Clinical trial NCT02389049: Genetics of Primary Ciliary Dyskinesia
Official title: Research Genetic Testing for Primary Ciliary Dyskinesia Using a Panel of Genes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Primary Ciliary Dyskinesia
Kartagener Syndrome
Keywords: Primary Ciliary Dyskinesia
Kartagener Syndrome
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Rare Diseases Clinical Research Network
name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2015-03-17
Enrollment: 320
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study participants should have 2 or more clinical features of PCD.

Brief 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.

Detailed 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.

Eligibility criteria: 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 α1-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.

Primary outcomes:
measure: Confirm PCD diagnosis in patients using a panel of 32 genes
timeFrame: Up to 5 years
Secondary outcomes:
measure: Identify patients with PCD who do not have a biallelic PCD-causing mutation
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: The Children's Hospital, Denver
state: Colorado
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Saint Louis
country: United States
facility: Washington University, St. Louis
state: Missouri
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center, Seattle
state: Washington
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: McGill University
state: Quebec
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Michael Knowles, MD
role: PRINCIPAL_INVESTIGATOR
References: