Clinical trial NCT04717115: Genotype/Phenotype Correlation With Focus on Lung Function in Primary Ciliary Dyskinesia (PCD)
Official title: An International Study on Genotype/Phenotype Correlation With Focus on Lung Function in Patients With Primary Ciliary Dyskinesia (PCD)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Ciliary Motility Disorders
Primary Ciliary Dyskinesia
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Hospital Vall d'Hebron
name: KU Leuven
name: Amsterdam UMC, location VUmc
name: University of Valencia
name: NOVA Medical School
name: University of Geneva, Switzerland
name: University of Bern
name: Ruhr University of Bochum
name: Charite University, Berlin, Germany
name: Hannover Medical School
name: Medical University of Vienna
name: Royal Brompton & Harefield NHS Foundation Trust
name: University College, London
name: University of Dundee
name: University of Southampton
name: University of Leicester
name: University of Pisa
name: Federico II University
name: Bambino Gesù Hospital and Research Institute
name: University of Nicosia
name: Oslo University Hospital
name: Hospital de Niños R. Gutierrez de Buenos Aires
name: Hacettepe University
name: Marmara University
name: University Hospital, Motol
name: University Children's Hospital, Zurich
name: The Leeds Teaching Hospitals NHS Trust
name: Hadassah Medical Organization
name: Göteborg University
name: Schneider Children's Medical Center, Israel
name: University of Sao Paulo
name: University Hospital of Cologne
name: University of Belgrade
name: University Hospital, Martin
name: Abderrahmane Mami Hospital
First posted: 2021-01-20
Enrollment: 1500
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: PCD patients with proven bi-allelic mutations in a gene known to cause PCD

Brief summary: Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder characterized by dysfunction of motile cilia associated with recurrent infections of the airways, laterality defects (Situs inversus totalis in about 50% of cases) and fertility problems. At present, mutations in \> 45 genes associated with PCD and mucociliary clearance disorders have been identified, representing most likely two thirds of all human cases.

Aim of this study are:

* Correlation between genotype and lung function of patients with genetically confirmed PCD in an international cohort on a longitudinal basis
* Determination of further parameters, such as body mass index (BMI), possibly associated with lung function in genetically confirmed PCD patients

Detailed description: Background Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder characterized by dysfunction of motile cilia associated with recurrent infections of the airways, laterality defects (Situs inversus totalis in about 50% of cases) and fertility problems. At present, mutations in \> 40 genes associated with PCD and mucociliary clearance disorders have been identified, representing most likely two thirds of all human cases. While being involved in the majority of identified PCD genes, our working group has a great expertise in genetic analysis and diagnostic work-up of patients with PCD.

Hallmark symptom of PCD is the chronic purulent lung disease due to the reduced mucociliary clearance. Chronic inflammation and recurrent infections of the airways promote continuous lung damage, bronchiectasis and could finally lead to total lung failure. For other congenital diseases with chronic lung conditions, e.g. cystic fibrosis (CF), an affected lung function with a steady decline is well described and spirometry is widely used to monitor disease progression. For PCD there are only limited data available and studies often comprise small cohorts. In general, available data assume a decline of lung function in PCD patients compared to healthy individuals, but less pronounced than in CF. Altogether, results of the studies remain heterogeneous, in particular concerning the influence of an early diagnosis and a proper treatment on lung function.

Furthermore, despite a significant progression in genetically solved cases there are almost no data on genotype specific lung function in patients with PCD. Recently, there are few studies indicating an association between specific ultrastructural or genetic defects, e.g. patients carrying mutations in the genes MCIDAS (Multicilin), CCNO (Cyclin O), CCDC39 (Coiled-Coil Domain Containing 39) and CCDC40 (Coiled-Coil Domain Containing 40) and a severe clinical course in particular a worse respiratory phenotype. There might be a less severe phenotype in PCD sub-types due to mutations in genes encoding radial spoke components.

Currently a systematic review shows the high variation of spirometric indices in a great PCD cohort. These findings underline the great necessity of detailed characterization of genotype specific phenotypes with focus on important parameters such as lung function to better understand the natural history of distinct PCD-variants with a view to improve individual patient care by tailored treatment activity according to likely disease severity.

Aim of this study are:

* Correlation between genotype and lung function of patients with genetically confirmed PCD in an international cohort on a longitudinal basis
* Determination of further parameters, such as body mass index (BMI), possibly associated with lung function in genetically confirmed PCD patients

Inclusion criteria:

* Patients with a genetically confirmed diagnosis of PCD (bi-allelic mutations in a gene, known to cause PCD) with typical clinical symptoms of PCD and at least one other method confirming PCD-diagnosis
* Children and adults diagnosed with PCD of all age groups and able to perform spirometry
* Longitudinal datasets with measurements of lung function (FEV1 (forced expiratory volume in 1 second), FVC (forced vital capacity), FEV1/FVC, FEF (forced expiratory flow) 25-75) (with date and height at the performed measurement, respectively)
* at least 3-4 different measurements in at least 2 years of follow up are expected - in cases where this is not possible, sporadic data could also be provided
* Delivery of datasets to the international PCD registry (NCT02419365) with all necessary values within the anticipated time schedules

Eligibility criteria: * Patients with a genetically confirmed diagnosis of PCD (bi-allelic mutations in a gene, known to cause PCD) with typical clinical symptoms of PCD and at least one other method confirming PCD-diagnosis
* Children and adults diagnosed with PCD of all age groups and able to perform spirometry
* Longitudinal datasets with measurements of lung function (FEV1, FVC, FEV1/FVC, FEF25-75) (with date and height at the performed measurement, respectively) at least 3-4 different measurements in at least 2 years of follow up are expected - in cases where this is not possible, sporadic data could also be provided
* Delivery of datasets to the international PCD registry (14) with all necessary values within the anticipated time schedules

Primary outcomes:
measure: Genotype-Lungfunction Correlation
timeFrame: up to 20 years (retrospective)
Secondary outcomes:
Other outcomes:
Locations:
city: Münster
country: Germany
facility: University Hospital Münster
state: NRW
Study officials:
affiliation: University Hospital Muenster
name: Heymut Omran, Prof., MD
role: STUDY_CHAIR
References: