StrokePhase 2EGRABINS1NCT02838589
The Effect of GLP-1 Receptor Agonist on Cerebral Blood Flow Velocity in Non-stroke Volunteers
A Phase 2 study testing Byetta and Isotonic saline in people with 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 on cerebral blood flow velocity and cortical oxygination in humans without cerebrovascular disease. Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Stroke
- What is being tested?
- Byetta and Isotonic saline
- 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 Feb 2017
- 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 50 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Person ≥ 50 years of age
- Has given written informed consent
Who cannot join
- 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
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 not expected to co-operate to the investigations
- Visualization of the middle cerebral artery bilaterally by transcranial doppler not possible
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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).
Read the 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.
- Conditions
- Stroke
- Being tested
- Byetta, Isotonic saline
- Keywords
- Cerebrovascular Stroke, Ischemic Stroke, Glucagon like peptide - 1
- Medical subject headings
- Stroke, Ischemic Stroke
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).
Isotonic salineDrug
Also called Normal saline
Single dose of subcutaneous injection of 20 μL isotonic saline (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)
3. Endothelial function/response by the methods:
* Biomarkers in blood (eg. e-selectin, VCAM, ICAM, endothelin, ADMA, miRNA)
* EndoPAT2000
* Ankle-brachial index Receives: Drug: Byetta |
| Isotonic saline | 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)
3. Endothelial function/response by the methods:
* Biomarkers in blood (eg. e-selectin, VCAM, ICAM, endothelin, ADMA, miRNA)
* EndoPAT2000
* Ankle-brachial index Receives: Drug: Isotonic saline |
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)
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.
Measured: 3 hours
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.
Measured: 3 hours
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.
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 posted20 Jul 2016 (estimated)
- Study startAug 2016
- Primary completionFeb 2017
- Study completionFeb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 (actual)
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, Consultant Neurologist, Dept Neurology, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02838589
- Sponsor's protocol ID
- H-16022532
- Other IDs
- 2016-001221-14, 2016
- Acronym
- EGRABINS1
- Status last verified
- Feb 2017
- First submitted
- 5 Jul 2016
- Last updated
- 7 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Olmestig J, Marlet IR, Vilsboll T, Rungby J, Rostrup E, Lambertsen KL, Kruuse C. A single dose of exenatide had no effect on blood flow velocity in the middle cerebral artery in elderly healthy volunteers: Randomized, placebo-controlled, double-blind clinical trial. Front Aging Neurosci. 2022 Jul 25;14:899389. doi: 10.3389/fnagi.2022.899389. eCollection 2022.
PubMed 36636739
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2017. 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 Non-Stroke Volunteers (EGRABINS1)
- ClinicalTrials.gov ID
- NCT02838589
- Acronym / sponsor ID
- EGRABINS1 / H-16022532
- Conditions
- Stroke
- Keywords
- Cerebrovascular Stroke, Ischemic Stroke, Glucagon like peptide - 1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Christina KruuseUniversity, hospital or other
- Study start
- Aug 2016
- Primary completion
- Feb 2017 (actual)
- Study completion
- Feb 2017 (actual)
- First posted
- 20 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 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).
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 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) 3. Endothelial function/response by the methods: * Biomarkers in blood (eg. e-selectin, VCAM, ICAM, endothelin, ADMA, miRNA) * EndoPAT2000 * Ankle-brachial index |
| Isotonic saline | Placebo comparator | Drug: Isotonic salinePre- 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 |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Person ≥ 50 years of age
- Has given written informed consent
Key exclusion criteria (17 listed)
- 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
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 |
| Isotonic salineAlso: Normal salineSingle dose of subcutaneous injection of 20 μL isotonic saline (placebo). | Drug | Isotonic saline |
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
Changes in the endothelial reactivity measured by non-invasive pletysmography.
Time frame: 3 hours
Changes in the endothelial/inflammatory biomarkers in blood.
Time frame: 3 hours
Changes in the ankle-brachial index.
Time frame: 3 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2017.
- Derived from this study: PubMed 36636739Olmestig J, Marlet IR, Vilsboll T, Rungby J, Rostrup E, Lambertsen KL, Kruuse C. A single dose of exenatide had no effect on blood flow velocity in the middle cerebral artery in elderly healthy volunteers: Randomized, placebo-controlled, double-blind clinical trial. Front Aging Neurosci. 2022 Jul 25;14:899389. doi: 10.3389/fnagi.2022.899389. eCollection 2022.
- 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
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 Isotonic saline in people with 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 2 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: finished, as of the sponsor's last update on 7 Feb 2017. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. 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?
On the ClinicalTrials.gov record for NCT02838589, which also lists 1 linked publication.
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 7 Feb 2017.