Acute Subcutaneous SemaglutidE in Acute Ischemic sTroke (ASSET)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Semaglutide; Other: Standard care

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).

• Study Type: Interventional
• Enrollment (Anticipated): 380
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Thomas Mellemkjaer, MD; Phone Number: 004551430175; Email: thomas.mellemkjaer@rm.dk
• Study Contact Backup: Name: Claus Z Simonsen, Professor; Phone Number: 004523669875; Email: clausimo@rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Recruiting
    • Aarhus University Hospital
    • Contact: Claus Z Simonsen, MD; Phone Number: 004523669875; Email: clasim@rm.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient reported outcome: Quality of Life (QoL)	European Quality of Life - 5 Dimension (EQ5D), 90 days - baseline	90 (+/- 14) days
Patient reported outcome: Major Depression Inventory (MDI)	Change in MDI (90 days - baseline)	90 (+/- 14) days
Patient reported outcome: SSQOL-DK	Difference in Stroke Specific Quality of Life Scale (SSQOL-DK, 90 days)	90 (+/- 14) days
Patient reported outcome: Activities of daily living	Difference in activities of daily living - Multi Data Set -Home Care (MDS-HC,90 days)	90 (+/- 14) days
Sub-study: 24-hour infarct growth	Infarct growth on diffusion-weigthed magnetic resonance imaging (DWI-MRI). Aarhus University Hospital (AUH) only	24 (+/-8) hours
Sub-study: Acute and long-term platelet inhibition in Semaglutide treated patients	AUH only	90 (+/- 14) days
Sub-study: The effect of semaglutide in non-diabetic stroke patients on insulin, c-peptide, glucagon and 3-hydroxybuturate levels	AUH only	90 (+/- 14) days
Sub-study: The effect of semaglutide in non-diabetic stroke patients on leptin, ghrelin, cholecystokinin (CCK) and gastric inhibitory polypeptide (GIP)	AUH only	90 (+/- 14) days

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: Odense University Hospital; Rigshospitalet, Denmark; Bispebjerg Hospital; Herning Hospital; Glostrup University Hospital, Copenhagen; Aalborg University Hospital
• Investigators: Principal Investigator: Claus Z Simonsen, Professor, Aarhus University Hospital

Publications and helpful links

Helpful Links

• Trial informaion on CTIS (Clinical Trials Information System), European Medicinal Agency

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2023
• Primary Completion (Anticipated): September 1, 2025
• Study Completion (Anticipated): December 1, 2027

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 18, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: ASSET; EUCT number: 2022-501072-25-02 (Other Identifier: European Medicines Agency (EMA))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No