Long-term Prospective Study of Korean CADASIL Patients

NCT07497867 | Recruiting

• 1 other identifier: JEJUNUH IRB 2023-05-034
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

K-CADASIL is a 10-year prospective study of 500 Korean patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic brain disease that causes stroke and dementia. The investigators will track symptoms, brain scans, memory tests, and gene information to understand disease progression in Koreans and identify better treatments. Participants will visit clinics regularly for check-ups and blood tests. This study aims to help improve care for CADASIL patients and families worldwide.

Conditions

CADASIL; Cerebral Autosomal Dominant Arteriopatie With Subcortical Infarcts and Leukoencephalopathy

Keywords

CADASIL; NOTCH3; Stroke; Cerebral Small Vessel Disease; Prospective Study; Korea

Outcome Measures

Primary Outcomes (2)

• New-onset stroke events

  Number of Participants with New-onset Stroke Events, Date of Occurrence, Subtype, Location, and National Institutes of Health Stroke Scale \[NIHSS\] Score.

  10 years from enrollment

• New-onset mild cognitive impairment (MCI) or dementia

  Number of Participants with New-onset MCI or Dementia, Date of Onset, and Dementia Subtype (Alzheimer Disease Dementia, Vascular Dementia, Mixed Dementia)

  10 years from enrollment

Secondary Outcomes (2)

• Cerebral small vessel disease burden on MRI

  Baseline, 3 years, 6 years

• Cognitive function composite score changes

  Baseline, 3 years, 6 years

Study Arms (1)

Korean CADASIL Cohort

Genetically confirmed NOTCH3 mutation carriers followed prospectively for 10 years with regular clinical evaluations, neuroimaging, neuropsychological assessments, and laboratory testing. No investigational interventions administered.

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Korean adults (≥19 years) with genetically confirmed or clinically suspected CADASIL (NOTCH3 mutation). Multicenter prospective cohort recruited from 28 hospitals across Korea. Approximately 500 participants will be followed for 10 years.

You may qualify if:

• Age ≥ 19 years
• CADASIL suspected or confirmed by genetic testing (NOTCH3 mutation)
• Able to provide written informed consent (participant or legally authorized representative)

You may not qualify if:

• Contraindication to MRI (claustrophobia, metal implants, pacemaker)
• Acute ischemic or hemorrhagic stroke within 180 days prior to enrollment

Sponsors & Collaborators

• Kangdong Sacred Heart Hospital: collaborator
• Severance Hospital: collaborator
• Asan Medical Center: collaborator
• Chungbuk National University Hospital: collaborator
• Dong-A University Hospital: collaborator
• Ewha Woman University Medical Center: collaborator
• Hallym University Medical Center: collaborator
• Hanyang University Seoul Hospital: collaborator
• Inje University Ilsan Paik Hospital: collaborator
• Keimyung University Dongsan Medical Center: collaborator
• Korea University Ansan Hospital: collaborator
• Korea University Guro Hospital: collaborator
• Kyung Hee University Hospital: collaborator
• Kyungpook National University Hospital: collaborator
• Nowon Eulji Medical Center: collaborator
• Pusan National University Hospital: collaborator
• Seoul Medical Center: collaborator
• Seoul National University Bundang Hospital: collaborator
• Seoul National University Hospital: collaborator
• Soonchunhyang University Hospital: collaborator
• Ulsan University Hospital: collaborator
• Yeungnam University Hospital: collaborator
• Jeonbuk National University Hospital: collaborator
• Chonnam National University Hospital: collaborator
• Jeju National University Hospital: lead
• Daejeon Eulji University Medical Center: collaborator
• DongGuk University: collaborator

Study Sites (1)

Jeju National University Hospital

Jeju City, Jeju-do, 63241, South Korea

RECRUITING

Related Publications (15)

• Gregoire SM, Chaudhary UJ, Brown MM, Yousry TA, Kallis C, Jager HR, Werring DJ. The Microbleed Anatomical Rating Scale (MARS): reliability of a tool to map brain microbleeds. Neurology. 2009 Nov 24;73(21):1759-66. doi: 10.1212/WNL.0b013e3181c34a7d.

