NCT06669182

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

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: Xijing Hospital · Academic / Other
• Sex: All
• Age: 50 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• Alzheimer Disease
• Transcranial Magnetic Stimulation
• Cerebellum

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2025-01-07
• Primary completion: 2026-03-10
• Completion: 2026-04-10
• First posted: 2024-11-01
• Last updated: 2025-11-24

Locations

4 sites across 1 country: China