Transcranial Alternating Current Stimulation Combined With 40Hz Sound Stimulation for Treatment Alzheimer's Disease

Transcranial Alternating Current Stimulation Combined With 40Hz Sound Stimulation for Treatment of Mild to Moderate Alzheimer's Disease

Alzheimer's disease is characterized by progressive cognitive decline, and cognition is associated with cerebral concussion. Previous studies have found reduced gamma energy in the brain of AD patients. Therefore, modulation of gamma activity in AD patients may help improve cognitive function.

The purpose of this study was to investigate the safety and tolerability of transcranial alternating current stimulation (tACS) combined with 40Hz sound stimulation in patients with mild to moderate Alzheimer's disease (AD); to compare the effects of tACS combined with sound stimulation, tACS, and 40Hz sound stimulation on cognition in AD patients; and the effects of tACS combined with sound stimulation, tACS, and 40Hz sound stimulation on brain network connectivity in AD patients before and after tACS.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Device: tACS combined with 40 Hz sound stimulation; Device: Transcranial alternating current stimulation; Device: 40 Hz sound stimulation

Detailed Description

The number of people with Alzheimer's disease is increasing every year, but the available drugs are not effective. Both transcranial alternating current stimulation (tACS) and sound stimulation are non-invasive methods to modulate Central Nervous System excitability. tACS has been shown to modulate cognitive processes by affecting intrinsic oscillatory manipulation and entrainment in the brain. And 40 Hz sound stimulation reduces Aβ amyloid deposition in the hippocampus of AD mice.

Sixty patients with mild-to-moderate AD will be recruited in this randomized, double-blind, controlled study. The researchers will evaluate whether tACS (40Hz) to the DLPFC region or 40Hz sound stimulation to both ears improves cognition in patients with mild to moderate AD. The study will also investigate which stimulation method has a more pronounced and sustained improvement in cognition in the following three groups of patients.

Subjects will be randomized into three groups, with the first group receiving tACS combined with sound stimulation, the second group receiving tACS alone, and the third group receiving sound stimulation alone. All will receive three weeks (15 sessions) of treatment. Patients will be assessed by neuropsychological testing at baseline, post-treatment (21 days) and at the 3-month follow-up. Subjects will be compared by functional MRI at baseline and post-treatment for brain network connectivity before and after treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhiqi Mao, Ph.D; Phone Number: 8618910155994; Email: markmaoqi@163.com

Study Locations

• China
  • Beijing, China, 100853
    • Recruiting
    • Chinese PLA General Hospital
    • Contact: Zhiqi Mao, Ph.D; Phone Number: 8618910155994; Email: markmaoqi@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 40-80 years, male or female;
2. Meet the diagnosis AD formulated by the National Institute on Aging and the Alzheimer's Association (NIA-AA) dementia diagnostic criteria;
3. Clinical Dementia Rating Scale (CDR) =1.0 or 2.0;
4. MMSE score ≤ 24;
5. Able to move freely or with the aid of a walker or crutches;
6. Good vision and hearing, able to cooperate with examination and treatment;
7. Subjects voluntarily joined and had a guardian to sign the informed consent.

Exclusion Criteria:

