The Effect of Glucagon-like Peptide 1 (GLP-1) Receptor Agonist on Cerebral Blood Flow Velocity in Non-Stroke Volunteers (EGRABINS1)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Changes in the mean flow velocity in the middle cerebral arteries and in cortical oxigination .
研究概览
简要总结
This randomized controlled trial investigates the effect of a single dose of glucagon-like peptide-1 (GLP-1) receptor agonist on cerebral blood flow velocity and cortical oxygination in humans without cerebrovascular disease. This study serves as a control for a similar study investigating the effect in stroke patients (ref. to EGRABIS1).
详细描述
Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used in the treatment of type 2 diabetes due to their ability to mimic the incretin hormone, GLP-1. GLP-1 increases glucose-dependent insulin secretion and thereby reduces plasma glucose level. Over the past few years, GLP-1 receptor agonists have been investigated as possible therapies for neurological disorders, due to their ability to cross the blood-brain-barrier. Evidence of the treatment of cerebrovascular diseases has been growing especially in animal stroke models. GLP-1 receptors, which are located in the central nervous system on neurons and endothelium, are upregulated in the brain due to ischemia. GLP-1 receptor agonists have shown anti-inflammatory and anti-apoptotic properties, and they may protect the cell from oxidative stress and may protect the endothelium. The inner lining of blood vessels, the endothelium, is an active component of the endocrine function. It affects the formation of blood clots and plays a role in the disease mechanisms of stroke. The current acute and prophylactic treatments of stroke are mainly target platelet function, but not endothelial function.
This double-blinded, randomized, controlled trial investigates the effect of a single dose of the GLP-1 receptor agonist, exenatide, on cerebral blood flow velocity, cortical oxygation and endothelial function in subjects free of cerebrovascular diseases. To our knowledge, the effect of GLP-1 receptor agonists on cerebral blood flow velocity in healthy subjects has not yet been clarified, and this study serves as a control for a similar study investigating the effect on stroke patients (ref. to EGRABIS1).
The primary endpoint is the change in mean flow velocity in the middle cerebral arteries measured by transcranial doppler. The secondary endpoints are the effects on the peripheral endothelium, hereby: 1) changes in the reactive hyperaemia index measured by EndoPAT2000, 2) changes in the ankle-brachial index, and 3) changes in endothelial/inflammatory biomarkers in the blood. The primary and secondary endpoints are measured before and up till three hours after administration of exenatide.
The overall hypothesis is that GLP-1 receptor agonists may represent a novel potential neuroprotective treatment in stroke.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Person ≥ 50 years of age
- •Has given written informed consent
排除标准
- •Intracerebral haemorrhage
- •Subdural / epidural hemorrhage
- •subarachnoid haemorrhage
- •previously major structural damage to the brain (eg. sequelae after large stroke or brain surgery)
- •Diabetes type 1
- •Diabetes type 2
- •Known atrial fibrillation
- •> 50% stenosis of internal carotid
- •Known allergy to GLP-1 receptor agonists
- •Hepatic impairment (ALT> 3 x upper normal limit)
- •Renal impairment (eGFR <30 ml / min)
- •Inflammatory bowel disease
- •Previous pancreatitis
- •Heart failure (NYHA class 3-4)
- •Pregnancy or lactation
- •Patient not expected to co-operate to the investigations
- •Visualization of the middle cerebral artery bilaterally by transcranial doppler not possible
研究组 & 干预措施
Byetta
Pre- and post treatment investigations:
- Mean flow velocity of the middle cerebral arteries bilateral by transcranial doppler
- Cerebral cortical oxygination by near infrared spectroscopy (NIRS)
- Endothelial function/response by the methods:
- Biomarkers in blood (eg. e-selectin, VCAM, ICAM, endothelin, ADMA, miRNA)
- EndoPAT2000
- Ankle-brachial index
干预措施: Byetta (Drug)
Isotonic saline
Pre- and post treatment investigations:
- Mean flow velocity of the middle cerebral arteries bilateral by transcranial doppler
- Cerebral cortical oxygination by near infrared spectroscopy (NIRS)
- Endothelial function/response by the methods:
- Biomarkers in blood (eg. e-selectin, VCAM, ICAM, endothelin, ADMA, miRNA)
- EndoPAT2000
- Ankle-brachial index
干预措施: Isotonic saline (Drug)
结局指标
主要结局
Changes in the mean flow velocity in the middle cerebral arteries and in cortical oxigination .
时间窗: Up till 3 hours
Change in the mean flow velocity in the middle cerebral arteries will be measured with transcranial doppler and cortical oxygination by near infrared spectroscopy (NIRS) before and up till tree hours after injection of exenatide/placebo.
次要结局
- Changes in the endothelial/inflammatory biomarkers in blood.(3 hours)
- Changes in the endothelial reactivity measured by non-invasive pletysmography.(3 hours)
- Changes in the ankle-brachial index.(3 hours)
研究者
Christina Kruuse
MD, PhD, DMSc, Consultant Neurologist, Associate Professor
Herlev Hospital