Clinical Core

临床核心

• 批准号: 10709634
• 负责人: Ziad Nahas
• 金额: $ 623.34万
• 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/10709634
• 关键词: Acceleration; Acute; Adipose tissue; Anatomy; Animal Model; 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; Dependence; Development; Devices; Echocardiography; Electric Stimulation; Electrocardiogram; Ensure; Epilepsy; Fiber; Frequencies; Gastric Emptying; Glucagon; Glucose; Glycosylated hemoglobin A; Goals; 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; 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 该揭示项目的总体目标（评估迷走神经激发和解剖联系的研究）是区分多个外围器官的有效与传入VNS调制的作用及其对刺激参数（例如频率，当前产出和占空比周期）的依赖性。我们提出了一种常见的研究方案（CSP），该协议旨在揭示特定的VNS参数设置，该设置调节了三种物理系统（心血管，免疫和代谢）的自主神经系统控制。 CSP由三个辅助项目完成：1）在体内人体电刺激和迷走神经的记录； 2）测量胃排空和住宿； 3）使用CSP中使用的标准Livanova VNS设备不可能对这四个不同系统上的高频刺激设置进行独特的评估。我们将对144例新植入的VNS患者（新植入= 96，先前植入= 48；在癫痫或抑郁症患者中均匀分布）进行评估，并具有标准的Livanova临床装置（用于抑郁症的癫痫和对称性的衰老）或新型Livanova Microburst设备。我们将通过测量以下几点来检查各种VNS刺激参数的急性和慢性效应：1）自主神经：MSNA，BaroreFlex敏感性，心脏交感神经音，自主反射，自主压力源； 2）心血管：心率（时间和频率分析），血压（时间和频率分析），ECG（时间，频率，特征，非线性分析），ECG电气伯恩，心脏力学（超声心动图），呼吸鼻窦鼻鼻涕； 3）免疫：细胞因子，C反应性蛋白，细胞计数，细胞胞质； 4）代谢：常规的临床生物标志物（例如葡萄糖，脂质，HBA1C），激素（肠道和脂肪衍生得出，例如胰岛素，胰高血糖素），血清LC-MS/MS代谢组学，PBMC LC-MS/MS/MS代谢组学。通过新的和先前植入的VNS患者的严格而复杂的研究设计，一系列的标准和领先的结果指标以及质量控制和法规监督的最高水平，我们将生成首个数据集，以迅速且广泛地与神经科学，自动临床和研究社区共享。这些数据将为迷走神经在人类中的功能连通性提供多系统的视图，填补了关键的知识差距并导致了新的疗法和研究。