  PMID: 19933977 RESULT

• Duering M, Biessels GJ, Brodtmann A, Chen C, Cordonnier C, de Leeuw FE, Debette S, Frayne R, Jouvent E, Rost NS, Ter Telgte A, Al-Shahi Salman R, Backes WH, Bae HJ, Brown R, Chabriat H, De Luca A, deCarli C, Dewenter A, Doubal FN, Ewers M, Field TS, Ganesh A, Greenberg S, Helmer KG, Hilal S, Jochems ACC, Jokinen H, Kuijf H, Lam BYK, Lebenberg J, MacIntosh BJ, Maillard P, Mok VCT, Pantoni L, Rudilosso S, Satizabal CL, Schirmer MD, Schmidt R, Smith C, Staals J, Thrippleton MJ, van Veluw SJ, Vemuri P, Wang Y, Werring D, Zedde M, Akinyemi RO, Del Brutto OH, Markus HS, Zhu YC, Smith EE, Dichgans M, Wardlaw JM. Neuroimaging standards for research into small vessel disease-advances since 2013. Lancet Neurol. 2023 Jul;22(7):602-618. doi: 10.1016/S1474-4422(23)00131-X. Epub 2023 May 23.

  PMID: 37236211 RESULT

• Zhang R, Chen CH, Tezenas Du Montcel S, Lebenberg J, Cheng YW, Dichgans M, Tang SC, Chabriat H. The CADA-MRIT: An MRI Inventory Tool for Evaluating Cerebral Lesions in CADASIL Across Cohorts. Neurology. 2023 Oct 24;101(17):e1665-e1677. doi: 10.1212/WNL.0000000000207713. Epub 2023 Aug 31.

  PMID: 37652700 RESULT

• Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O'Brien JT, Barkhof F, Benavente OR, Black SE, Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V, Oostenbrugge Rv, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, Chen C, Smith C, van Buchem M, Norrving B, Gorelick PB, Dichgans M; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013 Aug;12(8):822-38. doi: 10.1016/S1474-4422(13)70124-8.

  PMID: 23867200 RESULT

• Opherk C, Gonik M, Duering M, Malik R, Jouvent E, Herve D, Adib-Samii P, Bevan S, Pianese L, Silvestri S, Dotti MT, De Stefano N, Liem M, Boon EM, Pescini F, Pachai C, Bracoud L, Muller-Myhsok B, Meitinger T, Rost N, Pantoni L, Lesnik Oberstein S, Federico A, Ragno M, Markus HS, Tournier-Lasserve E, Rosand J, Chabriat H, Dichgans M. Genome-wide genotyping demonstrates a polygenic risk score associated with white matter hyperintensity volume in CADASIL. Stroke. 2014 Apr;45(4):968-72. doi: 10.1161/STROKEAHA.113.004461. Epub 2014 Feb 27.

  PMID: 24578207 RESULT

• Cho BPH, Nannoni S, Harshfield EL, Tozer D, Graf S, Bell S, Markus HS. NOTCH3 variants are more common than expected in the general population and associated with stroke and vascular dementia: an analysis of 200 000 participants. J Neurol Neurosurg Psychiatry. 2021 Jul;92(7):694-701. doi: 10.1136/jnnp-2020-325838. Epub 2021 Mar 12.

  PMID: 33712516 RESULT

• Desmond DW, Moroney JT, Lynch T, Chan S, Chin SS, Mohr JP. The natural history of CADASIL: a pooled analysis of previously published cases. Stroke. 1999 Jun;30(6):1230-3. doi: 10.1161/01.str.30.6.1230.

  PMID: 10356105 RESULT

• Opherk C, Peters N, Herzog J, Luedtke R, Dichgans M. Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients. Brain. 2004 Nov;127(Pt 11):2533-9. doi: 10.1093/brain/awh282. Epub 2004 Sep 13.

