The Effects of TRanscranial AlterNating Current Stimulation FOR Patients With Mild Alzheimer's Disease (TRANSFORM-AD Study): A Randomized Controlled Clinical Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Xuanwu Hospital, Beijing
- Enrollment
- 46
- Locations
- 1
- Primary Endpoint
- Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 11-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 mild Alzheimer's disease (AD). The study will recruit 40 individuals with mild AD 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 resting-state EEG measurement. The participants will be randomized to either a tACS group or a sham stimulation group. At the end of the intervention and 3-month follow-up, all subjects will repeat the baseline assessments.
Detailed Description
Background: Alzheimer's disease (AD) is the most prevalent cause of dementia. Given the limited efficacy of pharmacological treatments, non-pharmacological approaches in AD are of great interest. In these approaches, brain stimulation technique is an important one, because of its potential to modulate cognitive functions in many neuropsychiatric diseases. Transcranial alternating current stimulation (tACS), as a neuromodulatory technique, oscillates a sinusoidal current at a chosen frequency to interact with the brain's natural cortical oscillations. Hypothetically, tACS would reduce cortical hyperactivity and induces cognitive improvement or delay cognitive decline in patients with AD.
Objectives This double-blinded, randomized controlled trial evaluates the efficacy and safety of tACS in patients with mild AD. The second objective is to evaluate the effect of tACS on neural plasticity, which is assessed by structural and functional MRI, PiB-PET, and resting-state EEG.
Patients and Methods The proposed study is a double-blinded, randomized controlled trial that will include 40 individuals with mild AD with positive findings in amyloid PET imaging or amyloid protein levels in CSF. The participants will be randomized to either a tACS group or a sham stimulation group. Both groups will undergo 30 one-hour sessions in 3 weeks (21 days). All the outcomes will be assessed at baseline, end of intervention and 3 months after the first intervention to measure long-term resilience of the effect.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 45 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects with informed consent;
- •45-75 years of age;
- •At least 6 years of education;
- •AD according to the National Institute on Aging and the Alzheimer's Association (NIA-AA) guidelines;
- •Clinical Dementia Rating Scale (CDR)=1.0;
- •Positive findings in amyloid PET imaging or decreased CSF levels of Aβ1-42;
- •On a stable dose of cholinesterase inhibitors (e.g. donepezil or rivastigmine) as defined as 6 consecutive weeks of treatment at an unchanging dose, and without any intentions to modify the dosage during the observation period.
Exclusion Criteria
- •Current or past history of any neurological disorder other than dementia, such as epilepsy, stroke, progressive neurologic disease (e.g. multiple sclerosis), poorly controlled migraines or intracranial brain lesions; and history of previous neurosurgery or head trauma that resulted in residual neurologic impairment;
- •Contraindication for undergoing MRI or receiving tACS;
- •Eczema or sensitive skin;
- •Familial AD;
- •Depression or other psychiatric disorders;
- •Abnormal brain structural magnetic resonance imaging (MRI) scan, including hydrocephalus, stroke, structural lesions, etc. that would potentially confound the outcome;
- •Severe cardiovascular/pulmonary disorders;
- •Other conditions, in the investigator's opinion, might not be suitable for the study.
Arms & Interventions
tACS stimulation group
NEXALIN ADI transcranial alternating current stimulator
Intervention: transcranial alternating current stimulation (Device)
sham stimulation group
Sham stimulator provided by NEXALIN company
Intervention: sham stimulation (Device)
Outcomes
Primary Outcomes
Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 11-items version).
Time Frame: up to 21 days (end of intervention)
ADAS-cog 11 scale ranges from 0 to 70, 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 Mini-mental State Examination(up to 21 days (end of intervention), 3 months)
- Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 11-items version).(3 months)
- Change in brain connectivity(up to 21 days (end of intervention), 3 months)
- Change in Digit span forward(up to 21 days (end of intervention), 3 months)
- Side-effects of tACS(up to 21 days (end of intervention), 3 months)
- Change in brain volume and white matter integrity(up to 21 days (end of intervention), 3 months)
- Change in memory function(up to 21 days (end of intervention), 3 months)
- Change in Trail Making Test(up to 21 days (end of intervention), 3 months)
- Change in Neuropsychiatric Inventory (NPI)(up to 21 days (end of intervention), 3 months)
- Change in Geriatric Depression Scale (GDS)(up to 21 days (end of intervention), 3 months)
- Change in amyloid deposit in brain(up to 21 days (end of intervention))
- Change in Clinical Dementia Rating Scale sum of the boxes(up to 21 days (end of intervention), 3 months)
- Change in Boston Naming Test(up to 21 days (end of intervention), 3 months)
- Change in Activities of Daily Living(up to 21 days (end of intervention), 3 months)
- Change in Montreal Cognitive Assessment(up to 21 days (end of intervention), 3 months)
- Change in Digit span backward(up to 21 days (end of intervention), 3 months)