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 本REVEAL项目（迷走神经兴奋和解剖学联系评价研究）的总体目标是区分多个外周器官的传出与传入VNS调制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。我们提出了一个共同的研究协议（CSP），这是战略性的设计，以揭示特定的VNS参数设置，调节自主神经系统控制的三个生理系统（心血管，免疫和代谢）。CSP由三个辅助项目补充：1）体内人体电刺激和迷走神经记录; 2）胃排空和调节测量; 3）对这四种不同系统的高频刺激设置进行独特评估，其中IDE调节微脉冲群（LivaNova）是CSP中使用的标准LivaNova VNS器械无法实现的。我们将对144例大多数新植入VNS的患者（新植入=96例，既往植入=48例;平均分布在癫痫或抑郁患者中）进行评估，这些患者使用标准LivaNova临床器械（用于癫痫的Sentiva和用于抑郁的Symmetry）或新型LivaNova Microburst器械。我们将通过测量以下参数来检查各种VNS刺激参数的急性和慢性效应：1）自主神经：MSNA，压力反射敏感性，心脏交感迷走神经张力，自主反射，自主应激源; 2)心血管：心率（时间和频率分析）、血压（时间和频率分析）、ECG（时间、频率、特征、非线性分析）、ECG电负荷、心脏力学（超声心动图）、呼吸性窦性心律失常; 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、脂质、HbA 1c）、激素（肠道和脂肪来源的，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。通过对新近和先前植入VNS的患者进行严格和复杂的研究设计，一系列全面的标准和前沿结局指标，以及最高质量的质量控制和监管监督，我们将产生首个同类数据集，以快速和广泛地分享给神经科学和自主神经临床和研究社区。这些数据将提供人类迷走神经功能连接的多系统视图，填补关键的知识空白，并导致新的治疗和研究。