Ischemic StrokePhase 2EGRABIS1NCT02829502
The Effect of GLP-1 Receptor Agonist on Cerebral Blood Flow Velocity in Stroke
A Phase 2 study testing Byetta and Normosaline in people with Ischemic Stroke, run by Christina Kruuse at 1 site in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- Byetta and Normosaline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteDenmark
- Study dates
- Aug 2016to Nov 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Intracerebral haemorrhage
- Subdural / epidural hemorrhage
- Subarachnoid haemorrhage
- Previously major structural damage to the brain
- Diabetes type 1
- Diabetes type 2
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Department of Neurology, Herlev-Gentofte Hospital
Herlev, 2730
Christina Kruuse, MD, DMSc, +4538681233
About this study
Official title: 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.
Read the 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).
- Conditions
- Ischemic Stroke
- Being tested
- Byetta, Normosaline
- Keywords
- Cerebrovascular disease, Glucagon like peptide 1
- Medical subject headings
- Ischemic Stroke, Cerebrovascular Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ByettaDrug
Also called Exenatide, GLP-1 receptor analogue, GLP-1 receptor agonist
Single dose of subcutaneous injection of 5 μg exenatide (Byetta).
NormosalineDrug
Also called Isotonic saline
Single dose of subcutaneous injection of 20 μL normosaline (placebo).
| Study group | Role | What they receive |
|---|---|---|
| Byetta | Active comparator | 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 Receives: Drug: Byetta |
| Normosaline | Placebo comparator | 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 Receives: Drug: Normosaline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up till 3 hours
Secondary outcomes (3)
Endothelial reactivity
Measurement of endothelial reactivity in fingers post occlusion by non-invasive plethysmography (EndoPAT2000) before and three hours after injection of exenatide/placebo.
Measured: 3 hours
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.
Measured: 3 hours
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.
Measured: 3 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2016 (estimated)
- Study startAug 2016
- Primary completionAug 2023 (estimated)
- Study completionNov 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Christina Kruuse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Christina Kruuse, Herlev Hospital
- Investigators
- Christina R Kruuse, MD,PhD, Principal investigator, Study Principal Investigator, Consultant Neurologist, Dept. Neurology, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02829502
- Sponsor's protocol ID
- H-16022538
- Other IDs
- 2016-001219-18, 2016
- Acronym
- EGRABIS1
- Status last verified
- Mar 2023
- First submitted
- 5 Jul 2016
- Last updated
- 3 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Glucagon-like Peptide 1 (GLP-1) Receptor Agonist on Cerebral Blood Flow Velocity in Stroke Patients
- ClinicalTrials.gov ID
- NCT02829502
- Acronym / sponsor ID
- EGRABIS1 / H-16022538
- Conditions
- Ischemic Stroke
- Keywords
- Cerebrovascular disease, Glucagon like peptide 1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Christina KruuseUniversity, hospital or other
- Study start
- Aug 2016
- Primary completion
- Aug 2023 (estimated)
- Study completion
- Nov 2023 (estimated)
- First posted
- 12 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Byetta | Active comparator | Drug: ByettaPre- 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 |
| Normosaline | Placebo comparator | Drug: NormosalinePre- 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (17 listed)
- Intracerebral haemorrhage
- Subdural / epidural hemorrhage
- Subarachnoid haemorrhage
- Previously major structural damage to the brain
- Diabetes type 1
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ByettaAlso: Exenatide, GLP-1 receptor analogue, GLP-1 receptor agonistSingle dose of subcutaneous injection of 5 μg exenatide (Byetta). | Drug | Byetta |
| NormosalineAlso: Isotonic salineSingle dose of subcutaneous injection of 20 μL normosaline (placebo). | Drug | Normosaline |
Primary outcome
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.
3 secondary outcomes
Endothelial reactivity
Time frame: 3 hours
Changes in endothelial biomarkers in blood
Time frame: 3 hours
Endothelial function/response in ankle-brachial index
Time frame: 3 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christina R Kruuse, MD,PhD principal investigator
Study Principal Investigator, Consultant Neurologist, Dept. Neurology, Herlev Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Byetta and Normosaline in people with Ischemic Stroke, run by Christina Kruuse at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Christina R Kruuse, MD, PhD (+4538681233, ckruuse@dadlnet.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the mean flow velocity in the middle cerebral arteries and in cortical oxigination. (time frame: Up till 3 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2023.