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

February 6, 2017 updated by: Christina Kruuse

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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, 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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Herlev, Denmark, 2730
        • Department of Neurology, Herlev-Gentofte Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Byetta

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
Drug: Byetta
Single dose of subcutaneous injection of 5 μg exenatide (Byetta).
Other Names:
  • GLP-1 receptor agonist
  • exenatide
  • GLP-1 receptor analogue
PLACEBO_COMPARATOR: Isotonic saline

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
Drug: Isotonic saline
Single dose of subcutaneous injection of 20 μL isotonic saline (placebo).
Other Names:
  • Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in the mean flow velocity in the middle cerebral arteries and in cortical oxigination .
Time Frame: Up till 3 hours
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in the endothelial reactivity measured by non-invasive pletysmography.
Time Frame: 3 hours
Measurement of the endothelial function by non-invasive plethysmography (EndoPAT2000) before and three hours after injection of exenatide/placebo.
3 hours
Changes in the endothelial/inflammatory biomarkers in blood.
Time Frame: 3 hours
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
Changes in the ankle-brachial index.
Time Frame: 3 hours
Changes in the ankle-brachial index (systolic blood pressure in ankle/arm) measured before and three hours after injection of exenatide/placebo.
3 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Christina Kruuse

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2016

Primary Completion (ACTUAL)

February 1, 2017

Study Completion (ACTUAL)

February 1, 2017

Study Registration Dates

First Submitted

July 5, 2016

First Submitted That Met QC Criteria

July 15, 2016

First Posted (ESTIMATE)

July 20, 2016

Study Record Updates

Last Update Posted (ESTIMATE)

February 7, 2017

Last Update Submitted That Met QC Criteria

February 6, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-16022532
  • 2016-001221-14 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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