Long-term Lung Function and Disease Progression in Children With Early Onset Primary Ciliary Dyskinesia Lung Disease

NCT00722878 | Completed DMC

• 3 other identifiers: 08-0764U54HL096458RDCRN 5903
• Study Type: observational
• Target: 48
• Locations: 2 countries
• Sites: 6

Brief Summary

Primary ciliary dyskinesia (PCD), also known as Kartagener syndrome, is a genetic disorder of the cilia, which are microscopic hair-like cells. Cilia work to keep the respiratory system clean by moving mucus that contains debris to the large airways, where it can be coughed out. People with PCD have cilia that do not move properly and therefore are not effective in cleaning the respiratory system. This study will determine when PCD starts and how it changes over time, specifically in terms of how well the lungs work, what germs grow in lung secretions, and how the lungs look on computed tomography (CT) scans.

Conditions

Kartagener Syndrome

Keywords

Primary Ciliary Dyskinesia

Outcome Measures

Primary Outcomes (4)

• Infant lung function

  Measured at initial study visit (for children under 3)

• Spirometry measures

  Measured yearly for 5 years (after age of 3 years)

• Respiratory cultures

  Measured yearly for 5 years

• Chest CT scan results

  Measured at the initial study visit and at Years 3 and 5

Eligibility Criteria

• Age: Up to 4 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Participants in this study will be children younger than 5 years of age who have been diagnosed with PCD as based on electron microscopy and/or presence of two known disease-causing gene mutations or for whom a diagnosis of PCD has been determined probable as based on clinical features and very low nasal nitric oxide (less than 60 nl/minute).

You may qualify if:

• Younger than 5 years of age
• Diagnosis of PCD or probable PCD based on criteria listed above
• Parent or legal guardian willing to give informed consent

You may not qualify if:

• Unable to attend follow-up appointments
• History of lung transplant
• Any co-existing severe diseases that may have significant impact on lung function, respiratory infections, or overall health status (i.e., severe congenital heart disease, severe scoliosis, AIDS, cancer, or end-stage kidney disease)

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (6)

Stanford University, Palo Alto

Palo Alto, California, 94304, United States

Location

The Children's Hospital, Denver

Denver, Colorado, 80045, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Children's Hospital and Regional Medical Center, Seattle

Seattle, Washington, 98105, United States

Location

The Hospital for Sick Children, Toronto

Toronto, Ontario, Canada

Location

Related Publications (22)

• Imbrie JD. Kartagener's syndrome: a genetic defect affecting the function of cilia. Am J Otolaryngol. 1981 Aug;2(3):215-22. doi: 10.1016/s0196-0709(81)80018-x.

  PMID: 6974512 BACKGROUND

• Ramotowski R, Guz W, Zieba E, Zlomaniec G. Clinical and radiological aspects of Kartagener's syndrome. Ann Univ Mariae Curie Sklodowska Med. 2001;56:151-5.

  PMID: 11977302 BACKGROUND

• Newmark H 3rd, Willis G, Ablemayor E, Chakmakian V. Kartagener's syndrome seen on CT. Comput Radiol. 1985 Sep-Oct;9(5):279-81. doi: 10.1016/0730-4862(85)90052-6.

  PMID: 3877608 BACKGROUND

• 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.

  PMID: 19013090 BACKGROUND

• 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):1023-1025. doi: 10.1016/j.jpeds.2010.01.054. Epub 2010 Mar 29.

  PMID: 20350728 BACKGROUND

• 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.

  PMID: 21284095 BACKGROUND

• 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.

  PMID: 21926394 BACKGROUND

• 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.

  PMID: 21926395 BACKGROUND

• Sagel SD, Davis SD, Campisi P, Dell SD. Update of respiratory tract disease in children with primary ciliary dyskinesia. Proc Am Thorac Soc. 2011 Sep;8(5):438-43. doi: 10.1513/pats.201103-024SD.

  PMID: 21926396 BACKGROUND

• 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. No abstract available.

  PMID: 21926392 BACKGROUND

• 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.

  PMID: 21926393 BACKGROUND

• 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.

  PMID: 21514598 BACKGROUND

• 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.

  PMID: 22184204 BACKGROUND

• 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. doi: 10.1089/ped.2011.0099.

  PMID: 22276227 BACKGROUND

• 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. No abstract available.

  PMID: 22328589 BACKGROUND

• 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.

  PMID: 23040496 BACKGROUND

• 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. No abstract available.

  PMID: 22177992 BACKGROUND

• 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.

  PMID: 22499950 BACKGROUND

• 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.

  PMID: 23255504 BACKGROUND

• 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.

  PMID: 23144323 BACKGROUND

• 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.

  PMID: 23261302 BACKGROUND

• 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.

  PMID: 23477994 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Approximately 2 teaspoons of blood and a small amount of urine (if the child is able to urinate in a cup) will be collected and held at the specimen bank located at Denver Children's Hospital. These samples will be used to help identify markers that may predict the clinical course of PCD.

MeSH Terms

Conditions

Kartagener Syndrome; Ciliary Motility Disorders

Condition Hierarchy (Ancestors)

Bronchiectasis; Bronchial Diseases; Respiratory Tract Diseases; Respiratory System Abnormalities; Otorhinolaryngologic Diseases; Dextrocardia; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Situs Inversus; Genetic Diseases, Inborn

Study Officials

• Margaret W. Leigh, MD

  University of North Carolina, Chapel Hill

  STUDY CHAIR

• Margaret Rosenfeld, MD, MPH

  Seattle Children's Hospital

  STUDY CHAIR

• Stephanie Davis, MD

  University of North Carolina, Chapel Hill

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2008
• First Posted: July 28, 2008
• Study Start: July 1, 2008
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: October 7, 2019

Record last verified: 2019-10

Locations

CA (1); US (5)