Cerebral Small Vessel DiseasePhase 2GAPP-SVDNCT05356104
GLP-1 Analogue in Preventing Progression of Small Vessel Disease (GAPP-SVD)
A Phase 2 study testing GLP-1 receptor agonist in people with Cerebral Small Vessel Disease, run by Chinese University of Hong Kong at 2 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 55 to 80 years
- Conditions the study is for
- Cerebral Small Vessel Disease
- What is being tested?
- GLP-1 receptor agonist
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 25 May 2022to Dec 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chinese ethnicity;
- Age 55 to 80 years old;
- Age-Related White Matter Change (ARWMC) Scale of 2 or early 3 in FLAIR MRI;
- Modified Functional Ambulation Classification 5 or above;
- Montreal Cognitive Assessment (MoCA) score < 25;
- Both diabetic and non-diabetic patient are eligible;
- Patient who understands the purpose and requirements of the study, and able to provide an informed consent;
Who cannot join
- Dementia or MoCA score lower than 2nd percentile of the age and education adjusted cutoff ;
- Cerebral white matter changes unrelated to neurodegenerative, e.g. CADASIL, X-linked adrenoleukodystrophy, metabolic diseases, multiple sclerosis, etc.;
- Contraindication to GLP-1R agonist, including thyroid carcinoma, pancreatic pathology, proliferative retinopathy, hypersensitivity to GLP-1R agonist and history of family history of multiple endocrine neoplasia;
- BMI <18.5kg/m2;
- Contraindication to proposed imaging, e.g. chronic kidney disease (KDNIGO) stage 4 or above, acute kidney injury, hypersensitivity to gadolinium-based contrast, non-MRI conditional implants or prosthesis;
- Medical condition that would not allow the patient to adhere to the protocol or complete the study.;
- Patient with established neurodegenerative disorders (e.g. Parkinson's Disease, Alzheimer's Disease, etc.);
- Pregnancy.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
China1 site, 1 recruiting
- Recruiting
First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang
Zhen Wang, MD, wangzhen@wzhospital.cn
Hong Kong1 site, 1 recruiting
- Recruiting
Chinese University of Hong Kong
Hong Kong
Bonaventure Yiu Ming IP, MB ChB, 852-28902002, bonaventureip@cuhk.edu.hk
About this study
Official title: GLP-1 Analogue in Preventing Progression of Small Vessel Disease (GAPP-SVD) - A Pilot Study
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.
Read the detailed description
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
- Conditions
- Cerebral Small Vessel Disease
- Being tested
- GLP-1 receptor agonist
- Keywords
- cSVD
- Medical subject headings
- Cerebral Small Vessel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GLP-1 receptor agonistDrug
Also called Bydureon BCise, Ozempic
2mg once weekly via subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: GLP-1 receptor agonist |
| Standard of care | No intervention | Standard medical therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and week 78
Secondary outcomes (13)
Number of recurrent stroke
Record of any recurrent stroke from medical note/system
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, week 12, week 26, week 52 and week 78
Change of neurovascular inflammation
blood biomarker to investigate neurovascular inflammation that induce neurodegeneration
Measured: Baseline, week 12, week 26, week 52 and week 78
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2022
- Study start25 May 2022
- Primary completionMay 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral Small Vessel DiseaseStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- First Affiliated Hospital of Wenzhou Medical University
- Responsible party
- Principal investigator, Dr. IP Yiu Ming Bonaventure, Chinese University of Hong Kong
- Investigators
- Bonaventure Yiu Ming Ip, MBChB, PhD, Principal investigator, Chinese University of Hong KongZhen Wang, MD, Principal investigator, First Affiliated Hospital of Wenzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05356104
- Sponsor's protocol ID
- GAPP-SVD
- Acronym
- GAPP-SVD
- Status last verified
- Jun 2026
- First submitted
- 8 Apr 2022
- Last updated
- 5 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No