The Effect of GLP-1 Receptor Agonist on Cerebral Blood Flow Velocity in Stroke

2016-07-13 00:08:21 | BioPortfolio


This randomized controlled trial investigates the effect of a single dose of glucagon-like peptide-1 (GLP-1) receptor agonist in the subacute phase of stroke in humans. The primary endpoint is the mean flow velocity in the middle cerebral arteries measured by transcranial doppler. The secondary endpoints are changes in endothelial/inflammatory biomarkers in the blood, changes in the ancle-brachial index and changes in the reactive hyperaemia index measured by EndoPAT2000.


Glucagon-like peptide 1 (GLP-1) receptor agonists are widely used in the treatment of type 2 diabetes because of their ability to mimic the incretin hormone, GLP-1. GLP-1 increases glucose-dependent insulin secretion and thereby reduces the 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 CNS 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 mainly target platelet fuction, but not endothelial function.

This double-blinded, randomized, controlled, pilot trial investigates the effect of a single dose of the GLP-1 receptor agonist, exenatide, on cerebral blood flow velocity in the subacute phase of stroke in humans. The primary endpoint is the 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 ancle-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. Parallel to this study we investigate the effect of GLP-1 receptor agonist on people free of cerebrovascular diseases (ref. to EGRABINS1).

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Ischemic Stroke


Byetta, Normosaline


Not yet recruiting


Herlev Hospital

Results (where available)

View Results


Published on BioPortfolio: 2016-07-13T00:08:21-0400

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Medical and Biotech [MESH] Definitions

The application of repeated, brief periods of vascular occlusion at the onset of REPERFUSION to reduce REPERFUSION INJURY that follows a prolonged ischemic event. The techniques are similar to ISCHEMIC PRECONDITIONING but the time of application is after the ischemic event instead of before.

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Restoration of functions to the maximum degree possible in a person or persons suffering from a stroke.

Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing REPERFUSION INJURY.

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