Transcranial Photobiomodulation for Alzheimer's Disease (TRAP-AD)

经颅光生物调节治疗阿尔茨海默病 (TRAP-AD)

• 批准号: 10259725
• 负责人: PAOLO CASSANO
• 金额: $ 82.15万
• 依托单位: NEW YORK UNIVERSITY SCHOOL 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 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10259725
• 关键词: Acute; Adenosine Triphosphate; Adverse event; Age; Alzheimer disease prevention; Alzheimer' s Disease; Animal Model; Animals; Antioxidants; Bilateral; Bioenergetics; Biological Markers; Blood; Blood flow; Brain; Brain Pathology; Case Series; Cerebral cortex; Cerebrovascular Circulation; Cerebrum; Clinical; Cognition; Cognitive deficits; Data; Dementia; Devices; Disease; Dose; Double-Blind Method; Early Intervention; Electrodes; Electroencephalography; Feeling suicidal; Forehead; Functional Magnetic Resonance Imaging; Future; General Hospitals; Goals; Individual; Institutes; Intervention; Lasers; Light; Literature; Major Depressive Disorder; Massachusetts; Measures; Mediator of activation protein; Memory; Metabolic Pathway; Mitochondria; Monitor; Neuropsychological Tests; Neuropsychology; New York; Oxidative Phosphorylation; Participant; Patients; Phase; Physiologic pulse; Population; Positioning Attribute; Positron-Emission Tomography; Prefrontal Cortex; Prevalence; Production; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Reactive Oxygen Species; Reporting; Respiratory Chain; Safety; Signal Transduction; Site; Symptoms; Technology; Testing; Universities; Vitamins; acute stroke; amnestic mild cognitive impairment; antidepressant effect; biomarker development; blood oxygen level dependent; clinical development; cognitive function; cost; cytochrome c oxidase; dietary supplements; efficacy evaluation; efficacy outcomes; efficacy testing; glucose metabolism; improved; innovation; magnetic resonance spectroscopic imaging; neuroimaging; neuroregulation; novel; photobiomodulation; pre-clinical; primary outcome; prodromal Alzheimer' s disease; secondary outcome; sleep quality; stroke patient; tau Proteins; therapeutic target; treatment effect; treatment response; user-friendly

PROJECT SUMMARY The prevalence of Alzheimer disease (AD) is projected to increase as the population ages, and current treatments are only minimally effective. Recently, emphasis has been placed on understanding and treating the factors that influence early brain pathology in order to slow the ultimate clinical expression of AD. Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light penetrates robustly into the cerebral cortex, stimulating the mitochondrial respiratory chain, and also significantly increases cerebral blood flow (CBF). Early data suggests t-PBM may be efficacious in improving cognitive deficits in early AD and in amnestic mild cognitive impairment (aMCI). This project aims to test, in a randomized controlled trial, the efficacy and safety of 24 sessions of t-PBM, delivered over 8 weeks and compared to sham, in improving clinical symptoms of aMCI. Additionally, we will explore the brain mechanisms of t-PBM in aMCI, by testing whether baseline tau burden (measured with 18F-MK6240), or changes in mitochondrial function measures over 8 weeks (measured by 31P-MRSI) moderate the changes observed in cognitive functions after t-PBM therapy. We will also use changes in fMRI blood-oxygenation-level dependent (BOLD) after a single treatment, to demonstrate t-PBM-dependent increases in prefrontal cortex (PFC) cortical blood flow (CBF). The study will be done in parallel at New York University, Nathan Kline Institute and at Massachusetts General Hospital. The importance of this study is threefold: (1) it targets aMCI, an important prodromal stage of AD, which lacks adequate approved treatments, (2) it evaluates the efficacy and safety of t-PBM, an innovative, non-invasive technology which has a well-established safety profile, for improving brain function and cognition at the prodromal AD stages, and, (3) explores the association of t-PBM treatment effects with important biomarkers relevant for AD illness progression. If effects are confirmed, the present study will both support short-term clinical development of an easy to scale device for the treatment of aMCI and AD, while also validating biomarkers for the development of future, novel modulation strategies.

项目摘要 随着人口老龄化，阿尔茨海默病（AD）的患病率预计将增加，目前 治疗效果很低。最近，重点放在了解和治疗 影响早期脑病理的因素，以减缓AD的最终临床表现。 经颅光生物调节（t-PBM）与近红外（NIR）光穿透强大的大脑 皮质，刺激线粒体呼吸链，也显着增加脑血流量 （CBF）.早期数据表明，t-PBM可能有效改善早期AD的认知缺陷， 遗忘型轻度认知障碍（aMCI）。本项目旨在通过随机对照试验， 与假手术相比，在8周内给予24次t-PBM治疗， aMCI的临床症状此外，我们还将通过测试，探讨t-PBM在aMCI中的脑机制， 无论是基线tau负荷（用18F-MK 6240测量），还是线粒体功能测量的变化， 在8周内（通过31 P-MRSI测量），t-PBM后观察到的认知功能变化适度 疗法我们还将使用单次治疗后fMRI血氧水平依赖性（BOLD）的变化， 以证明前额叶皮层（PFC）皮质血流量（CBF）的t-PBM依赖性增加。这项研究将 在纽约大学、内森·克莱恩研究所和马萨诸塞州总医院同时进行。的 这项研究的重要性有三个方面：（1）它针对aMCI，一个重要的AD前驱期，它缺乏 充分批准的治疗，（2）它评估了t-PBM的有效性和安全性，一种创新的，非侵入性的 具有良好安全性的技术，用于改善大脑功能和认知， 前驱期AD阶段，以及（3）探索t-PBM治疗效果与重要生物标志物的关联 与AD疾病进展相关。如果效果得到证实，本研究将支持短期 临床开发一种易于扩展的用于治疗aMCI和AD的装置，同时还验证 生物标志物，用于开发未来的新的调节策略。