Rare Genetic Disorders of the Breathing Airways - Full Text View

Sponsors and Collaborators:	Office of Rare Diseases (ORD) Rare Diseases Clinical Research Network
Information provided by:	Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:	NCT00323167

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

Genetics Home Reference related topics: cystic fibrosis familial paroxysmal nonkinesigenic dyskinesia

MedlinePlus related topics: Cystic Fibrosis

U.S. FDA Resources

Study Type:	Observational
Study Design:	Cohort
Official Title:	Rare Genetic Disorders of the Airways: Cross-Sectional Comparison of Clinical Features, and Development of Novel Screening and Genetic Tests

Further study details as provided by Office of Rare Diseases (ORD):

Biospecimen Retention: Samples With DNA

Biospecimen Description:

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:	August 2012 (Final data collection date for primary outcome measure)

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.

Eligibility

Genders Eligible for Study:	Both
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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00323167

Locations

United States, California
Stanford University	Recruiting
Palo Alto, California, United States, 94304
Contact: Jackie Zirbes, DNP, RN, CNP, CCR 650-721-1132 jmzirbes@stanford.edu
Principal Investigator: Carlos Milla, MD
United States, Colorado
The Children's Hospital	Recruiting
Denver, Colorado, United States, 80218
Contact: Shelley Mann, RN, BSN 303-864-5416 Mann.Shelley@tchden.org
Principal Investigator: Scott Sagel, MD
United States, Maryland
Laboratory of Clinical Infectious Diseases, NIAID	Recruiting
Bethesda, Maryland, United States, 20892
Contact: Kenneth Olivier, MD, MPH olivierk@niaid.nih.gov
United States, Missouri
Washington University	Recruiting
St. Louis, Missouri, United States, 63130
Contact: Jane Quante, RN, BS 314-454-2353 quante_J@kids.wustl.edu
Principal Investigator: Thomas Ferkol, MD
United States, North Carolina
University of North Carolina at Chapel Hill	Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Susan Minnix, RN, BSN 919-843-5308 sminnix@med.unc.edu
Principal Investigator: Michael R. Knowles, MD
Sub-Investigator: Margaret W. Leigh, MD
Sub-Investigator: Maimoona Zariwala, PhD
United States, Washington
Children's Hospital and Regional Medical Center	Recruiting
Seattle, Washington, United States, 98105
Contact: Sharon McNamara, RN, MN 206-987-3921 ext 1 sharon.mcnamara@seattlechildrens.org
Principal Investigator: Margaret Rosenfeld, MD
Sub-Investigator: Ron Gibson, MD
Sub-Investigator: Moira Aitken, MD
Canada, Ontario
The Hospital for Sick Children	Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Donna Wilkes 416-813-4903 donna.wilkes@sickkids.ca
Principal Investigator: Sharon Dell, MD

Sponsors and Collaborators

Office of Rare Diseases (ORD)

Rare Diseases Clinical Research Network

More Information

Publications:

Kennedy MP, Ostrowski LE. Primary ciliary dyskinesia and upper airway diseases. Curr Allergy Asthma Rep. 2006 Nov;6(6):513-7. Review.

Ferkol T, Leigh M. Primary ciliary dyskinesia and newborn respiratory distress. Semin Perinatol. 2006 Dec;30(6):335-40. Review.

Zariwala MA, Knowles MR, Omran H. Genetic defects in ciliary structure and function. Annu Rev Physiol. 2007;69:423-50. Review.

Zariwala MA, Leigh MW, Ceppa F, Kennedy MP, Noone PG, Carson JL, Hazucha MJ, Lori A, Horvath J, Olbrich H, Loges NT, Bridoux AM, Pennarun G, Duriez B, Escudier E, Mitchison HM, Chodhari R, Chung EM, Morgan LC, de Iongh RU, Rutland J, Pradal U, Omran H, Amselem S, Knowles MR. Mutations of DNAI1 in primary ciliary dyskinesia: evidence of founder effect in a common mutation. Am J Respir Crit Care Med. 2006 Oct 15;174(8):858-66. Epub 2006 Jul 20.

Kennedy MP, Noone PG, Carson J, Molina PL, Ghio A, Zariwala MA, Minnix SL, Knowles MR. Calcium stone lithoptysis in primary ciliary dyskinesia. Respir Med. 2007 Jan;101(1):76-83. Epub 2006 Jun 6.

Hornef N, Olbrich H, Horvath J, Zariwala MA, Fliegauf M, Loges NT, Wildhaber J, Noone PG, Kennedy M, Antonarakis SE, Blouin JL, Bartoloni L, Nusslein T, Ahrens P, Griese M, Kuhl H, Sudbrak R, Knowles MR, Reinhardt R, Omran H. DNAH5 mutations are a common cause of primary ciliary dyskinesia with outer dynein arm defects. Am J Respir Crit Care Med. 2006 Jul 15;174(2):120-6. Epub 2006 Apr 20.

Horvath J, Fliegauf M, Olbrich H, Kispert A, King SM, Mitchison H, Zariwala MA, Knowles MR, Sudbrak R, Fekete G, Neesen J, Reinhardt R, Omran H. Identification and analysis of axonemal dynein light chain 1 in primary ciliary dyskinesia patients. Am J Respir Cell Mol Biol. 2005 Jul;33(1):41-7. Epub 2005 Apr 21.

Responsible Party:	University of North Carolina, Chapel Hill ( Mike Knowles, MD )
Study ID Numbers:	RDCRN 5902, U54 RR019480, MCC 5902
Study First Received:	May 8, 2006
Last Updated:	October 1, 2008
ClinicalTrials.gov Identifier:	NCT00323167
Health Authority:	United States: Federal Government

Keywords provided by Office of Rare Diseases (ORD):

Variant Cystic Fibrosis
Primary Ciliary Dyskinesia

Study placed in the following topic categories:

Fibrosis
Adrenal Gland Diseases
Hypoadrenalism
Dextrocardia
Kartagener Syndrome
Situs inversus viscerum
Metabolism, Inborn Errors
Signs and Symptoms
Urologic Diseases
Respiratory Tract Diseases
Movement Disorders
Infant, Newborn, Diseases
Kidney Diseases
Congenital Abnormalities
Cystic fibrosis

Adrenal Insufficiency
Metabolic Diseases
Otorhinolaryngologic Diseases
Heart Diseases
Primary ciliary dyskinesia
Cardiovascular Abnormalities
Bronchiectasis
Pseudohypoaldosteronism
Endocrine System Diseases
Central Nervous System Diseases
Situs Inversus
Dyskinesias
Adrenal gland hypofunction
Kartagener syndrome
Digestive System Diseases

Additional relevant MeSH terms:

Respiratory System Abnormalities
Disease
Pathologic Processes
Bronchial Diseases

Syndrome
Nervous System Diseases
Cardiovascular Diseases
Renal Tubular Transport, Inborn Errors

ClinicalTrials.gov processed this record on January 14, 2009