Alzheimer DiseaseNCT07031687
Effects and Mechanisms of Temporal Interference Brain Stimulation on Memory Function in Preclinical Alzheimer's Disease
A study testing Active TIBS in people with Alzheimer Disease, run by Xuanwu Hospital, Beijing at 2 sites in China.
Trial summary
The goal of this clinical trial is to learn if personalized, multimodal imaging-guided, EEG-based closed-loop Temporal Interference Brain Stimulation (TIBS) can improve memory function in individuals with preclinical Alzheimer's Disease (AD). The main questions it aims to answer are: 1. Read more about this study
- Who is it for?
- Ages 60 to 80 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Active TIBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,200 participants
- Where
- 2 sitesChina
- Study dates
- 1 Jul 2025to 31 Dec 2029
- Phase
- Interventional
- 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 60 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals recruited from neurology memory clinics or communities.
- Age between 60 and 80 years old, inclusive; no gender limitation.
- Right-handed.
- Cognitive function test results within normal range after age, gender, and education-level adjustment, OR mild cognitive impairment not yet meeting diagnostic criteria for Mild Cognitive Impairment (MCI), OR only subjective cognitive decline.
- Individuals classified as preclinical AD based on the revised 2024 AD diagnostic and staging criteria (i.e., cognitively normal with positive plasma p-tau217 or positive Aβ PET).
- Full understanding of the study, voluntary participation, and provision of written informed consent approved by the Ethics Committee.
Who cannot join
- Past or present neurological diseases (e.g., stroke, epilepsy, Parkinson's disease, multiple sclerosis).
- Psychiatric disorders such as severe depression or severe anxiety.
- Systemic diseases causing cognitive decline (e.g., severe thyroid dysfunction, severe liver or kidney disease, severe nutritional deficiencies).
- Currently taking medications that may affect cognitive function (e.g., anticholinergics, benzodiazepines, antipsychotics) that cannot be discontinued or adjusted.
- Other factors leading to cognitive decline that are not AD-related.
- Contraindications for MRI scans, such as claustrophobia, implanted metallic devices (e.g., pacemakers, cochlear implants, aneurysm clips), or history of head injury with retained metal fragments.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Xuanwu Hospital of Capital Medical University
Beijing
Ying Han, PhD, +86 13621011941, hanying@xwh.ccmu.edu.cn
- Recruiting
Hainan university
Sanya, Hainan
Hao Wang, PhD, +86 18512810570, haowang@hainanu.edu.cn
About this study
The goal of this clinical trial is to learn if personalized, multimodal imaging-guided, EEG-based closed-loop Temporal Interference Brain Stimulation (TIBS) can improve memory function in individuals with preclinical Alzheimer's Disease (AD).
The main questions it aims to answer are:
Read more
- Does personalized TIBS lead to significant changes in functional connectivity strength of hippocampal-cortical networks at the end of the 2-week intervention compared to baseline?
- What are the short-term (end of 2-week intervention) and medium-to-long-term (4 weeks and 12 weeks post-intervention) effects of personalized TIBS on episodic and working memory, as well as other cognitive domains in preclinical AD?
- How does personalized TIBS modulate brain activity and connectivity, as measured by EEG power spectra and functional MRI (fMRI) functional connectivity, in preclinical AD?
- What is the safety profile of personalized TIBS in this population?
Researchers will compare participants receiving active personalized TIBS to participants receiving sham (inactive) stimulation to see if TIBS effectively improves memory function and induces neural plasticity.
Participants will:
- Undergo initial screening including neuropsychological assessments and blood p-tau217 testing to identify preclinical AD.
- Receive either active personalized TIBS or sham stimulation daily for 40 minutes, 6 days a week, for 2 weeks.
- Have individualized TIBS parameters (e.g., target localization, intensity) determined using baseline structural MRI and DTI.
- Undergo real-time high-density EEG monitoring during daily stimulation sessions to enable closed-loop adjustment of stimulation parameters.
- Participate in follow-up assessments at the end of the 2-week intervention, and at 4 weeks and 12 weeks post-intervention.
- Receive multimodal imaging (sMRI, rs-fMRI, task-fMRI, DTI) and blood biomarker assessments at various time points.
- Receive Aβ-PET and tau-PET scans, along with comprehensive neuropsychological assessments, at the 12-week follow-up.
- Have their safety continuously monitored throughout the study.
