Cystic Fibrosis
Conditions
Brief summary
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.
Detailed description
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.
Interventions
PROCEDURENasal swab; rectal biopsy.
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.
Sponsors
Association Mucoviscidose-ABCF2
Vaincre la Mucoviscidose
Hôpital Necker-Enfants Malades
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Cystic fibrosis patients treated by CFTR modulators (Ivacaftor or the association Ivacaftor-Lumacaftor) * Cystic fibrosis patients non treated by CFTR modulators * Patients in whom cystic fibrosis diagnosis has been suspected, but excluded by physiological and genetic investigations
Exclusion criteria
* pregnant or lactating women * contraindication to nasal swab * contraindication to rectal biopsy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in 1 second | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months | Respiratory Function test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Forced Vital Capacity | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months | Respiratory Function test |
| Forced Expiratory Flow 25-75 | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months | Respiratory Function test |
| Residual Volume | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months | Respiratory Function test |
| elastase in sputum | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months | elastase activity in UI/g of sputum |
| calprotectin in sputum | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months | calprotectin in µg/g of sputum |
| IL-8 in sputum | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months | IL-8 in µg/g of sputum |
| Calprotectin in blood | initiation, 1 month, 3 Months, 6 months and every 6 months | calprotectin in µg/ml of blood |
| IL-8 in blood | initiation, 1 month, 3 Months, 6 months and every 6 months | IL-8 in µg/ml of blood |
| tumor necrosis factor in sputum | initiation, 1 month, 3 Months, 6 months and every 6 months | tumor necrosis factor in µg/g of sputum |
| liver function test in blood | initiation, 1 month, 3 Months, 6 months and every 6 months | serum glutamate oxaloacetate transaminase in ui/ml |
| liver function test/bilirubin in blood | initiation, 1 month, 3 Months, 6 months and every 6 months | Bilirubin in mg/ml |
| liver function test, gammaGT in blood | initiation, 1 month, 3 Months, 6 months and every 6 months | GammaGT in UI/ml |
| creatine phosphokinase in blood | initiation, 1 month, 3 Months, 6 months and every 6 months | CPK in mg/ml |
| Amylase in blood | initiation, 1 month, 3 Months, 6 months and every 6 months | amylase in mg/ml |
| Impedancemetry | initiation , 1 month, 3 Months, 6 months and every 6 months | ambulatory measurement of body composition |
| Dynamometry | initiation , 1 month, 3 Months, 6 months and every 6 months | ambulatory measurement of quadriceps strength |
| Sweat test | initiation ,1 month | chloride concentration in sweat |
| proteomics of sweat | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months | measurement of proteins in sweat |
| metabolomics of sweat | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months | measurement of métabolites in sweat |
| proteomics of exhalate | initiation, 7 days, 1 month, 6 months, 1 year and every 6 months | measurement of proteins in exhaled air |
| sputum bronchial microorganism colonization | initiation , 1 month, 3 Months, 6 months and every 6 months | bacterial, fungi and viral colonization |
| Lung MRI | initiation, at 1 year and every year | Lung Imaging evaluation : number of bronchiectasis, number of mucus plugs |
| osteodensitometry | initiation, 1 year, and every year | Bone mineralization body composition |
| fecal elastase | initiation, at 6 months and every year | elastase feces in µg/g feces |
| fecal calprotectin | initiation, at 6 months and every year | calprotectin, concentraion in feces in µg/g |
| Chest CT scan | initiation, 3 years and 5 years | Lung Imaging: % versuys normal of lung parenchuma with bronchiectasis, airway wall thickening, mucus plugs, air trapping |
| glycemic Holter | initiation, 1 year and every year | glycemia monitoring |
| abdominal ultrasonography | treatment initiation, 1 year and every year | presence of liver hyperechogenicity, fibrosis, as assessed by the radiologist |
| proton density fat fraction | treatment initiation, 1 year | magnetic resonance Imaging of the Pancreas |
| patient quality of life | initiation, 1 month, 6 months, 1 year and every 6 months | 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. |
| CFTR activity in nasal cells/chloride | initiation of treatment and repeated if cell culture failure | Chloride transport in primary nasal cell cultures obtained by nasal brushing and study in Ussing chamber (µA/cm2) |
| CFTR activity in nasal cells/bicarbonat | initiation of treatment and repeated if cell culture failure | Bicarbonate transport in primary nasal cell cultures obtained by nasal brushing and study in Ussing chamber (µA/cm2) |
| CFTR activity in intestinal epithelium/chloride | initiation of treatment and repeated of cell culture failure | Chloride transport in intestinal primary culture and study in Ussing chamber (µA/cm2) |
| CFTR activity in intestinal epithelium/bicarbonate | initiation of treatment and repeated of cell culture failure | Bicarbonate transport in intestinal primary culture and study in Ussing chamber (µA/cm2) |
| sweat evaporimetry | initiation and 1 month | quantity of sweat produced afer bet-adrenergic stimulation after subcutaneous injection |
| Elasto MRI | initiation and 1 year | measurement of liver fibrosis by MRI |
| Lung Clearance Index | initiation, 6 months, 1 year and every 6 months | Capacity of the lung to washout pure Oxygen, |
| liver function test/SGPT in blood | initiation, 1 month, 3 Months, 6 months and every 6 months | serum glutamate pyruvate transaminase in ui/ml |
| metabolomics in blood | initiation, 7 days, 1 month, 6 months, 1 year and every year | measurement of métabolites in blood |
| proteomic in urine | initiation, 7 days, 1 month, 6 months, 1 year and every year | measurement of proteins in blood |
| metabolomics in urine | initiation, 7 days, 1 month, 6 months, 1 year and every year | measurement of métabolites in urine |
| Exhaled air composition | initiation, 7 days, 1 month, 6 months, 1 year and every year | Volatile organic compounds in exhaled air |
| proteomics in blood | initiation, 7 days, 1 month, 6 months, 1 year and every year | measurement of proteins in blood |
Countries
France
Contacts
Primary ContactIsabelle Sermet, MD, PhD
Backup ContactJean-Louis Pérignon, MD, PhD
Outcome results
None listed