Clinical trial NCT03920826: Transcranial Alternating Current Stimulation for Patients With Mild Alzheimer's Disease (TRANSFORM-AD)
Official title: The Effects of TRanscranial AlterNating Current Stimulation FOR Patients With Mild Alzheimer's Disease (TRANSFORM-AD Study): A Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer Disease
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2019-04-19
Enrollment: 46
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria

1. Subjects with informed consent;
2. 45-75 years of age;
3. At least 6 years of education;
4. AD according to the National Institute on Aging and the Alzheimer's Association (NIA-AA) guidelines;
5. Clinical Dementia Rating Scale (CDR)=1.0;
6. Positive findings in amyloid PET imaging or decreased CSF levels of Aβ1-42;
7. 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

1. 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;
2. Contraindication for undergoing MRI or receiving tACS;
3. Eczema or sensitive skin;
4. Familial AD;
5. Depression or other psychiatric disorders;
6. Abnormal brain structural magnetic resonance imaging (MRI) scan, including hydrocephalus, stroke, structural lesions, etc. that would potentially confound the outcome;
7. Severe cardiovascular/pulmonary disorders;
8. Other conditions, in the investigator's opinion, might not be suitable for the study.

Primary outcomes:
measure: Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 11-items version).
timeFrame: up to 21 days (end of intervention)
Secondary outcomes:
measure: Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 11-items version).
timeFrame: 3 months
measure: Change in brain volume and white matter integrity
timeFrame: up to 21 days (end of intervention), 3 months
measure: Change in brain connectivity
timeFrame: up to 21 days (end of intervention), 3 months
measure: Change in amyloid deposit in brain
timeFrame: up to 21 days (end of intervention)
measure: Change in Mini-mental State Examination
timeFrame: up to 21 days (end of intervention), 3 months
measure: Change in Montreal Cognitive Assessment
timeFrame: up to 21 days (end of intervention), 3 months
measure: Change in Clinical Dementia Rating Scale sum of the boxes
timeFrame: up to 21 days (end of intervention), 3 months
measure: Change in memory function
timeFrame: up to 21 days (end of intervention), 3 months
measure: Change in Digit span forward
timeFrame: up to 21 days (end of intervention), 3 months
measure: Change in Digit span backward
timeFrame: up to 21 days (end of intervention), 3 months
measure: Change in Trail Making Test
timeFrame: up to 21 days (end of intervention), 3 months
measure: Change in Boston Naming Test
timeFrame: up to 21 days (end of intervention), 3 months
measure: Change in Neuropsychiatric Inventory (NPI)
timeFrame: up to 21 days (end of intervention), 3 months
measure: Change in Geriatric Depression Scale (GDS)
timeFrame: up to 21 days (end of intervention), 3 months
measure: Change in Activities of Daily Living
timeFrame: up to 21 days (end of intervention), 3 months
measure: Side-effects of tACS
timeFrame: up to 21 days (end of intervention), 3 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Yi Tang, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: