Rare Genetic Disorders of the Breathing Airways

Sponsor

University of North Carolina, Chapel Hill (Other)

Overall Status

Completed

CT.gov ID

NCT00323167

Collaborator

Rare Diseases Clinical Research Network (Other), National Center for Research Resources (NCRR) (NIH), National Institutes of Health (NIH) (NIH)

367

Enrollment

Locations

Duration (Months)

40.8

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Mucociliary clearance, in which mucus secretions are cleared from the breathing airways, is the primary defense mechanism for the lungs. Inhaled particles, including microbes that can cause infections, are normally entrapped in mucus on the airway surfaces and then cleared out by the coordinated action of tiny hair-like structures called cilia. Individuals with primary ciliary dyskinesia, variant cystic fibrosis, and pseudohypoaldosteronism have defective mucociliary clearance. The purpose of this study is to collect clinical and genetic information about these three airway diseases to improve current diagnostic procedures.

Condition or Disease	Intervention/Treatment	Phase
Kartagener Syndrome Cystic Fibrosis Pseudohypoaldosteronism Primary Ciliary Dyskinesia

Detailed Description

Two types of genetic diseases are associated with abnormal mucociliary clearance. The first type results in defective ciliary function and includes primary ciliary dyskinesia (PCD), also known as Kartagener Syndrome. The second type results in defective ion transportation and includes variant cystic fibrosis (CF) and pseudohypoaldosteronism (PHA). The clinical manifestations of these three diseases overlap, and current evaluation procedures are inadequate for an accurate and timely diagnosis. A delayed diagnosis, coupled with poorly defined disease categories, results in sub-optimal treatment regimens. The purpose of this study is to better define the clinical and genetic features of PCD, variant CF, and PHA to develop improved diagnostic procedures. The study will also compare prevalence and age-related information among the three diseases and classic CF. Outcomes of this study may lead to improved clinical care and novel therapeutic approaches for rare genetic disorders of the airways.

Prior to study entry, previous clinical data on all participants will be reviewed to ensure that individuals do not have common variants of asthma. In some cases, further clinical evaluation (sweat chloride testing, immunodeficiency testing, and a high-resolution computed tomography scan) may be recommended. Eligible participants will attend an initial six-hour study visit similar to a standard diagnostic evaluation. The participant's medical history will be reviewed and a physical examination will include height, weight, and vital sign measurements. Respiratory cultures, nasal samples, and blood will be collected. Non-invasive techniques will be used to measure oxyhemoglobin saturation levels and airflow; a chest x-ray will be required if none has been done in the last six months.

If a firm diagnosis of PCD or variant CF has not been established after completion of the first study visit, the participant may return for additional visits. Salivary and semen samples may be collected from some individuals. A sweat chloride test and nasal potential difference test may also be performed.

Study Design

Study Type:

Observational

Actual Enrollment :

367 participants

Observational Model:

Cohort

Time Perspective:

Other

Official Title:

Rare Genetic Disorders of the Airways: Cross-sectional Comparison of Clinical Features, and Development of Novel Screening and Genetic Tests

Study Start Date :

May 1, 2006

Actual Primary Completion Date :

Oct 1, 2012

Actual Study Completion Date :

Oct 1, 2012

Outcome Measures

Primary Outcome Measures

This is not an interventional study [This is not an interventional study]
Not applicable. This is not an interventional study.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Received a standard diagnostic evaluation prior to study entry that resulted in one of the following three profiles:

High likelihood of PCD diagnosis, based on ciliary ultrastructural changes seen on electron microscopy or clinical features (chronic sinopulmonary disease, chronic otitis media, history of neonatal respiratory distress or situs inversus) OR one clinical feature of PCD and a sibling with PCD
Chronic sino-pulmonary disease with clinical features that overlap with variant CF and PCD, but with diagnostic tests that rule out classical CF (sweat chloride testing and CF gene mutation screening)
Known or suspected PHA (or variant PHA), possibly including elevated (or borderline) sweat chloride values

Exclusion Criteria:

Has not received a standard clinical evaluation to rule out other disorders associated with chronic sino-pulmonary disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University	Palo Alto	California	United States	94304
2	National Jewish Health	Denver	Colorado	United States	80206
3	The Children's Hospital	Denver	Colorado	United States	80218
4	Laboratory of Clinical Infectious Diseases, NIAID	Bethesda	Maryland	United States	20892
5	Washington University	Saint Louis	Missouri	United States	63130
6	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
7	Children's Hospital and Regional Medical Center	Seattle	Washington	United States	98105
8	St. Michael's Hospital	Toronto	Ontario	Canada	M5B IW8
9	The Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8