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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
75
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.
Necker Hospital
Paris, France
RECRUITINGForced Expiratory Volume in 1 second
Respiratory Function test
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
Forced Vital Capacity
Respiratory Function test
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
Forced Expiratory Flow 25-75
Respiratory Function test
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
Residual Volume
Respiratory Function test
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
elastase in sputum
elastase activity in UI/g of sputum
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
calprotectin in sputum
calprotectin in µg/g of sputum
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
IL-8 in sputum
IL-8 in µg/g of sputum
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
Calprotectin in blood
calprotectin in µg/ml of blood
Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months
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IL-8 in blood
IL-8 in µg/ml of blood
Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months
tumor necrosis factor in sputum
tumor necrosis factor in µg/g of sputum
Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months
liver function test in blood
serum glutamate oxaloacetate transaminase in ui/ml
Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months
liver function test/SGPT in blood
serum glutamate pyruvate transaminase in ui/ml
Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months
liver function test/bilirubin in blood
Bilirubin in mg/ml
Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months
liver function test, gammaGT in blood
GammaGT in UI/ml
Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months
creatine phosphokinase in blood
CPK in mg/ml
Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months
Amylase in blood
amylase in mg/ml
Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months
Impedancemetry
ambulatory measurement of body composition
Time frame: initiation , 1 month, 3 Months, 6 months and every 6 months
Dynamometry
ambulatory measurement of quadriceps strength
Time frame: initiation , 1 month, 3 Months, 6 months and every 6 months
Sweat test
chloride concentration in sweat
Time frame: initiation ,1 month
proteomics of sweat
measurement of proteins in sweat
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
metabolomics of sweat
measurement of métabolites in sweat
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
proteomics of exhalate
measurement of proteins in exhaled air
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
sputum bronchial microorganism colonization
bacterial, fungi and viral colonization
Time frame: initiation , 1 month, 3 Months, 6 months and every 6 months
Lung MRI
Lung Imaging evaluation : number of bronchiectasis, number of mucus plugs
Time frame: initiation, at 1 year and every year
osteodensitometry
Bone mineralization body composition
Time frame: initiation, 1 year, and every year
fecal elastase
elastase feces in µg/g feces
Time frame: initiation, at 6 months and every year
fecal calprotectin
calprotectin, concentraion in feces in µg/g
Time frame: 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
Time frame: initiation, 3 years and 5 years
glycemic Holter
glycemia monitoring
Time frame: initiation, 1 year and every year
abdominal ultrasonography
presence of liver hyperechogenicity, fibrosis, as assessed by the radiologist
Time frame: treatment initiation, 1 year and every year
proton density fat fraction
magnetic resonance Imaging of the Pancreas
Time frame: 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.
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: initiation of treatment and repeated of cell culture failure
sweat evaporimetry
quantity of sweat produced afer bet-adrenergic stimulation after subcutaneous injection
Time frame: initiation and 1 month
Elasto MRI
measurement of liver fibrosis by MRI
Time frame: initiation and 1 year
Lung Clearance Index
Capacity of the lung to washout pure Oxygen,
Time frame: initiation, 6 months, 1 year and every 6 months
proteomics in blood
measurement of proteins in blood
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every year
metabolomics in blood
measurement of métabolites in blood
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every year
proteomic in urine
measurement of proteins in blood
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every year
metabolomics in urine
measurement of métabolites in urine
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every year
Exhaled air composition
Volatile organic compounds in exhaled air
Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every year