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)
One important mechanism of action of GLP1 RA is the improvement in endothelial function, which may be evaluated by the assessment of cerebral vasodilatory reserve (CVR) in patients with severe ICAD. The investigators believe that GLP1 RA would be beneficial for patients with severe ICAD and lead to an improvement in cerebral vasodilatory reserve (CVR) in patients with severe and recently symptomatic stenosis of intracranial carotid artery (ICA) or middle cerebral artery (MCA). In this open label randomised clinical trial, patients with recently symptomatic and severe stenosis of intracranial carotid artery (ICA) or middle cerebral artery (MCA) with impaired cerebral vasodilatory reserve (CVR) will be included. CVR will be measured with transcranial Doppler (TCD) breath holding index and acetazolamide-challenged single photon emission computed tomography (SPECT). Patients meeting the eligibility criteria would be randomised to receive best medical therapy (according to the international guidelines and institutional practices) or Dulaglutide subcutaneous injection (0.75mg and titrating to 1.5mg, if indicated) once a week, in addition to the best medical therapy. CVR will be measured again at the completion of 1 year. MRI of the brain will be repeated to evaluate any new ischaemic brain lesions. All patients would be followed up for two years for cerebral ischaemic events. The investigators hypothesize that addition of GLP1 RA therapy would lead to a reduction of at least 4 units in CVR on SPECT as compared to best medical therapy.
• 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