Cardiac ArrestGLIP1NCT02442791
GLP-1 Analogs for Neuroprotection After Cardiac Arrest
A study testing Byetta (Lilly, Exenatide) and 20% Human Albumin in people with Cardiac Arrest and Coma, run by Jesper Kjaergaard at 1 site in Denmark.
Trial summary
Experimental studies and previous clinical trials suggest neuroprotective effects of GLP-1 analogs in various degenerative neurological diseases, and in hypoxic brain injuries in experimental designs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Arrest, Coma
- What is being tested?
- Byetta (Lilly, Exenatide) and 20% Human Albumin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteDenmark
- Study dates
- Jun 2014to Jun 2016
- Phase
- Interventional
- 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
- Out of hospital cardiac arrest (OHCA) of presumed cardiac cause
- Sustained return of spontaneous circulation (ROSC)
- Unconsciousness (GCS <8 (Glasgow coma scale)) (patients not able to obey verbal commands)
- Sustained ROSC (Sustained ROSC: Sustained ROSC is when chest compressions have been not required for 20 consecutive minutes and signs of circulation persist)
Who cannot join
- Conscious patients (obeying verbal commands)
- Females of childbearing potential (unless a negative pregnancy test can rule out pregnancy within the inclusion window)
- In-hospital cardiac arrest (IHCA)
- OHCA of presumed non-cardiac cause, e.g. after trauma or dissection/rupture of major artery OR Cardiac arrest caused by initial hypoxia (i.e. drowning, suffocation, hanging).
- Known bleeding diathesis (medically induced coagulopathy (e.g. warfarin, clopidogrel) does not exclude the patient).
- Suspected or confirmed acute intracranial bleeding
Show all 19Show fewer
- Suspected or confirmed acute stroke
- Unwitnessed asystole
- Known limitations in therapy and Do Not Resuscitate-order
- Known disease making 180 days survival unlikely
- Known pre-arrest cerebral performance category 3 or 4
- >4 hours (240 minutes) from ROSC to screening
- Systolic blood pressure <80 mm Hg in spite of fluid loading/vasopressor and/or inotropic medication/intra aortic balloon pump/axial flow device*
- Temperature on admission <30°C.
- Known allergy to GLP-1 analogs, including Exenatide
- Known pancreatitis
- Diabetic ketoacidosis,
- Uncorrected blood glucose at admission < 2.5 mmol/l.
- If the systolic blood pressure (SBP) is recovering during the inclusion window (220 minutes) the patient can be included.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: GLP-1 Analogs for Neuroprotection After Out-of-hospital Cardiac Arrest, a Randomized Clinical Trail
Experimental studies and previous clinical trials suggest neuroprotective effects of GLP-1 analogs in various degenerative neurological diseases, and in hypoxic brain injuries in experimental designs. This study is designed as a safety and feasibility study with patients randomized 1:1 to receive GLP-1 analogs immediately after hospital admission after out of hospital cardiac arrest.
Read the detailed description
In comatose patients resuscitated from out of hospital cardiac arrest, neurological injuries remain the leading cause of death. The in-hospital mortality is reported at 30-50%, and the total mortality, although improved substantially over the last decade, remain to be significant, in most countries up to 90%. The brain of a patient resuscitated after cardiac arrest (CA) may have suffered ischemia and when the spontaneous circulation is re-established, the subsequent reperfusion may cause further damage. Brain ischemia and the reperfusion injury lead to tissue degeneration and loss of neurological function, the extent dependent on duration and density of the insult. Temperature control and mild induced hypothermia (MIH) (33-36°C) mitigate this damage in the experimental setting and clinical trials have shown promising results in improving neurological function and survival. Recent large scale clinical trials however have investigated milder degree of hypothermia in this setting, which suggest a role for active neuroprotection outside of temperature management. Also recently, increased attention to the possible role of Glucagon-Like Peptide-1 (GLP-1) in neuroprotection has been raised, both in the context of ameliorating degenerative disease and in reducing inflammation on ischemic cerebral stroke.
Several experimental studies have shown that GLP-1 analogs has a beneficial effect in the treatment of various degenerative neurological diseases such as Alzheimer's disease and Parkinson's disease. GLP-1 analogs have been shown to reduce brain infarct size in mice after focal brain ischemia as well as to reduce heart infarct size in swine in a model of myocardial infarction.
