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

Официальное название

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

Обзор

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.

Подробное описание

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

Вмешательства

• Препарат GLP-1 receptor agonist
  2mg once weekly via subcutaneous injection

Первичные конечные точки

• Change of Brain Peak Width of Skeletonized Mean Diffusivity [Срок оценки: Baseline and week 78]

Вторичные конечные точки (12)

• Number of recurrent stroke [Срок оценки: Baseline and week 78]
• Change of Hong Kong MOntreal Cognitive Assessment [Срок оценки: Baseline, week 12, week 26, week 52 and week 78]
• Change The Chinese Geriatric Depression Scale 30 [Срок оценки: Baseline, week 12, week 26, week 52 and week 78]
• Change of Pittsburgh sleep quality index [Срок оценки: Baseline, week 12, week 26, week 52 and week 78]
• Change of Hong Kong List Learning Test [Срок оценки: Baseline, week 12, week 26, week 52 and week 78]
• Change of Neuropsychiatric Inventory [Срок оценки: Baseline, week 12, week 26, week 52 and week 78]
• Change of disability assessment for dementia [Срок оценки: Baseline, week 12, week 26, week 52 and week 78]
• Change of Gait [Срок оценки: Baseline, week 12, week 26, week 52 and week 78]
• Change of balance [Срок оценки: Baseline, week 12, week 26, week 52 and week 78]
• Change of Pulsatility Index [Срок оценки: Baseline, week 12, week 26, week 52 and week 78]
• Change of Breath Holding Index [Срок оценки: Baseline, week 12, week 26, week 52 and week 78]
• Change of DNA methylation [Срок оценки: Baseline, week 12, week 26, week 52 and week 78]

Критерии участия

Критерии включения

• 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;

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• First Affiliated Hospital of Wenzhou Medical University — Wenzhou

Гонконг · 1 центр

• Chinese University of Hong Kong — Гонконг

Идентификаторы

NCT: NCT05356104 · GAPP-SVD

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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