Clinical trial NCT05473637: Taiwan Associated Genetic and Nongenetic Small Vessel Disease
Official title: Deciphering, Construction and Validation of Magnetic Resonance Imaging Maps, Clinical Features and Outcomes in Genetic and Nongenetic Cerebral Small Vessel Diseases
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cerebral Small Vessel Diseases
Cadasil
HTRA1-Related Autosomal Dominant Cerebral Angiopathy
COL4A1-Related Brain Small Vessel Disease With Haemorrhage
Fabry Disease
Magnetic Resonance Imaging
Next-generation Sequencing
Stroke
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2022-07-26
Enrollment: 500
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: This study enrolled patients with clini-cal and neuroimaging features of CSVD in the neurology outpatient clinic of National Taiwan University Hospital. The clinical features for being enrolled in the TAG-SVD cohort included stroke (especially small vessel occlusion type of ischaemic stroke, spontaneous ICH or young stroke), cognitive impairment, gait disturbance, parkinsonism, headache or a positive family history of hereditary CSVD. The neuroimaging features were at least one evident magnetic resonance imaging (MRI) feature of CSVD

Brief summary: The TAG-SVD enrolled patients with clinical and neuroimaging features of cerebral small vessel disease (CSVD). All enrolled patients will receive next-generation sequence (NGS) with probes designed to target five candidate CSVD genes, and patients will be divided into genetic or non-genetic groups accordingly. Their clinical features and outcome will be followed for at least 2 years.


Eligibility criteria: Inclusion Criteria:

Participants must have at least one of the following symptoms/signs or history

* stroke (especially small vessel occlusion type of ischaemic stroke, spontaneous ICH or young stroke)
* cognitive impairment or dementia
* gait disturbance
* parkinsonism (especially vascular parkinsonism features)
* headache (especially migraine)
* positive family history of hereditary CSVD
* MRI evidence of CSVD (MRI may be done for other reasons), including mild to moderate white matter hyper intensity, any lacune, or any cerebral microbleed

Exclusion Criteria:

* MRI evidence of CSVD due to other inflammatory, malignancy, or structural lesions
* patients or family members not willing to sign informed consent

Primary outcomes:
measure: Number of patients with incident stroke
timeFrame: 2 years
Secondary outcomes:
measure: Number of patients with incident dementia
timeFrame: 2 years
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Department of Neurology, National Taiwan University Hospital
Study officials:
References:
citation: Chen CH, Chu YT, Chen YF, Ko TY, Cheng YW, Lee MJ, Chen PL, Tang SC, Jeng JS. Comparison of clinical and neuroimaging features between NOTCH3 mutations and nongenetic spontaneous intracerebral haemorrhage. Eur J Neurol. 2022 Nov;29(11):3243-3254. doi: 10.1111/ene.15485. Epub 2022 Jul 18.
citation: Zhang R, Chen CH, Tezenas Du Montcel S, Lebenberg J, Cheng YW, Dichgans M, Tang SC, Chabriat H. The CADA-MRIT: An MRI Inventory Tool for Evaluating Cerebral Lesions in CADASIL Across Cohorts. Neurology. 2023 Oct 24;101(17):e1665-e1677. doi: 10.1212/WNL.0000000000207713. Epub 2023 Aug 31.
citation: Shen YC, Chen YF, Cheng YW, Chen CH, Jeng JS, Tang SC. Characteristics and temporal evolution of asymptomatic diffusion-weighted imaging lesions in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Eur J Neurol. 2024 Dec;31(12):e16519. doi: 10.1111/ene.16519. Epub 2024 Oct 11.
citation: Fislage M, Chen CH, Cheng YW, Chen YF, Tang SC. Subcortical volumes and cognition in CADASIL - A pilot study. Cereb Circ Cogn Behav. 2024 Oct 9;7:100371. doi: 10.1016/j.cccb.2024.100371. eCollection 2024.
citation: Cheng YW, Liao YC, Chen CH, Chung CP, Fann CSJ, Chang CC, Lee YC, Tang SC. Contribution of the APOE Genotype to Cognitive Impairment in Individuals With NOTCH3 Cysteine-Altering Variants. J Am Heart Assoc. 2023 Nov 21;12(22):e032689. doi: 10.1161/JAHA.123.032689. Epub 2023 Nov 20.
citation: Lin CW, Yang ZW, Chen CH, Cheng YW, Tang SC, Jeng JS. Reduced macular vessel density and inner retinal thickness correlate with the severity of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). PLoS One. 2022 May 26;17(5):e0268572. doi: 10.1371/journal.pone.0268572. eCollection 2022.