Recent clinical testing in humans have demonstrated a benefit of GLP-1 infusion on myocardial infarct size and a larger salvage index in patients with myocardial infarction. The GLP-1 analogs were infused in acutely ill patients in many ways similar to cardiac arrest patients with no increased risk of adverse events.
This study is a double blinded randomized study seeking to evaluate the potential neuroprotective effects of GLP-1 analogs infused in comatose patients after out of hospital cardiac arrest.
- Conditions
- Cardiac Arrest, Coma
- Being tested
- Byetta (Lilly, Exenatide), 20% Human Albumin
- Keywords
- Cardiac arrest, GLP-1, Neuroprotection
- Medical subject headings
- Heart Arrest, Coma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Byetta (Lilly, Exenatide)Drug
Also called Byetta
See description of Arms
20% Human AlbuminOther
See description of Arms
| Study group | Role | What they receive |
|---|---|---|
| GLP-1 | Experimental | Half of the participants will receive the study drug, that will be given as follows:
250 mL isotonic sodium chloride added 1.5 mL of 20% Human Albumin added 25 microg Byetta (Lilly, Exenatide).
The study drug infusion is initiated as soon as possible at rate of 72ml/hour (0.12 μg/min) for 15 min (set volume at 18 ml), followed by 26ml/hour (0.043 μg/min) to be continued for 6 hours (set volume at 156 ml). This concludes the pharmacological intervention. Receives: Drug: Byetta (Lilly, Exenatide); Other: 20% Human Albumin |
| Placebo | Placebo comparator | Half of the participants will receive placebo, that will be given as follows:
250 mL isotonic sodium chloride added 1.5 mL of 20% Human Albumin. The placebo infusion is administered exactly the same way as the study drug infusion. Receives: Other: 20% Human Albumin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility: Over 90% initiation of study drug infusion
Measured: 4 hours from return of spontaneous circulation
Efficacy assessed by Area under the Neuron-specific Enolase curve
Measured: 72 hours from admission
Secondary outcomes (6)
Neurological prognostication
Blinded neurological evaluation by neurologist on "VAS-scale"
Measured: Day 5
Area under Neuron-specific Enolase curves (NSE)
Daily measurements of NSE values
Measured: 48 hours
All cause mortality
Vital status by end of study by registry based follow-up
Measured: 180 days
Cerebral status
Telephone based assessment of Cerebral Performance Category and modified Rankin Scale.
Measured: 30 days, 90 days and 180 days
Safety: Cumulated incidence of serious adverse events related to study drug: death, need for mechanical hemodynamic support, hypoglycaemia < 3.0 mmol/l, pancreatitis (S-amylase > 3 UNL), need for renal replacement therapy in the first 3 days.
Measured: 180 days
Area under S100b curve
Daily measurements of S100b
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2015 (estimated)
- Study startJun 2014
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cardiac ArrestStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jesper Kjaergaard
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jesper Kjaergaard, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Jesper Kjaergaard, MD., DMSc., Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02442791
- Sponsor's protocol ID
- 2013-TTMPharma-001
- Acronym
- GLIP1
- Status last verified
- Sep 2017
- First submitted
- 25 Jan 2015
- Last updated
- 28 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Wiberg S, Hassager C, Schmidt H, Thomsen JH, Frydland M, Lindholm MG, Hofsten DE, Engstrom T, Kober L, Moller JE, Kjaergaard J. Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial. Circulation. 2016 Dec 20;134(25):2115-2124. doi: 10.1161/CIRCULATIONAHA.116.024088. Epub 2016 Nov 12.
PubMed 27838646Toftgaard Pedersen A, Kjaergaard J, Hassager C, Frydland M, Hartvig Thomsen J, Klein A, Schmidt H, Moller JE, Wiberg S. Association between inflammatory markers and survival in comatose, resuscitated out-of-hospital cardiac arrest patients. Scand Cardiovasc J. 2022 Dec;56(1):85-90. doi: 10.1080/14017431.2022.2074093.
PubMed 35546563Wiberg S, Kjaergaard J, Schmidt H, Thomsen JH, Frydland M, Winther-Jensen M, Lindholm MG, Hofsten DE, Engstrom T, Kober L, Moller JE, Hassager C. The Glucagon-Like Peptide-1 Analog Exenatide Increases Blood Glucose Clearance, Lactate Clearance, and Heart Rate in Comatose Patients After Out-of-Hospital Cardiac Arrest. Crit Care Med. 2018 Feb;46(2):e118-e125. doi: 10.1097/CCM.0000000000002814.
PubMed 29189347Wiberg S, Hassager C, Thomsen JH, Frydland M, Hofsten DE, Engstrom T, Kober L, Schmidt H, Moller JE, Kjaergaard J. GLP-1 analogues for neuroprotection after out-of-hospital cardiac arrest: study protocol for a randomized controlled trial. Trials. 2016 Jun 30;17(1):304. doi: 10.1186/s13063-016-1421-2.
PubMed 27363489
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GLP-1 Analogs for Neuroprotection After Out-of-hospital Cardiac Arrest, a Randomized Clinical Trail
- ClinicalTrials.gov ID
- NCT02442791
- Acronym / sponsor ID
- GLIP1 / 2013-TTMPharma-001
- Conditions
- Cardiac Arrest, Coma
- Keywords
- Cardiac arrest, GLP-1, Neuroprotection
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Jesper KjaergaardUniversity, hospital or other
- Study start
- Jun 2014
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 13 May 2015 (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.
Experimental studies and previous clinical trials suggest neuroprotective effects of GLP-1 analogs in various degenerative neurological diseases, and in hypoxic brain injuries in experimental designs. This study is designed as a safety and feasibility study with patients randomized 1:1 to receive GLP-1 analogs immediately after hospital admission after out of hospital cardiac arrest.
Detailed description
In comatose patients resuscitated from out of hospital cardiac arrest, neurological injuries remain the leading cause of death. The in-hospital mortality is reported at 30-50%, and the total mortality, although improved substantially over the last decade, remain to be significant, in most countries up to 90%. The brain of a patient resuscitated after cardiac arrest (CA) may have suffered ischemia and when the spontaneous circulation is re-established, the subsequent reperfusion may cause further damage. Brain ischemia and the reperfusion injury lead to tissue degeneration and loss of neurological function, the extent dependent on duration and density of the insult. Temperature control and mild induced hypothermia (MIH) (33-36°C) mitigate this damage in the experimental setting and clinical trials have shown promising results in improving neurological function and survival. Recent large scale clinical trials however have investigated milder degree of hypothermia in this setting, which suggest a role for active neuroprotection outside of temperature management. Also recently, increased attention to the possible role of Glucagon-Like Peptide-1 (GLP-1) in neuroprotection has been raised, both in the context of ameliorating degenerative disease and in reducing inflammation on ischemic cerebral stroke.
Several experimental studies have shown that GLP-1 analogs has a beneficial effect in the treatment of various degenerative neurological diseases such as Alzheimer's disease and Parkinson's disease. GLP-1 analogs have been shown to reduce brain infarct size in mice after focal brain ischemia as well as to reduce heart infarct size in swine in a model of myocardial infarction.
Recent clinical testing in humans have demonstrated a benefit of GLP-1 infusion on myocardial infarct size and a larger salvage index in patients with myocardial infarction. The GLP-1 analogs were infused in acutely ill patients in many ways similar to cardiac arrest patients with no increased risk of adverse events.
This study is a double blinded randomized study seeking to evaluate the potential neuroprotective effects of GLP-1 analogs infused in comatose patients after out of hospital cardiac arrest.
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 |
|---|---|---|
| GLP-1 | Experimental | Drug: Byetta (Lilly, Exenatide), Other: 20% Human AlbuminHalf of the participants will receive the study drug, that will be given as follows: 250 mL isotonic sodium chloride added 1.5 mL of 20% Human Albumin added 25 microg Byetta (Lilly, Exenatide). The study drug infusion is initiated as soon as possible at rate of 72ml/hour (0.12 μg/min) for 15 min (set volume at 18 ml), followed by 26ml/hour (0.043 μg/min) to be continued for 6 hours (set volume at 156 ml). This concludes the pharmacological intervention. |
| Placebo | Placebo comparator | Other: 20% Human AlbuminHalf of the participants will receive placebo, that will be given as follows: 250 mL isotonic sodium chloride added 1.5 mL of 20% Human Albumin. The placebo infusion is administered exactly the same way as the study drug infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Out of hospital cardiac arrest (OHCA) of presumed cardiac cause
- Sustained return of spontaneous circulation (ROSC)
- Unconsciousness (GCS <8 (Glasgow coma scale)) (patients not able to obey verbal commands)
- Sustained ROSC (Sustained ROSC: Sustained ROSC is when chest compressions have been not required for 20 consecutive minutes and signs of circulation persist)
Key exclusion criteria (19 listed)
- Conscious patients (obeying verbal commands)
- Females of childbearing potential (unless a negative pregnancy test can rule out pregnancy within the inclusion window)
- In-hospital cardiac arrest (IHCA)
- OHCA of presumed non-cardiac cause, e.g. after trauma or dissection/rupture of major artery OR Cardiac arrest caused by initial hypoxia (i.e. drowning, suffocation, hanging).
