The Effect of GLP-1 Receptor Agonist on Cerebral Blood Flow Velocity in Non-stroke Volunteers

What Was Tested

This registered phase 2 trial tested Exenatide.

This study serves as a control for a similar study investigating the effect in stroke patients (ref. to EGRABIS1).

It had two arms (groups): Byetta (active comparator) and Isotonic saline (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) 3. 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) 3. 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 due to 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

30 actual participants took part.

It was open to people of any sex aged from 50 years with no upper age limit.

Healthy volunteers could join, not only people with the condition.

Examples of who could join: Person ≥ 50 years of age. Has given written informed consent.

The full record lists 2 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.

Random assignment meant chance, not the researchers, decided who got Exenatide and who got the comparison, which limits bias.

Groups ran in parallel: each of the participants stayed in one arm throughout.

Blinding on both sides kept the participants and researchers unaware of who received Exenatide.

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

It started in 2016-08 with completion listed for 2017-02.

It ran at 1 site in Denmark.

Its stated primary purpose is treatment.

What Was Measured

Primary outcome: 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 Changes in the endothelial reactivity measured by non-invasive pletysmography, Changes in the endothelial/inflammatory biomarkers in blood and Changes in the 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.

The trial is marked completed; no results are posted to the registry yet, so nothing here describes outcomes.

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