Clinical trial NCT04232787: Southeast Asian Brugada Syndrome Cohort
Official title: Discovering the Genetic Causes of Brugada Syndrome in Thais and Southeast Asian Population
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Brugada Syndrome
Keywords: Brugada Syndrome
Genetics
Epidemiology
Thai
Southeast Asia
Lead sponsor: Chulalongkorn University
Sponsor class: OTHER
Collaborators: name: National Research Council of Thailand
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
First posted: 2020-01-18
Enrollment: 750
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Thai Brugada syndrome patients and healthy volunteers

Brief summary: Brugada syndrome (BrS) is the leading cause of sudden death in young Asian adults including Thailand. This syndrome may be hereditary and involve mutations in certain genes. Aim of the study is to identify the relationship between genetic variants and the diagnosis/clinical severity of patients with BrS.

Detailed description: This cohort study recruits BrS patients with confirmed Brugada type 1 ECG and healthy volunteers in Thailand. Data collection consists of demographic, clinical data, ECG and blood sample for genetic studies. Genotyping was done by whole genome sequencing and SNP array then compared between cases and controls. Each BrS patient will be followed up prospectively for symptoms and AICD shock. Subsequently, the study will analyze relationship between genetic variants and clinical data against clinical severity of BrS patients.

Eligibility criteria: Inclusion Criteria:

* Thai nationality
* The patient has at least one of confirmed Brugada type 1 ECG in at least one of right precordial leads (v1 or v2) with or without pharmacologic provocative testing. The confirmed ECG is standard 12 lead ECG or Brugada lead

Exclusion Criteria:

* The patient has other cardiac diseases such as ischemic heart disease, valvular heart disease, congenital heart disease, myocarditis and pericarditis
* The patient has type 2 or type 3 Brugada ECG without type 1 ECG during pharmacologic provocative testing and/or Brugada lead
* The patient had one time of Brugada type 1 ECG during drug use without reproducibility

Primary outcomes:
measure: Relationship between genetic variants and Brugada syndrome (Brugada syndrome phenotype)
timeFrame: 7 years
Secondary outcomes:
measure: Natural history of Brugada syndrome (survival from arrhythmic events)
timeFrame: 7 years
measure: Epidemiology of Brugada syndrome
timeFrame: 7 years
Other outcomes:
Locations:
city: Bangkok Noi
country: Thailand
facility: Siriraj Hospital, Mahidol University
state: Bangkok
city: Dusit
country: Thailand
facility: Vajira Hospital
state: Bangkok
city: Pathum Wan
country: Thailand
facility: Chulalongkorn University
state: Bangkok
city: Ratchathewi
country: Thailand
facility: Faculty of Medicine Ramathibodi Hospital, Mahidol University
state: Bangkok
city: Sai Mai
country: Thailand
facility: Bhumibol Adulyadej RTAF Hospital
state: Bangkok
city: Watthana
country: Thailand
facility: Bumrungrad International Hospital
state: Bangkok
city: Watthana
country: Thailand
facility: Pacific Rim Electrophysiology Research Institute Data Coordinating Center
state: Bangkok
city: Bangkok
country: Thailand
facility: Bangkok Hospital
city: Chiang Mai
country: Thailand
facility: Faculty of Medicine, Chiang Mai University
city: Khon Kaen
country: Thailand
facility: Queen Sirikit Heart Center of the Northeast
city: Nonthaburi
country: Thailand
facility: Central Chest Hospital
Study officials:
affiliation: Chulalongkorn University
name: Koonlawee Nademanee, MD
role: STUDY_CHAIR
affiliation: Chulalongkorn University
name: Yong Poovorawan, MD
role: STUDY_DIRECTOR
affiliation: Chulalongkorn University
name: Apichai Khongphatthanayothin, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Nademanee K, Veerakul G, Nimmannit S, Chaowakul V, Bhuripanyo K, Likittanasombat K, Tunsanga K, Kuasirikul S, Malasit P, Tansupasawadikul S, Tatsanavivat P. Arrhythmogenic marker for the sudden unexplained death syndrome in Thai men. Circulation. 1997 Oct 21;96(8):2595-600. doi: 10.1161/01.cir.96.8.2595.
citation: Bezzina CR, Barc J, Mizusawa Y, Remme CA, Gourraud JB, Simonet F, Verkerk AO, Schwartz PJ, Crotti L, Dagradi F, Guicheney P, Fressart V, Leenhardt A, Antzelevitch C, Bartkowiak S, Borggrefe M, Schimpf R, Schulze-Bahr E, Zumhagen S, Behr ER, Bastiaenen R, Tfelt-Hansen J, Olesen MS, Kaab S, Beckmann BM, Weeke P, Watanabe H, Endo N, Minamino T, Horie M, Ohno S, Hasegawa K, Makita N, Nogami A, Shimizu W, Aiba T, Froguel P, Balkau B, Lantieri O, Torchio M, Wiese C, Weber D, Wolswinkel R, Coronel R, Boukens BJ, Bezieau S, Charpentier E, Chatel S, Despres A, Gros F, Kyndt F, Lecointe S, Lindenbaum P, Portero V, Violleau J, Gessler M, Tan HL, Roden DM, Christoffels VM, Le Marec H, Wilde AA, Probst V, Schott JJ, Dina C, Redon R. Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death. Nat Genet. 2013 Sep;45(9):1044-9. doi: 10.1038/ng.2712. Epub 2013 Jul 21.
citation: Chimparlee N, Prechawat S, Khongphatthanayothin A, Mauleekoonphairoj J, Lekchuensakul S, Wongcharoen W, Makarawate P, Sahasatas D, Krittayaphong R, Amnueypol M, Anannab A, Ngarmukos T, Vardhanabhuti S, Sutjaporn B, Wandee P, Veerakul G, Bezzina CR, Poovorawan Y, Nademanee K. Clinical Characteristics of SCN5A p.R965C Carriers: A Common Founder Variant Predisposing to Brugada Syndrome in Thailand. Circ Genom Precis Med. 2021 Jun;14(3):e003229. doi: 10.1161/CIRCGEN.120.003229. Epub 2021 Jun 7. No abstract available.
citation: Makarawate P, Glinge C, Khongphatthanayothin A, Walsh R, Mauleekoonphairoj J, Amnueypol M, Prechawat S, Wongcharoen W, Krittayaphong R, Anannab A, Lichtner P, Meitinger T, Tjong FVY, Lieve KVV, Amin AS, Sahasatas D, Ngarmukos T, Wichadakul D, Payungporn S, Sutjaporn B, Wandee P, Poovorawan Y, Tfelt-Hansen J, Tanck MWT, Tadros R, Wilde AAM, Bezzina CR, Veerakul G, Nademanee K. Common and rare susceptibility genetic variants predisposing to Brugada syndrome in Thailand. Heart Rhythm. 2020 Dec;17(12):2145-2153. doi: 10.1016/j.hrthm.2020.06.027. Epub 2020 Jun 30.