Intracranial Atherosclerosis ICASMILESNCT07791823
Moderate Versus Intensive Lipid-lowering for Events in Asymptomatic Intracranial Stenosis
A study testing Lipid Lowering Treatment in people with Intracranial Atherosclerosis ICAS, run by Woo-Keun Seo at 1 site in South Korea.
Trial summary
It is designed to compare two different strengths of cholesterol-lowering treatment in patients who have narrowing of blood vessels inside the brain (intracranial atherosclerosis) but do not currently have symptoms such as stroke. Read more about this study
- Who is it for?
- Ages 19 to 80 years
- Conditions the study is for
- Intracranial Atherosclerosis ICAS
- What is being tested?
- Lipid Lowering Treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,626 participants
- Where
- 1 siteSouth Korea
- Study dates
- 30 Sep 2026to 30 Sep 2031
- Phase
- Interventional
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 19 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged 19 to 80 years at the time of screening
- Presence of ≥50% stenosis in at least one major intracranial artery confirmed within 12 months prior to randomization by magnetic resonance angiography (MRA), computed tomography angiography (CTA), or conventional cerebral angiography.(Target vessels include: Middle cerebral artery (M1 or M2 segment), Anterior cerebral artery (A1 or A2 segment), Posterior cerebral artery (P1 or P2 segment), Basilar artery, Vertebral artery (V4 segment)) Stenosis severity must be assessed according to the WASID (Warfarin-Aspirin Symptomatic Intracranial Disease) method
- Baseline low-density lipoprotein cholesterol (LDL-C) level of 100-190 mg/dL, or current use of lipid-lowering therapy
- Presence of at least one of the following vascular risk factors:
- Hypertension (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or current use of antihypertensive medication)
- Diabetes mellitus (fasting plasma glucose ≥126 mg/dL or ongoing antidiabetic treatment)
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- Current smoking
- Family history of premature coronary artery disease (onset age <55 years in men or <65 years in women)
- Chronic kidney disease (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m²)
Who cannot join
- Cerebrovascular Pathologies
- Prior history of symptomatic ischemic stroke or transient ischemic attack(TIA)
- Previous cerebrovascular interventions, including intracranial or extracranial stenting or carotid endarterectomy
- History of non-traumatic intracranial hemorrhage (ICH)
- Presence of cerebral aneurysms or arteriovenous malformations (AVM)
- Confirmed diagnosis of Moyamoya disease
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- Cardiovascular Comorbidities
- Unstable angina pectoris or myocardial infarction (MI) within the preceding 6 months
- Advanced heart failure, categorized as NYHA Class III or IV.
- Severe valvular heart disease
- Atrial fibrillation requiring chronic oral anticoagulation (CHA2DS2-VASc score ≥ 2, or persistent/permanent atrial fibrillation)
- Contraindications to Lipid-Lowering Therapy
- Known hypersensitivity to statins or ezetimibe
- History of severe statin-associated muscle symptoms (SAMS), including rhabdomyolysis
- Confirmed familial hypercholesterolemia
- Active hepatic disease within 1 month prior to screening, or serum transaminases (ALT/AST) exceeding 3 times the upper limit of normal (ULN)
- Type 2 diabetes mellitus requiring long-term insulin therapy, or those with established target organ damage (e.g., diabetic nephropathy, proliferative retinopathy, or clinically significant neuropathy), Type 1 diabetes mellitus with a disease duration of 20 years or more
- Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m²
- Women who are currently pregnant or breastfeeding
- Patients currently enrolled in other interventional clinical trials.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site
Samsung Medical Center
Seoul, 06351
Woo-Keun Seo, Ph.D, 82-2-3410-0799, mcastenosis@gmail.com
Seoha Kim, seoha88.kim@samsung.com
About this study
Official title: Effect of Moderate- vs High-Intensity Lipid-Lowering Therapy in Patients With Asymptomatic Intracranial Atherosclerotic Disease: A Multicenter, Prospective, Randomized, Open-Label Trial
It is designed to compare two different strengths of cholesterol-lowering treatment in patients who have narrowing of blood vessels inside the brain (intracranial atherosclerosis) but do not currently have symptoms such as stroke.
The purpose of this study is to find out whether more intensive cholesterol-lowering treatment provides better protection against future vascular events, such as stroke, compared to moderate treatment. Cholesterol, especially LDL cholesterol, is known to contribute to the buildup of plaques in blood vessels, which can lead to serious complications.
Read more
Participants in this study are adults diagnosed with asymptomatic intracranial arterial narrowing. Because they do not yet have symptoms, this study aims to prevent future problems before they occur.
This is a multicenter study, meaning it is conducted at multiple hospitals. It is prospective, so participants are followed over time. It is also randomized, which means participants are assigned by chance (like flipping a coin) into one of two groups. One group receives moderate-intensity cholesterol-lowering therapy, while the other receives high-intensity therapy. The study is open-label, meaning both doctors and patients know which treatment is being given.
