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

辅助项目3摘要：高频微下击暴流VNS对外周器官系统的影响 LivaNova最近推出了一种IDE监管的新型VNS设备，称为微脉冲群，它能够实现比临床可用的更广泛的刺激参数。它被认为对大脑和可能的心血管系统有更强大的电生理作用。我们建议扩展REVEAL和通用研究协议（CSP）的范围和多个外周器官的低频VNS调制（1至30 Hz）及其对较高频率（100至350 Hz）、脉冲集和脉冲串间隔的独特反应。新植入的微丛式VNS患者（m-VNS; N=30）将使用标准参数完成CSP。一旦他们退出主方案，他们将经历3周的洗脱期（VNS关闭），并使用微脉冲群设置重复CSP。我们将对受试者进行两次多器官测量生理结局测试：3周洗脱期后立即（早期微下击群效应-访视3;访视1和2是主要CSP）和12周后（晚期微下击群效应-访视4）。将在这2次访视内和访视之间评价每例患者的3种不同刺激设置（100、200和350 Hz）。成果指标包括：动脉压、心脏交感-迷走神经张力、肌肉交感神经活动（MSNA）、自主反射功能、心脏力学、葡萄糖和脂质代谢以及免疫功能。还将结果与CSP和标准刺激参数的结果进行比较。出于监管目的，将对m-VNS患者的临床结局进行长达一年的随访，以确保患者安全。我们组建了一支由高素质调查人员组成的多学科团队。通过使用新植入的高频m-VNS和一系列相关和领先的结局指标进行严格的研究设计，我们将补充REVEAL对人类迷走神经功能连接的多系统观点，并为新的基于VNS的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.