search
Back to results

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

Primary Purpose

Alzheimer Disease

Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
transcranial alternating current stimulation
sham stimulation
Sponsored by
Xuanwu Hospital, Beijing
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease

Eligibility Criteria

45 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Xuanwu Hospital, Capital Medical University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

tACS stimulation group

sham stimulation group

Arm Description

NEXALIN ADI transcranial alternating current stimulator

Sham stimulator provided by NEXALIN company

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Change in brain volume and white matter integrity
Structural MRI will be used to measure brain volume and white matter integrity.
Change in brain connectivity
Functional MRI and resting-state EEG will be used to measure brain connectivity.
Change in amyloid deposit in brain
PiB-PET will be used to analyze the amyloid deposit in brain.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Side-effects of tACS
Adverse Events as a result of tACS stimulation will be reported.

Full Information

First Posted
February 26, 2019
Last Updated
October 17, 2022
Sponsor
Xuanwu Hospital, Beijing
search

1. Study Identification

Unique Protocol Identification Number
NCT03920826
Brief Title
Transcranial Alternating Current Stimulation for Patients With Mild Alzheimer's Disease (TRANSFORM-AD)
Official Title
The Effects of TRanscranial AlterNating Current Stimulation FOR Patients With Mild Alzheimer's Disease (TRANSFORM-AD Study): A Randomized Controlled Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
September 11, 2019 (Actual)
Primary Completion Date
January 15, 2022 (Actual)
Study Completion Date
April 15, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xuanwu Hospital, Beijing

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

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
46 (Actual)

8. Arms, Groups, and Interventions

Arm Title
tACS stimulation group
Arm Type
Experimental
Arm Description
NEXALIN ADI transcranial alternating current stimulator
Arm Title
sham stimulation group
Arm Type
Sham Comparator
Arm Description
Sham stimulator provided by NEXALIN company
Intervention Type
Device
Intervention Name(s)
transcranial alternating current stimulation
Intervention Description
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
Intervention Name(s)
sham stimulation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 11-items version).
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)
Secondary Outcome Measure Information:
Title
Change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 11-items version).
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
3 months
Title
Change in brain volume and white matter integrity
Description
Structural MRI will be used to measure brain volume and white matter integrity.
Time Frame
up to 21 days (end of intervention), 3 months
Title
Change in brain connectivity
Description
Functional MRI and resting-state EEG will be used to measure brain connectivity.
Time Frame
up to 21 days (end of intervention), 3 months
Title
Change in amyloid deposit in brain
Description
PiB-PET will be used to analyze the amyloid deposit in brain.
Time Frame
up to 21 days (end of intervention)
Title
Change in Mini-mental State Examination
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 Montreal Cognitive Assessment
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 Clinical Dementia Rating Scale sum of the boxes
Description
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.
Time Frame
up to 21 days (end of intervention), 3 months
Title
Change in memory function
Description
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.
Time Frame
up to 21 days (end of intervention), 3 months
Title
Change in Digit span forward
Description
Digit span will be used to assess attention. It ranges from 3 to 10, and higher value represents a better outcome.
Time Frame
up to 21 days (end of intervention), 3 months
Title
Change in Digit span backward
Description
Digit span backward will be used to assess executive function. It ranges from 2 to 8, and higher value represents a better outcome.
Time Frame
up to 21 days (end of intervention), 3 months
Title
Change in Trail Making Test
Description
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.
Time Frame
up to 21 days (end of intervention), 3 months
Title
Change in Boston Naming Test
Description
Boston Naming Test 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)
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 Geriatric Depression Scale (GDS)
Description
The Geriatric Depression Scale will be used to measure neuropsychiatric symptoms. It ranges from 0 to 30, 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
Description
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.
Time Frame
up to 21 days (end of intervention), 3 months
Title
Side-effects of tACS
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
45 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria Subjects with informed consent; 45-75 years of age; At least 6 years of education; AD according to the National Institute on Aging and the Alzheimer's Association (NIA-AA) guidelines; Clinical Dementia Rating Scale (CDR)=1.0; Positive findings in amyloid PET imaging or decreased CSF levels of Aβ1-42; 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 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; Contraindication for undergoing MRI or receiving tACS; Eczema or sensitive skin; Familial AD; Depression or other psychiatric disorders; Abnormal brain structural magnetic resonance imaging (MRI) scan, including hydrocephalus, stroke, structural lesions, etc. that would potentially confound the outcome; Severe cardiovascular/pulmonary disorders; Other conditions, in the investigator's opinion, might not be suitable for the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yi Tang, M.D., Ph.D.
Organizational Affiliation
Xuanwu Hospital, Beijing
Official's Role
Principal Investigator
Facility Information:
Facility Name
Xuanwu Hospital, Capital Medical University
City
Beijing
ZIP/Postal Code
100053
Country
China

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs