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: 10612738
• 负责人: PAOLO CASSANO
• 金额: $ 80.83万
• 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/10612738
• 关键词: Acute; Adenosine Triphosphate; Adverse event; Age; Alzheimer disease prevention; Alzheimer' s Disease; Animal Model; Antioxidants; Bilateral; Bioenergetics; Biological Markers; Blood flow; Brain; Brain Pathology; Case Series; Cephalic; Cerebral cortex; Cerebrovascular Circulation; Clinical; Cognition; Cognitive deficits; Data; Dementia; Devices; Disease Progression; Dose; Double-Blind Method; Early Intervention; Electrodes; Electroencephalography; Feeling suicidal; Forehead; Functional Magnetic Resonance Imaging; Future; General Hospitals; Goals; Human; Individual; Intervention; Lasers; Light; Literature; Major Depressive Disorder; Massachusetts; Measures; Mediator; Memory; Metabolic Pathway; Mitochondria; Monitor; Neuropsychological Tests; Neuropsychology; New York; Oxidative Phosphorylation; Parkinson Disease; Participant; Patients; Penetration; Phase; Physiologic pulse; Population; Positioning Attribute; Positron-Emission Tomography; Prefrontal Cortex; Prevalence; Production; Randomized; Randomized, Controlled Trials; Reactive Oxygen Species; Reporting; Respiratory Chain; Safety; Signal Transduction; Site; Symptoms; Technology; Testing; Universities; Vitamins; absorption; acute stroke; amnestic mild cognitive impairment; antidepressant effect; biomarker development; biomarker validation; blood oxygen level dependent; clinical development; cognitive function; cost; cytochrome c oxidase; dietary supplements; dosage; 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; randomized, clinical trials; 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.

项目概要 阿尔茨海默病（AD）的患病率预计会随着人口老龄化而增加，目前 治疗效果甚微。最近，重点放在了解和治疗上 影响早期脑病理学的因素，以减缓 AD 的最终临床表现。 近红外 (NIR) 光的经颅光生物调节 (t-PBM) 能够强有力地穿透大脑 皮层，刺激线粒体呼吸链，还显着增加脑血流量 （CBF）。早期数据表明 t-PBM 可能有效改善早期 AD 和老年痴呆症的认知缺陷 遗忘性轻度认知障碍（aMCI）。该项目旨在通过随机对照试验测试 与假手术相比，在 8 周内进行 24 次 t-PBM 治疗的有效性和安全性 aMCI 的临床症状。此外，我们将通过测试来探索 aMCI 中 t-PBM 的大脑机制 基线 tau 负荷（使用 18F-MK6240 测量）或线粒体功能测量的变化 超过 8 周（通过 31P-MRSI 测量）缓和了 t-PBM 后观察到的认知功能变化 治疗。我们还将使用单次治疗后 fMRI 血氧水平依赖性 (BOLD) 的变化， 证明 t-PBM 依赖性前额皮质 (PFC) 皮质血流量 (CBF) 增加。该研究将 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。这 这项研究的重要性有三重：（1）它针对的是 aMCI，这是 AD 的一个重要前驱阶段，该阶段缺乏 (2) 它评估了 t-PBM 的有效性和安全性，t-PBM 是一种创新的、非侵入性的 具有完善的安全性的技术，可改善大脑功能和认知能力 AD 前驱阶段，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设备，用于治疗 aMCI 和 AD，同时也验证 用于开发未来新颖的调节策略的生物标志物。