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: 10020802
• 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/10020802
• 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。当前的PTSD治疗有 有限和可变的有效性。需要新的，更有效的治疗方法。 PTSD患者经常有 睡眠中断。这些患者每晚更有可能多次醒来，并且慢速降低 挥舞睡眠并增加REM睡眠。此外，睡眠期间的自主和行为组成部分是 与持续的战斗或飞行状态一致。这包括更高的心率，较低 副交感神经，噩梦的可能性更大。 PTSD也与较高的失眠有关 严重程度评分以及对影响调节至关重要的系统中的区域神经递质破坏。 睡眠质量较差与健康状况不佳有关，与经验丰富的结局有关 PTSD。这些包括与心血管疾病，糖尿病和炎症的发展有关 包括关节炎在内的疾病。有效治疗该人群中的睡眠问题可能会有大量 影响这些症状并改善生活质量。 PTSD中的异质性，包括高度 症状表达，在发生轻度创伤性脑损伤（MTBI）之前，可能会影响个体 治疗反应的差异。 MTBI是PTSD损伤之前的常见事件和损害 边缘白质结构可能会影响PTSD的表现。 当前的药物方法通常具有副作用，例如对睡眠结构的负面影响， 成瘾和认知表现后果。此外，退伍军人经常报告他们使用酒精和 其他药物为了入睡并停止噩梦，使问题更加复杂。迷走神经刺激（VNS） 方法具有潜力，尤其是在该人群中提高睡眠质量并改善睡眠的潜力 PTSD的高度符号。 迷走神经刺激（VNS）影响副交感神经系统的激活和抑制 杏仁核活性，解决PTSD高度符号的核心组成部分。常规VNS 需要神经外科手术。但是，我们将研究一种新颖的非侵入性方法：经皮迷走神经 神经刺激（TVN）。 TVNS在该人群中取得成功的潜力很高。 初步工作。我们的飞行员数据表明​​，慢波睡眠增加，并减少了REM睡眠和 在“灯光”上进行了一个小时的电视后，睡眠潜伏期。这样的机制可能是减少的结果 在睡眠的第一个小时内出现高音症状；所有参与者均显示高频心脏增加 与假相比，电视期间的速率可变性。我们以前还展示了TVN的改进 PTSD的高度迹象，包括副交感神经系统上调和衰减 在有或没有MTBI史的PTSD的退伍军人中，“惊吓”期间的交感神经系统活动。 计划我们的目标是在有或没有MTBI历史的PTSD的退伍军人中使用TVNS来评估其效率 在改变睡眠体系结构（AIM 1）和高度符号（AIM 2）中。我们还将评估 PTSD症状在治疗反应（AIM 3）以及安全性和安全性和安全性和安全性和异质性 耐受性功能。我们将使用受试者内的假手术跨界设计来评估 在几个关键的睡眠变量，包括睡眠，慢速，慢速的睡眠变量上，在“灯光熄灭”的电视中施用了一个小时 挥舞睡眠，REM睡眠和自主神经系统行为。