Advantage of Cerebellar Transcranial Magnetic Stimulation in Alzheimer's Diseases （ACT-AD）

November 18, 2025 updated by: Xijing Hospital

Effects of Cerebellar Transcranial Magnetic Stimulation on Patients With Alzheimer's Disease：A Multicenter Randomized Controlled Trial

Alzheimer's Disease (AD) is the primary cause of dementia, with its prominent feature being cognitive decline. The cerebellum plays a crucial role in cognitive processing, making it a potential target for therapeutic intervention. This study will be conducted to evaluate the efficacy and safety of cerebellar Intermittent theta-burst stimulation (CRB-iTBS) in participants with mild Alzheimer's disease on the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 3 months of treatment in the Core Study. This project aims to provide a valid treatment to improve the cognitive function and quality of life for those with Alzheimer's disease.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Background:

Alzheimer's disease (AD) is a progressive neurodegenerative disease that poses substantial challenges for both families and society. The primary pathological hallmarks of AD are β-amyloid plaque (Aβ) deposition and neurofibrillary tangles. Notably, the cerebellum seems to be resilient to these pathological developments in the initial phases of AD. This early resistance of the cerebellum suggests it might contribute to compensating for the cognitive impairments associated with AD. Enhancing cerebellar reserve is a potential therapeutic approach. Repetitive transcranial magnetic stimulation (rTMS) has been explored as a means to achieve this, attributed to synaptic plasticity in the cerebellar cortex.

Hypothesis:

The cerebellar dentate nucleus (CDN), a crucial node for information transmission between the cerebellum and cerebral cortex, shows abnormal functional connectivity with cortex in AD patients. Preclinical studies demonstrated that stimulating lateral cerebellar nucleus, the rodent homologue of the human CDN, enhanced cognitive rehabilitation and improved cortical plasticity in animals after brain injury, suggesting CDN as a neuromodulation target for cognitive networks. We speculate that intermittent θ-burst stimulation (iTBS) based TMS targeting the cerebellar dentate nucleus may improve cognitive function, brain function, and lymphatic drainage in AD patients.

Specific aims:

In this study, we will conduct a randomized, double-blind, sham-controlled clinical trial focusing on the cerebellum with iTBS to assess its efficacy, safety and potential mechanisms in the treatment of AD patients. The findings yielded by the present project will have a potential strong impact on clinical practice of AD patients. Since rTMS is well tolerated and relatively low-priced, a positive result could lead to a fast application of the present proposal to the clinical experience. If successful, the proposed project will provide support for a novel treatment for cognitive dysfunction in AD patients.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shaanxi
      • Xi'an, Shaanxi, China, 710032
        • Recruiting
        • Xijing Hospital of Air Force Military Medical University
        • Contact:
        • Contact:
    • Shannxi
      • Xi'an, Shannxi, China
        • Recruiting
        • Tangdu Hospital of Air Force Military Medical University
        • Contact:
      • Xi'an, Shannxi, China
        • Recruiting
        • The First Affiliated Hospital of Xi'an Medical University
        • Contact:
      • Xi'an, Shannxi, China
        • Recruiting
        • The Third Hospital of Xi'an
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age: 50-85 years old
  2. Meet the core clinical criteria of NIA-AA for possible Alzheimer's disease dementia, and PET or cerebrospinal fluid markers show elevated p-tau and decreased A β (1-42)
  3. MMSE score ranges from 18-26 points; CDR score 0.5-1 points
  4. The patient has received treatment with acetylcholinesterase inhibitors (AChEI), NMDA receptor antagonists, or mannequine therapy, and the current dosing regimen has remained stable for the 12 weeks prior to baseline assessment
  5. At least one adult caregiver
  6. The patient or legal guardian voluntarily signs the informed consent form

Exclusion Criteria:

  1. Neurodegenerative disorders other than AD.
  2. Significant intracranial focal or vascular pathology seen on brain MRI scan
  3. History of seizure (with the exception of febrile seizures in childhood)

