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| Name | Class |
|---|---|
| First Affiliated Hospital of Wenzhou Medical University | OTHER |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GLP-1 receptor agonist | Active Comparator | Prescribe study drug: GLP-1 receptor agonist. The dosage and frequency is 2mg once weekly via subcutaneous injection for 78 weeks for Bydureon bcise (exenatide), the dosage and frequency is 0.25mg once weekly for 4 weeks followed by 0.5mg once weekly for 74 weeks via subcutaneous injection for Ozempic (semaglutide) |
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| Standard of care | No Intervention | Standard medical therapy |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GLP-1 receptor agonist | Drug | 2mg once weekly via subcutaneous injection |
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| Measure | Description | Time Frame |
|---|---|---|
| Change 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. | Baseline and week 78 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of recurrent stroke | Record of any recurrent stroke from medical note/system | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Bonaventure Yiu Ming Ip, MBChB, PhD | Contact | 852-28902002 | bonaventureip@cuhk.edu.hk |
| Name | Affiliation | Role |
|---|---|---|
| Bonaventure Yiu Ming Ip, MBChB, PhD | Chinese University of Hong Kong | Principal Investigator |
| Zhen Wang, MD | First Affiliated Hospital of Wenzhou Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| First Affiliated Hospital of Wenzhou Medical University | Recruiting | Wenzhou | Zhejiang | China |
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| ID | Term |
|---|---|
| D059345 | Cerebral Small Vessel Diseases |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C000591245 | semaglutide |
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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.
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Assessors for TCD and Cognition and behavior assessments will be blinded to the randomization assignment
| 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 | 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 | 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 | 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 | 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. | 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. | 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. | 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. | 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. | 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. | Baseline, week 12, week 26, week 52 and week 78 |
| Change of neurovascular inflammation | blood biomarker to investigate neurovascular inflammation that induce neurodegeneration | Baseline, week 12, week 26, week 52 and week 78 |
| Chinese University of Hong Kong | Recruiting | Hong Kong | Hong Kong |
|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |