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Intracranial ArteriosclerosisPhase 4NCT07605130

Efficacy and Safety Study of Digital Cognitive Training and PCSK9 Inhibitor-Enhanced Lipid-lowering Strategy in Patients With Intracranial Atherosclerotic Stenosis: A 2x2 Factorial, Randomized, Parallel-Group, Multicenter Trial

A Phase 4 study testing Rosuvastatin, Ezetimibe and Recaticimab in people with Intracranial Arteriosclerosis and Cognitive Impairment, run by Peking Union Medical College Hospital at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This study aims to evaluate whether digital cognitive training and/or PCSK9 inhibitor-enhanced lipid-lowering therapy on top of moderate-intensity statin can improve cognitive function in patients with intracranial atherosclerosis (ICAS). Read more about this study

Who is it for?
Ages 55 to 80 years
What is being tested?
Rosuvastatin, Ezetimibe and Recaticimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
440 participants
Where
1 siteChina
Study dates
17 Sep 2026to 31 Jul 2029
Phase
Phase 4
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 55 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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 moderate-intensity statin and PCSK9 inhibitor therapy during the study period
  • Able to cooperate with neuropsychological and multimodal magnetic resonance examinations

Who cannot join

  • Extracranial cervical artery 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
Show all 14Show fewer
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Zijue Wang, MD contact

+86 15901586608

Zijue_wang@163.com

China1 site

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100730

    Zijue Wang, MD, +86 15901586608, Zijue_wang@163.com

Other trials in China

About this study

This study aims to evaluate whether digital cognitive training and/or PCSK9 inhibitor-enhanced lipid-lowering therapy on top of moderate-intensity statin 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 440 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.

Read more

Participants will be randomly assigned to one of four groups in a 2×2 factorial, parallel-group design:

No cognitive training + moderate-intensity statin therapy

Cognitive training + moderate-intensity statin therapy

No cognitive training + moderate-intensity statin plus PCSK9 inhibitor

Cognitive training + moderate-intensity statin plus PCSK9 inhibitor

Cognitive training consists of 30 minutes of tablet-based exercises, 5 days per week for 24 weeks (first 12 weeks as the intensive phase, followed by 12 weeks continuation phase). The PCSK9 inhibitor (Recaticimab) is administered subcutaneously according to the product label, on top of moderate-intensity statin.

The main outcome is change in a composite cognitive score from baseline to 24 weeks. Secondary outcomes include changes in specific cognitive domains, serum LDL-C, 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.

Read the detailed description

This is a national, multicenter, 2×2 factorial, randomized, parallel-group controlled trial with a PROBE design (Prospective, Randomized, Open-label, Blinded Endpoint assessment). The study is conducted in China and is approved by the Institutional Review Board of Peking Union Medical College Hospital.

Background and Rationale:

Intracranial atherosclerotic stenosis (ICAS) is highly prevalent in Asian populations and is associated with both ischemic stroke and vascular cognitive impairment. Chronic hypoperfusion, microemboli, and white matter damage contribute to cognitive decline. While digital cognitive training has shown benefit in mild cognitive impairment, and PCSK9 inhibitors profoundly lower LDL-C and stabilize plaque, no trial has directly tested their combined effect on cognition in ICAS patients. This study aims to fill that gap.

Study Objectives:

Primary Objective A: To evaluate the effect of digital cognitive training versus active control on change from baseline in a composite cognitive Z-score at 24 weeks.

Primary Objective B: To evaluate the effect of adding a PCSK9 inhibitor to moderate-intensity statin therapy versus not adding it on change from baseline in a composite cognitive Z-score at 24 weeks.

Secondary and exploratory objectives include assessing effects on cognitive domains, serum LDL-C, MRI markers, plasma biomarkers, and testing the interaction between the two interventions.

Sample Size:

A total of 440 participants will be enrolled (110 per group, 1:1:1:1). Power calculation assumes a standardized effect size dΔ = 0.30 for the composite cognitive Z-score change, two-sided α = 0.05, power = 80%, and 20% missing primary outcome at week 24. Both marginal comparisons are powered at 80%.