- Conditions
- Alzheimer Disease
- Being tested
- Active TIBS, Sham TIBS
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active TIBSDevice
Participants receive active TIBS targeted at the bilateral hippocampus. Stimulation parameters include a 5 Hz (Theta band) low-frequency modulation envelope, generated by two high-frequency current pairs (e.g., f1=2000 Hz, f2=2005 Hz). Peak-to-peak current intensity for each pair will be 2 mA (or 1 mA per electrode). Stimulation is delivered daily for 40 minutes, 6 days/week, for a total of 2 weeks. Individualized targeting and initial intensity optimization are guided by baseline sMRI and DTI. Real-time high-density EEG monitoring during each daily session (D2-D11) provides feedback on brain activity
Sham TIBSDevice
Participants receive sham stimulation designed to mimic the sensation of active TIBS without therapeutic output. This involves using a sham coil or a device mode with extremely low current intensity (e.g., 0.1-0.2 mA) or brief ramp-up/ramp-down sensations at the beginning and end of sessions, with no effective current delivery during the main stimulation period. The stimulation position and apparent parameters are identical to the active TIBS group to maintain blinding.
| Study group | Role | What they receive |
|---|---|---|
| Personalized Closed-Loop Temporal Interference Brain Stimulation | Experimental | Participants in this arm will receive active TIBS targeted at the bilateral hippocampus. Stimulation parameters include a 5 Hz (Theta band) low-frequency modulation envelope, generated by two high-frequency current pairs (e.g., f1=2000 Hz, f2=2005 Hz). Peak-to-peak current intensity for each pair will be 2 mA (or 1 mA per electrode). Stimulation will be delivered daily for 40 minutes, 6 days/week, for a total of 2 weeks. Individualized targeting and initial intensity optimization will be guided by baseline sMRI and DTI. Real-time high-density EEG monitoring during each daily session (D2-D11) will provide feedback on brain activity (e.g., EEG power spectra, functional connectivity features) to enable closed-loop optimization of transcranial stimulation intensity and phase parameters. Receives: Device: Active TIBS |
| Sham Temporal Interference Brain Stimulation | Sham comparator | Participants in this arm will receive sham stimulation designed to mimic the sensation of active TIBS without therapeutic output. This will involve using a sham coil or a device mode with extremely low current intensity (e.g., 0.1-0.2 mA) or brief ramp-up/ramp-down sensations at the beginning and end of sessions, with no effective current delivery during the main stimulation period. The stimulation position and apparent parameters will be identical to the active TIBS group to maintain blinding. Receives: Device: Sham TIBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in Functional Connectivity Strength of Hippocampal-Cortical Networks
Quantified by resting-state fMRI (rs-fMRI) functional connectivity strength within and between key memory-related networks (e.g., default mode network, hippocampal-cortical network) at the end of the 2-week intervention. Specific metrics will include ALFF, ReHo, FCS, and ACF.
Measured: Baseline, End of 2-week intervention.
Secondary outcomes (13)
Changes from Baseline in Hippocampal Gray Matter Density (sMRI)
Evaluation of changes in hippocampal gray matter density or volume, quantified using structural Magnetic Resonance Imaging (sMRI). This measure assesses the structural integrity and potential atrophy or increase in gray matter in a key brain region associated with memory.
Measured: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in Cortical Thickness (sMRI)
Evaluation of changes in cortical thickness across various brain regions, quantified using structural Magnetic Resonance Imaging (sMRI). This measure assesses the integrity and potential thinning or thickening of the cerebral cortex.
Measured: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in Resting-State Functional Connectivity (fMRI)
Evaluation of changes in resting-state functional connectivity using functional Magnetic Resonance Imaging (fMRI). This assesses the temporal correlations between spontaneous fluctuations in BOLD signals across different brain regions, reflecting synchronized neural activity. Specific brain networks (e.g., Default Mode Network, Salience Network) or seed-based connectivity will be analyzed.
Measured: Baseline, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in White Matter Integrity (DTI)
Evaluation of changes in white matter integrity, assessed using Diffusion Tensor Imaging (DTI). Key metrics to be analyzed include Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD), and Radial Diffusivity (RD), reflecting the directionality and magnitude of water diffusion in white matter tracts.
Measured: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in AD Molecular Pathologies and Blood Biomarkers
Evaluation of brain amyloid-beta (Aβ) deposition via Aβ-PET imaging, brain tau pathology via tau-PET imaging, and dynamic changes in plasma biomarkers (e.g., p-tau217, Aβ42/40 ratio, NfL, GFAP, α-synuclein, BDNF).
