Dulaglutide for improving blood flow in severe intracranial artery narrowing

Role of Glucagon-like Peptide 1 Receptor Agonist (GLP1 RA) Dulaglutide on Cerebral Hemodynamics In Patients With Severe and symptomAtic steNosis of inTracranial Internal Carotid Artery or Middle Cerebral Artery With Impaired Cerebral Vasodilatory Reserve- an Open-label Randomised Clinical Trial (RADIANT)

This trial will test whether dulaglutide can improve cerebral blood flow reserve in adults who recently had a TIA or mild ischemic stroke from severe narrowing of the intracranial carotid or middle cerebral artery.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 130 (estimated)
• Ages: 21 Years to 80 Years
• Sex: All
• Sponsor: National University of Singapore (Academic / other)
• Locations: 1 site (Singapore)
• Trial ID: NCT07282041 on ClinicalTrials.gov

What this trial studies

This is an open-label, randomized trial comparing dulaglutide plus best medical therapy versus best medical therapy alone in adults with recently symptomatic, severe intracranial carotid or middle cerebral artery stenosis and impaired cerebral vasodilatory reserve (CVR). CVR will be measured using transcranial Doppler breath-holding index and acetazolamide-challenged SPECT imaging at baseline and follow-up. Participants are adults aged 21–80 with TIA or mild stroke within the prior 3 months and modified Rankin Score ≤3. The primary approach tests whether the GLP-1 receptor agonist dulaglutide improves endothelial function and CVR in this high-risk group.

Who should consider this trial

Good fit: Adults 21–80 years old with a recent (within 3 months) TIA or mild ischemic stroke caused by severe intracranial ICA or MCA stenosis, documented impaired CVR, able to consent, and with mRS ≤3 are ideal candidates.

Not a fit: Patients with end-stage kidney disease, recent cancer, atrial fibrillation, a history of pancreatitis or medullary thyroid cancer, those planned for revascularization, or those who cannot stop certain diabetes medications are unlikely to benefit or may be excluded.

Why it matters

Potential benefit: If successful, dulaglutide could improve cerebral vasodilatory reserve and potentially reduce the risk of recurrent ischemic events in patients with severe intracranial atherosclerosis.

How similar studies have performed: Large cardiovascular outcome trials have shown GLP-1 receptor agonists lower major cardiovascular events including nonfatal stroke, but using dulaglutide specifically to improve cerebral vasodilatory reserve in severe intracranial atherosclerosis is a novel application.

Eligibility criteria

Inclusion Criteria:

* Adult patients aged 21 - 80 years old inclusive,
* Able to provide consent,
* Score 3 or less on the Modified Rankin Score (mRS),
* Patients with TIA or mild stroke with severe stenosis of intracranial ICA or MCA and impaired CVR within previous 3-months of acute stroke or TIA

Exclusion Criteria:

* Chronic kidney disease stage 5 (eGFR\<15 mL/min) or on dialysis,
* Cancer diagnosed within past 3 years,
* Currently being planned for coronary or carotid artery revascularization,
* History of previous pancreatitis,
* History of medullary thyroid cancer,
* Atrial fibrillation,
* Any other condition likely to limit protocol compliance (judged by investigator).
* For diabetic patients, patients should not be on Sodium-glucose cotransporter 2 (SGLT2) inhibitor or pioglitazone during the duration of the study, unless these drugs can be stopped without affecting participants' medical condition. For those on Dipeptidyl peptidase-4 (DPP IV) inhibitor, this agent will be discontinued if the patient is randomised to the intervention group.
* Known allergies to Acetazolamide.
* Women who are pregnant or breastfeeding.

Where this trial is running

Singapore

• National University Hospital — Singapore, Singapore (Recruiting)

Study contacts

• Principal investigator: vijay K sharma, MD — National University of Singapore
• Study coordinator: vijay K sharma, MD

Conditions Intracranial Atherosclerosis; Stroke, Ischemic