Randomization and Blinding:

Subjects are randomized 1:1:1:1 via an interactive web response system (IWRS), stratified by center and prior stroke/TIA status. Random block sizes are used. The study is open-label for interventions, but outcome assessors (neuropsychological testers, MRI readers) are blinded. Separate blinded and unblinded teams manage assessments and intervention delivery.

Interventions:

Factor A (cognitive training): The intervention group receives 24 weeks of adaptive, multi-domain digital cognitive training (first 12 weeks intensive phase, followed by 12 weeks continuation phase), 30 minutes/day, 5 days/week. The control group receives active control consisting of science popularization and health education push notifications.

Factor B (lipid-lowering): Both groups receive moderate-intensity statin (rosuvastatin 10 mg or atorvastatin 20 mg daily) with optional ezetimibe. The intervention group additionally receives subcutaneous PCSK9 inhibitor (Recaticimab) according to the product label.

Statistical Analysis:

Primary analysis will use a mixed model for repeated measures (MMRM) jointly analyzing the change from baseline in composite cognitive Z-score at weeks 12 and 24. Fixed effects include Factor A, Factor B, visit, A×visit, B×visit, and randomization stratification factors. Factor A and Factor B are tested at two-sided α = 0.05 without fixed sequence. The primary model does not include the A×B interaction term; interaction is assessed in an exploratory model. Intention-to-treat analysis is primary, with per-protocol and sensitivity analyses (including cLDA and MNAR scenarios).

Data Monitoring and Ethics:

The study is monitored by independent clinical research associates. Serious adverse events are reported within 24 hours. Data is collected via EDC. Written informed consent will be obtained from all participants.

Being tested
Rosuvastatin, Ezetimibe, Recaticimab, Digital Cognitive Training, Active Control
Keywords
Cognitive Dysfunction, Cognitive Training, Artificial Intelligence, Computerised Cognitive Training
Medical subject headings
Intracranial Arteriosclerosis, Cognitive Dysfunction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RosuvastatinDrug

    Rosuvastatin 10mg or Atorvastatin 20mg orally once daily, at the moderate-intensity dose, for 24 weeks. Dose may be adjusted for intolerance or safety.

  • EzetimibeDrug

    Ezetimibe 10mg orally once daily, at investigator's discretion, in combination with statin therapy for 24 weeks.

  • RecaticimabDrug

    Recaticimab (PCSK9 inhibitor) subcutaneous injection according to the product label, on top of moderate-intensity statin ± ezetimibe. Total treatment duration 24 weeks.

  • Digital Cognitive TrainingBehavioural

    Also called Computerized Cognitive Training (CCT)

    Tablet-based adaptive cognitive training covering six domains: processing speed, attention, perception, memory, language, and executive function. Participants are instructed to train 30 minutes/day, 5 days/week for 24 weeks (first 12 weeks as the intensive phase, followed by 12 weeks continuation phase). The system adjusts difficulty based on performance.

  • Active ControlBehavioural

    Participants receive science popularization and health education push notifications. Used to control for non-specific effects of study participation and attention.

Study groups in NCT07605130
Study groupRoleWhat they receive
Control groupActive comparatorNo digital cognitive training + moderate-intensity statin only. Participants receive moderate-intensity statin (rosuvastatin 10mg or atorvastatin 20mg daily, with optional ezetimibe 10mg at investigator discretion) for 24 weeks. No digital cognitive training. Instead, they receive science popularization and health education push notifications as active control.
Receives: Drug: Rosuvastatin; Drug: Ezetimibe; Behavioral: Active Control
Lipid-lowering intervention groupExperimentalNo digital cognitive training + moderate-intensity statin plus PCSK9 inhibitor. Participants receive moderate-intensity statin (as in Arm 1) plus subcutaneous PCSK9 inhibitor (Recaticimab) injections according to the product label. No digital cognitive training; they receive the same science popularization and health education push notifications as in Arm 1. Total treatment duration is 24 weeks.
Receives: Drug: Rosuvastatin; Drug: Ezetimibe; Drug: Recaticimab; Behavioral: Active Control
Training intervention groupExperimentalDigital cognitive training + moderate-intensity statin only. Participants receive moderate-intensity statin (as in Arm 1) for 24 weeks. In addition, they undergo 24 weeks of digital cognitive training: adaptive, multi-domain (processing speed, attention, perception, memory, language, executive function) delivered via tablet. The first 12 weeks are the intensive phase, followed by 12 weeks of continuation training. Participants are asked to train 30 minutes/day, 5 days/week. Minimum dose: ≥3 days/week and ≥20 minutes/session or ≥60 minutes/week.
Receives: Drug: Rosuvastatin; Drug: Ezetimibe; Behavioral: Digital Cognitive Training
Combined intervention groupExperimentalDigital cognitive training + moderate-intensity statin plus PCSK9 inhibitor. Participants receive both interventions: moderate-intensity statin plus PCSK9 inhibitor (Recaticimab injections according to the product label as in Arm 3) and 24 weeks of digital cognitive training (same adaptive program as in Arm 2, first 12 weeks intensive phase followed by 12 weeks continuation phase). Total treatment duration is 24 weeks.
Receives: Drug: Rosuvastatin; Drug: Ezetimibe; Drug: Recaticimab; Behavioral: Digital Cognitive Training

