The Effect of GLP-1 Receptor Agonist on Cerebral Blood Flow Velocity in Stroke (EGRABIS1)

March 1, 2023 updated by: Christina Kruuse

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

This randomized controlled trial investigates the effect of a single dose of glucagon-like peptide-1 (GLP-1) receptor agonist in the subacute phase of stroke in humans. 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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. GLP-1 increases glucose-dependent insulin secretion and thereby reduces the 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 mainly target platelet function, but not endothelial function.

This double-blinded, randomized, controlled, pilot trial investigates the effect of a single dose of the GLP-1 receptor agonist, exenatide, on cerebral blood flow velocity in the subacute phase of stroke in humans. 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 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. Parallel to this study we investigate the effect of GLP-1 receptor agonist on people free of cerebrovascular diseases (ref. to EGRABINS1).

Study Type

Interventional

Enrollment (Anticipated)

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 Contact

Study Contact Backup

Study Locations

  • Denmark
      • Herlev, Denmark, 2730
        • Recruiting
        • Department of Neurology, Herlev-Gentofte Hospital
        • Contact:
          • Christina Kruuse, MD, DMSc
          • Phone Number: +4538681233

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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
  • Has given written informed consent

Exclusion Criteria:

  • Intracerebral haemorrhage
  • Subdural / epidural hemorrhage
  • Subarachnoid haemorrhage
  • Previously major structural damage to the brain
  • 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 unable to co-operate to the investigation procedures
  • Visualization of the middle cerebral artery bilaterally by transcranial dopple 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 Assignment
  • 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)

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: Normosaline

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
Drug: Normosaline
Single dose of subcutaneous injection of 20 μL normosaline (placebo).
Other Names:
  • Isotonic 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
Endothelial reactivity
Time Frame: 3 hours
Measurement of endothelial reactivity in fingers post occlusion by non-invasive plethysmography (EndoPAT2000) before and three hours after injection of exenatide/placebo.
3 hours
Changes in endothelial biomarkers in blood
Time Frame: 3 hours
Venous blood samples to measure endothelial biomarkers (including V-CAM, I-CAM, endothelin, e-selectin, ADMA, hsCRP, miRNA) before and three hours after injection of exenatide/placebo.
3 hours
Endothelial function/response in ankle-brachial index
Time Frame: 3 hours
Measuring of the blood pressure in the ankles and in the arm calculate the ankle-brachial index 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

Investigators

  • Principal Investigator: Christina R Kruuse, MD,PhD, Study Principal Investigator, Consultant Neurologist, Dept. Neurology, Herlev Hospital

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 (Anticipated)

August 1, 2023

Study Completion (Anticipated)

November 1, 2023

Study Registration Dates

First Submitted

July 5, 2016

First Submitted That Met QC Criteria

July 8, 2016

First Posted (Estimate)

July 12, 2016

Study Record Updates

Last Update Posted (Actual)

March 3, 2023

Last Update Submitted That Met QC Criteria

March 1, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-16022538
  • 2016-001219-18 (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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