Alzheimer DiseaseNCT07230158
Transcranial Alternating Current Stimulation for Patients With Mild Alzheimer's Disease II (TRANSFORM-AD II)
A study testing transcranial alternating current stimulation in people with Alzheimer Disease, run by Xuanwu Hospital, Beijing at 1 site in China.
Trial summary
The goal of this study is to explore the efficacy and safety of transcranial alternating current stimulation (tACS) in patients with amnestic mild cognitive impairment due to Alzheimer's disease (AD-aMCI) and patients with mild Alzheimer's disease dementia (AD-MD). Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- transcranial alternating current stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteChina
- Study dates
- 30 Nov 2025to 1 Dec 2027
- 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 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 50-90 years, either inpatients or outpatients;
- Meeting the NIA-AA clinical diagnostic criteria established by the 2018 National Institute on Aging and Alzheimer's Association (NIA-AA) group for AD-related amnestic mild cognitive impairment (a-MCI) or AD-related mild dementia;
- Neuropsychological evaluation with MMSE score of 18-26 and CDR score of 0.5 or 1;
- Positive amyloid PET, or decreased amyloid levels in cerebrospinal fluid, or elevated serum phosphorylated Tau217 protein;
- Able to communicate proficiently in Chinese (non-illiterate);
- If currently receiving cholinesterase inhibitor treatment (such as donepezil or rivastigmine), the current treatment dose must be stable (i.e., fixed dose for at least 6 consecutive weeks), with no planned dose adjustments during the study observation period;
- Signed informed consent form.
Who cannot join
- Sudden onset;
- Early focal neurological manifestations or extrapyramidal manifestations;
- Systemic diseases that may cause cognitive impairment (such as liver or kidney insufficiency, endocrine diseases, or vitamin deficiency), or neurological diseases such as brain trauma, epilepsy, encephalitis, or normal pressure hydrocephalus;
- Meeting DSM-IV criteria for depression or schizophrenia;
- Ongoing drug treatments that may affect baseline or follow-up assessments;
- Contraindications for MRI or neurophysiological examinations, such as cardiac pacemakers, cardiac defibrillators, implanted electronic systems, vascular clips, mechanical heart valves, or cochlear implants;
- Cranial MRI showing ischemic lesions meeting NINCDS-AIREN criteria.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Xuanwu Hospital, Capital Medical University
Beijing, Beijing Municipality, 100053
Yi Tang, M.D., Ph.D., 00861083199456, tangyixw@vip.163.com
Yi Xing, M.D., 008613269627589, xingyi_211@163.com
About this study
Official title: The Effects of TRanscranial AlterNating Current Stimulation FOR Patients With Mild Alzheimer's Disease II (TRANSFORM-AD II Study): A Randomized Controlled Clinical Trial
The goal of this study is to explore the efficacy and safety of transcranial alternating current stimulation (tACS) in patients with amnestic mild cognitive impairment due to Alzheimer's disease (AD-aMCI) and patients with mild Alzheimer's disease dementia (AD-MD). The study will recruit 160 individuals with mild cognitive impairment with evidence of amyloid plaques in the brain through Positron Emission Tomography (PET) imaging. Participants will undergo baseline cognitive assessment, structural and functional MRI characterization, PiB-PET, and EEG measurement. The participants will be randomized to either a tACS group or a sham stimulation group. At the end of the intervention, all subjects will repeat the baseline assessments.
Read the detailed description
Background In our previous study, we applied 40 Hz transcranial alternating current stimulation (tACS) to patients with mild Alzheimer's disease (AD), and the results demonstrated significant improvements in cognitive function. Building upon these findings, the present study applies a combined high-gamma (77.5 Hz) and low-gamma (40 Hz) tACS protocol to target patients with amnestic mild cognitive impairment due to Alzheimer's disease (AD-aMCI) and those with mild Alzheimer's disease dementia (AD-MD). This dual-frequency stimulation aims to enhance cognitive performance through synergistic gamma-band modulation and to explore its underlying therapeutic mechanisms.
Methods The TRANSFORM-AD II trial is a double-blind, randomized controlled study that will enroll 160 participants diagnosed with AD-aMCI or AD-MD. Eligible participants must meet at least one of the following criteria: positive amyloid positron emission tomography (PET), decreased cerebrospinal fluid (CSF) amyloid-β levels, or elevated plasma phosphorylated tau 217 (p-Tau217) levels. Participants will be randomly assigned to either the active stimulation group (77.5 Hz + 40 Hz tACS) or the sham stimulation group. Both groups will receive 60 one-hour sessions over an 8-week period. Outcome measures will be assessed at baseline and immediately after the intervention.
The primary outcome is global cognitive function, measured using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 13).
