Genotype, Clinical Features and Imaging of Neuroradiological Abnormalities in CADASIL

NCT06938100 | Recruiting

• 1 other identifier: GENICa
• Study Type: observational
• Target: 100
• Locations: 2 countries
• Sites: 2

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.

Conditions

CADASIL; CADASIL (Diagnosis)

Keywords

CADASIL; NOTCH3

Outcome Measures

Primary Outcomes (2)

• Deepen the knowledge of the clinical phenotype CADASIL patient

  Each patient with CADASIL will undergo to neuroimaging, correlating it with genotype (NOTCH3 gene mutation search outcome), clinical (e.g., the index event, cerebrovascular risk factors, associated manifestations) and instrumental (radiological) characterization.

  T0- T1 (24 months)

• Identify potentially reversible risk factors for disease progression

  At baseline, each patient will undergo collection of demographic and clinical data (e.g., the index event, cerebrovascular risk factors, associated manifestations). Disability will be assessed with the modified Rankin Scale (mRS). Neuropsychological assessment will include administration of the Montreal Cognitive Assesment (MoCA) as a screening test. Some components of executive functions will be assessed by Frontal Assesment Battery (F.A.B) scale as a screening test of executive functions, Trail Making Test (TMT) A and B to assess visual search, psychomotor speed and selective attention (TMT test A) and in addition divided and alternating attention and cognitive flexibility by TMT test B, Attentional Matrices to assess sustained attention and visual search and Modified Five Point Test to assess spatial fluency. Finally by means of the Forward Word Span and Backward Digit Span, Verbal Short-Term Memory and Working Memory will be assessed. Alongside the neuropsychological assessment of

  0-24 months

Secondary Outcomes (2)

• Identify clinical, genetic, biological and neuroradiological markers

  0-30 months

• Deepen knowledge of the neuroradiological phenotype of CADASIL patients, depending on the NOTCH3 mutation locus identified (high, moderate or low risk)

  0-30 months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: lead

Study Sites (2)

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, Italy

RECRUITING

Hospital Universitario de la Princesa, Madrid

Madrid, Spain

NOT YET RECRUITING

Related Publications (4)

• 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.

  PMID: 30032161 BACKGROUND

• Ruchoux MM, Maurage CA. CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J Neuropathol Exp Neurol. 1997 Sep;56(9):947-64.

  PMID: 9291937 BACKGROUND

• 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.

  PMID: 19539236 BACKGROUND

• 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 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

In a subsample of patients will be collected plasma and/ or cells tissue specimens

MeSH Terms

Conditions

CADASIL; Disease

Condition Hierarchy (Ancestors)

Cerebral Infarction; Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Dementia, Vascular; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Stroke; 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

Anna Bersano, MD

CONTACT

+ 39 02.2394; anna.bersano@istituto-besta.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2025
• First Posted: April 22, 2025
• Study Start: November 21, 2023
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: April 22, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); ES (1)