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

抑郁症中的经颅近红外辐射和脑血流 (TRIADE)

• 批准号: 10495452
• 负责人: PAOLO CASSANO
• 金额: $ 81.29万
• 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: 2020-04-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10495452
• 关键词: Adenosine Triphosphate; Adoption; Affect; Aftercare; American; Anesthesia procedures; Animal Model; Bilateral; Biological Markers; Brain; Cephalic; Cerebral cortex; Cerebrovascular Circulation; Clinical; Data; Devices; Disease; Dose; Double-Blind Method; Drug Prescriptions; Electroconvulsive Therapy; Electrodes; Electroencephalography; Enzymes; Exposure to; FDA approved; Feeling suicidal; Forehead; Frontal gyrus; Functional Magnetic Resonance Imaging; Future; General Hospitals; Generations; Goals; Grant; Home; Human; Infrared Rays; Intervention; Lasers; Light; Literature; Major Depressive Disorder; Massachusetts; Measures; Medial; Mental Depression; Mitochondria; Mood Disorders; New York; Operative Surgical Procedures; Patients; Penetration; Pharmaceutical Preparations; Phase; Phototherapy; Pilot Projects; Positioning Attribute; Prefrontal Cortex; Production; Psychotherapy; Randomized; Reporting; Resistance; Respiratory Chain; Safety; Sample Size; Self Administration; Self Management; Signal Transduction; Site; Symptoms; Testing; Time; Universities; absorption; acute stroke; antidepressant effect; biomarker development; blood oxygen level dependent; clinical development; cost; cytochrome c oxidase; depressive symptoms; disability; effective therapy; experience; healthy volunteer; neuroregulation; novel; photobiomodulation; randomized, clinical trials; repetitive transcranial magnetic stimulation; research clinical testing; side effect; stroke patient; suicidal behavior; targeted biomarker; user-friendly; vagus nerve stimulation

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.

项目摘要 重度抑郁症（MDD）与高残疾率以及自杀意念和 行为。当前对MDD治疗的功效和副作用负担有重大限制，而FDA- 批准的MDD设备是繁重的，仅适用于严重患者。有急需 用于有效，耐受性且易于使用的MDD中基于设备的处理。经颅 带有近红外（NIR）光的光生物调节（T-PBM）可牢固地渗透到大脑皮层中，并 该项目着重于经颅光生物调节（T-PBM）的辅助使用 用于治疗MDD的红外（NIR）光。带有近红外（NIR）光的T-PBM强烈渗透到 脑皮质，刺激线粒体呼吸链，也显着增加脑血液 流（CBF）。在R61阶段，我们将进行目标参与研究以证明剂量依赖性 T-PBM对fMRI血氧水平的增加对额叶皮层（PFC）CBF的影响 依赖（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，我们将 在MDD中进行T-PBM与假手术的随机临床试验，以建立目标参与和 评估生物标志物变化（BOLD信号）与临床症状变化之间的关联， 同时还收集有关抗抑郁作用，安全性和耐受性的重要信息。该研究将是 在纽约大学/内森·克莱恩学院和马萨诸塞州综合医院并行完成。 这项研究的重要性是三重的：（1）它针对MDD，这是残疾wordwide的主要原因， 缺乏足够的治疗方法，（2）它评估了T-PBM，该T-PBM具有良好的安全性，并具有 在家中安全的潜力，（3）使用fMRI BOLD更改作为目标参与 生物标志物。如果确认效果，本研究都将支持 易于扩展MDD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。