Cholinergic Deep Brain Stimulation for Alzheimer's Disease
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Clinical Dementia Rating score change
研究概览
简要总结
This project will investigate the potential of Deep Brain Stimulation to improve cognitive abilities and counteract the effects of Alzheimer's disease. Deep Brain Stimulation electrodes targeting the Nucleus Basalis of Meynert (NB) will be implanted bilaterally in a cohort of patients. NB is the sole source of acetylcholine to the neocortex. Such stimulation may not only treat the cognitive symptoms but may have disease-modifying effects. Drawing from animal experiments in non-human primates that showed success of this approach, intermittent stimulation will be delivered at 60 pulses per second for 20 seconds of each minute for one hour per day. The study team will recruit patients, shortly after first being diagnosed with Alzheimer's disease. The study design will test the safety and efficacy of stimulation, potential benefits in cognitive function assessed with a battery of neurocognitive tests, cholinergic neurotransmission evaluated with Positron Emission Tomography, and ability to reverse Alzheimer's biomarkers, including beta amyloid and tau in the cerebrospinal fluid. Successful completion of this project will lead to a potential new intervention for the cognitive impairments of Alzheimer's disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Probable, early-stage AD, as defined by NIA-AA 2018 criteria, including amnestic Mild Cognitive Impairment (MCI)
- •Clinical Dementia Rating (CDR) global score of 0.5-1.0 with a memory box score of at least 0.5
- •MMSE ³ 23
- •Stable cognitive enhancer medication equivalent to 10 mg/day donepezil or less for at least 60 days
- •Stable other medications (e.g., psychotropics)
- •Valid informed consent if female, subjects who are post-menopausal or surgically sterile or willing to use birth control methods for the duration of the study
- •an available caregiver willing to participate
- •subject is living at home and likely to remain at home for the study duration.
排除标准
- •Active or unstable psychiatric illness
- •Inability to tolerate general anesthesia.
- •Another concurrent CNS condition or clinical co-morbidity interfering with the study (ie, stroke, Parkinson's disease, Lewy-Body dementia or other form of dementia, other evidence of significant structural brain pathology).
- •Current major psychiatric disorder such as schizophrenia, bipolar disorder or major depressive disorder based on psychiatric consult at screening visit
- •Verbal IQ<85
- •Contraindication regarding anesthesia, stereotactic operation, MRI (e.g. claustrophobia, or implants), or PET (e.g. insulin dependent diabetes) procedures
- •Inability to undergo PET or MRI imaging
- •Active alcohol or substance abuse as defined by DSM5
- •Is unable or unwilling to comply with protocol follow-up requirements
- •Is actively enrolled in another concurrent clinical trial.
- •Terminal illness associated with expected survival of <12 months
研究组 & 干预措施
Deep Brain Stimulation
Patients who are implanted and receive intermittent stimulation daily for the first 12 months
干预措施: Device Implantation- Boston Scientific, VERCISE GENUS™ system (Procedure)
Deep Brain Stimulation
Patients who are implanted and receive intermittent stimulation daily for the first 12 months
干预措施: DBS Stimulation - Boston Scientific, VERCISE GENUS™ system (Device)
结局指标
主要结局
Clinical Dementia Rating score change
时间窗: 12 - 24 Months
. The primary outcome indicating success will be an increase in the mean score of the Clinical Dementia Rating - Sum of Boxes of the pre-stimulation baseline that is equal or greater than the increase in the post-stimulation data by 1 point or more, after 12-36 months of stimulation.
次要结局
未报告次要终点
研究者
Christos Constantinidis
Professor
Vanderbilt University Medical Center