Genotype/Phenotype Correlation With Focus on Lung Function in Primary Ciliary Dyskinesia (PCD)

Primary Ciliary Dyskinesia Clinical Trial

— LuFu_PCD  

Official title:

An International Study on Genotype/Phenotype Correlation With Focus on Lung Function in Patients With Primary Ciliary Dyskinesia (PCD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04717115
• Other study ID #: JR_Lufu_PCD_01_2020-1
• Status: Recruiting
• Start date: November 1, 2019
• Est. completion date: November 30, 2023

Study information

• Verified date: June 2022
• Source: University Hospital Muenster
• Contact: Johanna Raidt, MD
• Phone: +49 251 83 40003
• Email: Johanna.Raidt[@]ukmuenster.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: November 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

• 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

Related Conditions & MeSH terms

• Ciliary Motility Disorders
• Dyskinesias
• Primary Ciliary Dyskinesia

Intervention

Genetic:
• Genetic diagnosis
No Intervention foreseen, but 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 is needed

Locations

Country	Name	City	State
Germany	University Hospital Münster	Münster	NRW

Sponsors (37)

Lead Sponsor

Collaborator

University Hospital Muenster

Abderrahmane Mami Hospital, Amsterdam UMC, location VUmc, Bambino Gesù Hospital and Research Institute, Charite University, Berlin, Germany, Federico II University, Göteborg University, Hacettepe University, Hadassah Medical Organization, Hannover Medical School, Hospital de Niños R. Gutierrez de Buenos Aires, Hospital Vall d'Hebron, KU Leuven, Marmara University, Medical University of Vienna, NOVA Medical School, Oslo University Hospital, Rigshospitalet, Denmark, Royal Brompton & Harefield NHS Foundation Trust, Ruhr University of Bochum, Schneider Children's Medical Center, Israel, The Leeds Teaching Hospitals NHS Trust, University Children's Hospital, Zurich, University College, London, University Hospital of Cologne, University Hospital, Martin, University Hospital, Motol, University of Belgrade, University of Bern, University of Dundee, University of Geneva, Switzerland, University of Leicester, University of Nicosia, University of Pisa, University of Sao Paulo, University of Southampton, University of Valencia

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genotype-Lungfunction Correlation	Lung function (FEV1, FVC, FEF) in correlation to the genetic make-up	up to 20 years (retrospective)