Rare Genetic Disorders of the Breathing Airways
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Purpose
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 |
|---|
|
Kartagener Syndrome Cystic Fibrosis Pseudohypoaldosteronism Primary Ciliary Dyskinesia |
| Study Type: | Observational |
| Study Design: | Observational Model: Cohort |
| Official Title: | Rare Genetic Disorders of the Airways: Cross-sectional Comparison of Clinical Features, and Development of Novel Screening and Genetic Tests |
Respiratory cultures, nasal samples, and blood samples
| Estimated Enrollment: | 360 |
| Study Start Date: | May 2006 |
| Estimated Study Completion Date: | January 2016 |
| Estimated Primary Completion Date: | October 2012 (Final data collection date for primary outcome measure) |
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.
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
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:
- 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| United States, California | |
| Stanford University | |
| Palo Alto, California, United States, 94304 | |
| United States, Colorado | |
| The Children's Hospital | |
| Denver, Colorado, United States, 80218 | |
| National Jewish Health | |
| Denver, Colorado, United States, 80206 | |
| United States, Maryland | |
| Laboratory of Clinical Infectious Diseases, NIAID | |
| Bethesda, Maryland, United States, 20892 | |
| United States, Missouri | |
| Washington University | |
| St. 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 | |
| The Hospital for Sick Children | |
| Toronto, Ontario, Canada, M5G 1X8 | |
| St. Michael's Hospital | |
| Toronto, Ontario, Canada, M5B IW8 | |
| Principal Investigator: | Michael R Knowles, MD | University of North Carolina, Chapel Hill |
More Information
Publications:
| Responsible Party: | Michael Knowles, MD, Professor of Medicine, University of North Carolina, Chapel Hill |
| ClinicalTrials.gov Identifier: | NCT00323167 History of Changes |
| Other Study ID Numbers: | RDCRN 5902, U54RR019480 |
| Study First Received: | May 8, 2006 |
| Last Updated: | October 22, 2012 |
| Health Authority: | United States: Federal Government United States: Institutional Review Board |
Keywords provided by University of North Carolina, Chapel Hill:
|
Variant Cystic Fibrosis Primary Ciliary Dyskinesia |
Additional relevant MeSH terms:
|
Ciliary Motility Disorders Kartagener Syndrome Cystic Fibrosis Dyskinesias Fibrosis Pseudohypoaldosteronism Respiratory Tract Diseases Otorhinolaryngologic Diseases Bronchiectasis Bronchial Diseases Respiratory System Abnormalities Dextrocardia Heart Defects, Congenital Cardiovascular Abnormalities Cardiovascular Diseases |
Heart Diseases Congenital Abnormalities Situs Inversus Genetic Diseases, Inborn Pancreatic Diseases Digestive System Diseases Lung Diseases Infant, Newborn, Diseases Movement Disorders Central Nervous System Diseases Nervous System Diseases Neurologic Manifestations Signs and Symptoms Pathologic Processes Renal Tubular Transport, Inborn Errors |
ClinicalTrials.gov processed this record on May 19, 2013