Secondary outcomes include changes in other neuropsychological test scores, multimodal magnetic resonance imaging (MRI) metrics, and resting-state as well as task-related electroencephalography (EEG) indicators.
Results This trial is currently ongoing, with recruitment expected to be completed by June 2026.
Conclusion This study will evaluate the efficacy and safety of combined 77.5 Hz and 40 Hz tACS in patients with AD-related aMCI and mild AD dementia. Furthermore, it will investigate potential therapeutic mechanisms using multimodal MRI to assess brain structure and function, and EEG to characterize both resting-state and task-related neural activity patterns.
- Conditions
- Alzheimer Disease
- Being tested
- sham stimulation, transcranial alternating current stimulation
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sham stimulationDevice
Electrodes will also be placed on the patient's forehead and behind both ears. The sham stimulator is identical in appearance to the true stimulator. Neither participants nor operators can distinguish whether the stimulator is real based on its appearance or the patient's sensations. However, when the device is activated, no current flows through the electrodes. Participants in this group will receive sham stimulation with 60 one-hour sessions within 8 weeks.
transcranial alternating current stimulationDevice
The alternating current is delivered through medical-grade conductive electrode pads manufactured specifically for Nexalin technology. The electrode pads are placed on the forehead and behind both ears, and are connected to the Nexalin device with thin cables. The intervention will be conducted with a tACS device: 50 minutes of high-gamma frequency (77.5 Hz) combined with 10 minutes of low-gamma frequency (40 Hz), with a peak-to-peak amplitude of 15 mA. A total of 60 one-hour sessions will be completed within 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| tACS stimulation group | Experimental | NEXALIN ADI transcranial alternating current stimulator Receives: Device: transcranial alternating current stimulation |
| sham stimulation group | Sham comparator | Sham stimulator provided by NEXALIN company Receives: Device: sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 13-items version).
ADAS-cog 13 scale ranges from 0 to 85, and higher value represents a worse outcome. This study will use ADAS-cog to assess changes in the global cognitive function after intervention.
Measured: up to 8 weeks (end of intervention)
Secondary outcomes (15)
Change in MRI brain connectivity
Functional MRI and DTI will be used to measure the connectivity of different ROIs, and the intervention effect will be evaluated by assessing changes in connectivity indicators before and after the intervention.
Measured: up to 8 weeks (end of intervention)
Temporal lobe cross-frequency coupling dynamics and intervention effects
This study aims to evaluate the dynamic changes in cross-frequency coupling (CFC) indices within the temporal lobe across different time points following intervention. By analyzing phase-amplitude coupling between distinct frequency bands, the study seeks to characterize alterations in α-γ and θ-γ coupling patterns in individuals with migraine and epilepsy. The findings will help elucidate the role of temporal lobe functional connectivity in disease progression and in the modulation of non-pain symptoms.
Measured: Up to 8 weeks (end of intervention)
Changes in brain volume and brain function
Structural and functional MRI will be used to measure brain structure and brain function
Measured: up to 8 weeks (end of intervention)
Change in Mini-mental State Examination
Mini-mental State Examination (MMSE) will be used to evaluate the general cognitive function. MMSE ranges from 0 to 30, and higher value represents a better outcome.
Measured: up to 8 weeks (end of intervention)
Change in Montreal Cognitive Assessment
Montreal Cognitive Assessment (MoCA) will be used to evaluate the general cognitive function. MoCA ranges from 0 to 30, and higher value represents a better outcome.
Measured: up to 8 weeks (end of intervention)
Change in Clinical Dementia Rating Scale sum of the boxes
Clinical Dementia Rating Scale sum of the boxes (CDR-SB) will be used to evaluate the general cognitive function. CDR-SB ranges from 0 to 18, and higher value represents a worse outcome.
Measured: up to 8 weeks (end of intervention)
Change in memory function
WHO-UCLA Auditory Verbal Learning Test will be used to assess memory function. It ranges from 0 to 45, and higher values represent better outcomes. In addition, task-related EEG will be conducted during memory tasks to further evaluate memory-related neural activity.
Measured: up to 8 weeks (end of intervention)
Change in Digit span forward
Digit span will be used to assess attention. It ranges from 3 to 10, and higher value represents a better outcome.
Measured: up to 8 weeks (end of intervention)
Change in Digit span backward
Digit span backward will be used to assess executive function. It ranges from 2 to 8, and higher value represents a better outcome.
Measured: up to 8 weeks (end of intervention)
Change in Trail Making Test
Trail-Making Test B minus A score will be used to assess executive function. Trail-Making Test B minus A ranges from -150 to 300, higher value represents a worse outcome.
Measured: up to 8 weeks (end of intervention)
Change in Boston Naming Test
Boston Naming Test will be used to assess language function. It ranges from 0 to 30, and higher value represents a better outcome.
