Taiwan Associated Genetic and Nongenetic Small Vessel Disease

NCT05473637 | Recruiting

• 1 other identifier: 201911029RINB
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

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.

Conditions

Cadasil; Cerebral Small Vessel Diseases; HTRA1-Related Autosomal Dominant Cerebral Angiopathy; COL4A1-Related Brain Small Vessel Disease With Haemorrhage; Fabry Disease; Magnetic Resonance Imaging; Next-generation Sequencing; Stroke

Outcome Measures

Primary Outcomes (1)

• Number of patients with incident stroke

  Clinical stroke, including transient ischemic attack, ischemic stroke, or intracerebral hemorrhage. The stroke is defined by a focal neurological deficits lasting more than 24 hours, with accompanied neuroimaging evidence of infarct or hemorrhage in corresponding brain area.

  2 years

Secondary Outcomes (1)

• Number of patients with incident dementia

  2 years

Study Arms (2)

Genetic group

Patients who have positive DNA results by NGS screening of the following 5 genes: NOTCH3 (19q13.12), HTRA1 (10q26.13), GLA (Xq22.1), TREX1 (3p1.31) and COL4A1 (13q34).

Diagnostic Test: MRI

Nongenetic group

Patients who have negative DNA results by NGS screening .

Diagnostic Test: MRI

Interventions

MRI DIAGNOSTIC_TEST

Patients will repeat study-protocol MRI at baseline (enrollment) and at least once in 1 year or 2 years follow-up (depends on availability).

Genetic group; Nongenetic group

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

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

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

Department of Neurology, National Taiwan University Hospital

Taipei, 100, Taiwan

RECRUITING

Related Publications (6)

• 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.

  PMID: 35781912 RESULT

• 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.

  PMID: 37652700 RESULT

• 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.

  PMID: 39392097 RESULT

• 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.

  PMID: 39493517 RESULT

• 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.

  PMID: 37982214 RESULT

• 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.

  PMID: 35617208 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Each patient had a blood sample collected, and their DNA was extracted and sent for next-generation sequencing (NGS) with probes designed to target five candidate CSVD genes.

MeSH Terms

Conditions

Cerebral Small Vessel Diseases; CADASIL; Fabry Disease; Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Cerebral Infarction; Brain Infarction; Brain Ischemia; Dementia, Vascular; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Dementia; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Central Study Contacts

Sung-Chun Tang, MD, PhD

CONTACT

886972651113; sctang@ntuh.gov.tw

Chih-Hao Chen, MD, PhD

CONTACT

886987392027; antonychen@ntu.edu.tw

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2022
• First Posted: July 26, 2022
• Study Start: January 1, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)