CADASILGENICaNCT06938100
Genotype, Clinical Features and Imaging of Neuroradiological Abnormalities in CADASIL
An observational study of CADASIL and CADASIL (Diagnosis), run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 2 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- CADASIL, CADASIL (Diagnosis)
- How many people
- 100 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 21 Nov 2023to 31 Oct 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan
Anna Bersano, MD, + 39 02.2394, anna.bersano@istituto-besta.it
Spain1 site, 1 recruiting
- Not yet recruiting
Hospital Universitario de la Princesa, Madrid
Madrid
Alicia Gonzales Martinez, 91 520 22 89, alicia.gonzalez.martinez@live.com
About this study
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
- Medical subject headings
- CADASIL, Disease
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 0-24 months
Secondary outcomes (2)
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).
Measured: 0-30 months
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.
Measured: 0-30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2025
- Study start21 Nov 2023
- Primary completion30 Apr 2027 (estimated)
- Study completion31 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for CADASILStudies of the same condition, open and under way.
- More trials run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaThe sponsor's other registered studies.
- 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
- 100 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06938100
- Sponsor's protocol ID
- GENICa
- Acronym
- GENICa
- Status last verified
- Aug 2026
- First submitted
- 3 Apr 2025
- Last updated
- 31 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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 30032161Ruchoux MM, Maurage CA. CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J Neuropathol Exp Neurol. 1997 Sep;56(9):947-64.
PubMed 9291937Chabriat 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 19539236Opherk 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
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genotype, Clinical Features and Imaging of Neuroradiological Abnormalities in CADASIL
- ClinicalTrials.gov ID
- NCT06938100
- Acronym / sponsor ID
- GENICa / GENICa
- Conditions
- CADASIL, CADASIL (Diagnosis)
- Keywords
- CADASIL, NOTCH3
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaUniversity, hospital or other
- Study start
- 21 Nov 2023 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 31 Oct 2027 (estimated)
- First posted
- 22 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Deepen the knowledge of the clinical phenotype CADASIL patient
Time frame: T0- T1 (24 months)
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.
Identify potentially reversible risk factors for disease progression
Time frame: 0-24 months
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
2 secondary outcomes
Identify clinical, genetic, biological and neuroradiological markers
Time frame: 0-30 months
Deepen knowledge of the neuroradiological phenotype of CADASIL patients, depending on the NOTCH3 mutation locus identified (high, moderate or low risk)
Time frame: 0-30 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
- Background: PubMed 30032161Rutten 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.
- Background: PubMed 9291937Ruchoux MM, Maurage CA. CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J Neuropathol Exp Neurol. 1997 Sep;56(9):947-64.
- Background: PubMed 19539236Chabriat 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.
- Background: PubMed 15364702Opherk 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of CADASIL and CADASIL (Diagnosis), run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anna Bersano, MD (+ 39 02.2394, anna.bersano@istituto-besta.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Deepen the knowledge of the clinical phenotype CADASIL patient (time frame: T0- T1 (24 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06938100, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.