4Hz Transcranial Alternating Current Stimulation for Patients With Mild Alzheimer's Disease

Not Applicable

• Conditions: Alzheimer Disease
• Interventions: Device: sham stimulation; Device: transcranial alternating current stimulation

• Registration Number: NCT04088643
• Lead Sponsor: Xuanwu Hospital, Beijing

Brief Summary

The goal of this study is to explore the efficacy and safety of 4Hz transcranial alternating current stimulation (tACS) in patients with mild Alzheimer's disease (AD). The study will recruit 40 individuals with mild AD, and the participants will be randomized to either a 4 Hz tACS group or a sham stimulation group. Both groups will undergo 30 one-hour sessions across 3 weeks (21 days). At the end of the intervention and 3-month follow-up, all subjects will repeat the baseline assessments.

Detailed Description

Background: Recently, transcranial alternating current stimulation (tACS), which could interact with ongoing neuronal activity, has emerged as a potentially effective and promising treatment for Alzheimer's disease (AD), and the 4Hz frequency was suggested to improve working memory Methods: The proposed study is a double-blinded, randomized controlled trial that will include 40 individuals with mild AD, and the participants will be randomized to either a 4Hz tACS group or a sham stimulation group. Both groups will undergo 30 one-hour sessions in 3 weeks (21 days). The outcome measures will be assessed at baseline, end of intervention and 3 months after the first session. Primary outcome is global cognitive function, assessed by the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), and the second outcomes include changes in other neuropsychological assessments, structural MRI, resting electroencephalogram (EEG) and simultaneous EEG-functional MRI (fMRI).

Study Timeline

• Study First Submitted: 2019-09-11
• Study First Submitted QC: 2019-09-11
• Study First Posted: 2019-09-13
• Study Start: 2019-10-14
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-12
• Last Update Posted: 2022-07-13
• Primary Completion: 2023-10
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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 amyloid protein levels in CSF;
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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
sham stimulation group	sham stimulation	Sham stimulator provided by NEXALIN company
tACS group	transcranial alternating current stimulation	NEXALIN ADI transcranial alternating current stimulator

Primary Outcome Measures

Name	Time	Method
Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 11-items version)	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 Outcome Measures

Name	Time	Method
Change in Geriatric Depression Scale (GDS)	up to 21 days (end of intervention), 3 months	The Geriatric Depression Scale will be used to measure neuropsychiatric symptoms. It ranges from 0 to 30, and higher value represents a worse outcome.
Change in memory function	up to 21 days (end of intervention), 3 months	WHO-UCLA Auditory Verbal Learning Test will be used to assess memory function. It ranges from 0 to 45, and higher value represents a better outcome.
Change in Mini-mental State Examination	up to 21 days (end of intervention), 3 months	Mini-mental State Examination (MMSE) will be used to evaluate the general cognitive function. MMSE ranges from 0 to 30, and higher value represents a better outcome.
Change in Montreal Cognitive Assessment	up to 21 days (end of intervention), 3 months	Montreal Cognitive Assessment (MoCA) will be used to evaluate the general cognitive function. MoCA ranges from 0 to 30, and higher value represents a better outcome.
Change in Clinical Dementia Rating Scale sum of the boxes	up to 21 days (end of intervention), 3 months	Clinical Dementia Rating Scale sum of the boxes (CDR-SB) will be used to evaluate the general cognitive function. CDR-SB ranges from 0 to 18, and higher value represents a worse outcome.
Change in Digit span forward	up to 21 days (end of intervention), 3 months	Digit span will be used to assess attention. It ranges from 3 to 10, and higher value represents a better outcome.
Change in Digit span backward	up to 21 days (end of intervention), 3 months	Digit span backward will be used to assess executive function. It ranges from 2 to 8, and higher value represents a better outcome.
Change in Neuropsychiatric Inventory (NPI)	up to 21 days (end of intervention), 3 months	The Neuropsychiatric Inventory will be used to measure neuropsychiatric symptoms. It ranges from 0 to 144, and higher value represents a worse outcome.
Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 11-items version).	3 months	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.
Change in brain connectivity	up to 21 days (end of intervention), 3 months	Functional MRI and resting-state EEG will be used to measure brain connectivity.
Change in Trail Making Test	up to 21 days (end of intervention), 3 months	Trail-Making Test B minus A score will be used to assess executive function. Trail-Making Test B minus A ranges from -150 to 300, higher value represents a worse outcome.
Side-effects of tACS	up to 21 days (end of intervention), 3 months	Adverse Events as a result of tACS stimulation will be reported.
Change in brain volume and white matter integrity	up to 21 days (end of intervention), 3 months	Structural MRI will be used to measure brain volume and white matter integrity.
Change in Boston Naming Test	up to 21 days (end of intervention), 3 months	Boston Naming Test will be used to assess language function. It ranges from 0 to 30, and higher value represents a better outcome.
Change in Activities of Daily Living	up to 21 days (end of intervention), 3 months	Activities of Daily Living (ADL) scale will be used to assess the change of life quality. It ranges from 20 to 80. The "20" represents normal life ability and the higher score presents the worse life ability.

Trial Locations

Locations (1)

Xuanwu Hospital, Capital Medical University; 🇨🇳 Beijing, China