Acute Subcutaneous SemaglutidE in Acute Ischemic sTroke

Study Overview
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Brief Summary
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Can Semaglutide help reduce the damage caused by a stroke? ASSET trial is a national, multicenter, clinical trial, investigating the safety and efficacy of Semaglutide in non-diabetic patients with acute ischemic stroke. Stroke is a worldwide leading cause of long-term disability and death. In the most common type of stroke (ischemic stroke), a blood clot obstructs an artery in the brain, and thereby prevents oxygenated blood from reaching an area of the brain. Brain cells are particularly vulnerable to the lack of oxygen. In the areas most severely affected by a stroke, brain cells die after 5 minutes. As more time pass, the affected area expands, and more brain cells perish. Today, efficient treatments aiming at reestablishing the flow of blood by either breaking down the blood clot (thrombolysis) or removing the clot (thrombektomi) are used. However, a significant amount of patients undergoing succesful treamtent, still suffer permanent disability following an ischemic stroke. Semaglutide mimics a naturally occurring hormone (glucagon-like peptide-1) and is currently used to treat diabetes and obesity. However, semaglutide has also been shown to possess neuroprotective abilities in recent animal studies, where it reduced the damage caused by ischemic stroke in rats. This study sets out to investigate if it's possible to utilize Semaglutide, to increase the resilience of brain cells in patients with an acute ischemic stroke, with the aim of bettering their outcome. The participants consist of non-diabetic patients with acute ischemic stroke, who will be randomized to: Treatment with subcutaneous Semaglutide, or No additional treatment (control group) Both groups will be treated according to the standard national guidelies for acute ischemic stroke. The two groups will then be compared to see, if patients in the group treated with Semaglutide are less impacted by their stroke.

Detailed Description
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For detailed project description, please refer to the full trial information at the Clinical Trials Information System (see 'More information' below for link).

Official Title
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The Safety and Efficacy of Acute Subcutaneous Administration of Semaglutide in Non-diabetic Patients With Acute Ischemic Stroke: A Multicentre, Phase 2, Prospective, Randomized, Open-label, Blinded Endpoint Trial

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: Semaglutide
* Other: Standard care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients (≥ 18 years) at the time of signed informed consent/proxy consent Acute ischemic stroke with disabling neurological deficits (defined as an impairment of one or more of the following: language, motor function, cognition, gaze, vision, neglect, or ataxia) Onset/last seen well to randomization < 4.5 hours None to moderate disability in daily living before symptom onset (pre-stroke modified Rankin Scale 0-3) Exclusion Criteria: Diabetes (known) or plasma/point of care test-glucose >11.1 mmol/L at admission BMI< 22 History of pancreatitis, medullary thyroid carcinoma Predisposition or known Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) Short remaining life expectancy (< 12months) and/or severe neurodegenerative disease Pregnancy or planned pregnancy within 12 months or breastfeeding Renal impairment measured as estimated glomerular filtration rate (eGFR) value of <30 mL/min/1.73 m2

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Semaglutide 0.5 mg<br>Inj. Semaglutide 0.5 mg s.c., 0.5 mg per week for 4 weeks + standard care | Drug: Semaglutide<br>* Subcutaneous Semaglutide, 0.5 mg weekly for 4 weeks. First dose given at inclusion.<br>* Other names: Ozempic;Other: Standard care<br>* Treatment according to Danish national clinical guidelines on stroke treatment, including reperfusion therapy if eligible.<br>|
| Other: Control<br>Standard care | Other: Standard care<br>* Treatment according to Danish national clinical guidelines on stroke treatment, including reperfusion therapy if eligible.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Ranking Scale | A shift towards better functional outcomes in the distribution of the modified Ranking Scale (mRS) | 90 (+/- 14) days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious Adverse Events and/or Serious Unexpected Serious Adverse Events | Proportion of patients with Serious Adverse Events (SAE) and/or Serious Unexpected Serious Adverse Events (SUSAR) within 90 days of randomization | 90 days | 
| 90-day mortality |  | 90 days | 
| One-year mortality |  | 1 year | 
| Predefined SAEs | Frequency of predefined serious adverse events | 1 year | 
| Excellent functional outcome at 90 days | mRS score of 0-1 | 90 (+/- 14) days | 
| MACCE and recurrent ischemic events, 90 days | Major Adverse Cardiac and Cerebral Events (MACCE) and recurrent ischemic events based on registry data at 3 months in AIS patients | 90 days | 
| MACCE and recurrent ischemic events, 12 months | Major Adverse Cardiac and Cerebral Events (MACCE) and recurrent ischemic events based on registry data at 12 months in AIS patients | 12 months | 
| Stroke recurrence at 12 months in patients with a stroke due to small vessel disease |  | 12 months | 
| Early neurological improvement | NIHSS_24hour - NIHSS_baseline (NIHSS National Institutes of Health Stroke Scale) | 24 (+/- 8) hours | 
| Change in body weight (kg) | 90 days - baseline | 90 (+/- 14) days | 
| Change in fasting plasma glucose | 90 days - baseline | 90 (+/- 14) days | 
| Change in body mass index (BMI) | 90 days - baseline | 90 (+/- 14) days | 
| Change in waist circumference | 90 days - baseline | 90 (+/- 14) days | 
| Difference in HbA1c | 90 days - baseline | 90 (+/- 14) days | 
| Diabetes diagnosis and/or antidiabetic medication | Diagnosed with and/or started antidiabetic medication within 1 year of enrollment | 12 months | 
| Blood pressure, 90 days | Systolic and diastolic blood pressure (90 days BP - discharge BP) | 90 (+/- 14) days |