Clinical Core

临床核心

• 批准号: 10865820
• 负责人: Ziad Nahas
• 金额: $ 6.08万
• 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/10865820
• 关键词: Acceleration; Acute; Adipose tissue; Anatomy; Animal Model; Attitude; Australia; Autonomic nervous system; Baroreflex; Blood Pressure; C-reactive protein; Caliber; Cardiac; Cardiovascular system; Cell Count; Cervical; Chronic; Clinic; Clinical; Clinical Research; Communities; Complement; Data; Data Set; Decision Making; Dependence; Development; Devices; Echocardiography; Electric Stimulation; Electrocardiogram; Ensure; Epilepsy; Fiber; Frequencies; Gastric Emptying; Glucagon; Glucose; Glycosylated hemoglobin A; Goals; Health Care Ethics; Heart Rate; Hormones; Hospitals; Human; Immune; Immune system; Implant; Insulin; Knowledge; Late Effects; Lipids; Literature; Maps; Measurement; Measures; Mechanics; Medical; Medical Device; Mental Depression; Metabolic; Minnesota; Nerve; Nervous System control; Neurosciences; Operative Surgical Procedures; Organ; Otolaryngology; Outcome; Outcome Measure; Output; Participant; Patients; Peripheral; Peripheral Blood Mononuclear Cell; Phase; Physiologic pulse; Physiological; Protocols documentation; Quality Control; Research; Research Design; Role; Serum; Sinus; Site; South Carolina; Specific qualifier value; Statistical Data Interpretation; Stimulus; System; TNF gene; Testing; Time; Titrations; Vagus nerve structure; Visit; Washington; Width; autonomic reflex; clinical biomarkers; clinical efficacy; cytokine; design; improved; in vivo; machine learning method; meetings; metabolomics; novel; novel therapeutics; patient safety; patient subsets; post stroke; prospective; recruit; respiratory; stressor; stroke recovery; therapeutic development; vagus nerve stimulation

CLINICAL CORE Abstract The overarching goal of this REVEAL Project (Research Evaluating Vagal Excitation and Anatomical Linkages) is to distinguish the contributing roles of efferent versus afferent VNS modulation of multiple peripheral organs and their dependence on stimulation parameters such as frequency, current output, and duty cycle. We propose a Common Study Protocol (CSP) that is strategically designed to reveal specific VNS parameter settings that modulate the autonomic nervous system control of three physiological systems (cardiovascular, immune, and metabolic). The CSP is complemented with three ancillary projects: 1) in vivo human electrical stimulation and recordings of the vagus nerve; 2) measurements of gastric emptying and accommodation; and 3) unique assessment of high frequency stimulation settings on these four different systems with the IDE-regulated Microburst (LivaNova) that is not possible with the standard LivaNova VNS devices used in the CSP. We will conduct assessments on 144 mostly newly implanted VNS patients (newly implanted=96, previously implanted=48; evenly distributed across epilepsy or depression patients) with either a standard LivaNova clinical device (Sentiva for epilepsy and Symmetry for depression) or a novel LivaNova Microburst device. We will examine the acute and chronic effects of various VNS stimulus parameters by measuring the following: 1) Autonomic: MSNA, baroreflex sensitivity, cardiac sympathovagal tone, autonomic reflexes, autonomic stressors; 2) Cardiovascular: heart rate (time & amp; frequency analyses), blood pressure (time & amp; frequency analyses), ECG (time, frequency, features, nonlinear analyses), ECG electrical burden, cardiac mechanics (Echocardiography), respiratory sinus arrythmia; 3) Immune: cytokines, C reactive protein, cell counts, CyTOF; 4) Metabolic: routine clinical biomarkers (e.g., glucose, lipids, HbA1c), hormones (gut and adipose derived, e.g., insulin, glucagon), serum LC-MS/MS metabolomics, PBMC LC-MS/MS metabolomics. Through a rigorous and sophisticated study design with both newly and previously implanted VNS patients, a comprehensive battery of standard and leading-edge outcome measures, and the highest caliber of quality control and regulatory oversight, we will produce a first-of-its-kind data set to share rapidly and broadly to the neuroscience and autonomic clinical and research communities. These data will provide a multi-system view of the vagus nerve’s functional connectivity in humans, filling a critical knowledge gap and leading to new therapies and research.

临床核心摘要 该 REVEAL 项目（评估迷走神经兴奋和解剖联系的研究）的总体目标是区分多个外周器官的传出与传入 VNS 调节的贡献作用及其对刺激参数（如频率、电流输出和占空比）的依赖性。提出了一个通用研究方案（CSP），其战略性设计旨在揭示调节三个生理系统（心血管、免疫和代谢）的自主神经系统控制的特定 VNS 参数设置。补充了三个辅助项目：1）体内人体电刺激和迷走神经记录；2）胃排空和调节的测量；3）使用 IDE 调节的这四个不同系统的高频刺激设置的独特评估微爆 (LivaNova) 是 CSP 中使用的标准 LivaNova VNS 设备无法实现的。我们将对 144 名大多数新植入的 VNS 患者进行评估（之前新植入的 = 96 名）。植入 = 48；均匀分布在癫痫或抑郁症患者中），使用标准 LivaNova 临床设备（用于癫痫的 Sentiva 和用于抑郁症的 Symmetry）或新型 LivaNova Microburst 设备我们将通过测量各种 VNS 刺激参数来检查急性和慢性影响。以下： 1) 自主神经：MSNA、压力反射敏感性、心脏交感迷走神经张力、自主神经反射、自主神经应激源； 2) 心血管：心率（时间和频率分析）、血压（时间和频率分析）、心电图（时间、频率、特征、非线性分析）、心电图电负荷、心脏力学（超声心动图）、呼吸窦心律失常；3）免疫：细胞因子、C反应蛋白、细胞计数、CyTOF； 4）代谢：常规临床生物标志物（例如，葡萄糖、血脂、HbA1c）、激素（肠道和脂肪来源，例如胰岛素、胰高血糖素）、血清LC-MS/MS代谢组学、PBMC LC-MS/MS代谢组学。针对新植入的和既往植入的 VNS 患者进行复杂的综合研究设计、一系列标准和前沿的结果测量以及最高水平的质量控制和在监管监督下，我们将制作首个此类数据集，以快速、广泛地与神经科学和自主临床和研究界共享。这些数据将提供人类迷走神经功能连接的多系统视图，填补这一空白。关键的知识差距并导致新的疗法和研究。