Clinical trial NCT05630586: Acute Subcutaneous SemaglutidE in Acute Ischemic sTroke
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Bispebjerg Hospital
name: Glostrup University Hospital, Copenhagen
name: Odense University Hospital
name: Herning Hospital
name: Aalborg University Hospital
name: Rigshospitalet, Denmark
First posted: 2022-11-29
Enrollment: 380
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Modified Ranking Scale
timeFrame: 90 (+/- 14) days
Secondary outcomes:
measure: Serious Adverse Events and/or Serious Unexpected Serious Adverse Events
timeFrame: 90 days
measure: 90-day mortality
timeFrame: 90 days
measure: One-year mortality
timeFrame: 1 year
measure: Predefined SAEs
timeFrame: 1 year
measure: Excellent functional outcome at 90 days
timeFrame: 90 (+/- 14) days
measure: MACCE and recurrent ischemic events, 90 days
timeFrame: 90 days
measure: MACCE and recurrent ischemic events, 12 months
timeFrame: 12 months
measure: Stroke recurrence at 12 months in patients with a stroke due to small vessel disease
timeFrame: 12 months
measure: Early neurological improvement
timeFrame: 24 (+/- 8) hours
measure: Change in body weight (kg)
timeFrame: 90 (+/- 14) days
measure: Change in fasting plasma glucose
timeFrame: 90 (+/- 14) days
measure: Change in body mass index (BMI)
timeFrame: 90 (+/- 14) days
measure: Change in waist circumference
timeFrame: 90 (+/- 14) days
measure: Difference in HbA1c
timeFrame: 90 (+/- 14) days
measure: Diabetes diagnosis and/or antidiabetic medication
timeFrame: 12 months
measure: Blood pressure, 90 days
timeFrame: 90 (+/- 14) days
Other outcomes:
measure: Patient reported outcome: Quality of Life (QoL)
timeFrame: 90 (+/- 14) days
measure: Patient reported outcome: Major Depression Inventory (MDI)
timeFrame: 90 (+/- 14) days
measure: Patient reported outcome: SSQOL-DK
timeFrame: 90 (+/- 14) days
measure: Patient reported outcome: Activities of daily living
timeFrame: 90 (+/- 14) days
measure: Sub-study: 24-hour infarct growth
timeFrame: 24 (+/-8) hours
measure: Sub-study: Acute and long-term platelet inhibition in Semaglutide treated patients
timeFrame: 90 (+/- 14) days
measure: Sub-study: The effect of semaglutide in non-diabetic stroke patients on insulin, c-peptide, glucagon and 3-hydroxybuturate levels
timeFrame: 90 (+/- 14) days
measure: Sub-study: The effect of semaglutide in non-diabetic stroke patients on leptin, ghrelin, cholecystokinin (CCK) and gastric inhibitory polypeptide (GIP)
timeFrame: 90 (+/- 14) days
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: Aarhus University Hospital
name: Claus Z Simonsen, Professor
role: PRINCIPAL_INVESTIGATOR
References: