VNS Modulation of the Central Autonomic Network and its Effects on ANS

辅助项目3摘要：高频微爆发VNS对周围器官系统的影响 LivaNova最近推出了一种名为MicroBurst的IDE调节的新型VNS设备，它可以实现比临床可用的更广泛的刺激参数范围。它被认为对大脑有更强大的电生理效应，可能还会对心血管系统产生影响。我们建议扩大Display和公共研究方案(CSP)的范围和多个外周器官的低频VNS调制(1到30赫兹)，以及它们对高频(100到350赫兹)、脉冲集和猝发间隔的独特反应。新植入的微爆发式VNS患者(m-VNS；N=30)将以标准参数完成CSP。一旦他们退出主协议，他们将经历3周的冲洗期(VNS关闭)，并使用微爆发设置重复CSP。我们将对参与者进行两次多器官测量的生理结果测试：紧接在3周冲洗期(早期微爆发效应-访问3；访问1和2是主要的CSP)之后和12周后(晚期微爆发效应-访问4)。每名患者三种不同的刺激设置(100、200和350赫兹)将在这两次就诊期间和之间进行评估。观察指标包括：动脉压、心脏交感迷走神经张力、肌交感神经活动(MSNA)、自主神经反射功能、心脏力学、糖脂代谢和免疫功能。结果还将与CSP和标准刺激参数的结果进行比较。出于监管目的和确保患者安全的目的，将对M-VNS患者进行长达一年的临床结果跟踪调查。我们已经组建了一支由高素质调查人员组成的多学科团队。通过对新植入的高频m-VNS进行严格的研究设计，以及一系列相关和尖端的结果指标，我们将补充Rave对人类迷走神经功能连通性的多系统观点，并为基于VNS的新研究和治疗奠定基础。

ANCILLARY PROJECT 3 Abstract: The effects of high frequency microburst VNS on peripheral organ systems LivaNova recently introduced an IDE-regulated novel VNS device called Microburst which enables a wider range of stimulation parameters than what is clinically available. It is thought to have more robust electrophysiological effects on the brain and possibly the cardiovascular system. We propose to expand REVEAL and the Common Study Protocol’s (CSP) scope and low frequency VNS modulation (1 to 30 Hz) of multiple peripheral organs and their unique responses to higher frequency (100 to 350 Hz), pulse set and interburst intervals. Newly implanted Microburst VNS patient (m-VNS; N=30) will complete the CSP with standard parameters. Once they exit the main protocol, they will undergo a 3-week washout period (VNS OFF) and repeat the CSP with Microburst settings. We will test participants on multi-organ measured physiological outcomes twice: immediately after a 3- week washout period (Early Microburst Effects - Visit 3; Visit 1 and 2 being the main CSP) and 12 weeks after (Late Microburst Effects - Visit 4). Three different stimulation settings (100, 200 and 350 Hz) per patient will be evaluated within and between each of these 2 visits. Outcome measures include: arterial pressure, cardiac sympatho-vagal tone, muscle sympathetic nerve activity (MSNA), autonomic reflex function, cardiac mechanics, glucose and lipid metabolism, and immune function. Results will also be compared to those from the CSP and standard stimulation parameters. m-VNS patients will be followed for up to one year on clinical outcomes for regulatory purposes and to ensure patient safety. We have assembled a multi-disciplinary team of highly qualified investigators. Through a rigorous study design with newly implanted high frequency m-VNS and a comprehensive battery of relevant and leading-edge outcome measures, we will complement REVEAL’s multi- system view of the vagus nerve’s functional connectivity in humans and lay the groundwork for new VNS-based research and therapies.