Response to CFTR Modulators in CF Patients Under 18 Years
- Conditions
- Cystic Fibrosis in Children
- Interventions
- Drug: CFTR Modulators
- Registration Number
- NCT04301856
- Lead Sponsor
- Societe Francaise de la Mucoviscidose
- Brief Summary
CFTR modulators should improve the prognosis of Cystic Fibrosis. Identifying patients under the age of 18 responding to CFTR modulators as well as detecting possible toxicity is an important medical objective given the potential side effects and the high cost of these molecules.
This observational follow-up cohort study is carried out as part of routine care.
The main objective is to assess the evolution of pulmonary structural impairment by low-dose CF scan at the end of the first year of CFTR modulator therapy.
The secondary objectives are to evaluate structural impairment at low dose scan at 3 years and 5 years of CFTR modulator treatment, the evolution of respiratory functional parameters, growth, puberty, lung infection, sweat test, quality of life and pancreatic function, as well as tolerance of modulators including liver toxicity.
- Detailed Description
Cystic fibrosis (CF) is a deadly disease. This is due to overinfected chronic obstructive pulmonary disease that progresses to end-stage respiratory failure. CFTR modulators should improve the prognosis of CF, as they may slow the progression of patients' lung disease. Assessing their impact in the paediatric population is becoming a major issue. Children and adolescents under the age of 18 are a target cohort because they have a lung disease that is still poorly developed. Early prescription of CFTR modulators is therefore a priority but requires evidence of absence of toxicity. Identifying patients under the age of 18 responding to CFTR modulators as well as detecting possible toxicity, is an important medical objective given the potential side effects and the high cost of these molecules.
The outcomes previously used in Phase III studies (FEV1, frequency of exacerbations, nutritional status) are insufficiently sensitive in this population.
Other criteria need to be analyzed to identify the response to CFTR modulators in the short and medium term. The investigators hypothesize that the assessment of pulmonary structural impairment by low-dose lung CT-scan as part of routine care could be a much more sensitive criterion for the development of lung disease under CFTR modulators.
This observational follow-up cohort study is carried out as part of routine care. It does not involve a specific collection for research. Excess bronchial secretions and blood will be kept instead of being discarded in the event of a possible requalification for research.
The main objective is to assess the evolution of pulmonary structural impairment by low-dose CF scan at the end of the first year of CFTR modulator therapy The secondary objectives are to assess following criteria
* Tolerance of modulators in this age group, including screening for bronchial reactivity at treatment, early liver toxicity
* Longitudinal evolution of pulmonary structural impairment by low dose scan at 3 years and 5 years of CFTR modulator treatment
* Evolution of respiratory functional parameters
* Measurement by spirometry and plethysmography
* Lung clearance index (if possible)
* Longitudinal evolution of bacterial colonization, compared to the year prior to modulating treatment
* Exacerbations: number, duration, days of antibiotics, hospitalizations, return to stable condition
* Colonization of bronchial secretions
* Changes in quality of life
* Evolution of the sweat test
* Longitudinal evaluation of pancreatic function
* Longitudinal evaluation of growth and puberty compared to the year prior to CFTR modulator
* Growth speed, and bone age
* Bone mineralization, body composition (if possible)
* Pubertal markers from 9 years in girls and 10 years in boys
* Evaluation of glycemic dysregulation if present
* Preservation of samples taken as part of routine care (serum, bronchial secretions) for possible research use
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 600
Children with cystic fibrosis under the age of 18 under CFTR modulator therapy
- Patients with cystic fibrosis without indication for CFTR modulator therapy
- Patients over the age of 18
- Pregnant or lactating women
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description CF children treated with CFTR modul CFTR Modulators Cystic fibrosis patients under 18 years treated with CFTR modulators according to french health recommendations observational cohort study
- Primary Outcome Measures
Name Time Method Lung Imaging at 5 years, as part of national guidelines Lung structural injury assessed by Low Dose CT, as part of routine care
- Secondary Outcome Measures
Name Time Method Lung Clearance Index - Lung Clearance Index longitudinal monitoring of assessments carried out as part of routine care during 5 yrs Lung clearance of nitrogen
colonization of bronchial secretions longitudinal monitoring of assessments carried out as part of routine care during 5 yrs bacteria, fungi, mycobacteria
weight in kilogrammes longitudinal monitoring of assessments carried out as part of routine care during 5 yrs weight in kilogrammes (associated with a retrospective collection in the year prior to treatment)
bronchial infectious exacerbations longitudinal monitoring of assessments carried out as part of routine care during 5 yrs bronchial infectious exacerbations (associated with a retrospective collection in the year prior to treatment)
quality of life questionnaire longitudinal monitoring of assessments carried out as part of routine care during 5 yrs CFQ questionnaire for children above 8 years: worse 0, better 100
height in meters longitudinal monitoring of assessments carried out as part of routine care during 5 yrs height in meters (associated with a retrospective collection in the year prior to treatment)
pubertal evolution longitudinal monitoring of assessments carried out as part of routine care during 5 yrs pubertal evolution (associated with a retrospective collection in the year prior to treatment)
Forced Vital Capacity (FVC) longitudinal monitoring of assessments carried out as part of routine care during 5 yrs Forced Vital Capacity (FVC) in liter
Force Expiratory Flow 50 (FEV50) longitudinal monitoring of assessments carried out as part of routine care during 5 yrs Force Expiratory Flow 50 (FEV50) in liter
Forced Expiratory Flow 25-75 (FEV25-75) longitudinal monitoring of assessments carried out as part of routine care during 5 yrs Forced Expiratory Flow 25-75 (FEV25-75) in liter
sweat test longitudinal monitoring of assessments carried out as part of routine care during 5 yrs sweat collection
puberty longitudinal monitoring of assessments carried out as part of routine care during 5 yrs serum dosage of FSH, LH, Estradiol, testosterone Pelvic ultrasound if puberty initiated in girls
intestine inflammation longitudinal monitoring of assessments carried out as part of routine care during 5 yrs fecal Calprotectine
side effects: declarative collection and monitoring longitudinal monitoring of assessments carried out as part of routine care during 5 yrs declarative collection and monitoring
Forced Expiratory Volume in 1 second(FEV1) longitudinal monitoring of assessments carried out as part of routine care during 5 yrs Forced Expiratory Volume in 1 second(FEV1) in liter
Residual Volume (RV) longitudinal monitoring of assessments carried out as part of routine care during 5 yrs Residual Volume (RV) in liter
Total Pulmonary Capacity longitudinal monitoring of assessments carried out as part of routine care during 5 yrs Total Pulmonary Capacity in liter
ENT quality of life questionnaire longitudinal monitoring of assessments carried out as part of routine care during 5 yrs SN-score: better score 1, worse 7
Abdominal quality of life questionnaire longitudinal monitoring of assessments carried out as part of routine care during 5 yrs better score: 0, worse: 25
liver ultrasound longitudinal monitoring of assessments carried out as part of routine care during 5 yrs liver ultrasound
serum and fecal pancreatic biological markers longitudinal monitoring of assessments carried out as part of routine care during 5 yrs immunoreactive trypsin, lipase, amylase, vitamin A and E, Prothrombin time, and fecal (fecal elastase
bone biological markers longitudinal monitoring of assessments carried out as part of routine care during 5 yrs 25OHvitD, Ca, P, PTH, Osteocalcin, IgF1, IgF1BP3, CTX
bone maturation longitudinal monitoring of assessments carried out as part of routine care during 5 yrs Zscore (in relation to height and sex and weight) (data available in centers with the necessary equipment)
elastometry (data available in centers with the necessary equipment) longitudinal monitoring of assessments carried out as part of routine care during 5 yrs elastometry (data available in centers with the necessary equipment)
glycemic regulation longitudinal monitoring of assessments carried out as part of routine care during 5 yrs monitoring of glycemic dysregulation ( as routinely done in the centers)
Trial Locations
- Locations (1)
Sermet-Gaudelus Isabelle
🇫🇷Paris, France