Clinical trial NCT06938100: Genotype, Clinical Features and Imaging of Neuroradiological Abnormalities in CADASIL
Official title: Genotype, Clinical Features and Imaging of Neuroradiological Abnormalities in CADASIL
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: CADASIL
CADASIL (Diagnosis)
Keywords: CADASIL
NOTCH3
Lead sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Sponsor class: OTHER
First posted: 2025-04-22
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients diagnosed with genetically confirmed CADASIL and followed in the Cerebrovascular Diseases Outpatient Clinic of Neurology Unit 9 from 2008 to 2023 will be enrolled in the study.

Brief summary: The project aims to retrospectively and prospectively analyze a population of CADASIL patients in order to study the natural history of the disease by correlating the symptom spectrum with genetic risk and specific neuroradiological and biological markers

- Stratifying patients according to their disease risk, this could contribute to the discovery of personalized therapeutic targets.


Eligibility criteria: Inclusion criteria:

* patients of either sex older than 18 years of age;
* finding of a pathogenic mutation on genetic analysis of NOTCH3;
* in the absence of unambiguous mutation, presence of characteristic deposits (GOM) within small vessels at skin biopsy

Exclusion criteria:

* do not meet the diagnostic criteria of CADASIL;
* are unable to give consent for the study due to aphasic or cognitive impairment or because they are deceased at the time of enrollment and their next of kin refuse to give consent for study participation.

Primary outcomes:
measure: Deepen the knowledge of the clinical phenotype CADASIL patient
timeFrame: T0- T1 (24 months)
measure: Identify potentially reversible risk factors for disease progression
timeFrame: 0-24 months
Secondary outcomes:
measure: Identify clinical, genetic, biological and neuroradiological markers
timeFrame: 0-30 months
measure: Deepen knowledge of the neuroradiological phenotype of CADASIL patients, depending on the NOTCH3 mutation locus identified (high, moderate or low risk)
timeFrame: 0-30 months
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa, Madrid
Study officials:
References:
citation: Rutten JW, Van Eijsden BJ, Duering M, Jouvent E, Opherk C, Pantoni L, Federico A, Dichgans M, Markus HS, Chabriat H, Lesnik Oberstein SAJ. 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 Mar;21(3):676-682. doi: 10.1038/s41436-018-0088-3. Epub 2018 Jul 22.
citation: Ruchoux MM, Maurage CA. CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J Neuropathol Exp Neurol. 1997 Sep;56(9):947-64.
citation: Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG. Cadasil. Lancet Neurol. 2009 Jul;8(7):643-53. doi: 10.1016/S1474-4422(09)70127-9.
citation: 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.