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

Stroke Clinical Trial

— EGRABINS1  

Official title:

The Effect of Glucagon-like Peptide 1 (GLP-1) Receptor Agonist on Cerebral Blood Flow Velocity in Non-Stroke Volunteers (EGRABINS1)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02838589
• Other study ID #: H-16022532
• Secondary ID: 2016-001221-14
• Status: Completed
• Phase: Phase 2
• First received: July 5, 2016
• Last updated: February 6, 2017
• Start date: August 2016
• Est. completion date: February 2017

Study information

• Verified date: February 2017
• Source: Herlev Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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, 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Person = 50 years of age

• Has given written informed consent

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Stroke

Intervention

Drug:
• Byetta
Single dose of subcutaneous injection of 5 µg exenatide (Byetta).
• Isotonic saline
Single dose of subcutaneous injection of 20 µL isotonic saline (placebo).

Locations

Country	Name	City	State
Denmark	Department of Neurology, Herlev-Gentofte Hospital	Herlev

Sponsors (1)

Lead Sponsor	Collaborator
Christina Kruuse

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in the mean flow velocity in the middle cerebral arteries and in cortical oxigination .	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.	Up till 3 hours
Secondary	Changes in the endothelial reactivity measured by non-invasive pletysmography.	Measurement of the endothelial function by non-invasive plethysmography (EndoPAT2000) before and three hours after injection of exenatide/placebo.	3 hours
Secondary	Changes in the endothelial/inflammatory biomarkers in blood.	Venous blood samples to measure changes in the endothelial/inflammatory biomarkers (eg. e-selectin, VCAM, ICAM, ADMA, endothelin, miRNA) before and three hours after injection of exenatide/placebo.	3 hours
Secondary	Changes in the ankle-brachial index.	Changes in the ankle-brachial index (systolic blood pressure in ankle/arm) measured before and three hours after injection of exenatide/placebo.	3 hours