DiViNAS study (Disease Variability in NOTCH3 Associated Small vessel disease): the NOTCH3 mutation position effect and other disease modifiers in CADASIL

DiViNAS study (Disease Variability in NOTCH3 Associated Small vessel disease): the NOTCH3 mutation position effect and other disease modifiers in CADASIL - DiViNAS study

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON50750

Enrollment

250

Registered

2019-03-14

Start date

2019-05-02

Completion date

Unknown

Last updated

2024-04-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

hereditary vascular dementia

Interventions

None listed

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: NOTCH3 spectrum cohort Patients will be recruited from our CADASIL registry. In order to be eligible to participate in this study, a subject must meet all of the following criteria: - Aged 20 years and older - Has a known heterozygous cysteine altering NOTCH3 mutation - Is able to travel to the LUMC - Is able to give informed consent, Elderly NOTCH3 sample Individuals will be recruited through CADASIL pedigrees and our CADASIL registry. In order to be eligible to participate in this study, a subject must meet all of the following criteria: - Aged above 60 years - Living independently (mRS

Exclusion criteria

Exclusion criteria: - contra-indication for MRI scanning: o Claustrophobia o Pacemakers and defibrillators o Nerve stimulators o Intracranial clips o Intraorbital or intraocular metallic fragments o Cochlear implants o Ferromagnetic implants o Hydrocephalus pump o Intra-utrine device (not all types) o Permanent make-up o Tattoos above the shoulders (only those older than 20 years), - Contra- indication for fMRI: o Seizure within prior year. o Non-correctable visual impairment.

Design outcomes

Primary

Measure	Time frame
Measures of clinical severity: - age at onset of first stroke, number of strokes - scores on disability scales - psychometric testing MRI lesion load: Brain imaging will be performed on a 3 Tesla MRI scan, including 3D high resolution T1-w, T2-w, SWI, DTI, MTR and FLAIR sequences. Main parameters will be brain volume, number of lacunes, lacune volume, number of microbleeds and volume of white matter hyperintensities.	—

Measure

Time frame

Measures of clinical severity: - age at onset of first stroke, number of strokes - scores on disability scales - psychometric testing MRI lesion load: Brain imaging will be performed on a 3 Tesla MRI scan, including 3D high resolution T1-w, T2-w, SWI, DTI, MTR and FLAIR sequences. Main parameters will be brain volume, number of lacunes, lacune volume, number of microbleeds and volume of white matter hyperintensities.

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Secondary

Measure	Time frame
Candidate read-outs: - fMRI after visual stimulus (non-invasive measurement of cerebrovascular reactivity) - NOTCH3 score in skin biopsy - Blood biomarkers (e.g. NOTCH3 levels, neurofilament light chain levels, endostatin levels and other potential biomarkers)	—

Countries

Netherlands

Outcome results