Efficacy and Safety of Temporal Interference Stimulation on Cognitive Function in Patients With Early-Stage Alzheimer's Disease

April 21, 2026 updated by: Shengdi Chen, Ruijin Hospital

A Randomized, Double-Blind, Controlled Trial to Evaluate the Efficacy and Safety of Temporal Interference Stimulation on Cognitive Function in Patients With Early-Stage Alzheimer's Disease

This study aims to investigate the efficacy and safety of a novel non-invasive brain stimulation technique-Temporal Interference Stimulation (TIS)-in patients with early-stage Alzheimer's disease. A total of 40 participants will be randomly assigned to either the TIS group or the sham stimulation group. The intervention will last for 2 weeks, with cognitive and safety assessments at baseline, post-treatment, and 12 weeks after treatment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 2000025
        • Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria：

  1. According to the 2024 NIA-AA Revised Criteria , defined as positivity for at least one Core 1 biomarker:

    • Positive plasma p-tau217 test (positivity defined by clinically validated diagnostic cutoffs provided by the assay manufacturer); or
    • Positive amyloid PET scan; or
    • Abnormal cerebrospinal fluid (CSF) ratios, including p-tau181/Aβ42, t-tau/Aβ42, or Aβ42/40.

    *Reference: Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimers Dement. 2024 Aug;20(8):5143-5169.*

  2. Age between 50 and 75 years, inclusive.
  3. Minimum of 6 years of formal education.
  4. Clinical Dementia Rating (CDR) global score of 0.5 or 1.0.
  5. MMSE≥21.
  6. Stable dosage of cognitive-enhancing medications (e.g., cholinesterase inhibitors and/or memantine) for at least 6 weeks prior to screening.

Exclusion Criteria:

  1. Current or past history of significant neurological disorders other than AD (e.g., epilepsy, stroke, multiple sclerosis), intracranial lesions, neurosurgery, or significant head trauma.
  2. Current use of medications that may substantially impair cognitive function (e.g., anticonvulsants, antipsychotics, benzodiazepines).
  3. Any contraindication for MRI or the stimulation device (e.g., metallic implants, pacemakers, severe claustrophobia).
  4. Significant structural brain abnormalities on MRI (e.g., hydrocephalus, stroke, or severe white matter lesions [Fazekas score ≥ 3]).
  5. Diagnosis of major depression or other active, uncontrolled psychiatric disorders.
  6. Any severe or unstable medical condition that, in the investigator's judgment, could compromise participant safety or study validity (e.g., cardiovascular, renal, hepatic, respiratory, active cancer), or a history of alcohol/substance dependence.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Sham Comparator: Sham Temporal Interference Stimulation
Device: Sham Stimulation

Device: The same NervioX device is used.

Stimulation Parameters:

The device is programmed to deliver a real stimulation (1.0-2.0 mA) for the initial 30 seconds of the session to mimic the initial sensation experienced by the active group.

Subsequently, the current is automatically reduced to 0 mA for the remainder of the 40-minute session.

The device screen continues to display the stimulation as ongoing to maintain the blinding.

The session frequency and total course (5 sessions/week for 2 weeks, 10 sessions total) are identical to the active intervention group.
Experimental: Temporal Interference Stimulation
Device: Temporal Interference Stimulation

Device: The non-invasive brain stimulator NervioX is used to administer Temporal Interference Stimulation (TIS).

Stimulation Parameters:

Frequencies: 2000 Hz and 2005 Hz (resulting in a 5 Hz theta rhythm envelope). Stimulation Intensity: 1.0-2.0 mA (peak current). Stimulation Target: Bilateral hippocampus Session Duration: 40 minutes per session. Treatment Course: 5 sessions per week, for 2 consecutive weeks, totaling 10 sessions.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 11) Score
Time Frame: Baseline, End of treatment (2 weeks)
The ADAS-Cog 11 is a rater-administered scale designed to assess the severity of cognitive dysfunction in Alzheimer's disease. The total score ranges from 0 to 70, with a lower score indicating better cognitive performance. The change from baseline to the end of treatment will be analyzed.
Baseline, End of treatment (2 weeks)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From baseline through study completion (up to 16 weeks)
The number and severity of all AEs and SAEs will be collected and monitored throughout the study to evaluate the safety and tolerability of the intervention.
From baseline through study completion (up to 16 weeks)
Change in Functional Connectivity measured by Resting-state Functional Magnetic Resonance Imaging (rs-fMRI)
Time Frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
Changes in brain network connectivity (e.g., within the default mode network and hippocampal connectivity) will be assessed using rs-fMRI.
Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
Change in Theta Band Power measured by Electroencephalography (EEG)
Time Frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
Changes in neural oscillatory activity will be assessed using high-density EEG.
Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
Change in Mini-Mental State Examination (MMSE) Score
Time Frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
The MMSE is a brief 30-point questionnaire used to screen for cognitive impairment. The total score ranges from 0 to 30, with a higher score indicating better cognitive function.
Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
Change in Montreal Cognitive Assessment (MoCA) Score
Time Frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
The MoCA is a widely used screening assessment for detecting mild cognitive impairment. The total score ranges from 0 to 30, with a higher score indicating better cognitive function.
Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
Change in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score
Time Frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
The CDR-SB is a numeric scale derived from the CDR global score, which provides a more detailed assessment of cognitive and functional performance across six domains. The total score ranges from 0 to 18, with a higher score indicating greater severity of dementia.
Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
Change in Shape Trails Test (STT) - Part A Time
Time Frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
The STT-A measures visual attention and processing speed. The time in seconds to complete the task is recorded, with a shorter time indicating better performance. This is a continuous measure without a predefined minimum/maximum range.
Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
Change in Shape Trails Test (STT) - Part B Time
Time Frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
The STT-B measures executive function, including task-switching and cognitive flexibility. The time in seconds to complete the task is recorded, with a shorter time indicating better performance. This is a continuous measure without a predefined minimum/maximum range.
Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
Change in Digit Span Test (DST) Score
Time Frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)
The DST is a component of cognitive tests that assesses attention and working memory. It includes forward span (attention) and backward span (working memory). The forward span typically ranges from 0 to 16, and the backward span from 0 to 14, with a higher number of correct sequences indicating better function.
Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ruijin 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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 14, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 14, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 21, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 24, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 21, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2025-621

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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