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

NCT05356104 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: GAPP-SVD
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cerebral Small Vessel Disease

Keywords

cSVD

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (13)

• Number of recurrent stroke

  Baseline and week 78

• Change of Hong Kong MOntreal Cognitive Assessment

  Baseline, week 12, week 26, week 52 and week 78

• Change The Chinese Geriatric Depression Scale 30

  Baseline, week 12, week 26, week 52 and week 78

• Change of Pittsburgh sleep quality index

  Baseline, week 12, week 26, week 52 and week 78

• Change of Hong Kong List Learning Test

  Baseline, week 12, week 26, week 52 and week 78

Study Arms (2)

Exenatide extended release

ACTIVE COMPARATOR

Prescribe study drug: Exenatide extended release. The dosage and frequency is 2mg once weekly via subcutaneous injection for 78 weeks

Drug: Exenatide extended release

Standard of care

NO INTERVENTION

Standard medical therapy

Interventions

Exenatide extended release DRUG

2mg once weekly via subcutaneous injection

Also known as: Bydureon BCise

Exenatide extended release

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Chinese University of Hong Kong

Hong Kong, Hong Kong

RECRUITING

MeSH Terms

Conditions

Cerebral Small Vessel Diseases

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Bonaventure Yiu Ming Ip, MBChB

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pauline Kwan, Master

CONTACT

+85226352160; paulinekwan@cuhk.edu.hk

Hung Trista, Bachelor

CONTACT

+85226352152; tristahung@cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Assessors for TCD and Cognition and behavior assessments will be blinded to the randomization assignment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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 exenatide, a GLP-1R agonist in SVD patients, together with changes in clinical, imaging and sonographic parameters.

Study Record Dates

• First Submitted: April 8, 2022
• First Posted: May 2, 2022
• Study Start: May 25, 2022
• Primary Completion: May 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)