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

Primary Purpose

Alzheimer Disease

Status

Recruiting

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

tACS combined with 40 Hz sound stimulation

Transcranial alternating current stimulation

40 Hz sound stimulation

About this trial

This is an interventional treatment trial for Alzheimer Disease

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

The presence of preoperative structural brain abnormalities (such as tumors, cerebral infarction, hydrocephalus or intracranial hemorrhage);
The presence of other neurological disorders such as multiple sclerosis, epilepsy, Parkinson's disease, etc;
Psychiatric system disorders: such as anxiety disorders, affective disorders such as depression, or pharmacogenic psychiatric disorders;
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;
Severe hearing and visual impairment;
Patients with clinical comorbidities with a life expectancy of less than 2 years;
Patients who have undergone cranial surgery;
Contraindications to undergoing magnetic resonance imaging or receiving transcranial alternating current stimulation (pacemakers, post DBS surgery);
Eczema or sensitive skin;
Familial Alzheimer's disease;
Presence of other types of dementia: vascular dementia, Lewy body dementia, frontotemporal dementia, infectious dementia, etc;
Other conditions that, in the opinion of the investigator, may not be suitable for this study.

Sites / Locations

Chinese PLA General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

tACS combined with 40 Hz sound stimulation group

tACS group

40 Hz sound stimulation group

Arm Description

15 daily (Monday-Friday) 20min sessions of tACS combined with 40 Hz sound stimulation

15 daily (Monday-Friday) 20min sessions of tACS stimulation

15 daily (Monday-Friday) 20min sessions of 40 Hz sound stimulation

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

Incidence of tACS Adverse events

Adverse Events as a result of tACS stimulation will be reported.

Full Information

NCT ID

NCT05251649

First Posted

January 19, 2022

Last Updated

February 22, 2022

Sponsor

Chinese PLA General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05251649

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Recruiting

Study Start Date

December 23, 2021 (Actual)

Primary Completion Date

January 2023 (Anticipated)

Study Completion Date

January 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chinese PLA General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

tACS combined with 40 Hz sound stimulation group

Arm Type

Experimental

Arm Description

15 daily (Monday-Friday) 20min sessions of tACS combined with 40 Hz sound stimulation

Arm Title

tACS group

Arm Type

Experimental

Arm Description

15 daily (Monday-Friday) 20min sessions of tACS stimulation

Arm Title

40 Hz sound stimulation group

Arm Type

Experimental

Arm Description

15 daily (Monday-Friday) 20min sessions of 40 Hz sound stimulation

Intervention Type

Device

Intervention Name(s)

tACS combined with 40 Hz sound stimulation

Intervention Description

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.

Intervention Type

Device

Intervention Name(s)

Transcranial alternating current stimulation

Intervention Description

Intervention Type

Device

Intervention Name(s)

40 Hz sound stimulation

Intervention Description

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).

Primary Outcome Measure Information:

Title

Change in Alzheimer's Disease Assessment Scale cognitive subscale scores

Description

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.

Time Frame

up to 21 days (end of intervention) ,3 months

Secondary Outcome Measure Information:

Title

Change in Montreal Cognitive Assessment scores

Description

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.

Time Frame

up to 21 days (end of intervention) ,3 months

Title

Change in Mini-mental State Examination scores

Description

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.

Time Frame

up to 21 days (end of intervention) ,3 months

Title

Change in Clinical Dementia Rating scores

Description

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.

Time Frame

up to 21 days (end of intervention) ,3 months

Title

Change in Auditory Verbal Learning Test scores

Description

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.

Time Frame

up to 21 days (end of intervention) ,3 months

Title

Change in Boston Naming Test scores

Description

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.

Time Frame

up to 21 days (end of intervention), 3 months

Title

Change in Neuropsychiatric Inventory (NPI) scores

Description

The Neuropsychiatric Inventory will be used to measure neuropsychiatric symptoms. It ranges from 0 to 144, and higher value represents a worse outcome.

Time Frame

up to 21 days (end of intervention), 3 months

Title

Change in Activities of Daily Living scores

Description

Time Frame

up to 21 days (end of intervention), 3 months

Title

Change in Magnetic Resonance Imaging performance

Description

Time Frame

up to 21 days (end of intervention), 3 months

Title

Incidence of tACS Adverse events

Description

Adverse Events as a result of tACS stimulation will be reported.

Time Frame

up to 21 days (end of intervention), 3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 40-80 years, male or female; Meet the diagnosis AD formulated by the National Institute on Aging and the Alzheimer's Association (NIA-AA) dementia diagnostic criteria; Clinical Dementia Rating Scale (CDR) =1.0 or 2.0; MMSE score ≤ 24; Able to move freely or with the aid of a walker or crutches; Good vision and hearing, able to cooperate with examination and treatment; Subjects voluntarily joined and had a guardian to sign the informed consent. Exclusion Criteria: The presence of preoperative structural brain abnormalities (such as tumors, cerebral infarction, hydrocephalus or intracranial hemorrhage); The presence of other neurological disorders such as multiple sclerosis, epilepsy, Parkinson's disease, etc; Psychiatric system disorders: such as anxiety disorders, affective disorders such as depression, or pharmacogenic psychiatric disorders; 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; Severe hearing and visual impairment; Patients with clinical comorbidities with a life expectancy of less than 2 years; Patients who have undergone cranial surgery; Contraindications to undergoing magnetic resonance imaging or receiving transcranial alternating current stimulation (pacemakers, post DBS surgery); Eczema or sensitive skin; Familial Alzheimer's disease; Presence of other types of dementia: vascular dementia, Lewy body dementia, frontotemporal dementia, infectious dementia, etc; Other conditions that, in the opinion of the investigator, may not be suitable for this study.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zhiqi Mao, Ph.D

Phone

8618910155994

markmaoqi@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhiqi Mao, Ph.D

Organizational Affiliation

Chinese PLA General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Chinese PLA General Hospital

City

Beijing

ZIP/Postal Code

100853

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhiqi Mao, Ph.D

Phone

8618910155994

markmaoqi@163.com

First Name & Middle Initial & Last Name & Degree

Zhiqi Mao, Ph.D

12. IPD Sharing Statement

Citations:

PubMed Identifier

36212652

Citation

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.

Results Reference

derived

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

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