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

Primary Purpose

Ischemic Stroke

Status
Recruiting
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Byetta
Normosaline
Sponsored by
Christina Kruuse
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke focused on measuring Cerebrovascular disease, Glucagon like peptide 1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Neurology, Herlev-Gentofte HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Byetta

Normosaline

Arm Description

Pre- and post treatment investigations: Mean flow velocity of the middle cerebral arteries bilateral by transcranial doppler 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

Pre- and post treatment investigations: Mean flow velocity of the middle cerebral arteries bilateral by transcranial doppler 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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Endothelial reactivity
Measurement of endothelial reactivity in fingers post occlusion by non-invasive plethysmography (EndoPAT2000) before and three hours after injection of exenatide/placebo.
Changes in endothelial biomarkers in blood
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.
Endothelial function/response in ankle-brachial index
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.

Full Information

First Posted
July 5, 2016
Last Updated
March 1, 2023
Sponsor
Christina Kruuse
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1. Study Identification

Unique Protocol Identification Number
NCT02829502
Brief Title
The Effect of GLP-1 Receptor Agonist on Cerebral Blood Flow Velocity in Stroke
Acronym
EGRABIS1
Official Title
The Effect of Glucagon-like Peptide 1 (GLP-1) Receptor Agonist on Cerebral Blood Flow Velocity in Stroke Patients
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 2016 (undefined)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
November 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Christina Kruuse

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke
Keywords
Cerebrovascular disease, Glucagon like peptide 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Byetta
Arm Type
Active Comparator
Arm Description
Pre- and post treatment investigations: Mean flow velocity of the middle cerebral arteries bilateral by transcranial doppler 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
Arm Title
Normosaline
Arm Type
Placebo Comparator
Arm Description
Pre- and post treatment investigations: Mean flow velocity of the middle cerebral arteries bilateral by transcranial doppler 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
Intervention Type
Drug
Intervention Name(s)
Byetta
Other Intervention Name(s)
Exenatide, GLP-1 receptor analogue, GLP-1 receptor agonist
Intervention Description
Single dose of subcutaneous injection of 5 μg exenatide (Byetta).
Intervention Type
Drug
Intervention Name(s)
Normosaline
Other Intervention Name(s)
Isotonic saline
Intervention Description
Single dose of subcutaneous injection of 20 μL normosaline (placebo).
Primary Outcome Measure Information:
Title
Changes in the mean flow velocity in the middle cerebral arteries and in cortical oxigination.
Description
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.
Time Frame
Up till 3 hours
Secondary Outcome Measure Information:
Title
Endothelial reactivity
Description
Measurement of endothelial reactivity in fingers post occlusion by non-invasive plethysmography (EndoPAT2000) before and three hours after injection of exenatide/placebo.
Time Frame
3 hours
Title
Changes in endothelial biomarkers in blood
Description
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.
Time Frame
3 hours
Title
Endothelial function/response in ankle-brachial index
Description
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.
Time Frame
3 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christina R Kruuse, MD, PhD
Phone
+4538681233
Email
ckruuse@dadlnet.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Bilal H Akram, med. student
Phone
+38681138
Email
bilal.hussain.akram.01@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christina R Kruuse, MD,PhD
Organizational Affiliation
Study Principal Investigator, Consultant Neurologist, Dept. Neurology, Herlev Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Neurology, Herlev-Gentofte Hospital
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christina Kruuse, MD, DMSc
Phone
+4538681233

12. IPD Sharing Statement

Plan to Share IPD
No

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

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