Efficacy and Safety Study of Digital Cognitive Training and PCSK9 Inhibitor-Enhanced Lipid-lowering Strategy in Patients With Intracranial Atherosclerotic Stenosis: A 2×2 Randomized Controlled Trial

Starting soon · Phase 4

Conditions studied: Intracranial Arteriosclerosis, Cognitive Impairment

In brief

This study aims to evaluate whether digital cognitive training and/or intensive lipid-lowering therapy with a PCSK9 inhibitor can improve cognitive function in patients with intracranial atherosclerosis (ICAS). ICAS is a common cause of stroke and is also linked to thinking and memory problems. The study will enroll 420 adults aged 55-80 years who have 50-99% narrowing of an intracranial artery, subjective memory complaints, and LDL cholesterol ≥1.8 mmol/L, but who are not demented. Participants will be randomly assigned to one of four groups in a 2×2 factorial design: 1. No cognitive training + standard statin therapy 2. Cognitive training + standard statin therapy 3. No cognitive training + intensive statin plus PCSK9 inhibitor 4. Cognitive training + intensive statin plus PCSK9 inhibitor Cognitive training consists of 30 minutes of tablet-based exercises, 5 days per week for 12 weeks. The intensive lipid-lowering group receives a PCSK9 inhibitor (Recaticimab) injection at weeks 0, 4, and 12, on top of maximally tolerated statin. The main outcome is change in a composite cognitive score from baseline to 24 weeks. Secondary outcomes include changes in specific cognitive domains, MRI markers of brain structure and function, and safety measures. The study is multicenter, open-label with blinded outcome assessment, and is conducted under the approval of the ethics committee of Peking Union Medical College Hospital.

Key facts

Study ID: NCT07605130
Run by: Peking Union Medical College Hospital
People needed: 420
Starts: 2026-05-25
Expected to finish: 2029-07-31
Last updated by the study team: 2026-05-22

Who can join

Age: 55 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Age 55-80 years old
The number of years of education is greater than or equal to 6 years
50%-99% stenosis of the intracranial artery confirmed by MRA, CTA or DSA
Head CT or MRI confirmed that there were no infarct lesions/softening foci larger than 3 cm in the brain
LDL-C ≥ 1.8mmol/L at baseline
Decline in cognitive function of the complainant
MMSE ≥ 24 points; no severe impairment of daily living and social functioning, and the daily living ability scale (ADL, 14-item BADL and IADL combined version, total score range of 14-56 points) <=18; and the investigator's clinical assessment does not meet the diagnosis of dementia (DSM-V or NIA-AA diagnostic criteria)
Proficient in operating electronic products such as mobile phones and tablets
Complete the operation evaluation through the introduction period (see the definition of the introduction period)
Agree to receive maximally tolerated statin and PCSK9 inhibitor therapy during the study period
Able to cooperate with neuropsychological and multimodal magnetic resonance examinations

You may not qualify if…

Extracranial vascular stenosis ≥ 50%
Acute cerebrovascular events within 90 days
Contraindications to MRI (metal implants in the body, claustrophobia, etc.)
Visual and auditory impairments, as well as communication difficulties, that affect cognitive training
Clinically diagnosed vascular dementia
Neuroimaging showing significant white matter lesions (Fazekas grade 3) or multiple microbleeds
Non-atherosclerotic intracranial artery stenosis (such as vasculitis, moyamoya disease, dissection, etc.)
Neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, etc.)
Severe comorbidities (tumors, multiple sclerosis, severe cardiopulmonary and renal diseases, intracranial aneurysms)
Other diseases that may affect cognition have been ruled out; severe anxiety, depression, or schizophrenia; a new stroke occurring within the 3 months prior to baseline; hereditary or inflammatory small vessel diseases; presence of any of the following clear sources of cardioembolic events: mitral stenosis, mechanical heart valves, endocarditis, intracardiac clots or vegetations, dilated cardiomyopathy, chronic or paroxysmal atrial fibrillation, ejection fraction less than 30%
Planning to use medications that may affect cognitive function within the past 3 months or in the following 24 weeks, including large amounts of sedatives, anti-anxiety drugs, cognitive enhancers, and cholinergic agents.(12) Previously treated with a PCSK9 inhibitor
Having a clear contraindication or severe intolerance to PCSK9 inhibitors or statins (such as a history of severe allergic reactions)
Presence of significant liver or muscle safety abnormalities at baseline, or the investigator deems the patient unsuitable for intensive lipid-lowering therapy (for example, significantly elevated ALT or AST, significantly elevated CK, etc.; the thresholds can be based on the reference ranges of each center's laboratory and specified in the protocol in advance)
Other circumstances deemed inappropriate for enrollment by the investigator

Where it is running

Peking Union Medical College Hospital — Beijing, Beijing Municipality, China

Full record on ClinicalTrials.gov

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