Surrogate Markers of Response to New Therapies in Cystic Fibrosis Patients
- Conditions
- Cystic Fibrosis
- Interventions
- Procedure: Nasal swab; rectal biopsy.
- Registration Number
- NCT02965326
- Lead Sponsor
- Hôpital Necker-Enfants Malades
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 75
- 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
- pregnant or lactating women
- contraindication to nasal swab
- contraindication to rectal biopsy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cystic fibrosis, treated Nasal swab; rectal biopsy. Cystic fibrosis patients treated either by Ivacaftor or by the association Ivacaftor-Lumacaftor Cystic fibrosis, non treated Nasal swab; rectal biopsy. Cystic fibrosis patients, non treated by a CFTR modulator Non-Cystic fibrosis Nasal swab; rectal biopsy. Patients in whom cystic fibrosis diagnosis has been suspected, but excluded by physiological and genetic investigations
- Primary Outcome Measures
Name Time Method Forced Expiratory Volume in 1 second initiation, 7 days, 1 month, 6 months, 1 year and every 6 months Respiratory Function test
- Secondary Outcome Measures
Name Time Method IL-8 in sputum initiation, 7 days, 1 month, 6 months, 1 year and every 6 months IL-8 in µg/g of sputum
Amylase in blood initiation, 1 month, 3 Months, 6 months and every 6 months amylase in mg/ml
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
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
abdominal ultrasonography treatment initiation, 1 year and every year presence of liver hyperechogenicity, fibrosis, as assessed by the radiologist
calprotectin in sputum initiation, 7 days, 1 month, 6 months, 1 year and every 6 months calprotectin in µg/g of sputum
proteomics of exhalate initiation, 7 days, 1 month, 6 months, 1 year and every 6 months measurement of proteins in exhaled air
proton density fat fraction treatment initiation, 1 year magnetic resonance Imaging of the Pancreas
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)
proteomics in blood initiation, 7 days, 1 month, 6 months, 1 year and every year measurement of proteins in blood
metabolomics in blood initiation, 7 days, 1 month, 6 months, 1 year and every year measurement of métabolites in blood
metabolomics in urine initiation, 7 days, 1 month, 6 months, 1 year and every year measurement of métabolites in urine
Forced Expiratory Flow 25-75 initiation, 7 days, 1 month, 6 months, 1 year and every 6 months Respiratory Function test
Forced Vital Capacity 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 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
sputum bronchial microorganism colonization initiation , 1 month, 3 Months, 6 months and every 6 months bacterial, fungi and viral colonization
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
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/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)
Residual Volume initiation, 7 days, 1 month, 6 months, 1 year and every 6 months Respiratory Function test
creatine phosphokinase in blood initiation, 1 month, 3 Months, 6 months and every 6 months CPK in mg/ml
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/SGPT in blood initiation, 1 month, 3 Months, 6 months and every 6 months serum glutamate pyruvate 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
metabolomics of sweat initiation, 7 days, 1 month, 6 months, 1 year and every 6 months measurement of métabolites in sweat
glycemic Holter initiation, 1 year and every year glycemia monitoring
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)
proteomic in urine initiation, 7 days, 1 month, 6 months, 1 year and every year measurement of proteins in blood
Exhaled air composition initiation, 7 days, 1 month, 6 months, 1 year and every year Volatile organic compounds in exhaled air
Impedancemetry initiation , 1 month, 3 Months, 6 months and every 6 months ambulatory measurement of body composition
proteomics of sweat initiation, 7 days, 1 month, 6 months, 1 year and every 6 months measurement of proteins in sweat
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
sweat evaporimetry initiation and 1 month quantity of sweat produced afer bet-adrenergic stimulation after subcutaneous injection
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)
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,
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
Trial Locations
- Locations (1)
Necker Hospital
🇫🇷Paris, France