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RecruitingNCT07497867K-CADASILUpdated May 14, 2026

Long-term Prospective Study of Korean CADASIL Patients

An observational study in CADASIL and Cerebral Autosomal Dominant Arteriopatie With Subcortical Infarcts and Leukoencephalopathy, sponsored by Jeju National University Hospital. Recruiting at 1 site in South Korea. Open to participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2026-05-14.

Sponsored by Jeju National University Hospital · Observational

From the registry’s dates

  • Started Jul 2023; still recruiting 3 years 4 months later.
Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
500
Ages
19 Years and older
Sex
All
01

Study 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.

Read the detailed description

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant small vessel disease caused by mutations in the NOTCH3 gene located on chromosome 19, leading to progressive involvement of small cerebral arteries. Clinical manifestations of CADASIL vary across populations. Unlike European patients, those from East Asia, including Korea, often show distinct genotypes, neuroimaging features, and clinical phenotypes.

To date, no large multicenter study has comprehensively described the clinical, genetic, and imaging characteristics of Korean patients with CADASIL. Furthermore, long-term prognostic data are lacking. It remains unclear how vascular comorbidities and their management influence disease progression and outcomes in this population.

The K-CADASIL study is designed as a nationwide, multicenter, prospective observational cohort enrolling approximately 500 Korean patients with CADASIL. Participants will be followed for 10 years, undergoing regular clinical evaluations, laboratory testing, neuropsychological assessments, and magnetic resonance imaging (MRI).

The primary goals of this study are to: (1) characterize the clinical, genetic, and neuroimaging features of Korean CADASIL patients, (2) investigate long-term prognosis and identify factors influencing disease outcomes, and (3) establish a genomic and proteomic biorepository to enable future multi-omics analyses exploring the molecular determinants of disease development and prognosis.

02

Conditions studied

  • CADASIL
  • Cerebral Autosomal Dominant Arteriopatie With Subcortical Infarcts and Leukoencephalopathy

Keywords

  • CADASIL
  • NOTCH3
  • Stroke
  • Cerebral Small Vessel Disease
  • Prospective Study
  • Korea
03

In context

CADASIL

33 studies on the registry are indexed under CADASIL; 18 are open to participants now.

This study's planned enrollment of 500 is above the median of 168 across 22 observational studies indexed under CADASIL.

Browse CADASIL studies →

Lead sponsor

Jeju National University Hospital is the lead sponsor of 4 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
19 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
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.

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

  • to MRI (claustrophobia, metal implants, pacemaker)
  • Acute ischemic or hemorrhagic stroke within 180 days prior to enrollment
Terms in these criteria, in plain language(2)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
500 participants (estimated)
Target follow-up
10 Years
Patient registry
Yes
Biospecimen retention
Samples with dna

Groups and cohorts

  • 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.

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What researchers measure

Primary outcomes

  1. 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.

    Time frame: 10 years from enrollment

  2. 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)

    Time frame: 10 years from enrollment

Secondary outcomes

  1. Cerebral small vessel disease burden on MRI

    Periventricular White Matter Hyperintensity (WMH) Fazekas Scale (0-3; higher scores indicate greater severity), Deep WMH Fazekas Scale (0-3; higher scores indicate greater severity), Number of Lacunes, Number of Cerebral Microbleeds, Normalized White Matter Hyperintensity (nWMH) Volume (%)

    Time frame: Baseline, 3 years, 6 years

  2. Cognitive function composite score changes

    Korean-Trail Making Test-Elderly's Version (K-TMT-E) Standard Score (higher scores indicate better performance), Korean-Mini Mental State Examination (K-MMSE) Standard Score (0-30; higher scores indicate better cognitive function), Clinical Dementia Rating (CDR) Global Score (0-3; higher scores indicate worse dementia severity), Korean version Montreal Cognitive Assessment (K-MoCA) Score (0-30; higher scores indicate better cognitive function)

    Time frame: Baseline, 3 years, 6 years

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Study locations

1 of 1 sites recruiting
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References and documents

Publications

  • 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. PubMed 19933977 ↗
  • 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. PubMed 37236211 ↗
  • 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. PubMed 37652700 ↗
  • 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. PubMed 23867200 ↗
  • 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. PubMed 24578207 ↗
  • 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. PubMed 33712516 ↗
  • 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. PubMed 10356105 ↗
  • 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. PubMed 15364702 ↗
  • 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. PubMed 9818928 ↗
  • 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. PubMed 30237574 ↗
  • 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. PubMed 27844030 ↗
  • 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. PubMed 34881353 ↗
  • 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. PubMed 22133740 ↗
  • 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. PubMed 8878478 ↗
  • 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. PubMed 20386637 ↗

Individual participant data

Plan to share: Yes — De-identified individual participant data (IPD) from the K-CADASIL prospective cohort, including demographic, clinical, imaging, and genetic variables, will be made available to qualified investigators upon reasonable request.

Supporting information: Study protocol, Statistical analysis plan

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.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Jul 2023 (actual). Primary completion is estimated for Dec 2035, 149 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Mar 23, 2026
First posted
Mar 27, 2026
StartActual
Jul 10, 2023
Primary completionEst.
Dec 31, 2035
CompletionEst.
Dec 31, 2040
Last update
May 14, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on May 14, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT07497867
Lead sponsor
Jeju National University Hospital
Collaborators
Asan Medical Center, Chonnam National University Hospital, Chungbuk National University Hospital, Dong-A University Hospital, Ewha Woman University Medical Center, Hallym University Medical Center, Hanyang University Seoul Hospital, Inje University Ilsan Paik Hospital, Kangdong Sacred Heart Hospital, Keimyung University Dongsan Medical Center, Korea University Ansan Hospital, Korea University Guro Hospital, Kyung Hee University Hospital, Kyungpook National University Hospital, Nowon Eulji Medical Center, Pusan National University Hospital, Seoul Medical Center, Seoul National University Bundang Hospital, Seoul National University Hospital, Severance Hospital, Soonchunhyang University Hospital, Ulsan University Hospital, Yeungnam University Hospital, Daejeon Eulji University Medical Center, Jeonbuk National University Hospital, DongGuk University
Responsible party
Jay Chol Choi (Professor, MD, PhD, Department of Neurology, Jeju National University Hospital) — Principal investigator
First posted
Mar 27, 2026
Start date
Jul 10, 2023
Primary completion
Dec 31, 2035 (estimated)
Completion
Dec 31, 2040 (estimated)
Last update
May 14, 2026

Study contacts

Jay Chol Professor Choi, MD, PhD, MD, PhD
Contact
jaychoi@jejunu.ac.kr
+82-64-754-8160

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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