Transcranial Magnetic Stimulation (TMS) to Slow Down Cognitive Decline in Alzheimer's Disease (AD): TMSLA - a Monocentric Randomized Controlled Trial.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- CDR - Sum of Boxes
研究概览
简要总结
New amyloid-targeting drugs for Alzheimer's disease (AD) offer minimal or unclear efficacy and often cause adverse events, highlighting the need for new therapies. In recent years, repetitive transcranial magnetic stimulation (rTMS) has shown increasing success. A recent randomized, double-blind, sham-controlled, phase 2 demonstrated promising results from a 24-week rTMS treatment protocol targeting the precuneus. This brain region is considered a main hub of the human brain connectome and a prominent area of AD pathology. The results showed stable cognitive performance and increased brain activity in the treatment group, whereas the sham group worsened. A replication study is planned to further investigate the working mechanism of precuneus-rTMS in AD and to improve understanding of its therapeutic potential.
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
- Double (Participant, 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
- •Biomarker-supported Alzheimer's disease (abnormal CSF p-tau/Aβ42 ratio of > 0.023 or amyloid PET positive).
- •Between 50 and 85 years old.
- •Clinical Dementia Rating (CDR) score of 0.5 or
- •Mini-Mental State Examination (MMSE) score between 18 and
- •Presence of a caregiver.
排除标准
- •Medical history of neurodegenerative diseases other than AD, stroke, or epilepsy.
- •Severe psychiatric dysregulation, hampering successful study participation and leading to possible cognitive impairment. Eligibility for participation will be based on clinical evaluation by an expert neurologist and/or psychiatrist.
- •Extensive cerebrovascular damage on MRI classified as Fazekas level 2 or
- •Patients with abnormalities classified as Fazekas level 3 are excluded. For Fazekas level 2, patient's eligibility for participation will be evaluated by an expert neurologist.
- •Presence of metal in the head or cranial/thoracic implants, including cochlear implants.
- •Cholinesterase inhibitors with unstable dosage in the last 2 months.
- •Extreme claustrophobia or metallic objects in or on the body, preventing MRI and MEG examination.
- •Previous rTMS treatment (for blinding reasons).
研究组 & 干预措施
Verum
Verum rTMS
干预措施: repetitive transcranial magnetic stimulation (Device)
Sham
sham rTMS
干预措施: sham repetitive transcranial magnetic stimulation (Device)
结局指标
主要结局
CDR - Sum of Boxes
时间窗: from enrollment to 3 month follow-up
Clinical dementia rating - sum of boxes
次要结局
- Neuropsychological evaluation: WAIS-III Digit Span (Forward and Backward)(baseline to week 24 (post-treatment))
- Neuropsychological evaluation: Rey Auditory Verbal Learning Test (RAVLT)(baseling to week 24 (post-treatment))
- Magnetoencephalography (MEG): Spectral analysis(from baseline to week 24 (post-treatment))
- Cerebrospinal fluid (CSF) biomarkers(from baseline to week 24 (post-treatment))
- Neuropsychological evaluation: Trail Making Test(from baseline to week 24 (post-treatment))
- Amsterdam instrumental activities of daily living questionnaire (AmsterdamiADL);(baseline to 3 month follow-up)
- Mini mental state examination (MMSE)(baseline to 3-month follow up.)
- Neuropsychiatric Inventory Questionnaire (NPI-Q)(baseline to 3 month follow up)
- Quick Inventory of Depressive Symptomatology (QIDS)(baseline to 3-month follow up)
- Magnetoencephalography (MEG): Corrected Amplitude Envelope Correlation (AEC-c)(From baseline to week 24 (post-treatment))
- Magnetoencephalography (MEG): Phase Lag Index (PLI)(baseline to week 24 (post-treatment))
- Magnetoencephalography (MEG): Joint Permutation Entropy (JPE)(baseline to week 24 (post-treatment))
- Neuropsychological evaluation: Verbal Fluency Test(baseline to week 24 (post-treatment))
- Neuropsychological evaluation: Visual Association Test (VAT)(baseline to week 24 (post-treatment))
- Neuropsychological evaluation: Stroop Color and Word Test(baseline to week 24 (post-treament))
研究者
Willem de Haan
Principal Investigator
Amsterdam UMC, location VUmc