Genetics of Primary Ciliary Dyskinesia

Primary Ciliary Dyskinesia Clinical Trial

Official title:

Research Genetic Testing for Primary Ciliary Dyskinesia Using a Panel of Genes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02389049
• Other study ID #: 14-1225
• Secondary ID: U54HL096458-11
• Status: Completed
• Start date: February 2015
• Est. completion date: July 2018

Study information

• Verified date: August 2022
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is designed to study DNA sequencings for mutations in a research genetic test panel of genes (which contains all 32 known and/or published genes associated with PCD). The study aims to show that about 70% of PCD patients have biallelic mutations in one of these genes. This project will enroll patients who have already had a clinical evaluation, and have clinical features consistent with PCD.

Description:

The investigators have established a Consortium of 9 geographically-dispersed clinical research sites to study rare disease of the airways, including Primary Ciliary Dyskinesia (PCD). PCD is a genetic disorder with defective mucociliary clearance (MCC), sinus and pulmonary disease with chronic infection, and organs located on the wrong side of the body in about 50% of patients (Kartagener Syndrome). Lung disease occurs early in children with PCD, but establishing a diagnosis remains a major challenge, based on the traditional approaches of using electron microscopy and/or ciliary waveform analysis to define abnormalities of ciliary ultrastructure and/or function.

For this study, blood or buccal samples for DNA will be collected and genetic testing in patients with known or suspected PCD will be performed. This study can include term neonates with respiratory distress of unknown etiology and features of PCD, particular laterality defects (situs inversus or heterotaxy). The key hypothesis for this study is that a genetic test panel of 32 genes will confirm a diagnosis in most patients with PCD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 320
• Est. completion date: July 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Any patient who has = 2 clinical features (+/- lab) characteristic of PCD, including:

• Neonatal respiratory distress after term (or near-term) birth

• and/or laterality defect ( situs inversus or heterotaxy)

• and/or daily wet cough before 6 months of age

• and/or middle ear disease

• and/or chronic nasal congestion before 6 months of age

• and/or bronchiectasis

• and/or male infertility due to sperm tail dysfunction

• and/or low nasal nitric oxide levels (<77 nanoliters/minute)

• and/or defective ciliary ultrastructure

Exclusion Criteria:

• Known diagnosis of cystic fibrosis with classic clinical presentation and elevated sweat chloride levels and/or two known disease-causing Cystic Fibrosis transmembrane conductance regulator (CFTR) mutations, or documented primary or acquired immunodeficiency.

• Known explanation for bronchiectasis (and other clinical features), such as a1-antitrypsin deficiency (ZZ or ZS), inflammatory bowel disease or rheumatoid arthritis.

• Any patient who is unwilling or unable to provide consent or to comply with the testing required in this protocol

A participant should not be in the study if they have not had a standard clinical evaluation to address other potential causes of chronic oto-sino- pulmonary disease.

Related Conditions & MeSH terms

• Ciliary Motility Disorders
• Dyskinesias
• Kartagener Syndrome
• Primary Ciliary Dyskinesia

Locations

Country	Name	City	State
Canada	McGill University	Montreal	Quebec
Canada	The Hospital for Sick Children	Toronto	Ontario
United States	The Children's Hospital, Denver	Aurora	Colorado
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Stanford University	Palo Alto	California
United States	Washington University, St. Louis	Saint Louis	Missouri
United States	Children's Hospital and Regional Medical Center, Seattle	Seattle	Washington

Sponsors (4)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Rare Diseases Clinical Research Network

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirm PCD diagnosis in patients using a panel of 32 genes	The primary objective is to perform research genetic (Ampliseq panel) testing in patients who are known or suspected to have PCD, based on previous research or future clinical and lab characterization by certified clinical research sites. We will define the prevalence of biallelic PCD-causing mutations in patients who fulfill criteria of very high likelihood of PCD, as well as prevalence in other patients with some features of PCD. We anticipate successful completion of this objective will provide the foundation for development of clinically available genetic test panels, particularly as additional PCD genes are identified.	Up to 5 years
Secondary	Identify patients with PCD who do not have a biallelic PCD-causing mutation	The secondary objective is to perform research genetic testing to identify patients with PCD who do not have biallelic PCD-causing mutations in known PCD genes, so they can be exome sequenced to discover novel genes associated with PCD. We anticipate that successful completion of this objective will enable the development of more extensive genetic test panels that are more robust to diagnose PCD.	Up to 5 years