Taiwan Associated Genetic and Nongenetic Small Vessel Disease (TAG-SVD)

Deciphering, Construction and Validation of Magnetic Resonance Imaging Maps, Clinical Features and Outcomes in Genetic and Nongenetic Cerebral Small Vessel Diseases

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.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Magnetic Resonance Imaging; Fabry Disease; Cerebral Small Vessel Diseases; Cadasil; HTRA1-Related Autosomal Dominant Cerebral Angiopathy; COL4A1-Related Brain Small Vessel Disease With Haemorrhage; Next-generation Sequencing
• Intervention / Treatment: Diagnostic test: MRI

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Sung-Chun Tang, MD, PhD; Phone Number: 886972651113; Email: sctang@ntuh.gov.tw
• Study Contact Backup: Name: Chih-Hao Chen, MD, PhD; Phone Number: 886987392027; Email: antonyneuro@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • Department of Neurology, National Taiwan University Hospital
    • Contact: Sung-Chun Tang, MD, PhD; Phone Number: 886972651113; Email: sctang@ntuh.gov.tw
    • Contact: Chih-Hao Chen, MD, PhD; Phone Number: 886987392027; Email: antonyneuro@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• 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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; Patients will repeat study-protocol MRI at baseline (enrollment) and at least once in 1 year or 2 years follow-up (depends on availability).
Nongenetic group; Patients who have negative DNA results by NGS screening .	Diagnostic test: MRI; Patients will repeat study-protocol MRI at baseline (enrollment) and at least once in 1 year or 2 years follow-up (depends on availability).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with incident dementia	Vascular cognitive impairment (VCI), vascular dementia (VaD), or Alzheimer's dementia or Vascular dementia according to latest diagnostic criteria. Alzheimer's disease diagnostic criteria: National Institute of Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease (PMID: 21514247) Vascular dementia diagnostic criteria: Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition	2 years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 18, 2022
• First Submitted That Met QC Criteria: July 24, 2022
• First Posted (Actual): July 26, 2022

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: August 15, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Brain Ischemia; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Dementia; Brain Diseases, Metabolic; Infarction; Stroke; Brain Infarction; Brain Diseases, Metabolic, Inborn; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Malformations of Cortical Development; Nervous System Malformations; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Cerebral Infarction; Dementia, Vascular; Malformations of Cortical Development, Group III; Microcephaly; Hemorrhage; Fabry Disease; Cerebral Small Vessel Diseases; CADASIL; Porencephaly
• Other Study ID Numbers: 201911029RINB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data that support the current study are available upon reasonable request to the corresponding author.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No