Non-Invasive Home Neurostimulation for Mild to Moderate Alzheimer's Disease: Double-Blind, Sham Controlled Randomized Clinical Trial

非侵入性家庭神经刺激治疗轻度至中度阿尔茨海默病：双盲、假对照随机临床试验

• 批准号: 10412139
• 负责人: Helena Knotkova
• 金额: $ 135.07万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10412139
• 关键词: Adherence; Adverse effects; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Animal Model; Behavioral; Benefits and Risks; Brain; Caregiver support; Caregivers; Characteristics; Client satisfaction; Clinical; Clinical Trials; Clinical Trials Design; Clinical dementia rating scale; Cognitive; Coupled; Depressed mood; Development; Devices; Diffusion Magnetic Resonance Imaging; Disease; Dose; Double-Blind Method; Elderly; Electrodes; FDA approved; Family; Family health status; Frequencies; Functional Magnetic Resonance Imaging; Healthcare Systems; Home; Human; Impaired cognition; Individual; Intervention; Intervention Studies; Measures; Medical; Metabolic; Monitor; Moods; Neurobehavioral Manifestations; Neuronal Plasticity; Neurons; Outcome Assessment; Participant; Patients; Performance; Pharmaceutical Preparations; Pilot Projects; Placebos; Population; Positron-Emission Tomography; Prefrontal Cortex; Prevalence; Procedures; Protocols documentation; Quality of life; Questionnaires; Randomized; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Reproducibility; Rest; Risk; Secure; Societies; Surveys; Symptoms; Tablets; Testing; Time; Training; United States; Videoconferencing; aged; arm; associated symptom; base; brain metabolism; clinical efficacy; cognitive control; cognitive performance; cognitive task; cognitive testing; comorbidity; dementia care; design; effective therapy; executive function; fluorodeoxyglucose; fluorodeoxyglucose positron emission tomography; follow-up; geriatric depression; improved; informal caregiver; innovation; minimal risk; neuroimaging marker; neuroregulation; novel; novel therapeutics; post intervention; primary outcome; reduce symptoms; response; secondary outcome; selective attention; side effect; symptom management; telehealth

Abstract The growing prevalence of Alzheimer’s Disease coupled with a dearth of effective treatment options necessitates the development of novel treatment approaches for Alzheimer’s Disease, particularly those that pose minimal risk of adverse effects in a medically fragile population. Minimal risk, non- invasive neuromodulatory therapies, such as transcranial direct current stimulation (tDCS), may relieve symptoms and enhance function in older adults with diverse conditions. We developed an at home tDCS and demonstrated the feasibility of this approach, and in a pilot study conducted in patients with early Alzheimer’s disease, at home tDCS improved cognitive performance as well as stability in brain metabolism. We now propose to build and expand on the pilot study to test the clinical efficacy of home based tDCS using a rigorous double blind randomized clinical trial design in 100 patients with mild to moderate Alzheimer’s disease who will be randomized to receive either tDCS five days per week for six months at home or to sham treatment at the same frequency. All participants will receive cognitive assessments at baseline, post-intervention, and at one month and three months after intervention to explore and document durability of effects. Our primary outcome is change in cognitive performance (assessed by the Alzheimer's Disease Assessment Scale - Cognitive subscale test). Secondary outcomes include measures of mood, quality of life, and patient satisfaction with both the device and procedure. Neuroimaging markers of potential neuroplasticity will also be evaluated at baseline, post-intervention, and at three months post-intervention. We predict that the active tDCS will result in better cognitive performance, and higher quality of life, as compared to sham, and will be a satisfactory treatment approach for patients and their families. We also hypothesize that the clinical response produced by active tDCS will be associated with improved functional and structural connectivity and use of the Dorsolateral Prefrontal Cortex and associated networks (e.g. executive control/salience networks). The proposed study is highly responsive to PAR-19-298, which solicits applications to establish initial efficacy of neurostimulation/neuromodulation in the treatment of Alzheimer’s disease and related dementia. Our proposed clinical trial will provide high-quality evidence about the efficacy of at-home tDCS in the treatment of Alzheimer’s Disease. If efficacy is demonstrated, this non-invasive, non- pharmacologic intervention may become an important part of dementia care.

摘要 阿尔茨海默病的日益流行，加上缺乏有效的治疗选择 有必要开发治疗阿尔茨海默病的新方法，特别是 那些在医学上脆弱的人群中产生不良影响的风险最小的药物。最低风险，非 侵入性神经调节疗法，如经颅直流电刺激(Tdcs)，可能会缓解 不同情况的老年人的症状和增强功能。我们在家里开发了一个 Tdcs，并证明了这种方法的可行性，并在一项针对 早期阿尔茨海默病，在家中tdcs改善认知能力和大脑稳定性 新陈代谢。 我们现在建议在先导研究的基础上进一步扩展，以测试基于家庭的tdcs的临床疗效。 采用严格的双盲随机临床试验设计对100例轻中度患者进行临床试验 阿尔茨海默病患者将随机接受TDCs治疗，每周五天，为期六个月 在家中或以相同的频率进行假治疗。所有参与者都将接受认知评估 在基线、干预后、干预后1个月和3个月探讨和 记录效果的耐久性。我们的主要结果是认知表现的变化(通过 阿尔茨海默病评定量表-认知分量表测试)。次要结果包括 测量情绪、生活质量，以及患者对设备和程序的满意度。 潜在神经可塑性的神经成像标记物也将在基线、干预后、 在干预后三个月。 我们预测，积极的tdcs将导致更好的认知表现和更高的生活质量，因为 与Sham相比，将是一种令患者及其家属满意的治疗方法。我们 还假设活跃的tDCs产生的临床反应将与改善相关 背外侧前额叶皮质的功能和结构连通性及用途 网络(例如执行控制/显著网络)。 拟议的研究高度响应了PAR-19-298，它征求申请，以建立初步的 神经刺激/神经调节治疗阿尔茨海默病及相关疾病的疗效 痴呆症。我们提议的临床试验将为家庭治疗的有效性提供高质量的证据。 TDCs在阿尔茨海默病治疗中的应用。如果疗效被证明，这种非侵入性、非侵入性的 药物干预可能成为痴呆症治疗的重要组成部分。