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.

项目概要 重度抑郁症 (MDD) 与高残疾率以及自杀意念和 行为。目前 MDD 的治疗方法在疗效和副作用负担方面存在显着局限性，而 FDA- 批准用于 MDD 的设备很麻烦，并且仅适用于病情严重的受试者。有一个迫切的需求 用于 MDD 的基于设备的治疗，该治疗有效、耐受性良好且易于使用。经颅 近红外 (NIR) 光的光生物调节 (t-PBM) 牢固地渗透到大脑皮层， 该项目重点关注经颅光生物调节（t-PBM）与近红外光的辅助使用 红外线 (NIR) 光用于治疗 MDD。具有近红外 (NIR) 光的 t-PBM 能够牢固地渗透到 大脑皮层，刺激线粒体呼吸链，也显着增加脑血流量 流量（CBF）。在R61阶段，我们将进行靶点参与研究，以证明剂量依赖性 利用 fMRI 血氧水平的增加，研究 t-PBM 对前额皮质 (PFC) CBF 的影响 依赖（粗体）信号水平作为我们的通过/不通过目标参与生物标志物。在R33阶段，我们将 对 MDD 进行 t-PBM 与假手术的随机临床试验，以确定目标参与度和 评估生物标志物（BOLD 信号）变化与临床症状变化之间的关联， 同时还收集有关抗抑郁效果、安全性和耐受性的重要信息。该研究将是 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重：(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，它具有完善的安全性，并且具有 在家管理中可能是安全的，并且（3）使用 fMRI BOLD 变化作为目标参与 生物标志物。如果效果得到证实，本研究将支持短期临床开发 易于扩展的设备用于治疗重度抑郁症，同时还验证未来发展的生物标志物， 新颖的调制策略。