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：高频微库VNS对外围器官系统的影响 Livanova最近引入了IDE调节的新型VNS设备，称为Microburst，该设备可实现与临床上可用的相比，可实现广泛的刺激参数。人们认为它对大脑具有更强大的电生理作用，并可能是心血管系统。我们建议扩大揭示的揭示，并提出普通研究方案（CSP）的范围和低频VNS调制（1至30 Hz）的多个外围器官及其对较高频率（100至350 Hz），脉冲集和爆破间隔的独特响应。新植入的Microburst VNS患者（M-VN; n = 30）将用标准参数完成CSP。一旦退出主要协议，他们将经历3周的冲洗期（VNS OFF），并使用Microburst设置重复CSP。我们将对参与者进行多器官测量的生理结果测试两次：在经过3周的冲洗期之后（早期的微型效果 - 访问3；访问1和2是主要的CSP），并在12周后（晚期微生物效应 - 访问4）。每个患者将在这2次访问中和每个患者之间评估每种患者的三种不同刺激设置（100、200和350 Hz）。结局措施包括：动脉压，心脏交感神经倾角，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。结果还将与CSP和标准刺激参数的结果进行比较。用于监管目的的临床结果并确保患者的安全性，最多将遵循M-VNS患者一年。我们组建了一个由高素质的调查员组成的多学科团队。通过对新植入的高频M-VN的严格研究设计以及一系列相关和领先的结果指标，我们将补充Replay Revales对人类中迷走神经功能连接的多系统观点，并为新的VNS基于VNS的研究和疗法奠定了基础。