Transcutaneous vagal nerve stimulation improvement of sleep quality in veterans with PTSD with or without history of mild TBI

经皮迷走神经刺激可改善患有 PTSD（有或没有轻度 TBI 病史）的退伍军人的睡眠质量

• 批准号: 10318075
• 负责人: John B Williamson
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10318075
• 关键词: Address; Adherence; Affect; Alcohol consumption; Amygdaloid structure; Animals; Apnea; Arthritis; Attenuated; Autonomic nervous system; Behavior; Behavioral; Brain; Cardiovascular Diseases; Chronic; Complex; Continuous Positive Airway Pressure; Crossover Design; Data; Dependence; Development; Diabetes Mellitus; Disease; Dose; Ear; Emotional; Environment; Evaluation; Event; Fostering; Frequencies; Glean; Health; Heart Rate; Heterogeneity; Home; Hour; Human; Impairment; Implant; Individual Differences; Inflammatory; Injury; Investigation; Knowledge; Literature; Measures; Methods; Monitor; Moods; Nerve; Neurotransmitters; Nightmare; Operative Surgical Procedures; Outcome; Parasympathetic Nervous System; Participant; Patient Self-Report; Patients; Pharmacological Treatment; Pharmacology; Phase; Population; Post-Traumatic Stress Disorders; Publishing; Quality of life; REM Sleep; Recording of previous events; Recovery; Regulation; Reporting; Rest; Risk; Role; Safety; Severities; Sleep; Sleep Architecture; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Sleeplessness; Slow-Wave Sleep; Source; Structure; Sympathetic Nervous System; Symptoms; System; Technology; Testing; Time; Translations; Up-Regulation; Vagus nerve structure; Veterans; Visual; Work; actigraphy; addiction; alcohol and other drug; attenuation; base; clinical care; clinically relevant; cognitive performance; disabling symptom; effective therapy; efficacy evaluation; experience; falls; fighting; heart rate variability; improved; improvement on sleep; innovation; mild traumatic brain injury; multimodality; neurophysiology; neurosurgery; non rapid eye movement; novel; poor sleep; post-traumatic symptoms; reduce symptoms; response; side effect; sleep onset; sleep quality; success; tool; treatment response; white matter

Problem: Post traumatic stress disorder (PTSD) severely limits quality of life. Current PTSD treatments have limited and variable efficacy. New and more effective treatments are necessary. Patients with PTSD often have disrupted sleep. These patients are more likely to wake up multiple times a night, and have decreased slow wave sleep and increased REM sleep. Further, autonomic and behavioral components during sleep are consistent with a continued fight or flight state while asleep. This includes higher heart rate, lower parasympathetic tone, and greater likelihood of nightmares. PTSD is also associated with higher insomnia severity scores as well as regional neurotransmitter disruptions in systems critical for the regulation of affect. Poor sleep quality is associated with poor health outcomes that overlap with those that are experienced in PTSD. These include associations with the development of cardiovascular disease, diabetes and inflammatory diseases including arthritis. Effective treatment of sleep problems in this population could have substantial impact on these symptoms and improve quality of life. Heterogeneity in PTSD, including hyperarousal symptom expression and prior occurring mild traumatic brain injury (mTBI), may influence individual differences in treatment response. mTBI is a common occurring preceding injury to PTSD and damage to limbic white matter structures may influence presentation of PTSD. Current pharmacological approaches often have side effects like negative impacts on sleep architecture, addiction, and cognitive performance consequences. Further, Veterans often report that they use alcohol and other drugs in order to fall asleep and stop nightmares, compounding the issue. Vagal nerve stimulation (VNS) approaches have potential, especially in this population to improve sleep quality and to also improve hyperarousal symptoms of PTSD. Vagal nerve stimulation (VNS) induces activation of the parasympathetic nervous system and suppression of amygdala activity, addressing the core components of hyperarousal symptoms of PTSD. Conventional VNS requires neurosurgery. However, we will investigate a novel, non-invasive approach: transcutaneous vagal nerve stimulation (tVNS). tVNS has a high potential for success in this population. Preliminary work. Our pilot data demonstrate increased slow wave sleep, and decreased REM sleep and sleep latency after one hour of tVNS at “lights out.” The mechanism for this may be the result of decreasing hyperarousal symptoms during the first hour of sleep; all participants showed increased high frequency heart rate variability during tVNS compared with sham. We have also previously demonstrated tVNS improvement of hyperarousal signs of PTSD including upregulation of parasympathetic nervous system and attenuation of sympathetic nervous system activity during ‘startle’ in Veterans with PTSD with or without history of mTBI. Plan Our objective is to use tVNS in Veterans with PTSD with or without history of mTBI to evaluate its efficacy in changing sleep architecture (aim 1) and hyperarousal symptoms (aim 2). We will also assess the impact of pre-occurring mTBI and heterogeneity of PTSD symptoms on treatment response (aim 3) as well as safety and tolerability features. We will use a within-subject sham-controlled cross-over design to assess the impact of tVNS administered at “lights out” for one hour on several critical sleep variables including sleep onset, slow wave sleep, REM sleep, and autonomic nervous system behavior.

问题：创伤后应激障碍（PTSD）严重限制了生活质量。目前的创伤后应激障碍治疗 有限和可变的功效。需要新的和更有效的治疗方法。创伤后应激障碍患者通常 扰乱睡眠。这些患者更有可能在一夜之间醒来多次， 波睡眠和快速眼动睡眠增加。此外，睡眠期间的自主和行为成分是 与睡眠时持续的战斗或逃跑状态相一致。这包括更高的心率，更低的 副交感神经张力和更大的噩梦可能性。创伤后应激障碍也与较高的失眠有关 严重程度评分以及对情绪调节至关重要的系统中的区域神经递质中断。 睡眠质量差与不良的健康结果有关，这些结果与在睡眠中经历的那些结果重叠。 创伤后应激障碍这些包括与心血管疾病、糖尿病和炎症的发展相关 包括关节炎在内的疾病。有效治疗这一人群的睡眠问题可能会产生重大影响。 改善这些症状，提高生活质量。创伤后应激障碍的异源性，包括过度觉醒 症状表达和先前发生的轻度创伤性脑损伤（mTBI），可能会影响个体 治疗反应的差异。创伤性脑损伤是一种常见的创伤后应激障碍的前期损伤， 边缘白色物质结构可能影响PTSD的表现。 目前的药理学方法通常有副作用，如对睡眠结构的负面影响， 成瘾和认知表现后果。此外，退伍军人经常报告说，他们使用酒精， 其他药物，以入睡和停止噩梦，使问题复杂化。迷走神经刺激（VNS） 这些方法有潜力，特别是在这一人群中，可以改善睡眠质量， 创伤后应激障碍的过度觉醒症状 迷走神经刺激（VNS）诱导副交感神经系统的激活和交感神经系统的抑制。 杏仁核活动，解决了创伤后应激障碍的过度觉醒症状的核心组成部分。常规VNS 需要神经外科手术然而，我们将研究一种新的，非侵入性的方法：经皮迷走神经 神经刺激（tVNS）。tVNS在该人群中具有很大的成功潜力。 前期工作我们的试验数据表明，慢波睡眠增加，快速眼动睡眠减少， 睡眠潜伏期后，一个小时的tVNS在“熄灯”。其机制可能是由于减少 在睡眠的第一个小时出现过度觉醒症状;所有参与者都表现出增加的高频心脏 与假手术相比，tVNS期间的心率变异性。我们以前也证明了tVNS改善 创伤后应激障碍的过度觉醒症状包括副交感神经系统的上调和 有或没有mTBI病史的PTSD退伍军人在“惊吓”期间的交感神经系统活动。 我们的目标是在有或没有mTBI病史的PTSD退伍军人中使用tVNS来评估其疗效 改变睡眠结构（目标1）和过度觉醒症状（目标2）。我们亦会评估 预先发生的mTBI和PTSD症状的异质性对治疗反应（目的3）以及安全性和 耐受性特征。我们将使用受试者内假对照交叉设计来评估 tVNS在“熄灯”时给药一小时，用于几个关键的睡眠变量，包括睡眠开始、缓慢 波动睡眠、快速眼动睡眠和自主神经系统行为。