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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Radiation: Lung CT scan

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.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75019
    • Robert Debre Hospital - Assistance Puplique - Hôpitaux de Paris

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 10 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Atypical and classic cystic fibrosis; Lung CT scan without injection	Radiation: Lung CT scan; Lung CT scan without injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Score Brody 2 (0 to 270) between the atypical and classical CF cohorts	Score Brody 2 (0 to 270) mesured by Lung CT scan without injection	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Wisconsin and Brasfield scores between the atypical and classical CF cohorts	Wisconsin and Brasfield scores will be mesured by Chest X-ray	1 day

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Vaincre la Mucoviscidose; French society of cystic fibrosis; AFDPHE : newborn screening of the French Society of Cystic Fibrosis

Publications and helpful links

General Publications

• Munck A, Bourmaud A, Bellon G, Picq P, Farrell PM; DPAM Study Group. Phenotype of children with inconclusive cystic fibrosis diagnosis after newborn screening. Pediatr Pulmonol. 2020 Apr;55(4):918-928. doi: 10.1002/ppul.24634. Epub 2020 Jan 9.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ACTUAL): March 1, 2015
• Study Completion (ACTUAL): March 1, 2015

Study Registration Dates

• First Submitted: January 9, 2015
• First Submitted That Met QC Criteria: August 12, 2016
• First Posted (ESTIMATE): August 17, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: P101003