1. The presence of preoperative structural brain abnormalities (such as tumors, cerebral infarction, hydrocephalus or intracranial hemorrhage);
2. The presence of other neurological disorders such as multiple sclerosis, epilepsy, Parkinson's disease, etc;
3. Psychiatric system disorders: such as anxiety disorders, affective disorders such as depression, or pharmacogenic psychiatric disorders;
4. Severe medical illness, current use of respiratory medications, cardiovascular medications, anticonvulsants or psychoactive drugs and clinically significant gastrointestinal, renal, hepatic, respiratory, infectious, endocrine or cardiovascular disease, cancer, alcoholism or drug addiction;
5. Severe hearing and visual impairment;
6. Patients with clinical comorbidities with a life expectancy of less than 2 years;
7. Patients who have undergone cranial surgery;
8. Contraindications to undergoing magnetic resonance imaging or receiving transcranial alternating current stimulation (pacemakers, post DBS surgery);
9. Eczema or sensitive skin;
10. Familial Alzheimer's disease;
11. Presence of other types of dementia: vascular dementia, Lewy body dementia, frontotemporal dementia, infectious dementia, etc;
12. Other conditions that, in the opinion of the investigator, may not be suitable for this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tACS combined with 40 Hz sound stimulation group; 15 daily (Monday-Friday) 20min sessions of tACS combined with 40 Hz sound stimulation	Device: tACS combined with 40 Hz sound stimulation; The tACS instrument (model: XPNS208-B). Two electrodes are placed in the dorsolateral prefrontal cortex and the contralateral supraorbital area. and connected to the tACS device via a thin cable. The intervention will be performed using tACS (40 Hz, 1.5 mA) for 15 sessions of 20 min over 3 weeks (21 days). Sound stimulation apparatus: Two sponge earplugs were placed in the ears and the sound stimulator was set to (40Hz, 60dB). Sound stimulation was turned on simultaneously at the beginning of tACS. The duration of sound stimulation was set to 5 min stimulation, 5 min rest, 5 min stimulation, 1 min rest, and continued stimulation until the end of electrical stimulation while sound stimulation was turned off.
Experimental: tACS group; 15 daily (Monday-Friday) 20min sessions of tACS stimulation	Device: Transcranial alternating current stimulation; The tACS instrument (model: XPNS208-B). Two electrodes are placed in the dorsolateral prefrontal cortex and the contralateral supraorbital area. and connected to the tACS device via a thin cable. The intervention will be performed using tACS (40 Hz, 1.5 mA) for 15 sessions of 20 min over 3 weeks (21 days).
Experimental: 40 Hz sound stimulation group; 15 daily (Monday-Friday) 20min sessions of 40 Hz sound stimulation	Device: 40 Hz sound stimulation; Sound stimulation apparatus: Two sponge earplugs were placed in the ears and the sound stimulator was set to (40Hz, 60dB). The duration of the sound stimulation was set to stimulate for 5 min, rest for 5 min, stimulate for 5 min, rest for 1 min, and last for a total of 20 min. 15 sessions of 20 min were performed over a period of 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 scores	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) ,3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montreal Cognitive Assessment scores	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 Mini-mental State Examination scores	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 Clinical Dementia Rating scores	Clinical Dementia Rating(CDR) will be used to evaluate the level of dementia in AD patients. Mild dementia CDR: 1.0; Moderate dementia CDR: 2.0; Severe dementia CDR: 3.0.	up to 21 days (end of intervention) ,3 months
Change in Auditory Verbal Learning Test scores	auditory verbal learning test（AVLT）will be used to evaluate the memory function. AVLT ranges from 0 to 36, and higher values representing better outcome.	up to 21 days (end of intervention) ,3 months
Change in Boston Naming Test scores	Boston Naming Test（BNT-30） 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) scores	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 Activities of Daily Living scores	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
Change in Magnetic Resonance Imaging performance	Function Magnetic Resonance Imaging (fMRI) will be used to measure changes in brain connectivity；Structural Magnetic Resonance Imaging (sMRI) will be used to measures structural changes in the brain.	up to 21 days (end of intervention), 3 months
Incidence of tACS Adverse events	Adverse Events as a result of tACS stimulation will be reported.	up to 21 days (end of intervention), 3 months

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital

Publications and helpful links

General Publications

• Liu Y, Tang C, Wei K, Liu D, Tang K, Chen M, Xia X, Mao Z. Transcranial alternating current stimulation combined with sound stimulation improves the cognitive function of patients with Alzheimer's disease: A case report and literature review. Front Neurol. 2022 Sep 23;13:962684. doi: 10.3389/fneur.2022.962684. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2021
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: January 19, 2022
• First Submitted That Met QC Criteria: February 22, 2022
• First Posted (Actual): February 23, 2022

Study Record Updates

• Last Update Posted (Actual): February 23, 2022
• Last Update Submitted That Met QC Criteria: February 22, 2022
• Last Verified: February 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: ChinaPLAGH_LY

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No