We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

Pathogenesis of Primary Ciliary Dyskinesia (PCD) Lung Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00807482
Recruitment Status : Recruiting
First Posted : December 12, 2008
Last Update Posted : September 14, 2017
Information provided by (Responsible Party):

December 11, 2008
December 12, 2008
September 14, 2017
January 2004
April 2021   (Final data collection date for primary outcome measure)
This is not an interventional study [ Time Frame: This is not an interventional study ]
Not applicable. This is not an interventional study.
Not Provided
Complete list of historical versions of study NCT00807482 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
Pathogenesis of Primary Ciliary Dyskinesia (PCD) Lung Disease
Diagnostic and Clinical Characterization of Patients With Unusual Genetic Disorders of the Airways
The overall short-term goals of this project include the following: 1) identify the genes that are key to the function of respiratory cilia to protect the normal lung; and 2) the effects of genetic mutations that adversely affect ciliary function and cause primary ciliary dyskinesia (PCD), which results in life-shortening lung disease. The long-term goal of this project is to develop better understanding of the underlying genetic variability that adversely modifies ciliary function, and predisposes to common airway diseases, such as asthma and chronic obstructive pulmonary disease.

A key component of lung defense is the efficiency of mucociliary clearance (MCC).

Primary ciliary dyskinesia (PCD) is a human genetic disorder with defective MCC. This ongoing project is designed to identify additional disease-causing mutations in PCD, and correlate the molecular etiologies with the ciliary phenotype (ultrastructure, wave form and beat frequency). We have recently shown that the normal human cilium has a distinctive waveform, i.e. beats in-plane with defined curvatures and amplitudes for the effective (forward) and recovery stroke. We hypothesize that discrete sets of genes contribute to the structure and function of the ciliary outer dynein arm (ODA), inner dynein arm (IDA), and central pair (CP) and radial spoke (RS) complex (CP/RS), and that we can identify novel genetic mutations in different structural components of the cilium that will have different effects on ciliary ultrastructure, wave form, and beat frequency. Importantly, we are now able to identify patients with PCD who do not have hallmark diagnostic ultrastructural defects, based on distinctive clinical phenotypes (including situs inversus), low or borderline nasal NO production, and abnormal ciliary motility. Identification of PCD patients with normal ciliary ultrastructure (~16% of PCD patients at UNC) offers the opportunity to discover mutations in genes that cause functional, but not ultrastructural, defects (such as DNAH11), and to correlate those mutations with ciliary waveform abnormalities. Over the past 4 years, we have made great progress in identifying mutations in 2 genes (DNAI1 and DNAH5) that cause ~60% of ODA defects in PCD, and ~35% of PCD overall. We will extend our search for disease causing mutations in PCD, using several different approaches, including studies of additional candidate genes, (guided by ultrastructure), plus insights from ciliary proteomics, and family-based studies. Taken together, these studies will provide new insights regarding the relationship of mutations in specific genes to ciliary ultrastructural and functional defects. These studies will not only greatly enhance our ability to diagnose PCD, but will also lead to discovery of "milder" genetic mutations associated with normal ciliary ultrastructure, and likely some residual ciliary function. Ultimately, this will allow future studies of the role of partial loss of ciliary function in the predisposition to more common airways diseases, such as chronic bronchitis and chronic obstructive pulmonary disease.

Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Blood samples, buckle scrape, semen, and scrape biopsy of nasal cells
Probability Sample
Patients who have a high suspicion for the diagnosis of PCD, based on clinical features.
Kartagener Syndrome
Not Provided
People who have been definitively diagnosed with primary ciliary dyskinesia (PCD).

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
April 2021
April 2021   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients who have a high suspicion for the diagnosis of PCD, based on clinical features

Healthy Volunteers who have a family member with confirmed PCD.

Sexes Eligible for Study: All
Child, Adult, Senior
United States
5R01HL071798 ( U.S. NIH Grant/Contract )
Not Provided
Not Provided
University of North Carolina, Chapel Hill
University of North Carolina, Chapel Hill
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Michael R. Knowles, MD University of North Carolina, Chapel Hill
University of North Carolina, Chapel Hill
September 2017