Acute Subcutaneous SemaglutidE in Acute Ischemic sTroke

Acute Ischemic Stroke Clinical Trial

— ASSET  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05630586
• Other study ID #: ASSET
• Secondary ID: EUCT number: 202
• Status: Recruiting
• Phase: Phase 2
• Start date: April 12, 2023
• Est. completion date: December 2027

Study information

• Verified date: November 2022
• Source: University of Aarhus
• Contact: Thomas Mellemkjaer, MD
• Phone: 004551430175
• Email: thomas.mellemkjaer[@]rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 380
• Est. completion date: December 2027
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• Semaglutide
Subcutaneous Semaglutide, 0.5 mg weekly for 4 weeks. First dose given at inclusion.

Other:
• Standard care
Treatment according to Danish national clinical guidelines on stroke treatment, including reperfusion therapy if eligible.

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus

Sponsors (7)

Lead Sponsor	Collaborator
Aarhus University Hospital	Aalborg University Hospital, Bispebjerg Hospital, Glostrup University Hospital, Copenhagen, Herning Hospital, Odense University Hospital, Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patient reported outcome: Quality of Life (QoL)	European Quality of Life - 5 Dimension (EQ5D), 90 days - baseline	90 (+/- 14) days
Other	Patient reported outcome: Major Depression Inventory (MDI)	Change in MDI (90 days - baseline)	90 (+/- 14) days
Other	Patient reported outcome: SSQOL-DK	Difference in Stroke Specific Quality of Life Scale (SSQOL-DK, 90 days)	90 (+/- 14) days
Other	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
Other	Sub-study: 24-hour infarct growth	Infarct growth on diffusion-weigthed magnetic resonance imaging (DWI-MRI). Aarhus University Hospital (AUH) only	24 (+/-8) hours
Other	Sub-study: Acute and long-term platelet inhibition in Semaglutide treated patients	AUH only	90 (+/- 14) days
Other	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
Other	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
Primary	Modified Ranking Scale	A shift towards better functional outcomes in the distribution of the modified Ranking Scale (mRS)	90 (+/- 14) days
Secondary	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
Secondary	90-day mortality		90 days
Secondary	One-year mortality		1 year
Secondary	Predefined SAEs	Frequency of predefined serious adverse events	1 year
Secondary	Excellent functional outcome at 90 days	mRS score of 0-1	90 (+/- 14) days
Secondary	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
Secondary	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
Secondary	Stroke recurrence at 12 months in patients with a stroke due to small vessel disease		12 months
Secondary	Early neurological improvement	NIHSS_24hour - NIHSS_baseline (NIHSS National Institutes of Health Stroke Scale)	24 (+/- 8) hours
Secondary	Change in body weight (kg)	90 days - baseline	90 (+/- 14) days
Secondary	Change in fasting plasma glucose	90 days - baseline	90 (+/- 14) days
Secondary	Change in body mass index (BMI)	90 days - baseline	90 (+/- 14) days
Secondary	Change in waist circumference	90 days - baseline	90 (+/- 14) days
Secondary	Difference in HbA1c	90 days - baseline	90 (+/- 14) days
Secondary	Diabetes diagnosis and/or antidiabetic medication	Diagnosed with and/or started antidiabetic medication within 1 year of enrollment	12 months
Secondary	Blood pressure, 90 days	Systolic and diastolic blood pressure (90 days BP - discharge BP)	90 (+/- 14) days

External Links

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