The Effects of TRanscranial AlterNating Current Stimulation FOR Patients With Mild Alzheimer's Disease II (TRANSFORM-AD II Study): A Randomized Controlled Clinical Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Xuanwu Hospital, Beijing
- Enrollment
- 160
- Locations
- 1
- Primary Endpoint
- Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 13-items version).
Study Overview
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.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 50 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
sham stimulation group
Sham stimulator provided by NEXALIN company
Intervention: sham stimulation (Device)
tACS stimulation group
NEXALIN ADI transcranial alternating current stimulator
Intervention: transcranial alternating current stimulation (Device)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- 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))
- Change in Clinical Dementia Rating Scale sum of the boxes(up to 8 weeks (end of intervention))
- Change in memory function(up to 8 weeks (end of intervention))
- Change in Digit span forward(up to 8 weeks (end of intervention))
- Change in Digit span backward(up to 8 weeks (end of intervention))
- Change in Trail Making Test(up to 8 weeks (end of intervention))
- Change in Boston Naming Test(up to 8 weeks (end of intervention))
- Change in Neuropsychiatric Inventory (NPI)(up to 8 weeks (end of intervention))
- Change in Geriatric Depression Scale (GDS)(up to 8 weeks (end of intervention))
- Change in Activities of Daily Living(up to 8 weeks (end of intervention))
- Side-effects of tACS(up to 8 weeks (end of intervention))