Role of GLP1 RA Dulaglutide on Severe Intracranial Atherosclerosis

NCT07282041 | Recruiting Phase 2 DMC

• 1 other identifier: RADIANT01
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stroke, Ischemic; Intracranial Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• To evaluate whether GLP1 RA (Dulaglutide) therapy would improveme cerebral vasodilatory reserve by at least 4 points in patients with severe stenosis of ICA or MCA

  To evaluate whether GLP1 RA (Dulaglutide) therapy would lead to an improvement in cerebral vasodilatory reserve (CVR) by at least 4 points in patients with recently symptomatic and severe stenosis of ICA or MCA.

  within 1 year

Secondary Outcomes (2)

• To evaluate the impact of Dulaglutide on recurrence of cerebral ischaemic event within 1 year.

  within 1year

• To evaluate whether Dulaglutide would reduce MACE within 2 years

  within 2 years

Study Arms (2)

Dulaglutide

EXPERIMENTAL

Study participants would receive standard medical therapy plus Dulaglutide

Drug: Dulaglutide

Standard medical therapy

NO INTERVENTION

Study participants would receive standard medical therapy

Interventions

Dulaglutide DRUG

Study participants would be randomised (1:1) to receive standard medical therapy or Dulaglutide plus standard medical therapy

Dulaglutide

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National University of Singapore: lead

Study Sites (1)

National University Hospital

Singapore, 119228, Singapore

RECRUITING

MeSH Terms

Conditions

Intracranial Arteriosclerosis; Ischemic Stroke

Interventions

dulaglutide

Condition Hierarchy (Ancestors)

Intracranial Arterial Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke

Study Officials

• vijay K sharma, MD

  National University of Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

vijay K sharma, MD

CONTACT

91389555; mdcvks@nus.edu.sg

Lily YH Wong, RN

CONTACT

67724126; lily_wong@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Study end-points would be assessed by independent investigator
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Randomised controlled trial

Study Record Dates

• First Submitted: December 2, 2025
• First Posted: December 15, 2025
• Study Start: December 17, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)