Cerebral small vessel disease (cSVD), a result of neurovascular cell dysfunction, is a major cause of stroke, dementia and mobility problems worldwide. Vascular risk factor control alone may not be sufficient to prevent the development of vascular cognitive impairment (VCI) in patients with cSVD according to previous clinical trials. The presence of glucagon-like peptide-1 receptor (GLP-1R) in cerebral microglia may reveal a potential therapeutic target for prevention of cSVD progression and its disabling clinical outcomes. At the cellular and animal experimentation levels, GLP-1R agonist demonstrated reversal of some pathogenic processes in cSVD. However, its application to cSVD patients remains to be elucidated. Investigator aims to investigate the safety and efficacy of GLP-1R agonist in patients with moderate-to-severe cSVD.
In this single-center, open-label (assessor blinded), randomized controlled study, 110 patients with cSVD of Age-Related White Matter Changes Scale of 2 or 3 will be randomized into "treatment arm" with GLP-1R agonist and standard medical therapy, and "control" arm with standard medical therapy alone in a 1:1 ratio. In this 78 weeks pilot study, investigators shall evaluate the tolerability and safety profile of GLP-1R agonist in SVD patients, together with changes in clinical, imaging and sonographic parameters. Clinical and biochemical measures will be assessed at baseline, 12 weeks, 26 weeks and 52 weeks. Transcranial Doppler Ultrasound (TCD) will be performed at baseline, 12 weeks, 26 weeks, 52 weeks and 78 weeks. MRI will be performed at baseline and 78 weeks
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
110
2mg once weekly via subcutaneous injection
First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, China
RECRUITINGChinese University of Hong Kong
Hong Kong, Hong Kong
RECRUITINGChange of Brain Peak Width of Skeletonized Mean Diffusivity
Peak Width of Skeletonized Mean Diffusivity is a robust, fully-automated and easy-to-implement marker for cerebral small vessel disease based on diffusion tensor imaging, white matter tract skeletonization and histogram analysis. It is a biomarker for brain MRI images.
Time frame: Baseline and week 78
Number of recurrent stroke
Record of any recurrent stroke from medical note/system
Time frame: Baseline and week 78
Change of Hong Kong MOntreal Cognitive Assessment
Hong Kong MOntreal Cognitive Assessment (HK-MoCA) is a cognitive assessment tool. Score from 0 to 30 . The lower score reflect the worse the outcome.
Time frame: Baseline, week 12, week 26, week 52 and week 78
Change The Chinese Geriatric Depression Scale 30
The Chinese Geriatric Depression Scale is used to detect depressive mood. Score 0 to 30. The higher the score, the worse the outcome
Time frame: Baseline, week 12, week 26, week 52 and week 78
Change of Pittsburgh sleep quality index
Pittsburgh sleep quality index Chinese Version is a self-report questionnaire that assesses sleep quality over a 1-month time interval. The questionnaire contains frequency questions related to sleep quality, each question scale from 0 to 3. The higher the score, the worse the outcome. There is no total score available for this assessment
Time frame: Baseline, week 12, week 26, week 52 and week 78
Change of Hong Kong List Learning Test
Hong Kong List Learning Test s a newly developed Chinese memory test designed for the assessment of the processes and organizational strategies involved in learning verbal information. The more negative the standard deviation the worse the outcome
Time frame: Baseline, week 12, week 26, week 52 and week 78
Change of Neuropsychiatric Inventory
Neuropsychiatric Inventory is a brief interview with a family member or friend who knows the study subject . It is used to measure behavioral symptoms. It evaluates 12 behavioral areas commonly affected in patients with dementia. It evaluates the frequency (scale from 1 to 4), severity (scale from 1 to 3), distress to caretaker (scale from 1 to 5) of each behavioral symptom. The higher the score of any area means the worse outcome. There is no total score available for this assessment
Time frame: Baseline, week 12, week 26, week 52 and week 78
Change of disability assessment for dementia
Disability assessment for dementia evaluates 11 basic daily activities of elderly people with dementia. It evaluates each activity in 3 stages: initiation, planning and organization, effective performance. Score 1 or 0 for each question. The higher the total score, the better the outcome. The total score is from 0 to 47.
Time frame: Baseline, week 12, week 26, week 52 and week 78
Change of Gait
Gait velocity will be assessed using the 8-meter walking time. Time for walking 8-m will be measured by a stopwatch. The faster of two trials will be used in the analysis The faster of the walking time the better outcome.
Time frame: Baseline, week 12, week 26, week 52 and week 78
Change of balance
Single leg stance time will be measured by asking individuals, with their hands on their hips, to balance as long as possible on one leg with an upper limit of 30 seconds. Two trials for each leg will be performed. The best time of the four trials will be used for analysis. The longer to time duration the better outcome.
Time frame: Baseline, week 12, week 26, week 52 and week 78
Change of Pulsatility Index
Pulsatility Index of Transcranial doppler ultrasound is a painless test that uses sound waves to detect medical problems that affect blood flow in your brain. It is a measure of vascular resistance of cerebral vessels. The higher the index means higher resistance and stiffness of blood vessels which lead to worse outcome. There is no minimum or maximum values available for this index.
Time frame: Baseline, week 12, week 26, week 52 and week 78
Change of Breath Holding Index
Breath Holding Index calculated based on the mean flow velocities of the middle cerebral artery using transcranial Doppler. It indicates the brain artery could react better to lowered oxygen level. The higher the index means better reaction to lowered oxygen level which leads to better outcome. There is no minimum or maximum values available for this index.
Time frame: Baseline, week 12, week 26, week 52 and week 78
Change of DNA methylation
blood biomarker. DNA methylation-derived epigenetic age clock is an indicator of biological aging.
Time frame: Baseline, week 12, week 26, week 52 and week 78
Change of neurovascular inflammation
blood biomarker to investigate neurovascular inflammation that induce neurodegeneration
Time frame: Baseline, week 12, week 26, week 52 and week 78
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