Transcranial Alternating Current Stimulation for Patients With Mild Alzheimer's Disease (TRANSFORM-AD)

NCT ID: NCT03920826

Last Updated: 2022-10-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-11
• Study Completion Date: 2022-04-15

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.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

tACS stimulation group

NEXALIN ADI transcranial alternating current stimulator

Group Type: EXPERIMENTAL

transcranial alternating current stimulation

Intervention Type: DEVICE

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 gamma-frequency (40 Hz) and a peak-to-peak amplitude of 15mA, 30 one-hour sessions in 3 weeks (21 days).

sham stimulation group

Sham stimulator provided by NEXALIN company

Group Type: SHAM_COMPARATOR

sham stimulation

Intervention Type: DEVICE

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.

Interventions

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 gamma-frequency (40 Hz) and a peak-to-peak amplitude of 15mA, 30 one-hour sessions in 3 weeks (21 days).

Intervention Type: 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.

Intervention Type: DEVICE

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.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xuanwu Hospital, Beijing

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yi Tang, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Xuanwu Hospital, Beijing

Locations

Xuanwu Hospital, Capital Medical University

Beijing, , China

Countries

China

References

Wang T, Yan S, Shan Y, Xue H, Xing Y, Bi S, Chen Z, Xi H, Qi Z, Tang Y, Lu J. Modulation of Cortical and Hippocampal Functional MRI Connectivity Following Transcranial Alternating Current Stimulation in Mild Alzheimer Disease. Radiology. 2025 Jun;315(3):e241463. doi: 10.1148/radiol.241463.

Reference Type: DERIVED

PMID: 40552996 (View on PubMed)

Tang Y, Xing Y, Sun L, Wang Z, Wang C, Yang K, Zhu W, Shi X, Xie B, Yin Y, Mi Y, Wei T, Tong R, Qiao Y, Yan S, Wei P, Yang Y, Shan Y, Zhang X, Jia J, Teipel SJ, Howard R, Lu J, Li C, Zhao G. TRanscranial AlterNating current stimulation FOR patients with mild Alzheimer's Disease (TRANSFORM-AD): a randomized controlled clinical trial. Alzheimers Res Ther. 2024 Sep 12;16(1):203. doi: 10.1186/s13195-024-01570-0.

Reference Type: DERIVED

PMID: 39267112 (View on PubMed)

Other Identifiers

2018077-XZ1

Identifier Type: -

Identifier Source: org_study_id