Transcranial Alternating Current Stimulation for Patients With Mild Alzheimer's Disease II (TRANSFORM-AD II)

NCT ID: NCT07230158

Last Updated: 2025-11-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-11-30

Study Completion Date

2027-12-01

Brief Summary

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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

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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

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Alzheimer Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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tACS stimulation group

NEXALIN ADI transcranial alternating current stimulator

Group Type EXPERIMENTAL

transcranial alternating current stimulation

Intervention Type DEVICE

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.

sham stimulation group

Sham stimulator provided by NEXALIN company

Group Type SHAM_COMPARATOR

sham stimulation

Intervention Type DEVICE

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.

Interventions

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sham stimulation

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.

Intervention Type DEVICE

transcranial alternating current stimulation

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.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. Patients aged 50-90 years, either inpatients or outpatients;
2. 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;
3. Neuropsychological evaluation with MMSE score of 18-26 and CDR score of 0.5 or 1;
4. Positive amyloid PET, or decreased amyloid levels in cerebrospinal fluid, or elevated serum phosphorylated Tau217 protein;
5. Able to communicate proficiently in Chinese (non-illiterate);
6. 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;
7. Signed informed consent form.

Exclusion Criteria

1. Sudden onset;
2. Early focal neurological manifestations or extrapyramidal manifestations;
3. 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;
4. Meeting DSM-IV criteria for depression or schizophrenia;
5. Ongoing drug treatments that may affect baseline or follow-up assessments;
6. Contraindications for MRI or neurophysiological examinations, such as cardiac pacemakers, cardiac defibrillators, implanted electronic systems, vascular clips, mechanical heart valves, or cochlear implants;
7. Cranial MRI showing ischemic lesions meeting NINCDS-AIREN criteria.
Minimum Eligible Age

50 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Beijing Geriatric Hospital

OTHER

Sponsor Role collaborator

The First Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role collaborator

First Affiliated Hospital of Chongqing Medical University

OTHER

Sponsor Role collaborator

The Fifth People's Hospital of Datong

UNKNOWN

Sponsor Role collaborator

Xuanwu Hospital, Beijing

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yi Tang, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Xuanwu Hospital, Beijing

Locations

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Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status

Countries

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China

Central Contacts

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Yi Tang, M.D., Ph.D

Role: CONTACT

00861083199456

Yi Xing, M.D.

Role: CONTACT

008613269627589

Facility Contacts

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Yi Tang, M.D., Ph.D.

Role: primary

00861083199456

Yi Xing, M.D.

Role: backup

008613269627589

Other Identifiers

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2023173

Identifier Type: -

Identifier Source: org_study_id

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