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

The Efficacy of 4Hz Transcranial Alternating Current Stimulation for Patients With Mild Alzheimer's Disease: A Randomized Controlled Clinical Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Device: sham stimulation; Device: transcranial alternating current stimulation

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 Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100053
    • Xuanwu Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: sham stimulation group; Sham stimulator provided by NEXALIN company	Device: sham stimulation; Electrodes will also be put on patient's forehead and behind each ear. The sham stimulator has the exactly same appearance with the true stimulator. Participants and operators cannot determine whether the stimulator is true based on its appearance or patients' feelings. However, when the device is started, no current flows through the electrodes. Participants in this controlled group will also receive sham stimulations with 30 one-hour sessions in 21 days.
Experimental: tACS group; NEXALIN ADI transcranial alternating current stimulator	Device: transcranial alternating current stimulation; The alternating current is administered through medical grade conductive pads that are produced specifically for the Nexalin technology. The pads are places on the forehead and behind each ear, and are connected to the Nexalin device with thin cables. Intervention will be implemented with a tACS device with 4Hz frequency and a peak-to-peak amplitude of 15mA, 30 one-hour sessions in 3 weeks (21 days).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 11-items version)	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.	up to 21 days (end of intervention)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 11-items version).	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.	3 months
Change in brain volume and white matter integrity	Structural MRI will be used to measure brain volume and white matter integrity.	up to 21 days (end of intervention), 3 months
Change in brain connectivity	Functional MRI and resting-state EEG will be used to measure brain connectivity.	up to 21 days (end of intervention), 3 months
Change in Mini-mental State Examination	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.	up to 21 days (end of intervention), 3 months
Change in Montreal Cognitive Assessment	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.	up to 21 days (end of intervention), 3 months
Change in Clinical Dementia Rating Scale sum of the boxes	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.	up to 21 days (end of intervention), 3 months
Change in memory function	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.	up to 21 days (end of intervention), 3 months
Change in Digit span forward	Digit span will be used to assess attention. It ranges from 3 to 10, and higher value represents a better outcome.	up to 21 days (end of intervention), 3 months
Change in Digit span backward	Digit span backward will be used to assess executive function. It ranges from 2 to 8, and higher value represents a better outcome.	up to 21 days (end of intervention), 3 months
Change in Trail Making Test	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.	up to 21 days (end of intervention), 3 months
Change in Boston Naming Test	Boston Naming Test will be used to assess language function. It ranges from 0 to 30, and higher value represents a better outcome.	up to 21 days (end of intervention), 3 months
Change in Neuropsychiatric Inventory (NPI)	The Neuropsychiatric Inventory will be used to measure neuropsychiatric symptoms. It ranges from 0 to 144, and higher value represents a worse outcome.	up to 21 days (end of intervention), 3 months
Change in Geriatric Depression Scale (GDS)	The Geriatric Depression Scale will be used to measure neuropsychiatric symptoms. It ranges from 0 to 30, and higher value represents a worse outcome.	up to 21 days (end of intervention), 3 months
Change in Activities of Daily Living	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.	up to 21 days (end of intervention), 3 months
Side-effects of tACS	Adverse Events as a result of tACS stimulation will be reported.	up to 21 days (end of intervention), 3 months

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Investigators: Principal Investigator: Yi Tang, M.D., Ph.D., Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2019
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: September 11, 2019
• First Submitted That Met QC Criteria: September 11, 2019
• First Posted (Actual): September 13, 2019

Study Record Updates

• Last Update Posted (Actual): July 13, 2022
• Last Update Submitted That Met QC Criteria: July 12, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 2018077

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No