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

What Was Tested

In this phase 2 trial, researchers set out to test Exenatide.

The primary endpoint is the mean flow velocity in the middle cerebral arteries measured by transcranial doppler and cortical oxygination measured by near infrared spectroscopy (NIRS).

The secondary endpoints are changes in endothelial/inflammatory biomarkers in the blood, changes in the ankle-brachial index and changes in the reactive hyperaemia index measured by EndoPAT2000.

It had two arms (groups): Byetta (active comparator) and Normosaline (placebo comparator).

Pre- and post treatment investigations: 1. Mean flow velocity of the middle cerebral arteries bilateral by transcranial doppler 2. 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.

Pre- and post treatment investigations: 1. Mean flow velocity of the middle cerebral arteries bilateral by transcranial doppler 2. 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.

The registry classes the interventions as drug.

More on the Plan

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.

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.

Who Took Part

Enrollment: 30 planned participants were the target.

It was open to people of any sex aged from 18 years with no upper age limit.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Patients ≥ 18 years with newly symptoms of stroke. Able to receive exenatide/placebo within 21 days after onset of symptoms. Radiological confirmed diagnoses of ischemic stroke. NIHSS between 1-20 at the onset of symptoms. Modified rankin scale (mRS) ≤ 2 prior to onset of symptoms.

The full record lists 6 inclusion and 17 exclusion criteria; among the exclusions: intracerebral haemorrhage; subdural / epidural hemorrhage; subarachnoid haemorrhage.

How the Study Was Run

The set-up was randomized, parallel-group and quadruple-blind.

Because people in this Exenatide study were split into groups at random, differences between the groups are less likely to reflect who happened to join each one.

The Exenatide group and the comparison group ran side by side rather than switching.

Neither the participants nor the staff measuring them knew who was on Exenatide, so expectations could not easily colour the readings.

Those kept unaware of assignments: participant, care provider, investigator and outcomes assessor.

It started in 2016-08 with completion listed for 2023-08.

It ran at 1 site in Denmark.

Its stated primary purpose is treatment.

What Was Measured

Researchers chose this as the main measure: Changes in the mean flow velocity in the middle cerebral arteries and in cortical oxigination (time frame: Up till 3 hours).

It also tracked 3 secondary outcomes, for example Endothelial reactivity, Changes in endothelial biomarkers in blood and Endothelial function/response in ankle-brachial index.

What This Means in Plain Language

Put simply, this is a phase 2, randomized trial of Exenatide in 30 people.

Its size is small, so on its own it can only give an early look.

Its status is unknown; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Exenatide compound page, all human trials.