweat | measurement of proteins in sweat | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months |
| metabolomics of sweat | measurement of métabolites in sweat | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months |
| proteomics of exhalate | measurement of proteins in exhaled air | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months |
| sputum bronchial microorganism colonization | bacterial, fungi and viral colonization | initiation , 1 month, 3 Months, 6 months and every 6 months |
| Lung MRI | Lung Imaging evaluation : number of bronchiectasis, number of mucus plugs | initiation, at 1 year and every year |
| osteodensitometry | Bone mineralization body composition | initiation, 1 year, and every year |
| fecal elastase | elastase feces in µg/g feces | initiation, at 6 months and every year |
| fecal calprotectin | calprotectin, concentraion in feces in µg/g | initiation, at 6 months and every year |
| Chest CT scan | Lung Imaging: % versuys normal of lung parenchuma with bronchiectasis, airway wall thickening, mucus plugs, air trapping | initiation, 3 years and 5 years |
| glycemic Holter | glycemia monitoring | initiation, 1 year and every year |
| abdominal ultrasonography | presence of liver hyperechogenicity, fibrosis, as assessed by the radiologist | treatment initiation, 1 year and every year |
| proton density fat fraction | magnetic resonance Imaging of the Pancreas | treatment initiation, 1 year |
| patient quality of life | Score tolerance of the treatment, perception of respiratory, digestive symptoms, energy, body image as assessed by the "Cystic Fibrosis Questionnaire" score a better quality of life is indicated by an increase in the score value. Minimum value is 0, maximum is 100. | initiation, 1 month, 6 months, 1 year and every 6 months |
| CFTR activity in nasal cells/chloride | Chloride transport in primary nasal cell cultures obtained by nasal brushing and study in Ussing chamber (µA/cm2) | initiation of treatment and repeated if cell culture failure |
| CFTR activity in nasal cells/bicarbonat | Bicarbonate transport in primary nasal cell cultures obtained by nasal brushing and study in Ussing chamber (µA/cm2) | initiation of treatment and repeated if cell culture failure |
| CFTR activity in intestinal epithelium/chloride | Chloride transport in intestinal primary culture and study in Ussing chamber (µA/cm2) | initiation of treatment and repeated of cell culture failure |
| CFTR activity in intestinal epithelium/bicarbonate | Bicarbonate transport in intestinal primary culture and study in Ussing chamber (µA/cm2) | initiation of treatment and repeated of cell culture failure |
| sweat evaporimetry | quantity of sweat produced afer bet-adrenergic stimulation after subcutaneous injection | initiation and 1 month |
| Elasto MRI | measurement of liver fibrosis by MRI | initiation and 1 year |
| Lung Clearance Index | Capacity of the lung to washout pure Oxygen, | initiation, 6 months, 1 year and every 6 months |
| proteomics in blood | measurement of proteins in blood | initiation, 7 days, 1 month, 6 months, 1 year and every year |
| metabolomics in blood | measurement of métabolites in blood | initiation, 7 days, 1 month, 6 months, 1 year and every year |
| proteomic in urine | measurement of proteins in blood | initiation, 7 days, 1 month, 6 months, 1 year and every year |
| metabolomics in urine | measurement of métabolites in urine | initiation, 7 days, 1 month, 6 months, 1 year and every year |
| Exhaled air composition | Volatile organic compounds in exhaled air | initiation, 7 days, 1 month, 6 months, 1 year and every year |
| Background |
| Graeber SY, Hug MJ, Sommerburg O, Hirtz S, Hentschel J, Heinzmann A, Dopfer C, Schulz A, Mainz JG, Tummler B, Mall MA. Intestinal Current Measurements Detect Activation of Mutant CFTR in Patients with Cystic Fibrosis with the G551D Mutation Treated with Ivacaftor. Am J Respir Crit Care Med. 2015 Nov 15;192(10):1252-5. doi: 10.1164/rccm.201507-1271LE. No abstract available. |
| 26135562 | Background | Quittner A, Suthoff E, Rendas-Baum R, Bayliss MS, Sermet-Gaudelus I, Castiglione B, Vera-Llonch M. Effect of ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation: patient-reported outcomes in the STRIVE randomized, controlled trial. Health Qual Life Outcomes. 2015 Jul 2;13:93. doi: 10.1186/s12955-015-0293-6. |
| 25266159 | Background | De Boeck K, Munck A, Walker S, Faro A, Hiatt P, Gilmartin G, Higgins M. Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation. J Cyst Fibros. 2014 Dec;13(6):674-80. doi: 10.1016/j.jcf.2014.09.005. Epub 2014 Sep 26. |
| 24973281 | Background | Boyle MP, Bell SC, Konstan MW, McColley SA, Rowe SM, Rietschel E, Huang X, Waltz D, Patel NR, Rodman D; VX09-809-102 study group. A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med. 2014 Jul;2(7):527-38. doi: 10.1016/S2213-2600(14)70132-8. Epub 2014 Jun 24. |
| 25981758 | Background | Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, Colombo C, Davies JC, De Boeck K, Flume PA, Konstan MW, McColley SA, McCoy K, McKone EF, Munck A, Ratjen F, Rowe SM, Waltz D, Boyle MP; TRAFFIC Study Group; TRANSPORT Study Group. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. N Engl J Med. 2015 Jul 16;373(3):220-31. doi: 10.1056/NEJMoa1409547. Epub 2015 May 17. |
| 22878883 | Background | De Boeck K, Kent L, Davies J, Derichs N, Amaral M, Rowe SM, Middleton P, de Jonge H, Bronsveld I, Wilschanski M, Melotti P, Danner-Boucher I, Boerner S, Fajac I, Southern K, de Nooijer RA, Bot A, de Rijke Y, de Wachter E, Leal T, Vermeulen F, Hug MJ, Rault G, Nguyen-Khoa T, Barreto C, Proesmans M, Sermet-Gaudelus I; European Cystic Fibrosis Society Clinical Trial Network Standardisation Committee. CFTR biomarkers: time for promotion to surrogate end-point. Eur Respir J. 2013 Jan;41(1):203-16. doi: 10.1183/09031936.00057512. Epub 2012 Aug 9. |
| 23727931 | Background | Dekkers JF, Wiegerinck CL, de Jonge HR, Bronsveld I, Janssens HM, de Winter-de Groot KM, Brandsma AM, de Jong NW, Bijvelds MJ, Scholte BJ, Nieuwenhuis EE, van den Brink S, Clevers H, van der Ent CK, Middendorp S, Beekman JM. A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nat Med. 2013 Jul;19(7):939-45. doi: 10.1038/nm.3201. Epub 2013 Jun 2. |
| 30326728 | Derived | Pranke I, Hatton A, Masson A, Flament T, Le Bourgeois M, Chedevergne F, Bailly C, Urbach V, Hinzpeter A, Edelman A, Sermet-Gaudelus I. Might Brushed Nasal Cells Be a Surrogate for CFTR Modulator Clinical Response? Am J Respir Crit Care Med. 2019 Jan 1;199(1):123-126. doi: 10.1164/rccm.201808-1436LE. No abstract available. |
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |