WGS of Korean Idiopathic Bronchiectasis

Cystic Fibrosis Clinical Trial

— WGS_UNK_BE  

Official title:

Whole Genome Sequencing of Korean Patients With Idiopathic Bronchiectasis for Identification of Disease-Causing Variants

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03809091
• Other study ID #: WGS_UNK_BE
• Status: Recruiting
• Start date: January 2019
• Est. completion date: December 2021

Study information

• Verified date: January 2019
• Source: Seoul National University Hospital
• Contact: Jae-June Yim, MD
• Phone: +82-2-2072-2059
• Email: yimjj[@]snu.ac.kr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Whole genome sequencing of Korean patients with idiopathic bronchiectasis and their family will perform to identify disease-causing variants.

Description:

Idiopathic bronchiectasis may be a manifestation of genetic diseases such as cystic fibrosis, primary ciliary dyskinesia, etc. Diagnosis of these rare genetic diseases is crucial not only because some of the rare diseases developed already effective treatment options, but also the detection of syndrome enables us to detect other organ damages before the deterioration of them.

Several diagnostic tools have been developed; however, the genetic panel has limited screening efficacy due to the genetic heterogeneity of diseases. Even more, especially in Korea, the incidence of idiopathic bronchiectasis caused by the genetic disease is rare, most clinics have limited to assess specialized diagnostic tools such as the specialized genetic panels, sweat chloride test, and the electromagnetic detection tools for ciliary movement.

Whole genome sequencing may be an excellent solution to identify the neglected genetic diseases causing idiopathic bronchiectasis and explore the heterogeneity of disease-causing variants in Korean patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2021
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• If the patient has bronchiectasis proved by computed tomography (CT).

• The clinical features of the patient are suitable for ciliary dysfunction disease (primary ciliary dyskinesia, cystic fibrosis), alpha1-antitrypsin deficiency, and primary immune deficiency (hyper-immunoglobulin E syndrome, hypogammaglobulinemia, activated phosphoinositide 3-kinase (PI3K) delta syndrome, bare lymphocyte syndrome)

• The patient has no apparent medical events causing bronchiectasis.

Exclusion Criteria:

• If the patient does not agree or withdraw

• If the patient has any clear etiology causing bronchiectasis including AIDS, malignancy, receiving immunosuppressant or chemotherapy.

Related Conditions & MeSH terms

• Bronchiectasis
• Bronchiectasis Idiopathic
• Ciliary Motility Disorders
• Cystic Fibrosis
• Dyskinesias
• Kartagener Syndrome
• Primary Ciliary Dyskinesia

Intervention

Diagnostic Test:
• Whole genome sequencing
Whole genome sequencing of patients and their family will be performed. Among the variants detected by WGS, disease-causing variants will be analyzed by using segregation analysis.

Locations

Country	Name	City	State
Korea, Republic of	Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (4)

Chandrasekaran R, Mac Aogáin M, Chalmers JD, Elborn SJ, Chotirmall SH. Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis. BMC Pulm Med. 2018 May 22;18(1):83. doi: 10.1186/s12890-018-0638-0. Review. — View Citation

Lonni S, Chalmers JD, Goeminne PC, McDonnell MJ, Dimakou K, De Soyza A, Polverino E, Van de Kerkhove C, Rutherford R, Davison J, Rosales E, Pesci A, Restrepo MI, Torres A, Aliberti S. Etiology of Non-Cystic Fibrosis Bronchiectasis in Adults and Its Correlation to Disease Severity. Ann Am Thorac Soc. 2015 Dec;12(12):1764-70. doi: 10.1513/AnnalsATS.201507-472OC. — View Citation

Splinter K, Adams DR, Bacino CA, Bellen HJ, Bernstein JA, Cheatle-Jarvela AM, Eng CM, Esteves C, Gahl WA, Hamid R, Jacob HJ, Kikani B, Koeller DM, Kohane IS, Lee BH, Loscalzo J, Luo X, McCray AT, Metz TO, Mulvihill JJ, Nelson SF, Palmer CGS, Phillips JA 3rd, Pick L, Postlethwait JH, Reuter C, Shashi V, Sweetser DA, Tifft CJ, Walley NM, Wangler MF, Westerfield M, Wheeler MT, Wise AL, Worthey EA, Yamamoto S, Ashley EA; Undiagnosed Diseases Network. Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease. N Engl J Med. 2018 Nov 29;379(22):2131-2139. doi: 10.1056/NEJMoa1714458. Epub 2018 Oct 10. — View Citation

T Hill A, L Sullivan A, D Chalmers J, De Soyza A, Stuart Elborn J, Andres Floto R, Grillo L, Gruffydd-Jones K, Harvey A, S Haworth C, Hiscocks E, R Hurst J, Johnson C, Peter Kelleher W, Bedi P, Payne K, Saleh H, J Screaton N, Smith M, Tunney M, Whitters D, Wilson R, R Loebinger M. British Thoracic Society Guideline for bronchiectasis in adults. Thorax. 2019 Jan;74(Suppl 1):1-69. doi: 10.1136/thoraxjnl-2018-212463. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of diagnosed patients by using whole genome sequencing	The primary objective of this study is to evaluate the effectiveness of whole-genome sequencing (WGS) for idiopathic bronchiectasis patients in Korea. The number of patients newly diagnosed with WGS who are previously not diagnosed will be the primary outcome.	3 years

External Links

•   Whole genome sequencing enables definitive diagnosis of Cystic Fibrosis and Primary Ciliary Dyskinesia, bioRxiv, 2018