- Known bleeding diathesis (medically induced coagulopathy (e.g. warfarin, clopidogrel) does not exclude the patient).
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 |
|---|---|---|
| Byetta (Lilly, Exenatide)Also: ByettaSee description of Arms | Drug | GLP-1 |
| 20% Human AlbuminSee description of Arms | Other | GLP-1, Placebo |
Primary outcome
Feasibility: Over 90% initiation of study drug infusion
Time frame: 4 hours from return of spontaneous circulation
Efficacy assessed by Area under the Neuron-specific Enolase curve
Time frame: 72 hours from admission
6 secondary outcomes
Neurological prognostication
Time frame: Day 5
Area under Neuron-specific Enolase curves (NSE)
Time frame: 48 hours
All cause mortality
Time frame: 180 days
Cerebral status
Time frame: 30 days, 90 days and 180 days
Safety: Cumulated incidence of serious adverse events related to study drug: death, need for mechanical hemodynamic support, hypoglycaemia < 3.0 mmol/l, pancreatitis (S-amylase > 3 UNL), need for renal replacement therapy in the first 3 days.
Time frame: 180 days
Area under S100b curve
Time frame: 48 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 28 Sep 2017.
- Results publication: PubMed 27838646Wiberg S, Hassager C, Schmidt H, Thomsen JH, Frydland M, Lindholm MG, Hofsten DE, Engstrom T, Kober L, Moller JE, Kjaergaard J. Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial. Circulation. 2016 Dec 20;134(25):2115-2124. doi: 10.1161/CIRCULATIONAHA.116.024088. Epub 2016 Nov 12.
- Derived from this study: PubMed 35546563Toftgaard Pedersen A, Kjaergaard J, Hassager C, Frydland M, Hartvig Thomsen J, Klein A, Schmidt H, Moller JE, Wiberg S. Association between inflammatory markers and survival in comatose, resuscitated out-of-hospital cardiac arrest patients. Scand Cardiovasc J. 2022 Dec;56(1):85-90. doi: 10.1080/14017431.2022.2074093.
- Derived from this study: PubMed 29189347Wiberg S, Kjaergaard J, Schmidt H, Thomsen JH, Frydland M, Winther-Jensen M, Lindholm MG, Hofsten DE, Engstrom T, Kober L, Moller JE, Hassager C. The Glucagon-Like Peptide-1 Analog Exenatide Increases Blood Glucose Clearance, Lactate Clearance, and Heart Rate in Comatose Patients After Out-of-Hospital Cardiac Arrest. Crit Care Med. 2018 Feb;46(2):e118-e125. doi: 10.1097/CCM.0000000000002814.
- Derived from this study: PubMed 27363489Wiberg S, Hassager C, Thomsen JH, Frydland M, Hofsten DE, Engstrom T, Kober L, Schmidt H, Moller JE, Kjaergaard J. GLP-1 analogues for neuroprotection after out-of-hospital cardiac arrest: study protocol for a randomized controlled trial. Trials. 2016 Jun 30;17(1):304. doi: 10.1186/s13063-016-1421-2.
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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.
Jesper Kjaergaard, MD., DMSc. principal investigator
Copenhagen University Hospital, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Byetta (Lilly, Exenatide) and 20% Human Albumin in people with Cardiac Arrest and Coma, run by Jesper Kjaergaard 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 4 inclusion and 19 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 28 Sep 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.
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?
Feasibility: Over 90% initiation of study drug infusion (time frame: 4 hours from return of spontaneous circulation). The study lists 2 primary outcomes in all. 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 NCT02442791, which also lists 4 linked publications.
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 28 Sep 2017.