  4. Any of the following psychotic disorders (DSM IV-TR criteria):

    • Major depressive disorder (current)
    • Schizophrenia
    • Other psychotic disorders, bipolar disorder, or substance related disorders (within the past 5 years)
  5. GDS score ≥ 8 points in baseline assessment
  6. Cerebrovascular disease, severe infection, malignant tumor, or severe dysfunction of organs such as heart, liver, and kidney.
  7. Pregnant or lactating women
  8. Contraindications for TMS or MRI, metal or implanted devices in the body (such as pacemakers, deep brain stimulators).
  9. Participate in AD related clinical trials within 6 months prior to research registration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arms
Participants will receive iTBS-TMS once a day for 4 weeks, followed by once a week for 8 weeks.
Device: Intermittent Theta-Burst Transcranial Magnetic Stimulation
50Hz, stimulation intensity of 100% RMT, duration of 40s as a group of stimulation, 600 stimulation pulses, repeated stimulation of bilateral cerebellar dentate nuclei, with a 5-minute interval between each group, 1200 stimulation pulses per site, 5 times a week, treatment for 4 weeks, then treat once a week for 8 weeks.
Sham Comparator: Assigned Interventions
Participants will receive sham iTBS-TMS once a day for 4 weeks, followed by once a week for 8 weeks.
Device: Intermittent Theta-Burst Transcranial Magnetic Stimulation
50Hz, stimulation intensity of 100% RMT, duration of 40s as a group of stimulation, 600 stimulation pulses, repeated stimulation of bilateral cerebellar dentate nuclei, with a 5-minute interval between each group, 1200 stimulation pulses per site, 5 times a week, treatment for 4 weeks, then treat once a week for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The changes in CDR-SB（Clinical Dementia Rating-Sum of Boxes）
Time Frame: baseline, 12 weeks after start of the treatment
The changes in CDR-SB will constitute the major research outcome measure used to assess response to rTMS.There are two scoring methods for the CDR scale, namely Total Score Calculation (CDR-GS) and Sum of Six Content Calculation (CDR-SB). The scoring method used in this study is CDR-SB, with a total score of 18 points. The lower the score, the milder the symptoms
baseline, 12 weeks after start of the treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The changes in MMSE（Mini Mental State Examination）
Time Frame: baseline, 12 weeks ,24 weeks and 36 weeks after start of the treatment
The changes in MMSE will constitute the secondary research outcome.The full name of MMSE is mini-mental state examination. The higher the score, the better. In this study, changes in MMSE scores before and after treatment were used as secondary observations.
baseline, 12 weeks ,24 weeks and 36 weeks after start of the treatment
The changes in ADCS-ADL（Alzheimer's Disease Cooperative Study - Activities of Daily Living）
Time Frame: baseline, 12 weeks, 24 weeks and 36 weeks after start of the treatment
ADCS-ADL total score is 54 points, the higher the score，the lighter the symptoms.
baseline, 12 weeks, 24 weeks and 36 weeks after start of the treatment
The changes in NPI（Neuropsychiatric Inventory）
Time Frame: baseline, 12 weeks, 24 weeks and 36 weeks after treatment
The changes in NPI will constitute the secondary research outcome. The Neuropsychology Scale (NPI) evaluates 12 neuropsychiatric disorders which included 10 neuropsychiatric symptoms and 2 autonomic neurological symptoms based on the caregiver's perception of the patient's behavior and the perceived distress. The lower the score, the lighter the symptoms.
baseline, 12 weeks, 24 weeks and 36 weeks after treatment
The changes in MRI（Magnetic Resonance Imaging）
Time Frame: baseline and 12 weeks after treatment
This study mainly applied resting blood oxygen level dependent functional magnetic resonance imaging (BOLD), arterial spin labeling (ASL), and magnetic resonance diffusion tensor imaging (DTI) techniques to evaluate the changes in functional connectivity of the cerebellar dentate nucleus in healthy subjects and patients before and after 12 weeks of TMS treatment, as well as the changes in the cerebellar cortical white matter fiber bundles two month after treatment.
baseline and 12 weeks after treatment
The changes in CDR-SB（Clinical Dementia Rating-Sum of Boxes）
Time Frame: 24 weeks and 36 weeks after start of the treatment
The changes in CDR-SB will constitute the major research outcome measure used to assess response to rTMS.There are two scoring methods for the CDR scale, namely Total Score Calculation (CDR-GS) and Sum of Six Content Calculation (CDR-SB). The scoring method used in this study is CDR-SB, with a total score of 18 points. The lower the score, the milder the symptoms
24 weeks and 36 weeks after start of the treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xijing Hospital

Collaborators

First Affiliated Hospital Xi'an Jiaotong University
Tang-Du Hospital
Xi'an No.3 Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 7, 2025

Primary Completion (Estimated)

March 10, 2026

Study Completion (Estimated)

April 10, 2026

Study Registration Dates

First Submitted

October 31, 2024

First Submitted That Met QC Criteria

October 31, 2024

First Posted (Actual)

November 1, 2024

Study Record Updates

Last Update Posted (Actual)

November 24, 2025

Last Update Submitted That Met QC Criteria

November 18, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KY20242285jiangwen

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Transcranial Magnetic Stimulation

Clinical Trials on Intermittent Theta-Burst Transcranial Magnetic Stimulation

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Trinidad & Tobago

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe