Intracranial AtherosclerosisNUANCE-ICADNCT06714526
Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy in Symptomatic ICAD
A study testing Point-of-Care CYP2C19 Testing, ticagrelor + aspirin and clopidogrel + aspirin in people with Intracranial Atherosclerosis, run by Sunnybrook Health Sciences Centre at 2 sites in Canada.
Trial summary
Stroke is an important cause of death, disability, and memory problems in adults. The build-up of plaque in arteries inside the brain is known as "intracranial atherosclerotic disease" or "ICAD" for short, and can reduce blood flow in the brain. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Intracranial Atherosclerosis
- What is being tested?
- Point-of-Care CYP2C19 Testing, ticagrelor + aspirin and clopidogrel + aspirin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 2 sitesCanada
- Study dates
- 7 Oct 2025to Aug 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 40 years old, male and female.
- TIA or ischemic stroke secondary to symptomatic atherosclerotic stenosis of 30- 99% involving the intracranial ICA or MCA or posterior circulation arteries as evidenced by CT or MR angiography.
- Index TIA or ischemic stroke event occurred within past 30 days.
- Clinical indication for DAPT for at least 3 months.
Who cannot join
- Any contraindication to DAPT.
- Any contraindication to use of clopidogrel (Plavix) or ticagrelor (Brilinta), such as pregnancy. A pregnancy test will be performed on all women of child-bearing age prior to enrollment in the study.
- Indication for chronic anticoagulation based on guideline recommendations or investigator's judgment (e.g., atrial fibrillation, mechanical heart valve, intracardiac clot, dilated cardiomyopathy, ejection fraction <30%, etc.).
- Intracranial arterial occlusion (i.e. 100% stenosis) responsible for the acute brain ischemia.
- Intracranial arterial stenosis secondary to causes other than atherosclerosis.
- Extracranial carotid disease with a plan for carotid revascularization.
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- Intraluminal thrombus.
- Unstable subdural hematoma within 12 months of randomization not amenable to embolization.
- Previous spontaneous hemorrhagic stroke.
- Traumatic brain hemorrhage within 1 month of randomization.
- Living in a nursing home or requiring daily nursing care or assistance with activities of daily living.
- Intracranial tumor (except meningioma) or any intracranial vascular malformation.
- Life expectancy less than 6 months.
- Enrolment in another study that would conflict with the current study.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada2 sites, 2 recruiting
- Not yet recruiting
University of Calgary
Calgary, Alberta
Mohammed Almekhlafi, 413-944-1883, mohammed.almekhlafi1@ucalgary.ca
- Recruiting
Dr. Mark I. Boulos - Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N3M5
Mark I Boulos, MD, MSc, 4164804473, mark.boulos@utoronto.ca
About this study
Official title: Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy in Symptomatic Intracranial Atherosclerotic Disease: A Pilot Prospective, Randomized, Open-label, Blinded-endpoint (PROBE) Multi- Centre Study
Stroke is an important cause of death, disability, and memory problems in adults. The build-up of plaque in arteries inside the brain is known as "intracranial atherosclerotic disease" or "ICAD" for short, and can reduce blood flow in the brain. Clopidogrel is a medicine used to prevent strokes because it stops blood from clotting. However, there are some people who do not get as much benefit from Clopidogrel because of differences in their genes; they have a variation in a certain gene and their body is not able to properly process Clopidogrel. Another medication called Ticagrelor can benefit people who have this genetic variation. The study investigators will randomize patients who have had a stroke due to ICAD to receive genetic testing, or standard of care. The standard-of-care group will take Clopidogrel for 90 days. The genetic testing group will complete a genetic test to see if they can properly process Clopidogrel. Depending on the results of the genetic test, patients will either take Clopidogrel or Ticagrelor for 90 days. All patients will have a brain scan at baseline and 90 days to see if they had any new strokes. Patients will also complete tests and questionnaires about function and memory at baseline and 90 days. This study will be one of the first to see if it is feasible and safe to use genetic testing to help choose medications for patients who have had a stroke. This will help the study investigators design a larger study that can test if genetic testing in stroke patients reduces future stroke risk and improves health outcomes.
