GLP-1 Analogue in Preventing Progression of Small Vessel Disease (GAPP-SVD) - Clinical Trial for Cerebral Small Vessel Disease | NCT05356104

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Primary Purpose

Status

Recruiting

Phase

Phase 2

Locations

Hong Kong

Study Type

Interventional

Intervention

Exenatide extended release

About this trial

This is an interventional treatment trial for Cerebral Small Vessel Disease focused on measuring cSVD

Eligibility Criteria

55 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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;

Exclusion Criteria:

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.

Sites / Locations

Chinese University of Hong KongRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

Exenatide extended release

Standard of care

Arm Description

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

Standard medical therapy

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number of recurrent stroke

Record of any recurrent stroke from medical note/system

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.

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

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

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

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

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.

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.

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.

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.

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.

Change of DNA methylation

blood biomarker. DNA methylation-derived epigenetic age clock is an indicator of biological aging.

Change of neurovascular inflammation

blood biomarker to investigate neurovascular inflammation that induce neurodegeneration

Full Information

NCT ID

NCT05356104

First Posted

April 8, 2022

Last Updated

July 18, 2022

Sponsor

Chinese University of Hong Kong

1. Study Identification

Unique Protocol Identification Number

NCT05356104

Brief Title

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

Acronym

GAPP-SVD

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Recruiting

Study Start Date

May 25, 2022 (Actual)

Primary Completion Date

May 2026 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chinese University of Hong Kong

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

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 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cerebral Small Vessel Disease

Keywords

cSVD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

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

Masking

Outcomes Assessor

Masking Description

Assessors for TCD and Cognition and behavior assessments will be blinded to the randomization assignment

Allocation

Randomized

Enrollment

110 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Exenatide extended release

Arm Type

Active Comparator

Arm Description

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

Arm Title

Standard of care

Arm Type

No Intervention

Arm Description

Standard medical therapy

Intervention Type

Drug

Intervention Name(s)

Exenatide extended release

Other Intervention Name(s)

Bydureon BCise

Intervention Description

2mg once weekly via subcutaneous injection

Primary Outcome Measure Information:

Title

Change of Brain Peak Width of Skeletonized Mean Diffusivity

Description

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.

Time Frame

Baseline and week 78

Secondary Outcome Measure Information:

Title

Number of recurrent stroke

Description

Record of any recurrent stroke from medical note/system

Time Frame

Baseline and week 78

Title

Change of Hong Kong MOntreal Cognitive Assessment

Description

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.

Time Frame