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from baseline in composite cognitive Z-score at week 24

    The composite cognitive Z-score is derived from five cognitive domains: memory, executive function, visuospatial ability, attention, and language. Each individual test score is first standardized to a Z-score using normative mean and SD, with direction aligned so that higher scores indicate better function (reaction times are reverse-coded). Domain Z-scores are the equally weighted average of the prespecified core tests within each domain. The overall composite Z-score is the equally weighted average of the five domain Z-scores. The outcome is the change from baseline to week 24, with positive values indicating improvement.

    Measured: Baseline to 24 weeks

Secondary outcomes (6)

  1. Change from baseline in composite cognitive score at week 12

    Same composite Z-score as primary outcome, derived from memory, executive, visuospatial, attention, and language domains. Outcome is change from baseline to week 12.

    Measured: Baseline to 12 weeks

  2. Change from baseline in MoCA total score at week 12 and week 24

    Montreal Cognitive Assessment (MoCA) total score. The MoCA scale ranges from 0 to 30, with higher scores indicating better cognitive function. Outcome is change from baseline at week 12 and week 24.

    Measured: Baseline to 12 weeks and Baseline to 24 weeks

  3. Change from baseline in five cognitive domain Z-scores at week 12 and week 24

    Domain-specific Z-scores for memory, executive function, visuospatial ability, attention, and language. Each domain Z-score is the equally weighted average of prespecified core tests within that domain. Outcome is change from baseline at week 12 and week 24.

    Measured: Baseline to 12 weeks and Baseline to 24 weeks

  4. Change from baseline in whole-brain atherosclerotic burden at week 24

    Whole-brain atherosclerotic burden is assessed by TOF-MRA, summing stenosis scores (0, 1, 2, 3, 4) across 11 intracranial arterial segments (range 0-44, higher indicates greater burden). Outcome is change from baseline to week 24.

    Measured: Baseline to 24 weeks

  5. Change from baseline in plaque burden at the most stenotic site at week 24

    Plaque burden measured by high-resolution MRI (HRMRI) at the most stenotic intracranial artery site. Plaque burden = (vessel wall area - lumen area)/vessel wall area × 100%. Outcome is change from baseline to week 24.

    Measured: Baseline to 24 weeks

  6. Change from baseline in serum LDL-C at week 12 and week 24

    Serum LDL-C levels. Outcome is change from baseline at week 12 and week 24. Higher values indicate worse lipid control.

    Measured: Baseline to 12 weeks and Baseline to 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 May 2026
  2. Study start17 Sep 2026 (estimated)
  3. Primary completion30 Sep 2028 (estimated)
  4. Study completion31 Jul 2029 (estimated)

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Model description
This study used a 2×2 factorial, parallel-group design: Factor A (digital cognitive training: with/without) and Factor B (moderate-intensity statin with/without PCSK9 inhibitor), with a total of 4 groups. Randomization was performed using a centralized randomization system (IWRS) with 1:1:1:1 allocation to four intervention combinations. Stratification factors were limited to the study center and prior stroke/TIA (yes/no), with variable block sizes used to keep allocation concealed.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
440 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07605130
Sponsor's protocol ID
K10526
Status last verified
Sep 2026
First submitted
17 May 2026
Last updated
15 Sep 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No plan to share IPD due to absence of consent for data sharing and institutional policies protecting participant confidentiality.

