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Evaluating Progression of and Diagnostic Tools for Primary Ciliary Dyskinesia in Children and Adolescents

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00450918
First Posted: March 22, 2007
Last Update Posted: September 13, 2017
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.
Collaborators:
Office of Rare Diseases (ORD)
National Center for Research Resources (NCRR)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Margaret Leigh, MD, University of North Carolina, Chapel Hill
  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 (PCD) have defective mucociliary clearance, which in turn leads to lung infections and disease. The purpose of this study is to determine how lung disease progresses over time in children and adolescents with PCD.

Condition
Primary Ciliary Dyskinesia

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Longitudinal Study of Primary Ciliary Dyskinesia: Participants 5-18 Years of Age

Resource links provided by NLM:


Further study details as provided by Margaret Leigh, MD, University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Spirometry Measures [ Time Frame: Measured yearly for 5 years ]
  • HRCT scan of the chest to image lungs [ Time Frame: At visits 1, 3, and 5 ]

Biospecimen Retention:   Samples With DNA
Blood samples

Estimated Enrollment: 150
Study Start Date: August 2006
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Detailed Description:

PCD is a rare genetic disorder in which impaired mucus clearance commonly results in chronic cough and infections in the airways, sinuses, and middle ears. Long lasting airway infection ultimately leads to structural damage to the airways, known as bronchiectasis, and, in turn, loss of lung function. While PCD shares some similarities with the disease cystic fibrosis, it is important to distinguish PCD from cystic fibrosis. In particular, the age of onset and progression of PCD's clinical lung disease, including timing of specific microbial pathogen infections and bronchiectasis, remain poorly defined. The purpose of this study is to determine how lung disease progresses over time in children and adolescents with PCD. Specific attention will be directed toward determining whether certain factors play a role in lung disease progression. The study will also evaluate diagnostic tools and quality of life among individuals with PCD. Filling these gaps of knowledge may help to improve the clinical management of PCD in the future.

This longitudinal study will last 5 years. There will be a total of 5 study visits, and these visits will occur yearly. Each study visit will last 3 to 4 hours. All study visits will include a medical history review; physical exam; height, weight, and vital sign measurements; sampling of respiratory fluids and mucus; lung function tests; and questionnaires. The initial visit may also include using a probe to measure nasal nitric oxide levels and blood collection for genetic testing. Study visits 1, 3, and 5 will also include blood collection for pregnancy testing and a high resolution computed tomography (HRCT) scan of the chest to image the lungs. At the end of each month, participants will report any use of oral, inhaled, or intravenous antibiotics.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   5 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Children and adolescents with primary ciliary dyskinesia
Criteria

Inclusion Criteria:

  • Diagnosis of PCD or probable PCD. More information about the criteria for a PCD diagnosis can be found in the protocol.
  • Parent or guardian willing to provide informed consent

Exclusion Criteria:

  • Inability to attend follow-up appointments
  • Previously received lung transplant
  • Any disease that may have significant impact on lung function (e.g., severe congenital heart disease, severe scoliosis), respiratory infections (e.g., AIDS), or overall health status (e.g., cancer, end-stage kidney disease)
  • Pregnant or breastfeeding
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT00450918


Locations
United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Colorado
The Children's Hospital
Denver, Colorado, United States, 80218
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
The Hospital for Sick Children
Toronto, Ontario, Canada
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Office of Rare Diseases (ORD)
National Center for Research Resources (NCRR)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Margaret W Leigh, MD University of North Carolina, Chapel Hill
  More Information

