Assessing the feasibility and acceptability of using non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) to reduce PTSD symptoms in WTC responders

摘要 创伤后应激障碍(PTSD)仍然是第一次最常见的精神健康(MH)诊断 参与应对9/11世界贸易中心(WTC)恐怖袭击的响应者，比率 创伤后应激障碍远高于一般人群。有许多基于证据的治疗方法 (EBT)用于创伤后应激障碍，具有以创伤为重点的治疗的最强有力的证据基础，这通常需要 患者参与了创伤指数以及相关的恐惧和认知。这可能特别困难 对于回避是关键症状的创伤后应激障碍患者。尽管这些治疗方法得到了很好的支持，但它们 尤其是在军人和退伍军人群体中效果较差。此外，还观察到高辍学率。 在创伤后应激障碍的治疗中，一些研究产生了超过30%的辍学率。鉴于较高的 创伤后应激障碍和应答者对有效的创伤后应激障碍治疗的接受率较低，显然需要提供 WTC响应者可以简单、方便地接受治疗，以缓解创伤后应激障碍症状。有一具正在生长的身体 支持使用迷走神经刺激(VNS)治疗多种不同疾病的文献 关于使用VNS来解决创伤后应激障碍的一些特征的动物模型研究前景看好， 具体地说，由于VNS对大脑中与恐惧消退相关的关键区域产生了影响 尤其是过度唤醒。目前的研究旨在确定使用一种新颖、安全、非 侵袭性的VNS形式，经皮耳廓VNS(TaVNS)将被接受并可行用于 WTC应答者是否有创伤后应激障碍，以及方法学是否涉及更大规模的随机对照 测试taVNS疗效的试验(RCT)将是可接受和可行的。因此，目前的研究涉及 在重点小组的背景下与WTC响应者一起进行形成性阶段评估 创伤后应激障碍症状，以量身定制taVNS干预和先导研究方法，使其与 并且可以接受使用。然后，将在随机、双盲安慰剂中进行taVNS干预试验 30名隶属于诺斯韦尔皇后区WTC健康中心的WTC应答者的对照平行设计研究 有创伤后应激障碍的人。结果包括TAVNS干预和研究方法的可行性和 可接受性。此外，将利用基线和治疗后卫生保健措施之间的差异来 为未来旨在评估taVNS在PTSD症状缓解中的疗效的更大规模的随机对照试验生成假设 在患有创伤后应激障碍的WTC应答者中有更大的样本。我们还将使用结果来生成假设 关于潜在的作用机制，包括各种炎症、神经和心血管 与治疗结果相关的变化。这项试点可行性研究是将 非侵入性、易于使用的生物电子医学技术在高发病率人群中的最新进展 创伤后应激障碍患者在参与治疗和坚持治疗方面遇到障碍。

ABSTRACT Posttraumatic Stress Disorder (PTSD) remains the most prevalent mental health (MH) diagnosis for first responders involved with responding to the 9/11 World Trade Center (WTC) terrorist attacks, with rates of PTSD much higher than that of the general population. There are a number of evidence-based treatments (EBT) for PTSD, with the strongest evidence base for trauma focused therapies, which typically require that patients engage with the index trauma and the associated fears and cognitions. This can be particularly difficult for PTSD patients for whom avoidance is a key symptom. Although these treatments are well supported, they are less effective in military and veteran populations in particular. Additionally, high dropout rates are observed across treatments for PTSD, with some studies yielding dropout rates of over 30%. Given the high rates of PTSD and the lower uptake of effective PTSD treatment among responders, there is a clear need to provide brief, easily accessible treatments to WTC responders to alleviate PTSD symptoms. There is a growing body of literature to support the use of vagus nerve stimulation (VNS) to treat a number of different disorders with promising animal model research regarding the use of VNS to address some of the features of PTSD, specifically, due to the impact that VNS has on key areas of the brain that are associated with fear extinction and hyperarousal in particular. The current study aims to determine whether the use of a novel, safe, non- invasive form of VNS, transcutaneous auricular VNS (taVNS), would be acceptable and feasible for use with WTC responders who have PTSD, and whether the methodology involved with a larger randomized controlled trial (RCT) to test taVNS efficacy would be acceptable and feasible. As such, the current study involves conducting a formative phase evaluation in the context of a focus group with WTC responders with elevated PTSD symptoms, in order to tailor the taVNS intervention and the pilot study methodology so that it’s relevant and acceptable for use. The taVNS intervention will then be piloted in a randomized, double-blind placebo controlled parallel-design study with 30 WTC responders affiliated with the Northwell Queens WTC Health Program who have PTSD. Outcomes include taVNS intervention and study methodology feasibility and acceptability. In addition, differences between baseline and post-treatment MH measures will be used to generate hypotheses for a future larger RCT aimed at evaluating taVNS efficacy in PTSD symptom reduction among a larger sample of WTC responders with PTSD. We will also use results to generate hypotheses regarding potential mechanisms of action including the various inflammatory, neural and cardiovascular changes that correlate with treatment outcomes. This pilot feasibility study is a first step toward bringing the latest advances in non-invasive, easy to use bioelectronic medicine technology to a population with high rates of PTSD who experience barriers to treatment engagement and adherence.