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

项目总结 严重抑郁障碍(MDD)与高致残率以及自杀意念和 行为。目前治疗MDD的方法在疗效和副作用负担方面有很大限制，而FDA- 经批准的MDD设备负担沉重，仅适用于病情严重的受试者。有一种迫切的需要 用于MDD中有效、耐受性好且易于使用的基于设备的治疗。经颅 近红外线(NIR)光生物调节(t-PBM)强健地穿透大脑皮层和 本项目的重点是辅助应用经颅光生物调节(t-PBM)与近红外 红外线(NIR)光治疗MDD。具有近红外(NIR)光的T-PBM强韧地穿透到 大脑皮层，刺激线粒体呼吸链，也显著增加大脑血液 流量(CBF)。在R61阶段，我们将进行目标参与研究，以证明剂量依赖 利用fMRI血氧水平升高观察t-PBM对前额叶脑血流的影响 依赖(粗体)信号水平作为我们进行/不进行目标接触的生物标记物。在R33阶段，我们将 进行t-PBM与Sham在MDD中的随机临床试验，以建立目标参与和 评估生物标记物变化(粗体信号)与临床症状变化之间的关系， 同时还收集有关抗抑郁效果、安全性和耐受性的重要信息。这项研究将是 在纽约大学/内森·克莱恩研究所和马萨诸塞州综合医院同时进行。 这项研究的重要性有三个方面：(1)它针对的是MDD，这是全球残疾的主要原因，它 缺乏适当的治疗，(2)它评估t-PBM，它具有良好的安全性概况，并具有 在家庭管理中具有潜在的安全性，以及(3)使用功能磁共振成像大胆的变化作为目标参与 生物标志物。如果效果得到证实，本研究将支持AN的短期临床开发 易于扩展的MDD治疗装置，同时也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.