Measured: Baseline, 12 weeks post-intervention
Changes from Baseline in Auditory Verbal Learning Test-H (AVLT-H) Score
Measures episodic memory. The Auditory Verbal Learning Test - Delayed Recall (AVLT-H) score typically represents the number of words recalled after a delay.
Full Scale Name: Auditory Verbal Learning Test-H Minimum Value: 0 Maximum Value: Delayed Recall--12; Recognition--24 Higher Scores Mean: Better memory.
Measured: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in n-back Task Performance Score
Measures working memory. Performance on the n-back task is typically measured by accuracy (percentage of correct responses) or the highest 'n' level achieved.
Full Scale Name: n-back Task Performance Minimum Value: 0% accuracy or lowest 'n' level Maximum Value: 100% accuracy or highest 'n' level tested Higher Scores Mean: Better working memory.
Measured: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in Mini-Mental State Examination (MMSE) Score
Measures global cognitive function. Full Scale Name: Mini-Mental State Examination (MMSE) Minimum Value: 0 Maximum Value: 30 Higher Scores Mean: A better global cognitive function.
Measured: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in Montreal Cognitive Assessment - Basic (MoCA-B) Score
Measures global cognitive function. Full Scale Name: Montreal Cognitive Assessment - Basic (MoCA-B) Minimum Value: 0 Maximum Value: 30 Higher Scores Mean: A better global cognitive function.
Measured: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in Verbal Fluency Test Score
Measures language function. The score represents the number of words generated. Full Scale Name: Verbal Fluency Test Minimum Value: 0 Maximum Value: None Higher Scores Mean: A better verbal fluency.
Measured: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in Boston Naming Test (BNT) Score
Measures language function. The score represents the number of words generated. Full Scale Name: Boston Naming Test Minimum Value: 0 Maximum Value: 30 Higher Scores Mean: A better naming ability.
Measured: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in Shape trails test A&B (STT-A&B) Score
Measures visual scanning and motor speed. The score is the time taken to complete the task.
Full Scale Name: Shape trails test Minimum Value: 0 Maximum Value: None Higher Scores Mean: Slower completion time
Measured: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Incidence and Severity of Adverse Events (AEs)
Monitoring and reporting of all adverse events and serious adverse events related to the intervention, including their frequency, severity, and relationship to the study intervention
Measured: through study completion, an average of 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2025
- Study start1 Jul 2025
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 1,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xuanwu Hospital, Beijing
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ying Han, Xuanwu Hospital, Beijing
- Investigators
- Ying Han, PhD, Principal investigator, Xuanwu Hospital of Capital Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07031687
- Sponsor's protocol ID
- TIBS_hanying_0605
- Status last verified
- Aug 2026
- First submitted
- 6 Jun 2025
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lv X, Cheng Z, Wang Q, Gao F, Dai L, Du C, Liu C, Xie Q, Shen Y, Shi J; China Aging and Neurodegenerative Initiative (CANDI) Consortium. High burdens of phosphorylated tau protein and distinct precuneus atrophy in sporadic early-onset Alzheimer's disease. Sci Bull (Beijing). 2023 Nov 30;68(22):2817-2826. doi: 10.1016/j.scib.2023.10.019. Epub 2023 Oct 27.
PubMed 37919158Chen Q, Chen F, Long C, Zhu Y, Jiang Y, Zhu Z, Lu J, Zhang X, Nedelska Z, Hort J, Zhang B. Spatial navigation is associated with subcortical alterations and progression risk in subjective cognitive decline. Alzheimers Res Ther. 2023 Apr 25;15(1):86. doi: 10.1186/s13195-023-01233-6.
PubMed 37098612Zhao K, Wang D, Wang D, Chen P, Wei Y, Tu L, Chen Y, Tang Y, Yao H, Zhou B, Lu J, Wang P, Liao Z, Chen Y, Han Y, Zhang X, Liu Y. Macroscale connectome topographical structure reveals the biomechanisms of brain dysfunction in Alzheimer's disease. Sci Adv. 2024 Oct 11;10(41):eado8837. doi: 10.1126/sciadv.ado8837. Epub 2024 Oct 11.
PubMed 39392880Violante IR, Alania K, Cassara AM, Neufeld E, Acerbo E, Carron R, Williamson A, Kurtin DL, Rhodes E, Hampshire A, Kuster N, Boyden ES, Pascual-Leone A, Grossman N. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci. 2023 Nov;26(11):1994-2004. doi: 10.1038/s41593-023-01456-8. Epub 2023 Oct 19.
