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

The Chinese University of Hong Kong

Status and phase: Enrolling; Phase 2

Conditions: Cerebral Small Vessel Disease

Treatments: Drug: Exenatide extended release

Study type: Interventional

Funder types: Other

Identifiers

NCT05356104

GAPP-SVD

Details and patient eligibility

About

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.

Full 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 exenatide, a 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

Enrollment: 110 estimated patients

Sex: All

Ages: 55 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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110 participants in 2 patient groups

Exenatide extended release

Active Comparator group

Description:

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

Treatment:

Drug: Exenatide extended release

Standard of care

No Intervention group

Description:

Standard medical therapy