Transcranial Near Infrared Radiation and Cerebral Blood Flow in Depression (TRIADE)

项目摘要 重度抑郁症（MDD）与高残疾率以及自杀意念和 行为目前的MDD治疗在疗效和副作用负担方面具有显著的局限性，而FDA- 经批准用于MDD的器械负担沉重，仅适用于重症受试者。迫切需要 用于MDD中有效、耐受性良好且易于使用的基于器械的治疗。经颅 利用近红外（NIR）光的光生物调节（t-PBM）稳健地穿透到大脑皮层中， 该项目的重点是连续使用经颅光生物调节（t-PBM）与近， 用于治疗MDD的红外（NIR）光。具有近红外（NIR）光的t-PBM稳健地穿透到 大脑皮层，刺激线粒体呼吸链，也显着增加大脑血液 血流（CBF）。在R61阶段，我们将进行靶向接合研究，以证明剂量依赖性 t-PBM对前额叶皮层（PFC）CBF的影响，使用fMRI血氧水平的增加 依赖性（BOLD）信号水平作为我们的Go/No-go目标参与生物标志物。在R33阶段， 在MDD中进行t-PBM与假手术的随机临床试验，以确定目标参与度， 评估生物标志物（BOLD信号）变化与临床症状变化之间的关联， 同时也收集关于抗抑郁作用、安全性和耐受性的重要信息。本研究将 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。 这项研究的重要性有三个方面：（1）它针对MDD，这是全球残疾的主要原因， 缺乏足够的治疗，（2）它评估了t-PBM，它具有良好的安全性， 潜在的安全在家里管理，（3）使用功能磁共振成像粗体变化作为目标的参与 生物标志物。如果效果得到证实，本研究将支持短期临床开发， 用于治疗MDD的易于扩展的设备，同时还验证了未来发展的生物标志物， 新颖的调制策略。

PROJECT SUMMARY Major depressive disorder (MDD) is associated with high rates of disability, as well as suicidal ideation and behavior. Current treatments for MDD have significant limitations in efficacy and side effect burden, while FDA- approved devices for MDD are burdensome and only suitable for severely ill subjects. There is a critical need for device-based treatments in MDD that are efficacious, well-tolerated and easy to use. Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light penetrates robustly into the cerebral cortex and This project focuses on the adjunctive use of the transcranial photobiomodulation (t-PBM) with near- infrared (NIR) light for the treatment of MDD. 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). In the R61 phase, we will conduct target engagement studies to demonstrate dose-dependent effects of t-PBM on the prefrontal cortex (PFC) CBF, using the increase in fMRI blood-oxygenation-level dependent (BOLD) signal levels as our Go/No-go target engagement biomarker. In the R33 phase, we will conduct a randomized clinical trial of t-PBM vs. sham for in MDD, to establish the target engagement and evaluate the association between changes in the biomarker (BOLD signal) and changes in clinical symptoms, while also collecting important information on antidepressant effects, safety and tolerability. The study will be done in parallel at the New York University/ Nathan Kline Institute and at Massachusetts General Hospital. The importance of this study is threefold: (1) it targets MDD, a leading cause of disability wordwide, which lacks adequate treatments, (2) it evaluates t-PBM, which has a well-established safety profile and has the potential to be safe in at-home administration, and (3) uses fMRI BOLD changes as a target engagement biomarker. If effects are confirmed, the present study will both support short-term clinical development of an easy to scale device for the treatment of MDD, while also validating a biomarker for the development of future, novel modulation strategies.