GLP-1 Analogue in Preventing Progression of Small Vessel Disease (GAPP-SVD) - A Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 110
- 试验地点
- 2
- 主要终点
- Change of Brain Peak Width of Skeletonized Mean Diffusivity
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Assessors for TCD and Cognition and behavior assessments will be blinded to the randomization assignment
入排标准
- 年龄范围
- 55 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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;
排除标准
- •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.);
研究组 & 干预措施
Standard of care
Standard medical therapy
结局指标
主要结局
Change of Brain Peak Width of Skeletonized Mean Diffusivity
时间窗: Baseline and week 78
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.
次要结局
- 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 Neuropsychiatric Inventory(Baseline, week 12, week 26, week 52 and week 78)
- Change of balance(Baseline, week 12, week 26, week 52 and week 78)
- Change of Pulsatility Index(Baseline, week 12, week 26, week 52 and week 78)
- Change of Breath Holding Index(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)
- Change of disability assessment for dementia(Baseline, week 12, week 26, week 52 and week 78)
- Change of Gait(Baseline, week 12, week 26, week 52 and week 78)
- Change of DNA methylation(Baseline, week 12, week 26, week 52 and week 78)
- Change of neurovascular inflammation(Baseline, week 12, week 26, week 52 and week 78)
研究者
Dr. IP Yiu Ming Bonaventure
Assistant Professor
Chinese University of Hong Kong