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

中枢自主网络的 VNS 调节及其对 ANS 的影响

• 批准号: 10709642
• 负责人: Ziad Nahas
• 金额: $ 23.44万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-23 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10709642
• 关键词: Acute; Anatomy; Ancillary Study; Animal Model; Autonomic nervous system; Brain; Cardiac; Cardiovascular system; Cervical; Chronic; Clinic; Clinical; Clinical Research; Communities; Complement; Coupled; Data; Data Set; Devices; Electrophysiology (science); Ensure; Epilepsy; Frequencies; Future; Hospitals; Human; Immune; Implant; Measures; Mechanics; Medical; Medical Device; Mental Depression; Metabolic; Minnesota; Muscle; Nerve; Nervous System control; Neurosciences; Operative Surgical Procedures; Organ; Otolaryngology; Outcome; Outcome Measure; Participant; Patients; Peripheral; Phase; Physiologic pulse; Physiological; Physiology; Protocols documentation; Qualifying; Research; Research Contracts; Research Design; Research Personnel; Resources; Site; South Carolina; Statistical Data Interpretation; System; Testing; Universities; Vagus nerve structure; Visit; Washington; autonomic reflex; body system; depressed patient; design; experience; glucose metabolism; immune function; lipid metabolism; machine learning method; meetings; multidisciplinary; novel; patient safety; post stroke; pressure; recruit; response; stroke recovery; vagus nerve stimulation

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.

辅助项目 3 摘要：高频微爆 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，它可以提供比临床上可用的更广泛的刺激参数，我们建议扩展 REVEAL 和心血管系统。通用研究方案 (CSP) 范围和多个外周器官的低频 VNS 调制（1 至 30 Hz）及其对更高频率（100 至 350 Hz）、脉冲设置和新植入的微爆发 VNS 患者 (m-VNS；N=30) 将使用标准参数完成 CSP，一旦退出主方案，他们将经历 3 周的清除期 (VNS OFF)，并使用标准参数重复 CSP。我们将测试参与者的多器官测量生理结果两次：在 3 周的冲洗期之后立即进行（早期微爆发效应 - 访问 3；访问 1 和 2 是主要的） CSP）和 12 周后（晚期微爆发效应 - 第 4 次就诊），将在这 2 次就诊期间和每次就诊之间评估每位患者的三种不同刺激设置（100、200 和 350 Hz），结果测量包括：动脉压、心脏交感神经。 -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结果也将与来自 CSP 和标准刺激的结果进行比较。出于监管目的，我们将对 m-VNS 患者的临床结果进行长达一年的跟踪，并确保患者安全，我们通过严格的研究设计和新植入的高频 m-VNS 组建了一支由高素质研究人员组成的多学科团队。以及一系列全面的相关和前沿结果测量，我们将补充 REVEAL 关于人类迷走神经功能连接的多系统观点，并为基于 VNS 的新研究和疗法奠定基础。