Measured: up to 8 weeks (end of intervention)
Change in Neuropsychiatric Inventory (NPI)
The Neuropsychiatric Inventory will be used to measure neuropsychiatric symptoms. It ranges from 0 to 144, and higher value represents a worse outcome.
Measured: up to 8 weeks (end of intervention)
Change in Geriatric Depression Scale (GDS)
The Geriatric Depression Scale will be used to measure neuropsychiatric symptoms. It ranges from 0 to 30, and higher value represents a worse outcome.
Measured: up to 8 weeks (end of intervention)
Change in Activities of Daily Living
Activities of Daily Living (ADL) scale will be used to assess the change of life quality. It ranges from 20 to 80. The "20" represents normal life ability and the higher score presents the worse life ability.
Measured: up to 8 weeks (end of intervention)
Side-effects of tACS
Adverse Events as a result of tACS stimulation will be reported.
Measured: up to 8 weeks (end of intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2025
- Study start30 Nov 2025 (estimated)
- Primary completion1 Sep 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Xuanwu Hospital, BeijingThe sponsor's other registered studies.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xuanwu Hospital, Beijing
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing Geriatric Hospital, The First Affiliated Hospital of Zhengzhou University, First Affiliated Hospital of Chongqing Medical University, The Fifth People's Hospital of Datong
- Responsible party
- Sponsor
- Investigators
- Yi Tang, M.D., Ph.D., Principal investigator, Xuanwu Hospital, Beijing
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07230158
- Sponsor's protocol ID
- 2023173
- Status last verified
- Nov 2025
- First submitted
- 21 Sep 2025
- Last updated
- 17 Nov 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study Protocol, Statistical Analysis Plan (SAP), Informed Consent Form (ICF), Clinical Study Report (CSR), Analytic Code
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of TRanscranial AlterNating Current Stimulation FOR Patients With Mild Alzheimer's Disease II (TRANSFORM-AD II Study): A Randomized Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT07230158
- Acronym / sponsor ID
- 2023173
- Conditions
- Alzheimer Disease
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Xuanwu Hospital, BeijingUniversity, hospital or other
- Collaborators
- Beijing Geriatric Hospital, The First Affiliated Hospital of Zhengzhou University, First Affiliated Hospital of Chongqing Medical University, The Fifth People's Hospital of Datong
- Study start
- 30 Nov 2025 (estimated)
- Primary completion
- 1 Sep 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 17 Nov 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 study is to explore the efficacy and safety of transcranial alternating current stimulation (tACS) in patients with amnestic mild cognitive impairment due to Alzheimer's disease (AD-aMCI) and patients with mild Alzheimer's disease dementia (AD-MD). The study will recruit 160 individuals with mild cognitive impairment with evidence of amyloid plaques in the brain through Positron Emission Tomography (PET) imaging. Participants will undergo baseline cognitive assessment, structural and functional MRI characterization, PiB-PET, and EEG measurement. The participants will be randomized to either a tACS group or a sham stimulation group. At the end of the intervention, all subjects will repeat the baseline assessments.
Detailed description
Background In our previous study, we applied 40 Hz transcranial alternating current stimulation (tACS) to patients with mild Alzheimer's disease (AD), and the results demonstrated significant improvements in cognitive function. Building upon these findings, the present study applies a combined high-gamma (77.5 Hz) and low-gamma (40 Hz) tACS protocol to target patients with amnestic mild cognitive impairment due to Alzheimer's disease (AD-aMCI) and those with mild Alzheimer's disease dementia (AD-MD). This dual-frequency stimulation aims to enhance cognitive performance through synergistic gamma-band modulation and to explore its underlying therapeutic mechanisms.
Methods The TRANSFORM-AD II trial is a double-blind, randomized controlled study that will enroll 160 participants diagnosed with AD-aMCI or AD-MD. Eligible participants must meet at least one of the following criteria: positive amyloid positron emission tomography (PET), decreased cerebrospinal fluid (CSF) amyloid-β levels, or elevated plasma phosphorylated tau 217 (p-Tau217) levels. Participants will be randomly assigned to either the active stimulation group (77.5 Hz + 40 Hz tACS) or the sham stimulation group. Both groups will receive 60 one-hour sessions over an 8-week period. Outcome measures will be assessed at baseline and immediately after the intervention.
The primary outcome is global cognitive function, measured using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 13).
Secondary outcomes include changes in other neuropsychological test scores, multimodal magnetic resonance imaging (MRI) metrics, and resting-state as well as task-related electroencephalography (EEG) indicators.
Results This trial is currently ongoing, with recruitment expected to be completed by June 2026.
