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Rare Genetic Disorders of the Breathing Airways

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. Read our disclaimer for details. Identifier: NCT00323167
Recruitment Status : Completed
First Posted : May 9, 2006
Last Update Posted : February 6, 2019
Rare Diseases Clinical Research Network
National Center for Research Resources (NCRR)
National Institutes of Health (NIH)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

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
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.

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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 2006
Actual Primary Completion Date : October 2012
Actual Study Completion Date : October 2012

Primary Outcome Measures :
  1. This is not an interventional study [ Time Frame: This is not an interventional study ]
    Not applicable. This is not an interventional study.

Biospecimen Retention:   Samples With DNA
Respiratory cultures, nasal samples, and blood samples

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Individuals with suspected primary ciliary dyskinesia, non-classical or variant cystic fibrosis, and pseudohypoaldosteronism

Inclusion Criteria:

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

    1. 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
    2. 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)
    3. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00323167

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United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
The Children's Hospital
Denver, Colorado, United States, 80218
United States, Maryland
Laboratory of Clinical Infectious Diseases, NIAID
Bethesda, Maryland, United States, 20892
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63130
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Washington
Children's Hospital and Regional Medical Center
Seattle, Washington, United States, 98105
Canada, Ontario
St. Michael's Hospital
Toronto, Ontario, Canada, M5B IW8
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Rare Diseases Clinical Research Network
National Center for Research Resources (NCRR)
National Institutes of Health (NIH)
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Principal Investigator: Michael R Knowles, MD University of North Carolina, Chapel Hill
Publications of Results:

Other Publications:

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University of North Carolina, Chapel Hill Identifier: NCT00323167    
Other Study ID Numbers: 05-2979
U54RR019480 ( U.S. NIH Grant/Contract )
RDCRN 5902 ( Other Identifier: UNC )
First Posted: May 9, 2006    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: February 2019
Keywords provided by University of North Carolina, Chapel Hill:
Variant Cystic Fibrosis
Primary Ciliary Dyskinesia
Additional relevant MeSH terms:
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Cystic Fibrosis
Ciliary Motility Disorders
Kartagener Syndrome
Genetic Diseases, Inborn
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Infant, Newborn, Diseases
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Otorhinolaryngologic Diseases
Abnormalities, Multiple
Congenital Abnormalities
Bronchial Diseases
Respiratory System Abnormalities
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Situs Inversus