- Conditions
- Intracranial Atherosclerosis
- Being tested
- Point-of-Care CYP2C19 Testing, ticagrelor + aspirin, clopidogrel + aspirin
- Medical subject headings
- Intracranial Arteriosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Point-of-Care CYP2C19 TestingGenetic
Genetic testing with the Genomadix cube to determine P2Y12 inhibitor
ticagrelor + aspirinDrug
If patients are poor or intermediate metabolizers of clopidogrel, they will receive ticagrelor (90 mg PO BID) + aspirin (81 mg PO daily)
clopidogrel + aspirinDrug
Normal, rapid, and ultra-rapid metabolizers of clopidogrel will receive 75 mg PO daily of clopidogrel and 81 mg PO daily of aspirin.
| Study group | Role | What they receive |
|---|---|---|
| Point-of-Care CYP2C19 Testing | Experimental | Patients will undergo point-of-care CYP2C19 testing with the Research Use Only (RUO) Genomadix Cube to inform the choice of P2Y12 inhibitor (i.e. clopidogrel vs ticagrelor). Receives: Genetic: Point-of-Care CYP2C19 Testing; Drug: ticagrelor + aspirin; Drug: clopidogrel + aspirin |
| Standard of Care | No intervention | Patients will receive standard-of-care ASA + clopidogrel. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of recruitment
The number of patients who provide informed consent, or are deemed ineligible after screening.
Measured: Through study completion, an average of 90 days
Rate of study completion
The number of patients who complete the entire study protocol
Measured: Through study completion, an average of 90 days
Rate of protocol deviations
The number of patients who encounter at least one protocol deviation during the study
Measured: Through study completion, an average of 90 days
Proportion of patients with Symptomatic intracerebral hemorrhage (ICH)
New symptomatic ICH OR worsening existing ICH with a ≥33% increase in hematoma volume AND NIHSS score increase of ≥4 points AND clinical change is thought to be attributable to ICH
Measured: Through study completion, an average of 90 days
Proportion of patients with major extracranial bleeding
Bleeding in a critical area or organ, including intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, intramuscular with compartment syndrome, and/or bleeding causing a drop in hemoglobulin by 20g/L or more
Measured: Through study completion, an average of 90 days
Proportion of patients with non-bleeding adverse events
Non-bleeding adverse events related to the study drug including dyspnea, bradyarrhythmia, and/or chest pain
Measured: Through study completion, an average of 90 days
Secondary outcomes (10)
Proportion of patients who have Microembolic Signals on Transcranial Doppler Ultrasound
Measured: Day 5 ± 2
Change in volume of ischemic strokes and white matter hyperintensities (optional)
Measured: Day 0 + 14 and Day 90 ± 14
Change in number of ischemic strokes and white matter hyperintensities
Measured: Day 0 + 3 and Day 90 ± 14
Number of patients with ischemic stroke, myocardial infarction, or death
Measured: Day 90 ± 14
Change in Montreal Cognitive Assessment (MoCA) score from baseline to follow-up
To MoCA is a validated cognitive screening tool. Possible scores range from 0 (worst score) to 31 (best score). Change = Follow-up - baseline.
Measured: Day 0 and Day 90 ± 14
Change in NIH Stroke Scale (NIHSS) score from baseline to follow-up
This scale is a 15 item tool used to quantify stroke severity. Scores range from 0 (no stroke) to 42 (most severe stroke). Change = Follow-up - baseline.
Measured: Day 0 and Day 90 ± 14
Change or shift in modified Rankin Scale (mRS) score from baseline to follow-up
The MRS is a single item rating of stroke outcomes. Scores range from 0 (no symptoms) to 6 (death). Change = Follow-up - baseline.