Participants will undergo regular follow-up visits during the study. These visits may include blood tests, imaging studies, and clinical assessments to monitor cholesterol levels, blood vessel condition, and overall health. The researchers will track whether participants experience any vascular events, such as stroke or transient ischemic attack (TIA).
The study will also monitor safety. Any side effects or adverse reactions to the medications will be carefully recorded. This ensures that both the effectiveness and safety of the treatments are evaluated.
Read the detailed description
- Background and Rationale Asymptomatic intracranial atherosclerotic stenosis (aICAS) is increasingly recognized as a clinically significant condition associated with an elevated risk of ischemic stroke and systemic vascular events. Despite this, there is a paucity of randomized evidence defining optimal lipid-lowering strategies in this population. Current lipid management guidelines are predominantly informed by studies in symptomatic atherosclerosis or coronary artery disease and may not be directly generalizable to patients with aICAS. This study is designed to test the hypothesis that intensive lipid-lowering therapy targeting LDL70 mg/dL provides superior reduction in vascular events compared with a standard LDL-C target of <100 mg/dL.
- Study Design This study is a multicenter, prospective, randomized, open-label, active-controlled clinical trial. A total of 1,626 participants will be enrolled and randomized in a 1:1 ratio to one of two treatment arms. Randomization will be performed using a centralized web-based system and stratified according to intracranial stenosis burden, baseline statin use, and the presence of diabetes mellitus.
- Intervention Participants assigned to the moderate-intensity group will receive lipid-lowering therapy titrated to achieve and maintain LDL-C levels <100 mg/dL. Participants assigned to the intensive treatment group will receive statin-based therapy with additional lipid-lowering agents as needed to achieve and maintain LDL-C levels <70 mg/dL.
- Follow-up and Assessments The enrollment period is expected to span 2 years. Participants will undergo a core follow-up period of 3 years, with study visits at 3, 12, 24, and 36 months. Extended follow-up will continue annually for up to 7 years.
- Conditions
- Intracranial Atherosclerosis ICAS
- Being tested
- Lipid Lowering Treatment
- Keywords
- AICAS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lipid Lowering TreatmentDrug
Lipid-lowering therapy will be administered using one or more lipid-lowering agents, as clinically appropriate. The type, dosage, and combination of lipid-lowering agents may be selected and adjusted by the treating investigator according to the participant's clinical condition, in accordance with relevant clinical practice guidelines and approved prescribing information.
| Study group | Role | What they receive |
|---|---|---|
| High-Intensity Lipid-Lowering Therapy | Experimental | The group will receive medication to maintain LDL-C levels below 70 mg/dL throughout the study period. There are no restrictions on the type of lipid-lowering agents used; all medications may be appropriately adjusted based on the participant's condition, provided they are administered within the approved dosage and administration guidelines. Receives: Drug: Lipid Lowering Treatment |
| Moderate-Intensity Lipid-Lowering Therapy | Active comparator | The group will receive medication to maintain LDL-C levels below 100 mg/dL throughout the study period. There are no restrictions on the type of lipid-lowering agents used; all medications may be appropriately adjusted based on the participant's condition, provided they are administered within the approved dosage and administration guidelines. Receives: Drug: Lipid Lowering Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of composite cardiovascular events
Cumulative incidence of composite cardiovascular events. The composite cardiovascular and cerebrovascular events are defined as follows:
- Stroke (either ischemic or hemorrhagic)
- Acute Coronary Syndrome (myocardial infarction or unstable angina)
- Vascular Revascularization (cerebrovascular, cardiovascular, peripheral vascular, or aortic)
- Cardiovascular-related death
Measured: From enrollment until 36months
Secondary outcomes (7)
Percentage change in LDL-C (from baseline)
Measured: From enrollment until 36months
Changes in total cholesterol, HDL-C, and triglycerides
Measured: From enrollment until 36months
Proportion of patients achieving target LDL-C
Measured: From enrollment until 36months
Changes in the degree of cerebrovascular stenosis
Measured: From enrollment until 36months
Occurrence of new cerebrovascular stenosis
Measured: From enrollment until 36months
Assessment of quality of life using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire
The EQ-5D-5L descriptive system assesses health status across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 5-level scale from 1 to 5, with 1 indicating no problems and 5 indicating extreme problems or inability to perform the activity. Lower scores indicate better health status.
Measured: From enrollment until 36months
Individual cardiovascular events
- Ischemic stroke
- Hemorrhagic stroke
- Transient Ischemic Attack (TIA)
- Myocardial infarction
- Coronary revascularization (Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting)
- All-cause mortality
Measured: From enrollment until 36months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2026
- Study start30 Sep 2026 (estimated)
- Primary completion30 Sep 2031 (estimated)
- Study completion30 Sep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intracranial Atherosclerosis ICASStudies of the same condition, open and under way.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,626 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Woo-Keun Seo
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Woo-Keun Seo, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07791823
- Sponsor's protocol ID
- SMC IRB 2026-06-082
- Acronym
- MILES
- Status last verified
- Aug 2026
- First submitted
- 6 Aug 2026
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No