Multisensory 40-Hz Stimulation for Alzheimer's Disease

August 6, 2026 updated by: huang yue, Beijing Tiantan Hospital

A Randomized, Sham-Controlled Study of the Safety and Efficacy of Multisensory 40-Hz Stimulation in Patients With Alzheimer's Disease

This study aims to evaluate the safety and preliminary efficacy of combined auditory and visual 40-Hz stimulation in participants with biomarker-confirmed Alzheimer's disease spectrum disorders. A total of 60 participants with mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia will be randomly assigned in a 1:1 ratio to receive either active multisensory 40-Hz stimulation or sham stimulation. The intervention will be administered for 60 minutes once daily for 4 consecutive weeks. Clinical assessments, electroencephalography, multimodal magnetic resonance imaging, and blood biomarkers will be evaluated before and after the intervention. Additional clinical, electroencephalographic, and blood biomarker assessments will be performed at 3 and 6 months after the intervention.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Alzheimer's disease is associated with abnormalities in neural network activity and gamma-frequency oscillations. Preclinical studies suggest that sensory stimulation at 40 Hz may entrain gamma oscillations and influence Alzheimer's disease-related pathological and functional changes.

This single-center, prospective, randomized, sham-controlled study will investigate the safety and preliminary efficacy of combined auditory and visual 40-Hz stimulation in participants with mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia. Eligible participants will have evidence of Alzheimer's disease pathology based on positron emission tomography, cerebrospinal fluid, or blood biomarkers.

Participants will be randomly assigned in a 1:1 ratio to active multisensory 40-Hz stimulation or sham stimulation. Both interventions will be administered for 60 minutes once daily for 4 weeks. Clinical assessments, electroencephalography, multimodal magnetic resonance imaging, and blood biomarkers will be obtained at baseline and after completion of the intervention. Clinical assessments, electroencephalography, and blood biomarkers will also be collected at 3 and 6 months after treatment to assess the durability of treatment effects. Safety will be evaluated through the incidence and severity of adverse events throughout the intervention and follow-up periods.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Jinhui Yin, MD
  • Phone Number: +8619801177703
  • Email: yjh_hw@163.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Provision of written informed consent by the participant or the participant's legally authorized representative.
  2. Age 45 to 75 years, inclusive.
  3. Completion of at least primary school education.
  4. Diagnosis within the Alzheimer's disease spectrum according to the National 5.Institute on Aging and Alzheimer's Association criteria.

Mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia, defined by a Montreal Cognitive Assessment score of ≤24 for participants with middle school education or above, or ≤23 for participants with primary school education, and a Clinical Dementia Rating global score of 0.5 or 1.

6.Evidence of Alzheimer's disease pathology based on a positive positron emission tomography, cerebrospinal fluid, or blood biomarker result.

7.Alzheimer's disease-related medications are expected to remain stable during the study period.

Exclusion Criteria:

  1. Current or previous history of a neurological disorder other than Alzheimer's disease that may affect cognition or study assessments, including epilepsy, stroke, multiple sclerosis, poorly controlled migraine, intracranial injury, previous neurosurgery, or head trauma with residual neurological impairment.
  2. Contraindication to magnetic resonance imaging, electroencephalography, auditory stimulation, visual stimulation, or noninvasive brain stimulation.
  3. Current major depressive disorder or another psychiatric disorder that, in the investigator's judgment, may interfere with study participation or outcome assessment.
  4. Clinically significant structural abnormalities on brain magnetic resonance imaging, including hydrocephalus, stroke, or another structural lesion that may confound study results.
  5. Severe cardiovascular or pulmonary disease.
  6. Cognitive impairment primarily attributable to another disorder, including frontotemporal dementia, dementia with Lewy bodies, Parkinson's disease dementia, or vascular dementia.
  7. Clinically significant suicide risk or a suicide attempt within the previous 12 months.
  8. Behavioral disturbance, including severe aggression, agitation, or impulsivity, that may interfere with adherence to study procedures.
  9. Current or planned treatment with an anti-amyloid monoclonal antibody during the study period.
  10. Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active Multisensory 40-Hz Stimulation
Device: Multisensory 40-Hz Stimulation Device
A device delivering synchronized auditory and visual stimulation at a frequency of 40 Hz. Each intervention session will last 60 minutes and will be administered once daily for 4 consecutive weeks.
Sham Comparator: Sham Multisensory Stimulation
Device: Sham Multisensory Stimulation
The sham device will reproduce the appearance, setup, and duration of the active intervention but will not deliver synchronized 40-Hz auditory and visual stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale Score
Time Frame: Baseline to 1 week after completion of the 4-week intervention
The Alzheimer's Disease Assessment Scale-Cognitive Subscale 11-item version assesses cognitive performance in domains including memory, language, and praxis. Total scores range from 0 to 70, with higher scores indicating greater cognitive impairment. Change from baseline will be calculated as the post-intervention score minus the baseline score.
Baseline to 1 week after completion of the 4-week intervention
Incidence of Treatment-Emergent Adverse Events
Time Frame: From the first intervention session through 6 months after completion of the intervention
Number and proportion of participants experiencing one or more treatment-emergent adverse events from the first intervention session through completion of follow-up. Adverse events will be graded according to the Common Terminology Criteria for Adverse Events, version 5.0.
From the first intervention session through 6 months after completion of the intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Resting-State Electroencephalographic Gamma-Band Power
Time Frame: Baseline to 1 week after completion of the 4-week intervention
Change in resting-state electroencephalographic power within the predefined gamma-frequency band following the intervention. Gamma-band power will be calculated using a prespecified electroencephalographic preprocessing and spectral analysis pipeline.
Baseline to 1 week after completion of the 4-week intervention
Change From Baseline in Montreal Cognitive Assessment Score
Time Frame: Baseline to 1 week after completion of the 4-week intervention
The Montreal Cognitive Assessment evaluates global cognitive function. Total scores range from 0 to 30, with higher scores indicating better cognitive performance.
Baseline to 1 week after completion of the 4-week intervention
Change From Baseline in Plasma Phosphorylated Tau 217 Concentration
Time Frame: Baseline to 1 week after completion of the 4-week intervention
Plasma phosphorylated tau 217 concentration will be measured in fasting blood samples using a prespecified validated assay.
Baseline to 1 week after completion of the 4-week intervention
Glymphatic MRI marker
Time Frame: Baseline to 1 week after completion of the 4-week intervention
The DTI-ALPS index will be calculated from diffusion magnetic resonance imaging as a noninvasive imaging marker related to water diffusivity along perivascular spaces.
Baseline to 1 week after completion of the 4-week intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Tiantan Hospital

Investigators

  • Principal Investigator: Yue Huang, Beijing Tiantan Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

October 30, 2027

Study Completion (Estimated)

October 30, 2027

Study Registration Dates

First Submitted

August 6, 2026

First Submitted That Met QC Criteria

August 6, 2026

First Posted (Actual)

August 11, 2026

Study Record Updates

Last Update Posted (Actual)

August 11, 2026

Last Update Submitted That Met QC Criteria

August 6, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HX-A-2025116

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Deidentified individual participant data underlying the results reported in the primary publication may be shared with qualified researchers upon reasonable request, following approval by the principal investigator and the institutional ethics committee.

IPD Sharing Time Frame

Beginning 12 months after publication of the primary study results and available for 3 years.

IPD Sharing Access Criteria

Requests must include a scientifically sound research proposal and a statistical analysis plan. Data access will require institutional approval and execution of a data use agreement.

IPD Sharing Supporting Information Type

  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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