Measured: Day 0 and Day 90 ± 14
Self-reported Quality of Life as assessed by the EQ-5D-5L
The EQ-5D-5L questionnaire has 5 dimensions: Mobility, Self-Care, Usual Activity, Pain/Discomfort, Anxiety/Depression, with each dimension rated on a level from 1-5 where higher scores indicate more severe problems.
Measured: Day 90 ± 14
Self-reported Dementia Screening assessed by the AD8 Dementia Screening Interview
The AD8 Dementia Screening Interview has 8 questions that ask if there has been a change in the last several years caused by cognitive (thinking and memory) problems. The score is the sum of all items marked "Yes, A change".
Measured: Day 90 ± 14
Self-reported functional status assessed by the Lawton-Brody Instrumental Activities of Daily Living Scale
The Lawton-Brody Instrumental Activities of Daily Living Scale has 8 categories where participants can rate their functional level. Scores range from 0 (low function, dependent) to 8 (high function, independent).
Measured: Day 90 ± 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2024
- Study start7 Oct 2025
- Primary completionAug 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intracranial AtherosclerosisStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark I Boulos, MD, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06714526
- Sponsor's protocol ID
- 5902
- Acronym
- NUANCE-ICAD
- Status last verified
- Oct 2025
- First submitted
- 25 Nov 2024
- Last updated
- 20 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy in Symptomatic Intracranial Atherosclerotic Disease: A Pilot Prospective, Randomized, Open-label, Blinded-endpoint (PROBE) Multi- Centre Study
- ClinicalTrials.gov ID
- NCT06714526
- Acronym / sponsor ID
- NUANCE-ICAD / 5902
- Conditions
- Intracranial Atherosclerosis
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 7 Oct 2025 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 3 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Stroke is an important cause of death, disability, and memory problems in adults. The build-up of plaque in arteries inside the brain is known as "intracranial atherosclerotic disease" or "ICAD" for short, and can reduce blood flow in the brain. Clopidogrel is a medicine used to prevent strokes because it stops blood from clotting. However, there are some people who do not get as much benefit from Clopidogrel because of differences in their genes; they have a variation in a certain gene and their body is not able to properly process Clopidogrel. Another medication called Ticagrelor can benefit people who have this genetic variation. The study investigators will randomize patients who have had a stroke due to ICAD to receive genetic testing, or standard of care. The standard-of-care group will take Clopidogrel for 90 days. The genetic testing group will complete a genetic test to see if they can properly process Clopidogrel. Depending on the results of the genetic test, patients will either take Clopidogrel or Ticagrelor for 90 days. All patients will have a brain scan at baseline and 90 days to see if they had any new strokes. Patients will also complete tests and questionnaires about function and memory at baseline and 90 days. This study will be one of the first to see if it is feasible and safe to use genetic testing to help choose medications for patients who have had a stroke. This will help the study investigators design a larger study that can test if genetic testing in stroke patients reduces future stroke risk and improves health outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Point-of-Care CYP2C19 Testing | Experimental | Genetic: Point-of-Care CYP2C19 Testing, Drug: ticagrelor + aspirin, Drug: clopidogrel + aspirinPatients will undergo point-of-care CYP2C19 testing with the Research Use Only (RUO) Genomadix Cube to inform the choice of P2Y12 inhibitor (i.e. clopidogrel vs ticagrelor). |
| Standard of Care | No intervention | –Patients will receive standard-of-care ASA + clopidogrel. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 40 years old, male and female.
- TIA or ischemic stroke secondary to symptomatic atherosclerotic stenosis of 30- 99% involving the intracranial ICA or MCA or posterior circulation arteries as evidenced by CT or MR angiography.
- Index TIA or ischemic stroke event occurred within past 30 days.
- Clinical indication for DAPT for at least 3 months.
Key exclusion criteria (14 listed)
- Any contraindication to DAPT.
- Any contraindication to use of clopidogrel (Plavix) or ticagrelor (Brilinta), such as pregnancy. A pregnancy test will be performed on all women of child-bearing age prior to enrollment in the study.
