The Effect of GLP-1 Receptor Agonist on Cerebral Blood Flow Velocity in Non-stroke Volunteers "EGRABINS1"

Recruiting

Phase 2 Results N/A

Trial Description

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 in humans without cerebrovascular disease. This study serves as a control for a similar study investigating the effect in stroke patients (ref. to EGRABIS1).

Detailed Description

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 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.

Conditions

Interventions

  • Byetta Drug
    Other Names: Exenatide; GLP-1 receptor analogue; GLP-1 receptor agonist
    Intervention Desc: Single dose of subcutaneous injection of 5 μg exenatide (Byetta).
    ARM 1: Kind: Experimental
    Label: Byetta
    Description: Pre- and post treatment investigations: Mean flow velocity of the middle cerebral arteries bilateral by transcranial doppler Endothelial function/response by the methods: Biomarkers in blood (eg. e-selectin, VCAM, ICAM, endothelin, ADMA, miRNA) EndoPAT2000 Ankle-brachial index
  • Isotonic saline Drug
    Other Names: Normal saline
    Intervention Desc: Single dose of subcutaneous injection of 20 μL isotonic saline (placebo).
    ARM 1: Kind: Experimental
    Label: Isotonic saline
    Description: Pre- and post treatment investigations: Mean flow velocity of the middle cerebral arteries bilateral by transcranial doppler Endothelial function/response by the methods: Biomarkers in blood (eg. e-selectin, VCAM, ICAM, endothelin, ADMA, miRNA) EndoPAT2000 Ankle-brachial index

Trial Design

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

Outcomes

Type Measure Time Frame Safety Issue
Primary Changes in the mean flow velocity in the middle cerebral arteries. Up till 3 hours No
Secondary Changes in the endothelial reactivity measured by non-invasive pletysmography. 3 hours No
Secondary Changes in the endothelial/inflammatory biomarkers in blood. 3 hours No
Secondary Changes in the ankle-brachial index. 3 hours No

Sponsors