PubMed 37857775Vassiliadis P, Beanato E, Popa T, Windel F, Morishita T, Neufeld E, Duque J, Derosiere G, Wessel MJ, Hummel FC. Non-invasive stimulation of the human striatum disrupts reinforcement learning of motor skills. Nat Hum Behav. 2024 Aug;8(8):1581-1598. doi: 10.1038/s41562-024-01901-z. Epub 2024 May 29.
PubMed 38811696Beanato E, Moon HJ, Windel F, Vassiliadis P, Wessel MJ, Popa T, Pauline M, Neufeld E, De Falco E, Gauthier B, Steiner M, Blanke O, Hummel FC. Noninvasive modulation of the hippocampal-entorhinal complex during spatial navigation in humans. Sci Adv. 2024 Nov;10(44):eado4103. doi: 10.1126/sciadv.ado4103. Epub 2024 Oct 30.
PubMed 39475597Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Cassara AM, Neufeld E, Kuster N, Tsai LH, Pascual-Leone A, Boyden ES. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields. Cell. 2017 Jun 1;169(6):1029-1041.e16. doi: 10.1016/j.cell.2017.05.024.
PubMed 28575667Jack CR Jr, Andrews JS, Beach TG, Buracchio T, Dunn B, Graf A, Hansson O, Ho C, Jagust W, McDade E, Molinuevo JL, Okonkwo OC, Pani L, Rafii MS, Scheltens P, Siemers E, Snyder HM, Sperling R, Teunissen CE, Carrillo MC. Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimers Dement. 2024 Aug;20(8):5143-5169. doi: 10.1002/alz.13859. Epub 2024 Jun 27.
PubMed 38934362
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects and Mechanisms of Temporal Interference Brain Stimulation on Memory Function in Preclinical Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT07031687
- Acronym / sponsor ID
- TIBS_hanying_0605
- Conditions
- Alzheimer Disease
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,200 participants (estimated)
- Lead sponsor
- Xuanwu Hospital, BeijingUniversity, hospital or other
- Study start
- 1 Jul 2025 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 22 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn if personalized, multimodal imaging-guided, EEG-based closed-loop Temporal Interference Brain Stimulation (TIBS) can improve memory function in individuals with preclinical Alzheimer's Disease (AD).
The main questions it aims to answer are:
- Does personalized TIBS lead to significant changes in functional connectivity strength of hippocampal-cortical networks at the end of the 2-week intervention compared to baseline?
- What are the short-term (end of 2-week intervention) and medium-to-long-term (4 weeks and 12 weeks post-intervention) effects of personalized TIBS on episodic and working memory, as well as other cognitive domains in preclinical AD?
- How does personalized TIBS modulate brain activity and connectivity, as measured by EEG power spectra and functional MRI (fMRI) functional connectivity, in preclinical AD?
- What is the safety profile of personalized TIBS in this population?
Researchers will compare participants receiving active personalized TIBS to participants receiving sham (inactive) stimulation to see if TIBS effectively improves memory function and induces neural plasticity.
Participants will:
- Undergo initial screening including neuropsychological assessments and blood p-tau217 testing to identify preclinical AD.
- Receive either active personalized TIBS or sham stimulation daily for 40 minutes, 6 days a week, for 2 weeks.
- Have individualized TIBS parameters (e.g., target localization, intensity) determined using baseline structural MRI and DTI.
- Undergo real-time high-density EEG monitoring during daily stimulation sessions to enable closed-loop adjustment of stimulation parameters.
- Participate in follow-up assessments at the end of the 2-week intervention, and at 4 weeks and 12 weeks post-intervention.
- Receive multimodal imaging (sMRI, rs-fMRI, task-fMRI, DTI) and blood biomarker assessments at various time points.
- Receive Aβ-PET and tau-PET scans, along with comprehensive neuropsychological assessments, at the 12-week follow-up.
