GLP-1 Analogue in Preventing Progression of Small Vessel Disease (GAP-SVD)

• Status: Not yet recruiting
• Trial end date: 2026-12-01
• Target enrollment: 0
• Participant gender: All

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 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Chinese University of Hong Kong
• Treatments: Exenatide

Criteria

Inclusion Criteria:

1. Chinese ethnicity;

2. Age 55 to 80 years old;

3. Age-Related White Matter Change (ARWMC) Scale of 2 or early 3 in FLAIR MRI;

4. Modified Functional Ambulation Classification 5 or above;

5. Montreal Cognitive Assessment (MoCA) score < 25;

6. Both diabetic and non-diabetic patient are eligible;

7. Patient who understands the purpose and requirements of the study, and able to provide an informed consent;

Exclusion Criteria:

1. Dementia or MoCA score lower than 2nd percentile of the age and education adjusted cutoff ;

2. Cerebral white matter changes unrelated to neurodegenerative, e.g. CADASIL, X-linked adrenoleukodystrophy, metabolic diseases, multiple sclerosis, etc.;

3. 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;

4. BMI <18.5kg/m2;

5. 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;

6. Medical condition that would not allow the patient to adhere to the protocol or complete the study.;

7. Patient with established neurodegenerative disorders (e.g. Parkinson's Disease, Alzheimer's Disease, etc.);

8. Pregnancy.