Rare Genetic Disorders of the Breathing Airways

August 9, 2022 updated by: University of North Carolina, Chapel Hill

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

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.

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

367

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Individuals with suspected primary ciliary dyskinesia, non-classical or variant cystic fibrosis, and pseudohypoaldosteronism

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
This is not an interventional study
Time Frame: This is not an interventional study
Not applicable. This is not an interventional study.
This is not an interventional study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of North Carolina, Chapel Hill

Collaborators

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

Investigators

  • Principal Investigator: Michael R Knowles, MD, University of North Carolina, Chapel Hill

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2006

Primary Completion (ACTUAL)

October 1, 2012

Study Completion (ACTUAL)

October 1, 2012

Study Registration Dates

First Submitted

May 8, 2006

First Submitted That Met QC Criteria

May 8, 2006

First Posted (ESTIMATE)

May 9, 2006

Study Record Updates

Last Update Posted (ACTUAL)

August 10, 2022

Last Update Submitted That Met QC Criteria

August 9, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05-2979
  • U54RR019480 (NIH)
  • RDCRN 5902 (OTHER: UNC)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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