Effects of Cerebellar Transcranial Magnetic Stimulation on Patients With Alzheimer's Disease：A Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 4
- 主要终点
- The changes in CDR-SB（Clinical Dementia Rating-Sum of Boxes）
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 50-85 years old
- •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)
- •MMSE score ranges from 18-26 points; CDR score 0.5-1 points
- •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
- •At least one adult caregiver
- •The patient or legal guardian voluntarily signs the informed consent form
排除标准
- •Neurodegenerative disorders other than AD.
- •Significant intracranial focal or vascular pathology seen on brain MRI scan
- •History of seizure (with the exception of febrile seizures in childhood)
- •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)
- •GDS score ≥ 8 points in baseline assessment
- •Cerebrovascular disease, severe infection, malignant tumor, or severe dysfunction of organs such as heart, liver, and kidney.
- •Pregnant or lactating women
- •Contraindications for TMS or MRI, metal or implanted devices in the body (such as pacemakers, deep brain stimulators).
- •Participate in AD related clinical trials within 6 months prior to research registration
结局指标
主要结局
The changes in CDR-SB（Clinical Dementia Rating-Sum of Boxes）
时间窗: 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
次要结局
- The changes in MMSE（Mini Mental State Examination）(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）(baseline, 12 weeks, 24 weeks and 36 weeks after start of the treatment)
- The changes in NPI（Neuropsychiatric Inventory）(baseline, 12 weeks, 24 weeks and 36 weeks after treatment)
- The changes in MRI（Magnetic Resonance Imaging）(baseline and 12 weeks after treatment)
- The changes in CDR-SB（Clinical Dementia Rating-Sum of Boxes）(24 weeks and 36 weeks after start of the treatment)