Conclusion This study will evaluate the efficacy and safety of combined 77.5 Hz and 40 Hz tACS in patients with AD-related aMCI and mild AD dementia. Furthermore, it will investigate potential therapeutic mechanisms using multimodal MRI to assess brain structure and function, and EEG to characterize both resting-state and task-related neural activity patterns.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| tACS stimulation group | Experimental | Device: transcranial alternating current stimulationNEXALIN ADI transcranial alternating current stimulator |
| sham stimulation group | Sham comparator | Device: sham stimulationSham stimulator provided by NEXALIN company |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients aged 50-90 years, either inpatients or outpatients;
- Meeting the NIA-AA clinical diagnostic criteria established by the 2018 National Institute on Aging and Alzheimer's Association (NIA-AA) group for AD-related amnestic mild cognitive impairment (a-MCI) or AD-related mild dementia;
- Neuropsychological evaluation with MMSE score of 18-26 and CDR score of 0.5 or 1;
- Positive amyloid PET, or decreased amyloid levels in cerebrospinal fluid, or elevated serum phosphorylated Tau217 protein;
- Able to communicate proficiently in Chinese (non-illiterate);
Key exclusion criteria (7 listed)
- Sudden onset;
- Early focal neurological manifestations or extrapyramidal manifestations;
- Systemic diseases that may cause cognitive impairment (such as liver or kidney insufficiency, endocrine diseases, or vitamin deficiency), or neurological diseases such as brain trauma, epilepsy, encephalitis, or normal pressure hydrocephalus;
- Meeting DSM-IV criteria for depression or schizophrenia;
- Ongoing drug treatments that may affect baseline or follow-up assessments;
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 |
|---|---|---|
| sham stimulationElectrodes will also be placed on the patient's forehead and behind both ears. The sham stimulator is identical in appearance to the true stimulator. Neither participants nor operators can distinguish whether the stimulator is real based on its appearance or the patient's sensations. However, when the device is activated, no current flows through the electrodes. Participants in this group will receive sham stimulation with 60 one-hour sessions within 8 weeks. | Device | sham stimulation group |
| transcranial alternating current stimulationThe alternating current is delivered through medical-grade conductive electrode pads manufactured specifically for Nexalin technology. The electrode pads are placed on the forehead and behind both ears, and are connected to the Nexalin device with thin cables. The intervention will be conducted with a tACS device: 50 minutes of high-gamma frequency (77.5 Hz) combined with 10 minutes of low-gamma frequency (40 Hz), with a peak-to-peak amplitude of 15 mA. A total of 60 one-hour sessions will be completed within 8 weeks. | Device | tACS stimulation group |
Primary outcome
Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 13-items version).
Time frame: up to 8 weeks (end of intervention)
ADAS-cog 13 scale ranges from 0 to 85, and higher value represents a worse outcome. This study will use ADAS-cog to assess changes in the global cognitive function after intervention.
15 secondary outcomes
Change in MRI brain connectivity
Time frame: up to 8 weeks (end of intervention)
Temporal lobe cross-frequency coupling dynamics and intervention effects
Time frame: Up to 8 weeks (end of intervention)
Changes in brain volume and brain function
Time frame: up to 8 weeks (end of intervention)
Change in Mini-mental State Examination
Time frame: up to 8 weeks (end of intervention)
Change in Montreal Cognitive Assessment
Time frame: up to 8 weeks (end of intervention)
Change in Clinical Dementia Rating Scale sum of the boxes
Time frame: up to 8 weeks (end of intervention)
Change in memory function
Time frame: up to 8 weeks (end of intervention)
Change in Digit span forward
Time frame: up to 8 weeks (end of intervention)
Change in Digit span backward
Time frame: up to 8 weeks (end of intervention)
Change in Trail Making Test
Time frame: up to 8 weeks (end of intervention)
Change in Boston Naming Test
Time frame: up to 8 weeks (end of intervention)
Change in Neuropsychiatric Inventory (NPI)
Time frame: up to 8 weeks (end of intervention)
Change in Geriatric Depression Scale (GDS)
Time frame: up to 8 weeks (end of intervention)
Change in Activities of Daily Living
Time frame: up to 8 weeks (end of intervention)
Side-effects of tACS
Time frame: up to 8 weeks (end of intervention)
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 17 Nov 2025.
- Individual participant dataSharing planned: Yes. Study Protocol, Statistical Analysis Plan (SAP), Informed Consent Form (ICF), Clinical Study Report (CSR), Analytic Code
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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.
Yi Tang, M.D., Ph.D. principal investigator
Xuanwu Hospital, Beijing
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing transcranial alternating current stimulation in people with Alzheimer Disease, run by Xuanwu Hospital, Beijing 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 7 inclusion and 7 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 17 Nov 2025. 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. 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 Yi Tang, M.D., Ph.D (00861083199456, tangyixw@vip.163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 13-items version). (time frame: up to 8 weeks (end of intervention)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Nov 2025.