Rare Genetic Disorders of the Breathing Airways

Completed

• Conditions: Primary Ciliary Dyskinesia; Cystic Fibrosis; Pseudohypoaldosteronism; Kartagener Syndrome

• Registration Number: NCT00323167
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2006-05
• Study First Submitted: 2006-05-08
• Study First Submitted QC: 2006-05-08
• Study First Posted: 2006-05-09
• Primary Completion: 2012-10
• Study Completion: 2012-10
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-09
• Last Update Posted: 2022-08-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 367

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

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Exclusion Criteria

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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
This is not an interventional study	This is not an interventional study	Not applicable. This is not an interventional study.

Trial Locations

Locations (9)

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada

Children's Hospital and Regional Medical Center; 🇺🇸 Seattle, Washington, United States

St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada

Laboratory of Clinical Infectious Diseases, NIAID; 🇺🇸 Bethesda, Maryland, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

National Jewish Health; 🇺🇸 Denver, Colorado, United States

The Children's Hospital; 🇺🇸 Denver, Colorado, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States