CADASILK-CADASILNCT07497867
Long-term Prospective Study of Korean CADASIL Patients
An observational study of CADASIL and Cerebral Autosomal Dominant Arteriopatie With Subcortical Infarcts and Leukoencephalopathy, run by Jeju National University Hospital at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- CADASIL, Cerebral Autosomal Dominant Arteriopatie With Subcortical Infarcts and Leukoencephalopathy
- How many people
- 500 participants
- Where
- 1 siteSouth Korea
- Study dates
- 10 Jul 2023to 31 Dec 2040
- How long will I take part?
- 10 Years
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Age ≥ 19 years
- CADASIL suspected or confirmed by genetic testing (NOTCH3 mutation)
- Able to provide written informed consent (participant or legally authorized representative)
Who cannot join
- Contraindication to MRI (claustrophobia, metal implants, pacemaker)
- Acute ischemic or hemorrhagic stroke within 180 days prior to enrollment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site, 1 recruiting
- Recruiting
Jeju National University Hospital
Jeju City, Jeju-do, 63241
JI HYE Oh, RN, PhD, RN, PhD, +82-64-717-2153, sophia7240@gmail.com
About this study
Official title: Long-term Prognosis of Korean Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy(CADASIL) Patients: A Multicenter Prospective Study
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.
- Conditions
- CADASIL, Cerebral Autosomal Dominant Arteriopatie With Subcortical Infarcts and Leukoencephalopathy
- Keywords
- CADASIL, NOTCH3, Stroke, Cerebral Small Vessel Disease, Prospective Study, Korea
- Medical subject headings
- CADASIL, Leukoencephalopathies, Stroke, Cerebral Small Vessel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: 10 years from enrollment
Secondary outcomes (2)
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 (%)
Measured: Baseline, 3 years, 6 years
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)
Measured: Baseline, 3 years, 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2026
- Study start10 Jul 2023
- Primary completion31 Dec 2035 (estimated)
- Study completion31 Dec 2040 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for CADASILStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
- Target duration
- 10 Years
Sponsor and investigators
- Lead sponsor
- Jeju National University Hospital
- Sponsor type
- University, hospital or other
- 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
- Principal investigator, Jay Chol Choi, Jeju National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07497867
- Sponsor's protocol ID
- JEJUNUH IRB 2023-05-034
- Acronym
- K-CADASIL
- Status last verified
- May 2026
- First submitted
- 23 Mar 2026
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
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 19933977Duering 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 37236211Zhang 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 37652700Wardlaw 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 23867200Opherk 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 24578207Cho 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 33712516Desmond 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 10356105Opherk 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 15364702Dichgans 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 9818928Rutten 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 30237574Rutten 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 27844030Kang 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 34881353Choi 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 22133740Joutel 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 8878478Choi 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