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Prospective Study of the Phenotypic Expression of Cystic Fibrosis (CF) Screened Positive Newborns With an Atypical Form of CF (DPAM)

Not Applicable
Completed
Conditions
Cystic Fibrosis
Interventions
Radiation: Lung CT scan
Registration Number
NCT02869932
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
Brief Summary

The strategy of neonatal screening for Cystic Fibrosis in France relies on Immuno Reactive Trypsinogen (IRT) at day 3/DNA analysis with a CF Elucigen 30 mutations kit/ IRT safety-net at day 21. This strategy has significantly improved the performance of CF neonatal screening (NNS) in terms of positive predictive value and sensitivity but revealed new difficulties. Up to 85-90% of CF patients detected through the NNS program has a classical CF form with a positive sweat test and 2, 1 or no CF causing mutations but the remainder has either 2 CFTR mutations with at least one non-CF causing mutation and a sweat test \<60mmol/L or 1, 0 CFTR mutation and an intermediate sweat test value ≥ 30 et \< 60mmol/L raising a diagnosis and prognosis dilemma. Meanwhile the vast majority of these cohorts will remain asymptomatic over time, some will develop symptoms prompting clinicians to maintain a rigorous surveillance for the entire atypical cohort, whose modalities vary a lot among centers and countries.

This prospective multicenter study with a standardized assessment of a matched cohort with "atypical" CF versus "classical" CF from 6 years of age (60-65 cases in each cohort) is aimed at evaluating pulmonary and nutritional status to, better define the best monitoring follow-up, therapeutic management and familial genetic counseling.

Detailed Description

The strategy of neonatal screening for Cystic Fibrosis in France relies on Immuno Reactive Trypsinogen (IRT) at day 3/DNA analysis with a CF Elucigen 30 mutations kit/ IRT safety-net at day 21. This strategy has significantly improved the performance of CF neonatal screening (NNS) in terms of positive predictive value and sensitivity but revealed new difficulties. Up to 85-90% of CF patients detected through the NNS program has a classical CF form with a positive sweat test and 2, 1 or no CF causing mutations but the remainder has either 2 CFTR mutations with at least one non-CF causing mutation and a sweat test \<60mmol/L or 1, 0 CFTR mutation and an intermediate sweat test value ≥ 30 et \< 60mmol/L raising a diagnosis and prognosis dilemma. Meanwhile the vast majority of these cohorts will remain asymptomatic over time, some will develop symptoms prompting clinicians to maintain a rigorous surveillance for the entire atypical cohort, whose modalities vary a lot among centers and countries.

This prospective multicenter study with a standardized assessment of a matched cohort with "atypical" CF versus "classical" CF from 6 years of age (60-65 cases in each cohort) is aimed at evaluating pulmonary and nutritional status to, better define the best monitoring follow-up, therapeutic management and familial genetic counseling.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
130
Inclusion Criteria
  • Atypical CF cohort: children identified trough newborn screening on a hypertrypsinemia, who are older than 6 years of age at the time of inclusion and who carry a) 2 CFTR gene mutations of the CF30 kit with at least one R117H whatever the value of the sweat test or b) 2 CFTR gene mutations of the CF30 kit with a sweat test chloride < 60mmol/L or c) 1 or 0 mutation in the CF30 kit with a sweat test ≥ 30 and <60mmol/L and identification of additional mutations by comprehensive screening of the gene
  • Classical CF cohort: children identified by newborn screening on a hypertrypsinemia, who are matched with an Atypical CF by age and sex if possible and who were diagnosed with a classical CF based on a sweat test > 60 mmol/ L with 0, 1 or 2 CF causing gene mutations.
Exclusion Criteria
  • • Drugs such as CFTR modulators interfering with the phenotypic expression of the disease.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Atypical and classic cystic fibrosisLung CT scanLung CT scan without injection
Primary Outcome Measures
NameTimeMethod
Comparison of Score Brody 2 (0 to 270) between the atypical and classical CF cohorts1 day

Score Brody 2 (0 to 270) mesured by Lung CT scan without injection

Secondary Outcome Measures
NameTimeMethod
Comparison of Wisconsin and Brasfield scores between the atypical and classical CF cohorts1 day

Wisconsin and Brasfield scores will be mesured by Chest X-ray

Trial Locations

Locations (1)

Robert Debre Hospital - Assistance Puplique - Hôpitaux de Paris

🇫🇷

Paris, France

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