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）仍然是最普遍的心理健康（MH）诊断的第一个 参与应对9/11世界贸易中心（WTC）恐怖袭击的响应者， PTSD的发病率远高于普通人群。有很多基于证据的治疗方法 (EBT)对于创伤后应激障碍，有最强有力的证据基础，以创伤为重点的治疗，这通常需要， 患者参与索引创伤以及相关的恐惧和认知。这可能特别困难 对于那些以逃避为主要症状的创伤后应激障碍患者虽然这些治疗方法得到了很好的支持， 尤其是在军队和退伍军人群体中效果较差。此外，辍学率很高， 在PTSD的治疗中，一些研究得出的辍学率超过30%。鉴于高比率的 创伤后应激障碍和有效的创伤后应激障碍治疗反应者中的低吸收，有一个明确的需要， 简单，容易获得的治疗，以减轻创伤后应激障碍的症状。有越来越多 文献支持使用迷走神经刺激（VNS）治疗多种不同疾病， 关于使用VNS来解决PTSD的一些特征的有希望的动物模型研究， 特别是，由于VNS对大脑中与恐惧消退相关的关键区域的影响， 尤其是过度兴奋目前的研究旨在确定是否使用一种新的，安全的，非 侵入性形式的VNS，经皮耳VNS（taVNS），将是可接受的，并可用于 有PTSD的WTC应答者，以及该方法是否涉及更大的随机对照研究。 用于测试taVNS疗效的随机对照试验（RCT）是可接受和可行的。因此，目前的研究涉及 在一个焦点小组的背景下进行形成阶段评估， 创伤后应激障碍症状，以调整taVNS干预和试点研究方法，使其相关 并且可接受使用。然后将在随机、双盲安慰剂中试用taVNS干预 对照平行设计研究，30名WTC应答者隶属于Northwell Queens WTC Health 有PTSD的人。结果包括taVNS干预和研究方法的可行性， 可接受性此外，基线和治疗后MH测量值之间的差异将用于 为未来更大规模的RCT生成假设，旨在评估taVNS在减轻PTSD症状方面的疗效 有创伤后应激障碍的世贸中心反应者中的一个较大的样本。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。这一试点可行性研究是实现 最新进展的非侵入性，易于使用的生物电子医学技术，以人口与高利率 在治疗参与和依从性方面遇到障碍的PTSD患者。

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.