  PMID: 15364702 RESULT

• Dichgans M, Mayer M, Uttner I, Bruning R, Muller-Hocker J, Rungger G, Ebke M, Klockgether T, Gasser T. The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann Neurol. 1998 Nov;44(5):731-9. doi: 10.1002/ana.410440506.

  PMID: 9818928 RESULT

• Rutten JW, Van Eijsden BJ, Duering M, Jouvent E, Opherk C, Pantoni L, Federico A, Dichgans M, Markus HS, Chabriat H, Oberstein SAJL. Correction: The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1-6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7-34 pathogenic variant. Genet Med. 2019 Aug;21(8):1895. doi: 10.1038/s41436-018-0306-z.

  PMID: 30237574 RESULT

• Rutten JW, Dauwerse HG, Gravesteijn G, van Belzen MJ, van der Grond J, Polke JM, Bernal-Quiros M, Lesnik Oberstein SA. Archetypal NOTCH3 mutations frequent in public exome: implications for CADASIL. Ann Clin Transl Neurol. 2016 Sep 28;3(11):844-853. doi: 10.1002/acn3.344. eCollection 2016 Nov.

  PMID: 27844030 RESULT

• Kang CH, Kim YM, Kim YJ, Hong SJ, Kim DY, Woo HG, Kim YR, Kim JG, Lee JS, Kong MH, Kim HJ, Choi JC. Pathogenic NOTCH3 Variants Are Frequent Among the Korean General Population. Neurol Genet. 2021 Dec 6;7(6):e639. doi: 10.1212/NXG.0000000000000639. eCollection 2021 Dec.

  PMID: 34881353 RESULT

• Choi JC, Lee KH, Song SK, Lee JS, Kang SY, Kang JH. Screening for NOTCH3 gene mutations among 151 consecutive Korean patients with acute ischemic stroke. J Stroke Cerebrovasc Dis. 2013 Jul;22(5):608-14. doi: 10.1016/j.jstrokecerebrovasdis.2011.10.013. Epub 2011 Nov 30.

  PMID: 22133740 RESULT

• Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, Alamowitch S, Domenga V, Cecillion M, Marechal E, Maciazek J, Vayssiere C, Cruaud C, Cabanis EA, Ruchoux MM, Weissenbach J, Bach JF, Bousser MG, Tournier-Lasserve E. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature. 1996 Oct 24;383(6602):707-10. doi: 10.1038/383707a0.

  PMID: 8878478 RESULT

• Choi JC. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a genetic cause of cerebral small vessel disease. J Clin Neurol. 2010 Mar;6(1):1-9. doi: 10.3988/jcn.2010.6.1.1. Epub 2010 Mar 26.

  PMID: 20386637 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Blood (EDTA, SST, PAXgene tubes) for genomic, transcriptomic, and proteomic analyses; optional skin biopsy for GOM detection.

MeSH Terms

Conditions

CADASIL; Leukoencephalopathies; Stroke; Cerebral Small Vessel Diseases

Condition Hierarchy (Ancestors)

Cerebral Infarction; Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia, Vascular; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Dementia; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Central Study Contacts

Jay Chol Professor Choi, MD, PhD, MD, PhD

CONTACT

+82-64-754-8160; jaychoi@jejunu.ac.kr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, PhD, Department of Neurology

Study Record Dates

• First Submitted: March 23, 2026
• First Posted: March 27, 2026
• Study Start: July 10, 2023
• Primary Completion (Estimated): December 31, 2035
• Study Completion (Estimated): December 31, 2040
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available after publication of the primary study results and remain accessible for five years following publication.
• Access Criteria: Researchers must submit a proposal describing the scientific rationale and analysis plan. Requests will be reviewed and approved by the K-CADASIL Steering Committee and the Data Access Committee of Jeju National University Hospital. Data will be shared under a secure Data Transfer Agreement (DTA) and in compliance with Korean privacy laws and institutional IRB requirements.

Locations

KR (1)