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

NCT07230158 | Not Yet Recruiting

• 1 other identifier: 2023173
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  up to 8 weeks (end of intervention)

Secondary Outcomes (15)

• Change in MRI brain connectivity

  up to 8 weeks (end of intervention)

• Temporal lobe cross-frequency coupling dynamics and intervention effects

  Up to 8 weeks (end of intervention)

• Changes in brain volume and brain function

  up to 8 weeks (end of intervention)

• Change in Mini-mental State Examination

  up to 8 weeks (end of intervention)

• Change in Montreal Cognitive Assessment

  up to 8 weeks (end of intervention)

Study Arms (2)

tACS stimulation group

EXPERIMENTAL

NEXALIN ADI transcranial alternating current stimulator

Device: transcranial alternating current stimulation

sham stimulation group

SHAM COMPARATOR

Sham stimulator provided by NEXALIN company

Device: sham stimulation

Interventions

sham stimulation 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.

sham stimulation group

transcranial alternating current stimulation 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.

tACS stimulation group

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead
• Beijing Geriatric Hospital: collaborator
• The First Affiliated Hospital of Zhengzhou University: collaborator
• First Affiliated Hospital of Chongqing Medical University: collaborator
• The Fifth People's Hospital of Datong: collaborator

Study Sites (1)

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, 100053, China

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Yi Tang, M.D., Ph.D.

  Xuanwu Hospital, Beijing

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yi Tang, M.D., Ph.D

CONTACT

00861083199456; tangyixw@vip.163.com

Yi Xing, M.D.

CONTACT

008613269627589; xingyi_211@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2025
• First Posted: November 17, 2025
• Study Start: November 30, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 2025.9.20-2027.9.20

Locations

CN (1)