The Origin and Role of Thromboembolism in the Pathogenesis of Ischaemic Stroke

NCT05636748 | Recruiting

• 1 other identifier: AC21130
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Ischaemic stroke is usually due to occlusion of a cerebral artery by thrombus. However, it is often difficult to identify the source of thrombus, or to confirm thrombus as a cause of ischaemic stroke. Moreover, it is debated whether thrombosis plays any role in certain types of stroke such as lacunar stroke. In preliminary studies, the investigators have evaluated a novel clinical grade thrombus-specific radiotracer, 18F-GP1, which has a high specificity for the glycoprotein IIb/IIIa receptor on activated platelets. The investigations have demonstrated that 18F-GP1 is highly sensitive to in vivo thrombus formation and demonstrates avid binding to thrombus associated with myocardial infarction, pulmonary embolism and aortic bioprosthesis. This study will use this imaging approach to define the role and origin of thrombus in patients with ischaemic stroke, cryptogenic stroke and lacunar stroke.The investigators will also assess its added clinical value in assessing patients with ischaemic stroke.

Conditions

Stroke; PET; Thrombosis

Outcome Measures

Primary Outcomes (1)

• The primary outcome measure will be the degree and location of platelet activation as determined by the target to background ratio of 18F-GP1.

  < 21 days

Secondary Outcomes (4)

• Measuring the presence of platelet activation in cardio-embolic, artery to artery and in situ arterial thrombosis.

  < 21 days

• Identifying the presence and site of platelet activation in cryptogenic and lacunar strokes.

  < 21 days

• Identifying sites of platelet activation in patients with atrial fibrillation or atrial flutter.

  < 21 days

• Correlation and comparison between platelet activation with excised carotid atheroma in patients referred for carotid endarterectomy.

  < 21 days

Study Arms (1)

Ischaemic Stroke

Diagnostic Test: 18F-GP1 PET/CT; Diagnostic Test: Agitated Contrast Echocardiogram; Diagnostic Test: MRI Head; Diagnostic Test: ECG Monitoring

Interventions

18F-GP1 PET/CT DIAGNOSTIC_TEST

Patient will receive 1 18F-GP1 PET/CT

Ischaemic Stroke

Agitated Contrast Echocardiogram DIAGNOSTIC_TEST

Agitated saline and ultrasound contrast will be performed to assess for intracardiac shunts and left ventricular thrombus.

Ischaemic Stroke

MRI Head DIAGNOSTIC_TEST

Where necessary, if the CT head is normal or the clinical diagnosis of a stroke is not definite, a research MRI head will be undertaken if this has not already been performed as part of standard care.

Ischaemic Stroke

ECG Monitoring DIAGNOSTIC_TEST

All patients who do not have evidence of atrial fibrillation or atrial flutter on their 12-lead ECG will undergo an ECG Holter monitor for up to 7 days. This will be part of their standard care. If this has not been arranged by the usual care team this will be performed as a research procedure.

Ischaemic Stroke

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

120 patients following acute ischaemic stroke

You may qualify if:

• Males and females ≥18 years old
• Diagnoses of acute ischaemic stroke (within 21 days of symptom onset) as per American Heart and Stroke Association guidelines

You may not qualify if:

• Inability or unwillingness to provide informed written consent (ie lack capacity)
• Inability to undergo the scanning protocol including ability to transfer onto the scanner
• Women of child- bearing potential in whom pregnancy cannot be excluded
• Contraindication to PET-CT scanning including estimated glomerular filtration rate \<30 mL/min/1.73 m2
• Participation in the study would result in a delay to carotid endarterectomy surgery
• Known allergy to iodinated contrast or radiotracer
• Severe or significant comorbidity precluding ability to complete study procedures.
• Haemorrhagic stroke
• Contra-indication to Magnetic Resonance imaging for those patients requiring a MRI Head

Sponsors & Collaborators

• University of Edinburgh: lead
• British Heart Foundation: collaborator

Study Sites (1)

Clinical Research Facility

Edinburgh, United Kingdom

RECRUITING

Related Publications (14)

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  PMID: 25104492 BACKGROUND

• Saver JL. Cryptogenic Stroke. N Engl J Med. 2016 Sep 15;375(11):e26. doi: 10.1056/NEJMc1609156. No abstract available.

  PMID: 27626542 BACKGROUND

• Hart RG, Catanese L, Perera KS, Ntaios G, Connolly SJ. Embolic Stroke of Undetermined Source: A Systematic Review and Clinical Update. Stroke. 2017 Apr;48(4):867-872. doi: 10.1161/STROKEAHA.116.016414. Epub 2017 Mar 6.

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• Kim C, Lee JS, Han Y, Chae SY, Jin S, Sung C, Son HJ, Oh SJ, Lee SJ, Oh JS, Cho YP, Kwon TW, Lee DH, Jang S, Kim B, Koglin N, Berndt M, Stephens AW, Moon DH. Glycoprotein IIb/IIIa receptor imaging with 18F-GP1 positron emission tomography for acute venous thromboembolism: an open-label, non-randomized, first-in-human phase 1 study. J Nucl Med. 2018 Jun 29;60(2):244-9. doi: 10.2967/jnumed.118.212084. Online ahead of print.

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• Dweck MR, Jones C, Joshi NV, Fletcher AM, Richardson H, White A, Marsden M, Pessotto R, Clark JC, Wallace WA, Salter DM, McKillop G, van Beek EJ, Boon NA, Rudd JH, Newby DE. Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis. Circulation. 2012 Jan 3;125(1):76-86. doi: 10.1161/CIRCULATIONAHA.111.051052. Epub 2011 Nov 16.

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  PMID: 35033495 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Carotid Endarterectomy samples

MeSH Terms

Conditions

Stroke; Thrombosis

Interventions

Electrocardiography, Ambulatory

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis

Intervention Hierarchy (Ancestors)

Electrocardiography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Monitoring, Ambulatory; Monitoring, Physiologic

Central Study Contacts

Beth Whittington, MD

CONTACT

01312426200; bwhittin@ed.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2022
• First Posted: December 5, 2022
• Study Start: February 28, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: December 2, 2025

Record last verified: 2025-12

Locations

GB (1)