- Indication for chronic anticoagulation based on guideline recommendations or investigator's judgment (e.g., atrial fibrillation, mechanical heart valve, intracardiac clot, dilated cardiomyopathy, ejection fraction <30%, etc.).
- Intracranial arterial occlusion (i.e. 100% stenosis) responsible for the acute brain ischemia.
- Intracranial arterial stenosis secondary to causes other than atherosclerosis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Point-of-Care CYP2C19 TestingGenetic testing with the Genomadix cube to determine P2Y12 inhibitor | Genetic | Point-of-Care CYP2C19 Testing |
| ticagrelor + aspirinIf patients are poor or intermediate metabolizers of clopidogrel, they will receive ticagrelor (90 mg PO BID) + aspirin (81 mg PO daily) | Drug | Point-of-Care CYP2C19 Testing |
| clopidogrel + aspirinNormal, rapid, and ultra-rapid metabolizers of clopidogrel will receive 75 mg PO daily of clopidogrel and 81 mg PO daily of aspirin. | Drug | Point-of-Care CYP2C19 Testing |
Primary outcome
Rate of recruitment
Time frame: Through study completion, an average of 90 days
The number of patients who provide informed consent, or are deemed ineligible after screening.
Rate of study completion
Time frame: Through study completion, an average of 90 days
The number of patients who complete the entire study protocol
Rate of protocol deviations
Time frame: Through study completion, an average of 90 days
The number of patients who encounter at least one protocol deviation during the study
Proportion of patients with Symptomatic intracerebral hemorrhage (ICH)
Time frame: Through study completion, an average of 90 days
New symptomatic ICH OR worsening existing ICH with a ≥33% increase in hematoma volume AND NIHSS score increase of ≥4 points AND clinical change is thought to be attributable to ICH
Proportion of patients with major extracranial bleeding
Time frame: Through study completion, an average of 90 days
Bleeding in a critical area or organ, including intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, intramuscular with compartment syndrome, and/or bleeding causing a drop in hemoglobulin by 20g/L or more
Proportion of patients with non-bleeding adverse events
Time frame: Through study completion, an average of 90 days
Non-bleeding adverse events related to the study drug including dyspnea, bradyarrhythmia, and/or chest pain
10 secondary outcomes
Proportion of patients who have Microembolic Signals on Transcranial Doppler Ultrasound
Time frame: Day 5 ± 2
Change in volume of ischemic strokes and white matter hyperintensities (optional)
Time frame: Day 0 + 14 and Day 90 ± 14
Change in number of ischemic strokes and white matter hyperintensities
Time frame: Day 0 + 3 and Day 90 ± 14
Number of patients with ischemic stroke, myocardial infarction, or death
Time frame: Day 90 ± 14
Change in Montreal Cognitive Assessment (MoCA) score from baseline to follow-up
Time frame: Day 0 and Day 90 ± 14
Change in NIH Stroke Scale (NIHSS) score from baseline to follow-up
Time frame: Day 0 and Day 90 ± 14
Change or shift in modified Rankin Scale (mRS) score from baseline to follow-up
Time frame: Day 0 and Day 90 ± 14
Self-reported Quality of Life as assessed by the EQ-5D-5L
Time frame: Day 90 ± 14
Self-reported Dementia Screening assessed by the AD8 Dementia Screening Interview
Time frame: Day 90 ± 14
Self-reported functional status assessed by the Lawton-Brody Instrumental Activities of Daily Living Scale
Time frame: Day 90 ± 14
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mark I Boulos, MD principal investigator
Sunnybrook Health Sciences Centre
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Point-of-Care CYP2C19 Testing, ticagrelor + aspirin and clopidogrel + aspirin in people with Intracranial Atherosclerosis, run by Sunnybrook Health Sciences Centre at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mark I Boulos, MD (416-480-4473, mark.boulos@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of recruitment (time frame: Through study completion, an average of 90 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2025.