Publications:
Corbelli R, Bringolf-Isler B, Amacher A, Sasse B, Spycher M, Hammer J. Nasal nitric oxide measurements to screen children for primary ciliary dyskinesia. Chest. 2004 Oct;126(4):1054-9.
Hossain T, Kappelman MD, Perez-Atayde AR, Young GJ, Huttner KM, Christou H. Primary ciliary dyskinesia as a cause of neonatal respiratory distress: implications for the neonatologist. J Perinatol. 2003 Dec;23(8):684-7.
Noone PG, Leigh MW, Sannuti A, Minnix SL, Carson JL, Hazucha M, Zariwala MA, Knowles MR. Primary ciliary dyskinesia: diagnostic and phenotypic features. Am J Respir Crit Care Med. 2004 Feb 15;169(4):459-67. Epub 2003 Dec 4.
Fliegauf M, Olbrich H, Horvath J, Wildhaber JH, Zariwala MA, Kennedy M, Knowles MR, Omran H. Mislocalization of DNAH5 and DNAH9 in respiratory cells from patients with primary ciliary dyskinesia. Am J Respir Crit Care Med. 2005 Jun 15;171(12):1343-9. Epub 2005 Mar 4.
Horváth 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.
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, Nüsslein 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.
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, Leigh MW. Primary Ciliary Dyskinesia. 2007 Jan 24 [updated 2015 Sep 3]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from http://www.ncbi.nlm.nih.gov/books/NBK1122/
Kennedy MP, Noone PG, Leigh MW, Zariwala MA, Minnix SL, Knowles MR, Molina PL. High-resolution CT of patients with primary ciliary dyskinesia. AJR Am J Roentgenol. 2007 May;188(5):1232-8.
Zariwala MA, Knowles MR, Omran H. Genetic defects in ciliary structure and function. Annu Rev Physiol. 2007;69:423-50. Review.
Morillas HN, Zariwala M, Knowles MR. Genetic causes of bronchiectasis: primary ciliary dyskinesia. Respiration. 2007;74(3):252-63. Review.
Kennedy MP, Omran H, Leigh MW, Dell S, Morgan L, Molina PL, Robinson BV, Minnix SL, Olbrich H, Severin T, Ahrens P, Lange L, Morillas HN, Noone PG, Zariwala MA, Knowles MR. Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Circulation. 2007 Jun 5;115(22):2814-21. Epub 2007 May 21.
Loges NT, Olbrich H, Becker-Heck A, Häffner K, Heer A, Reinhard C, Schmidts M, Kispert A, Zariwala MA, Leigh MW, Knowles MR, Zentgraf H, Seithe H, Nürnberg G, Nürnberg P, Reinhardt R, Omran H. Deletions and point mutations of LRRC50 cause primary ciliary dyskinesia due to dynein arm defects. Am J Hum Genet. 2009 Dec;85(6):883-9. doi: 10.1016/j.ajhg.2009.10.018.
Leigh MW, Pittman JE, Carson JL, Ferkol TW, Dell SD, Davis SD, Knowles MR, Zariwala MA. Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome. Genet Med. 2009 Jul;11(7):473-87. doi: 10.1097/GIM.0b013e3181a53562. Review.
Lie H, Zariwala MA, Helms C, Bowcock AM, Carson JL, Brown DE 3rd, Hazucha MJ, Forsen J, Molter D, Knowles MR, Leigh MW, Ferkol TW. Primary ciliary dyskinesia in Amish communities. J Pediatr. 2010 Jun;156(6):1023-5. doi: 10.1016/j.jpeds.2010.01.054. Epub 2010 Mar 29.
Griggs RC, Batshaw M, Dunkle M, Gopal-Srivastava R, Kaye E, Krischer J, Nguyen T, Paulus K, Merkel PA; Rare Diseases Clinical Research Network. Clinical research for rare disease: opportunities, challenges, and solutions. Mol Genet Metab. 2009 Jan;96(1):20-6. doi: 10.1016/j.ymgme.2008.10.003. Epub 2008 Nov 13.
Olin JT, Burns K, Carson JL, Metjian H, Atkinson JJ, Davis SD, Dell SD, Ferkol TW, Milla CE, Olivier KN, Rosenfeld M, Baker B, Leigh MW, Knowles MR, Sagel SD; Genetic Disorders of Mucociliary Clearance Consortium. Diagnostic yield of nasal scrape biopsies in primary ciliary dyskinesia: a multicenter experience. Pediatr Pulmonol. 2011 May;46(5):483-8. doi: 10.1002/ppul.21402. Epub 2011 Jan 31.
Zariwala MA, Omran H, Ferkol TW. The emerging genetics of primary ciliary dyskinesia. Proc Am Thorac Soc. 2011 Sep;8(5):430-3. doi: 10.1513/pats.201103-023SD. Review.
Leigh MW, O'Callaghan C, Knowles MR. The challenges of diagnosing primary ciliary dyskinesia. Proc Am Thorac Soc. 2011 Sep;8(5):434-7. doi: 10.1513/pats.201103-028SD. Review.
Davis SD, Knowles M, Leigh M. Introduction: primary ciliary dyskinesia and overlapping syndromes. Proc Am Thorac Soc. 2011 Sep;8(5):421-2. doi: 10.1513/pats.201103-026SD.
Ostrowski LE, Dutcher SK, Lo CW. Cilia and models for studying structure and function. Proc Am Thorac Soc. 2011 Sep;8(5):423-9. doi: 10.1513/pats.201103-027SD. Review.
Mateos-Corral D, Coombs R, Grasemann H, Ratjen F, Dell SD. Diagnostic value of nasal nitric oxide measured with non-velum closure techniques for children with primary ciliary dyskinesia. J Pediatr. 2011 Sep;159(3):420-4. doi: 10.1016/j.jpeds.2011.03.007. Epub 2011 Apr 22.
Knowles MR, Leigh MW, Carson JL, Davis SD, Dell SD, Ferkol TW, Olivier KN, Sagel SD, Rosenfeld M, Burns KA, Minnix SL, Armstrong MC, Lori A, Hazucha MJ, Loges NT, Olbrich H, Becker-Heck A, Schmidts M, Werner C, Omran H, Zariwala MA; Genetic Disorders of Mucociliary Clearance Consortium. Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure. Thorax. 2012 May;67(5):433-41. doi: 10.1136/thoraxjnl-2011-200301. Epub 2011 Dec 18.
Stillwell PC, Wartchow EP, Sagel SD. Primary Ciliary Dyskinesia in Children: A Review for Pediatricians, Allergists, and Pediatric Pulmonologists. Pediatr Allergy Immunol Pulmonol. 2011 Dec;24(4):191-196.
Knowles MR, Leigh MW, Zariwala MA. Cutting edge genetic studies in primary ciliary dyskinesia. Thorax. 2012 May;67(5):464; author reply 464. doi: 10.1136/thoraxjnl-2012-201609. Epub 2012 Feb 10.
Horani A, Druley TE, Zariwala MA, Patel AC, Levinson BT, Van Arendonk LG, Thornton KC, Giacalone JC, Albee AJ, Wilson KS, Turner EH, Nickerson DA, Shendure J, Bayly PV, Leigh MW, Knowles MR, Brody SL, Dutcher SK, Ferkol TW. Whole-exome capture and sequencing identifies HEATR2 mutation as a cause of primary ciliary dyskinesia. Am J Hum Genet. 2012 Oct 5;91(4):685-93. doi: 10.1016/j.ajhg.2012.08.022.
Ferkol TW, Leigh MW. Ciliopathies: the central role of cilia in a spectrum of pediatric disorders. J Pediatr. 2012 Mar;160(3):366-71. doi: 10.1016/j.jpeds.2011.11.024. Epub 2011 Dec 16. Review.
Nakhleh N, Francis R, Giese RA, Tian X, Li Y, Zariwala MA, Yagi H, Khalifa O, Kureshi S, Chatterjee B, Sabol SL, Swisher M, Connelly PS, Daniels MP, Srinivasan A, Kuehl K, Kravitz N, Burns K, Sami I, Omran H, Barmada M, Olivier K, Chawla KK, Leigh M, Jonas R, Knowles M, Leatherbury L, Lo CW. High prevalence of respiratory ciliary dysfunction in congenital heart disease patients with heterotaxy. Circulation. 2012 May 8;125(18):2232-42. doi: 10.1161/CIRCULATIONAHA.111.079780. Epub 2012 Apr 12.
Antony D, Becker-Heck A, Zariwala MA, Schmidts M, Onoufriadis A, Forouhan M, Wilson R, Taylor-Cox T, Dewar A, Jackson C, Goggin P, Loges NT, Olbrich H, Jaspers M, Jorissen M, Leigh MW, Wolf WE, Daniels ML, Noone PG, Ferkol TW, Sagel SD, Rosenfeld M, Rutman A, Dixit A, O'Callaghan C, Lucas JS, Hogg C, Scambler PJ, Emes RD; Uk10k, Chung EM, Shoemark A, Knowles MR, Omran H, Mitchison HM. Mutations in CCDC39 and CCDC40 are the major cause of primary ciliary dyskinesia with axonemal disorganization and absent inner dynein arms. Hum Mutat. 2013 Mar;34(3):462-72. doi: 10.1002/humu.22261. Epub 2013 Feb 11.
Sears PR, Thompson K, Knowles MR, Davis CW. Human airway ciliary dynamics. Am J Physiol Lung Cell Mol Physiol. 2013 Feb 1;304(3):L170-83. doi: 10.1152/ajplung.00105.2012. Epub 2012 Nov 9.
Knowles MR, Leigh MW, Ostrowski LE, Huang L, Carson JL, Hazucha MJ, Yin W, Berg JS, Davis SD, Dell SD, Ferkol TW, Rosenfeld M, Sagel SD, Milla CE, Olivier KN, Turner EH, Lewis AP, Bamshad MJ, Nickerson DA, Shendure J, Zariwala MA; Genetic Disorders of Mucociliary Clearance Consortium. Exome sequencing identifies mutations in CCDC114 as a cause of primary ciliary dyskinesia. Am J Hum Genet. 2013 Jan 10;92(1):99-106. doi: 10.1016/j.ajhg.2012.11.003. Epub 2012 Dec 20.
Ferkol TW, Puffenberger EG, Lie H, Helms C, Strauss KA, Bowcock A, Carson JL, Hazucha M, Morton DH, Patel AC, Leigh MW, Knowles MR, Zariwala MA. Primary ciliary dyskinesia-causing mutations in Amish and Mennonite communities. J Pediatr. 2013 Aug;163(2):383-7. doi: 10.1016/j.jpeds.2013.01.061. Epub 2013 Mar 7.

Responsible Party: Margaret Leigh, MD, Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00450918     History of Changes
Other Study ID Numbers: RDCRN 5901
U54HL096458 ( U.S. NIH Grant/Contract )
First Submitted: March 20, 2007
First Posted: March 22, 2007
Last Update Posted: September 13, 2017
Last Verified: September 2017

Keywords provided by Margaret Leigh, MD, University of North Carolina, Chapel Hill:
Kartagener Syndrome

Additional relevant MeSH terms:
Ciliary Motility Disorders
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Bronchial Diseases
Cardiovascular Diseases
Heart Diseases
Genetic Diseases, Inborn
Dyskinesias
Kartagener Syndrome
Neurologic Manifestations
Signs and Symptoms
Bronchiectasis
Respiratory System Abnormalities
Dextrocardia
Heart Defects, Congenital
Cardiovascular Abnormalities
Congenital Abnormalities
Situs Inversus


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