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

  • STATUS
    Recruiting
  • End date
    Nov 30, 2022
  • participants needed
    1500
  • sponsor
    University Hospital Muenster
Updated on 21 October 2021

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

Details
Condition Kartagener Syndrome, Immotile Cilia Syndrome, primary ciliary dyskinesia
Treatment genetic diagnosis
Clinical Study IdentifierNCT04717115
SponsorUniversity Hospital Muenster
Last Modified on21 October 2021

Eligibility

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note