Publications

  • Giugliano RP, Sabatine MS, Ott BR. Cognitive Function in a Randomized Trial of Evolocumab. N Engl J Med. 2017 Nov 16;377(20):1997. doi: 10.1056/NEJMc1712102. No abstract available.

    PubMed 29141161

  • Tang Y, Xing Y, Zhu Z, He Y, Li F, Yang J, Liu Q, Li F, Teipel SJ, Zhao G, Jia J. The effects of 7-week cognitive training in patients with vascular cognitive impairment, no dementia (the Cog-VACCINE study): A randomized controlled trial. Alzheimers Dement. 2019 May;15(5):605-614. doi: 10.1016/j.jalz.2019.01.009. Epub 2019 Mar 17.

    PubMed 30894299

  • Chapman SB, Aslan S, Spence JS, Hart JJ Jr, Bartz EK, Didehbani N, Keebler MW, Gardner CM, Strain JF, DeFina LF, Lu H. Neural mechanisms of brain plasticity with complex cognitive training in healthy seniors. Cereb Cortex. 2015 Feb;25(2):396-405. doi: 10.1093/cercor/bht234. Epub 2013 Aug 28.

    PubMed 23985135

  • Risk Reduction of Cognitive Decline and Dementia: WHO Guidelines. Geneva: World Health Organization; 2019. Available from http://www.ncbi.nlm.nih.gov/books/NBK542796/

    PubMed 31219687

  • Chan ATC, Ip RTF, Tran JYS, Chan JYC, Tsoi KKF. Computerized cognitive training for memory functions in mild cognitive impairment or dementia: a systematic review and meta-analysis. NPJ Digit Med. 2024 Jan 3;7(1):1. doi: 10.1038/s41746-023-00987-5.

    PubMed 38172429

  • Petersen RC, Lopez O, Armstrong MJ, Getchius TSD, Ganguli M, Gloss D, Gronseth GS, Marson D, Pringsheim T, Day GS, Sager M, Stevens J, Rae-Grant A. Practice guideline update summary: Mild cognitive impairment [RETIRED]: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018 Jan 16;90(3):126-135. doi: 10.1212/WNL.0000000000004826. Epub 2017 Dec 27.

    PubMed 29282327

  • Graessel E, Jank M, Scheerbaum P, Scheuermann JS, Pendergrass A. Individualised computerised cognitive training (iCCT) for community-dwelling people with mild cognitive impairment (MCI): results on cognition in the 6-month intervention period of a randomised controlled trial (MCI-CCT study). BMC Med. 2024 Oct 15;22(1):472. doi: 10.1186/s12916-024-03647-x.

    PubMed 39407328

  • Sabayan B, Goudarzi R, Ji Y, Borhani-Haghighi A, Olson-Bullis BA, Murray AM, Sedaghat S. Intracranial Atherosclerosis Disease Associated With Cognitive Impairment and Dementia: Systematic Review and Meta-Analysis. J Am Heart Assoc. 2023 Nov 21;12(22):e032506. doi: 10.1161/JAHA.123.032506. Epub 2023 Nov 20.

    PubMed 37955546

  • Qureshi AI, Caplan LR. Intracranial atherosclerosis. Lancet. 2014 Mar 15;383(9921):984-98. doi: 10.1016/S0140-6736(13)61088-0. Epub 2013 Sep 2.

    PubMed 24007975

  • Yang WJ, Wong KS, Chen XY. Intracranial Atherosclerosis: From Microscopy to High-Resolution Magnetic Resonance Imaging. J Stroke. 2017 Sep;19(3):249-260. doi: 10.5853/jos.2016.01956. Epub 2017 Sep 6.

    PubMed 28877564

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Rosuvastatin, Ezetimibe and Recaticimab in people with Intracranial Arteriosclerosis and Cognitive Impairment, run by Peking Union Medical College Hospital at 1 site in China.

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 11 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: opening soon, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. 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.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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 Zijue Wang, MD (+86 15901586608, Zijue_wang@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline in composite cognitive Z-score at week 24 (time frame: Baseline to 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07605130, which also lists 10 linked publications.

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 15 Sep 2026.

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