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RecruitingNCT06938100GENICaUpdated Aug 31, 2026

Genotype, Clinical Features and Imaging of Neuroradiological Abnormalities in CADASIL

An observational study in CADASIL and CADASIL (Diagnosis), sponsored by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta. Recruiting at 2 sites in 2 countries. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-31.

Sponsored by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta · Observational

From the registry’s dates

  • Started Nov 2023; still recruiting 2 years 11 months later.
Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
100
Ages
18 Years and older
Sex
All
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Study 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.

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Conditions studied

  • CADASIL
  • CADASIL (Diagnosis)

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Keywords

  • CADASIL
  • NOTCH3
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In context

CADASIL

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

This study's planned enrollment of 100 is below the median of 168 across 22 observational studies indexed under CADASIL.

Browse CADASIL studies →

Lead sponsor

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta is the lead sponsor of 84 studies on the registry; 32 are open to participants now.

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

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Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes
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.

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

  • 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

Exclusion criteria

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.
Terms in these criteria, in plain language(1)

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.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

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Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
100 participants (estimated)
Patient registry
No
Biospecimen retention
Samples with dna
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What researchers measure

Primary outcomes

  1. 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.

    Time frame: T0- T1 (24 months)

  2. 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

    Time frame: 0-24 months

Secondary outcomes

  1. Identify clinical, genetic, biological and neuroradiological markers

    Patients will undergo an MRI study with high-field (3T) equipment consisting of standard morphologic sequences (T1 3D TSE, T2 TSE, 3D FLAIR, SWI, DWI) to assess the extent of leukoencephalopathy, its distribution pattern, the presence of gaps and/or recent ischemic lesions in DWI sequences, perivascular spaces, and concomitant microhemorrhages. Laboratory approaches aimed at differentiating progenitors of specific cell populations (e.g., endothelial and vascular smooth muscle cells) from peripheral blood mononuclear cells (PBMCs) or fibroblasts from skin will be performed. In addition, it will be possible to isolate from peripheral blood the plasma component, intended for research and characterization of potential circulating biomarkers, by appropriate multi-omics approaches (transcriptomics, proteomics, lipidomics).

    Time frame: 0-30 months

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

    Patients will undergo an MRI study with high-field (3T), in particular, high-resolution volumetric FLAIR sequences will be used to allow subsequent segmentation analyses of vascular lesions and a more correct quantitative assessment of cortical thickness values of brain areas. Advanced imaging sequences, particularly epi bold resting state for the study of functional brain connectivity, will also be provided.

    Time frame: 0-30 months

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Study locations

1 of 2 sites recruiting
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References and documents

Publications

  • 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. PubMed 30032161 ↗
  • Ruchoux MM, Maurage CA. CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J Neuropathol Exp Neurol. 1997 Sep;56(9):947-64. PubMed 9291937 ↗
  • 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. PubMed 19539236 ↗
  • 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 ↗

Individual participant data

Plan to share: No

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 31, 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
NCT06938100
Lead sponsor
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Responsible party
Sponsor
First posted
Apr 22, 2025
Start date
Nov 21, 2023
Primary completion
Apr 30, 2027 (estimated)
Completion
Oct 31, 2027 (estimated)
Last update
Aug 31, 2026

Study contacts

Anna Bersano, MD
Contact
anna.bersano@istituto-besta.it
+ 39 02.2394

Oversight

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

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