- Have their safety continuously monitored throughout the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Personalized Closed-Loop Temporal Interference Brain Stimulation | Experimental | Device: Active TIBSParticipants in this arm will receive active TIBS targeted at the bilateral hippocampus. Stimulation parameters include a 5 Hz (Theta band) low-frequency modulation envelope, generated by two high-frequency current pairs (e.g., f1=2000 Hz, f2=2005 Hz). Peak-to-peak current intensity for each pair will be 2 mA (or 1 mA per electrode). Stimulation will be delivered daily for 40 minutes, 6 days/week, for a total of 2 weeks. Individualized targeting and initial intensity optimization will be guided by baseline sMRI and DTI. Real-time high-density EEG monitoring during each daily session (D2-D11) will provide feedback on brain activity (e.g., EEG power spectra, functional connectivity features) to enable closed-loop optimization of transcranial stimulation intensity and phase parameters. |
| Sham Temporal Interference Brain Stimulation | Sham comparator | Device: Sham TIBSParticipants in this arm will receive sham stimulation designed to mimic the sensation of active TIBS without therapeutic output. This will involve using a sham coil or a device mode with extremely low current intensity (e.g., 0.1-0.2 mA) or brief ramp-up/ramp-down sensations at the beginning and end of sessions, with no effective current delivery during the main stimulation period. The stimulation position and apparent parameters will be identical to the active TIBS group to maintain blinding. |
Who may qualify
- Ages
- 60 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Individuals recruited from neurology memory clinics or communities.
- Age between 60 and 80 years old, inclusive; no gender limitation.
- Right-handed.
- Cognitive function test results within normal range after age, gender, and education-level adjustment, OR mild cognitive impairment not yet meeting diagnostic criteria for Mild Cognitive Impairment (MCI), OR only subjective cognitive decline.
- Individuals classified as preclinical AD based on the revised 2024 AD diagnostic and staging criteria (i.e., cognitively normal with positive plasma p-tau217 or positive Aβ PET).
Key exclusion criteria (6 listed)
- Past or present neurological diseases (e.g., stroke, epilepsy, Parkinson's disease, multiple sclerosis).
- Psychiatric disorders such as severe depression or severe anxiety.
- Systemic diseases causing cognitive decline (e.g., severe thyroid dysfunction, severe liver or kidney disease, severe nutritional deficiencies).
- Currently taking medications that may affect cognitive function (e.g., anticholinergics, benzodiazepines, antipsychotics) that cannot be discontinued or adjusted.
- Other factors leading to cognitive decline that are not AD-related.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active TIBSParticipants receive active TIBS targeted at the bilateral hippocampus. Stimulation parameters include a 5 Hz (Theta band) low-frequency modulation envelope, generated by two high-frequency current pairs (e.g., f1=2000 Hz, f2=2005 Hz). Peak-to-peak current intensity for each pair will be 2 mA (or 1 mA per electrode). Stimulation is delivered daily for 40 minutes, 6 days/week, for a total of 2 weeks. Individualized targeting and initial intensity optimization are guided by baseline sMRI and DTI. Real-time high-density EEG monitoring during each daily session (D2-D11) provides feedback on brain activity | Device | Personalized Closed-Loop Temporal Interference Brain Stimulation |
| Sham TIBSParticipants receive sham stimulation designed to mimic the sensation of active TIBS without therapeutic output. This involves using a sham coil or a device mode with extremely low current intensity (e.g., 0.1-0.2 mA) or brief ramp-up/ramp-down sensations at the beginning and end of sessions, with no effective current delivery during the main stimulation period. The stimulation position and apparent parameters are identical to the active TIBS group to maintain blinding. | Device | Sham Temporal Interference Brain Stimulation |
Primary outcome
Change from Baseline in Functional Connectivity Strength of Hippocampal-Cortical Networks
Time frame: Baseline, End of 2-week intervention.
Quantified by resting-state fMRI (rs-fMRI) functional connectivity strength within and between key memory-related networks (e.g., default mode network, hippocampal-cortical network) at the end of the 2-week intervention. Specific metrics will include ALFF, ReHo, FCS, and ACF.
13 secondary outcomes
Changes from Baseline in Hippocampal Gray Matter Density (sMRI)
Time frame: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in Cortical Thickness (sMRI)
Time frame: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in Resting-State Functional Connectivity (fMRI)
Time frame: Baseline, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in White Matter Integrity (DTI)
Time frame: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in AD Molecular Pathologies and Blood Biomarkers
Time frame: Baseline, 12 weeks post-intervention
Changes from Baseline in Auditory Verbal Learning Test-H (AVLT-H) Score
Time frame: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in n-back Task Performance Score
Time frame: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in Mini-Mental State Examination (MMSE) Score
Time frame: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in Montreal Cognitive Assessment - Basic (MoCA-B) Score
Time frame: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in Verbal Fluency Test Score
Time frame: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in Boston Naming Test (BNT) Score
Time frame: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Changes from Baseline in Shape trails test A&B (STT-A&B) Score
Time frame: Baseline, End of 2-week intervention, 4 weeks post-intervention, 12 weeks post-intervention
Incidence and Severity of Adverse Events (AEs)
Time frame: through study completion, an average of 14 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2026.
- Background: PubMed 37919158Lv X, Cheng Z, Wang Q, Gao F, Dai L, Du C, Liu C, Xie Q, Shen Y, Shi J; China Aging and Neurodegenerative Initiative (CANDI) Consortium. High burdens of phosphorylated tau protein and distinct precuneus atrophy in sporadic early-onset Alzheimer's disease. Sci Bull (Beijing). 2023 Nov 30;68(22):2817-2826. doi: 10.1016/j.scib.2023.10.019. Epub 2023 Oct 27.
- Background: PubMed 37098612Chen Q, Chen F, Long C, Zhu Y, Jiang Y, Zhu Z, Lu J, Zhang X, Nedelska Z, Hort J, Zhang B. Spatial navigation is associated with subcortical alterations and progression risk in subjective cognitive decline. Alzheimers Res Ther. 2023 Apr 25;15(1):86. doi: 10.1186/s13195-023-01233-6.
- Background: PubMed 39392880Zhao K, Wang D, Wang D, Chen P, Wei Y, Tu L, Chen Y, Tang Y, Yao H, Zhou B, Lu J, Wang P, Liao Z, Chen Y, Han Y, Zhang X, Liu Y. Macroscale connectome topographical structure reveals the biomechanisms of brain dysfunction in Alzheimer's disease. Sci Adv. 2024 Oct 11;10(41):eado8837. doi: 10.1126/sciadv.ado8837. Epub 2024 Oct 11.
- Background: PubMed 37857775Violante IR, Alania K, Cassara AM, Neufeld E, Acerbo E, Carron R, Williamson A, Kurtin DL, Rhodes E, Hampshire A, Kuster N, Boyden ES, Pascual-Leone A, Grossman N. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci. 2023 Nov;26(11):1994-2004. doi: 10.1038/s41593-023-01456-8. Epub 2023 Oct 19.
- Background: PubMed 38811696Vassiliadis P, Beanato E, Popa T, Windel F, Morishita T, Neufeld E, Duque J, Derosiere G, Wessel MJ, Hummel FC. Non-invasive stimulation of the human striatum disrupts reinforcement learning of motor skills. Nat Hum Behav. 2024 Aug;8(8):1581-1598. doi: 10.1038/s41562-024-01901-z. Epub 2024 May 29.
- Background: PubMed 39475597Beanato E, Moon HJ, Windel F, Vassiliadis P, Wessel MJ, Popa T, Pauline M, Neufeld E, De Falco E, Gauthier B, Steiner M, Blanke O, Hummel FC. Noninvasive modulation of the hippocampal-entorhinal complex during spatial navigation in humans. Sci Adv. 2024 Nov;10(44):eado4103. doi: 10.1126/sciadv.ado4103. Epub 2024 Oct 30.
- Background: PubMed 28575667Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Cassara AM, Neufeld E, Kuster N, Tsai LH, Pascual-Leone A, Boyden ES. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields. Cell. 2017 Jun 1;169(6):1029-1041.e16. doi: 10.1016/j.cell.2017.05.024.
- Background: PubMed 38934362Jack CR Jr, Andrews JS, Beach TG, Buracchio T, Dunn B, Graf A, Hansson O, Ho C, Jagust W, McDade E, Molinuevo JL, Okonkwo OC, Pani L, Rafii MS, Scheltens P, Siemers E, Snyder HM, Sperling R, Teunissen CE, Carrillo MC. Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimers Dement. 2024 Aug;20(8):5143-5169. doi: 10.1002/alz.13859. Epub 2024 Jun 27.
- Individual participant dataSharing planned: No
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Enrolling by invitationPhase 2
Tau PET Outcomes With Anti-amyloid Immunotherapies
Cognitive Impairment, Mild, Dementia, Mild
Active, not recruiting
Primary Care Detection of Cognitive Impairment Leveraging Health & Consumer Technologies in Underserved Communities: The MyCog Trial
Dementia, Cognitive Impairment
RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ying Han, PhD principal investigator
Xuanwu Hospital of Capital Medical University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active TIBS in people with Alzheimer Disease, run by Xuanwu Hospital, Beijing at 2 sites 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 6 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 21 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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 Ying Han, PhD (+86 13621011941, hanying@xwh.ccmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline in Functional Connectivity Strength of Hippocampal-Cortical Networks (time frame: Baseline, End of 2-week intervention.). 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 NCT07031687, which also lists 8 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 21 Aug 2026.