Response to CFTR Modulators in CF Patients Under 18 Years (MODUL-CF)

Societe Francaise de la Mucoviscidose

Status

Enrolling

Conditions

Cystic Fibrosis in Children

Treatments

Drug: CFTR Modulators

Study type

Observational

Funder types

Other

Identifiers

NCT04301856

0011928

Details and patient eligibility

About

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.

Full 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