NCT07618481

Brief Summary

This study aims to evaluate the efficacy and safety of non-invasive brain-computer interface (BCI) neuromodulation technique combined with 40Hz audio-visual stimulation on cognitive function in patients with Alzheimer's disease (AD). This is a single-center, randomized, double-blind, sham-controlled trial. A total of 90 participants with Aβ-PET positive AD diagnosed according to NIA-AA criteria will be enrolled and randomly assigned to three groups in a 1:1:1 ratio: (1) 40Hz stimulation group (fixed 40Hz audio-visual stimulation, 60 minutes daily for 6 months), (2) individualized stimulation group (closed-loop BCI with real-time EEG feedback to adjust stimulation parameters, 60 minutes daily for 6 months), and (3) sham stimulation group (inactive stimulation, same duration). The primary outcome is the change in MoCA-B score from baseline to 6 months. Secondary outcomes include changes in cognitive domain-specific assessments (AVLT, STT, DST), multimodal brain imaging, EEG parameters, peripheral blood AD biomarkers, safety, tolerability, and comparison of efficacy between open-loop and closed-loop stimulation.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
90

participants targeted

Target at P50-P75 for not_applicable

Timeline
16mo left

Started May 2026

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress8%
May 2026Oct 2027

Study Start

First participant enrolled

May 1, 2026

Completed
24 days until next milestone

First Submitted

Initial submission to the registry

May 25, 2026

Completed
7 days until next milestone

First Posted

Study publicly available on registry

June 1, 2026

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2027

Last Updated

June 3, 2026

Status Verified

June 1, 2026

Enrollment Period

1.5 years

First QC Date

May 25, 2026

Last Update Submit

June 2, 2026

Conditions

Keywords

Alzheimer's DiseaseNon-Invasive Brain Stimulation

Outcome Measures

Primary Outcomes (1)

  • Change in Montreal Cognitive Assessment - Basic (MoCA-B) Score

    The primary outcome is the change in MoCA-B score from baseline to 6 months. The MoCA-B is a validated cognitive screening tool for assessing global cognitive function. The score ranges from 0 to 30, with higher scores indicating better cognitive function. The change score (ΔMoCA-B) will be calculated as the 6-month score minus the baseline score. Assessments will be performed by trained neuropsychologists who are blinded to group assignment.

    Baseline (pre-treatment) and 6 months (end of treatment)

Secondary Outcomes (10)

  • Change in Auditory Verbal Learning Test (AVLT) Score

    Baseline, 3 months, and 6 months

  • Change in Shape Trails Test (STT-A and STT-B) Score

    Baseline, 3 months, and 6 months

  • Change in Digit Span Test (DST) Score

    Baseline, 3 months, and 6 months

  • Change in Structural MRI Parameters

    Baseline and 6 months

  • Change in Functional MRI (fMRI) Parameters

    Baseline and 6 months

  • +5 more secondary outcomes

Study Arms (3)

40Hz Stimulation Group

EXPERIMENTAL

Fixed 40Hz combined audio-visual stimulation, 60 minutes per day, once daily, for 6 consecutive months.

Device: 40Hz Stimulation Group

Individualized Stimulation Group

EXPERIMENTAL

40Hz combined audio-visual stimulation with EEG-based closed-loop feedback adjustment, 60 minutes per day, once daily, for 6 consecutive months.

Device: Individualized Stimulation Group

Sham Stimulation Group

SHAM COMPARATOR

Identical appearance and operation as the active device, but without effective individualized audio-visual stimulation. Only low-intensity, randomized flashes and audio cues are delivered.

Device: Sham Stimulation Group

Interventions

Participants receive fixed 40Hz combined audio-visual stimulation (visual + auditory) for 60 minutes per day, once daily, for 6 consecutive months. The stimulation parameters are fixed and do not adjust based on EEG feedback.

40Hz Stimulation Group

Participants receive sham stimulation using a device identical in appearance and weight to the active device. The sham device does not output effective individualized audio-visual stimulation; only low-intensity, randomized flashes and audio cues are delivered.

Sham Stimulation Group

Participants receive 40Hz combined audio-visual stimulation (visual + auditory) for 60 minutes per day, once daily, for 6 consecutive months. In addition, the device performs EEG acquisition and closed-loop feedback adjustment based on preset algorithms. This allows individualized, closed-loop neuromodulation.

Individualized Stimulation Group

Eligibility Criteria

Age50 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of Alzheimer's disease according to the NIA-AA 2018 diagnostic criteria.
  • Age between 50 and 80 years, inclusive.
  • Positive Aβ-PET scan result.
  • Has a stable caregiver who can assist with daily stimulation intervention.
  • Chronic medical conditions stable for at least 30 days.
  • Adequate vision and hearing to perform testing (at minimum, ability to perceive light and communicate in daily conversation).
  • Good mobility (able to walk independently or with assistive devices).
  • Willing and able to provide voluntary signed informed consent.

You may not qualify if:

  • History of epilepsy or seizure disorder.
  • Inability to undergo MRI or presence of significant abnormalities on MRI screening.
  • Geriatric Depression Scale (GDS) score \> 6.
  • Current suicidal ideation or suicide attempt within the past 6 months.
  • Other major neurological disorders, including but not limited to: dementia with Lewy bodies, frontotemporal dementia, Huntington's disease, Creutzfeldt-Jakob disease, Down syndrome, or mixed dementia; other neurodegenerative diseases (Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, etc.); history of severe brain infection (meningitis/encephalitis) or multiple concussions; metabolic/systemic diseases causing cognitive impairment (syphilis, vitamin B12 or folate deficiency, etc.).
  • Psychiatric disorders.
  • Severe cardiac disease, chronic liver/kidney/respiratory disease, or uncontrolled diabetes mellitus or thyroid disease.
  • History of drug or alcohol abuse within the past 12 months.
  • Current exposure to anti-Aβ antibody immunotherapies.
  • Current use of memantine within 30 days prior to intervention.
  • Life expectancy \< 24 months.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 2000025, China

RECRUITING

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 2000025, China

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Chief Physician, Chief of Neurology

Study Record Dates

First Submitted

May 25, 2026

First Posted

June 1, 2026

Study Start

May 1, 2026

Primary Completion (Estimated)

October 31, 2027

Study Completion (Estimated)

October 31, 2027

Last Updated

June 3, 2026

Record last verified: 2026-06

Locations