Meal-Triggered Vagal Nerve Stimulation for Obesity

膳食触发迷走神经刺激治疗肥胖

• 批准号: 8980658
• 负责人: Jieyun None Yin
• 金额: $ 20.75万
• 依托单位: TRANSTIMULATION RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-05 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8980658
• 关键词: Acute; Adverse effects; Adverse event; Algorithms; Animal Model; Body Weight; Body Weight decreased; Cessation of life; Charge; Chronic; Clinical; Clinical Research; Comorbidity; Consult; Control Groups; Data; Detection; Device or Instrument Development; Devices; Diet; Eating; Electric Stimulation; Electrodes; Epilepsy; Failure; Family suidae; Feeling; Food; Frequencies; Gastrointestinal Hormones; Health; Hormones; Human; Ingestion; Laboratories; Mental Depression; Methodology; Methods; Modeling; Multicenter Studies; Nerve; Obesity; Outcome; Patients; Performance; Phase; Physiologic pulse; Rattus; Reporting; Resistance; Safety; Satiation; Series; Signal Transduction; Stomach; Testing; Time; Training; Vagus nerve structure; Weight; Width; bariatric surgery; base; cell motility; clinically relevant; cost; design; effective therapy; ghrelin; glucagon-like peptide; heart rate variability; innovation; meetings; neuroregulation; novel; obesity treatment; open label; polypeptide; public health relevance; research study; software development

 DESCRIPTION (provided by applicant): Obesity and its co-morbidities cause about 400,000 deaths and cost more than $140 billion per year in USA. However, current treatment options for obesity are very limited. Vagal nerve stimulation (VNS) as a potential therapy for treating obesity has been explored in both laboratory and clinical settings. However, there is lack of systematic studies investigating the effects of various stimulation parameters and configurations on food intake and body weight. Consequently, no clinically relevant methodologies are currently available. In this project, we propose an innovative method of VNS for treating obesity by optimizing methodologies and providing automated delivery of electrical stimulation upon food ingestion. Our preliminary data in obese rats have demonstrated a significant and clinically relevant weight loss, attributed to the inhibition in food intake. The main aim of this project is o prove the feasibility of the proposed VNS for treating obesity in a large animal model of obesity using an implantable pulse generator. Specific objectives are as follows: 1) to derive most effective parameters for VNS to inhibit food intake in a swine model of obesity. Experiments are designed to obtain most effective stimulation frequencies, pulse width and stimulation configurations; 2) to study the efficacy and safety of chronic VNS using optimized stimulation parameters in treating obesity in pigs and also to explore possible mechanisms involving autonomic functions, gastric motility and gastrointestinal hormones, such as orexigenic hormone, ghrelin, and anorexigenic hormones, glucagon-like peptide-1 and polypeptide YY; The performance of on-demand meal-triggered VNS method in reducing body weight will be compared with the conventional VNS; 3) to develop an algorithm and use it to detect food intake and automatically initiate VNS upon meal ingestion. It will be designed based on changes in autonomic functions upon food intake. The autonomic functions will be assessed using spectral analysis of the heart rate variability signal that is obtained from stimulation electrodes. A comprehensive and competitive team has been assembled with expertise in neuromodulation, software and device development, obesity, and surgery. A consulting statistician is also included in the team. The accomplishment of this project will prove the feasibility of the proposed method for treating obesity.

 描述（由申请人提供）：在美国，肥胖及其并发症每年导致约 40 万人死亡，花费超过 1,400 亿美元。然而，目前迷走神经刺激 (VNS) 作为潜在疗法的治疗选择非常有限。治疗肥胖 已经在实验室和临床环境中进行了探索，但是缺乏系统研究来调查各种刺激参数和配置对食物摄入和体重的影响，目前我们建议没有临床相关的方法。 VNS 是一种通过优化方法和在食物摄入时自动提供电刺激来治疗肥胖的创新方法。我们对肥胖大鼠的初步数据表明，由于抑制食物摄入，可实现显着且具有临床意义的体重减轻。这个项目证明了所提出的使用植入式脉冲发生器在大型动物肥胖模型中治疗肥胖的可行性具体目标如下： 1) 导出 VNS 在肥胖猪模型中抑制食物摄入的最有效参数。获得最有效的刺激频率、脉冲宽度和刺激配置；2）研究使用优化刺激参数治疗猪肥胖的慢性VNS的有效性和安全性，并探索涉及自主神经功能、胃动力和胃肠道的可能机制。激素，如促食欲激素、生长素释放肽、促食欲激素、胰高血糖素样肽-1和多肽YY；将按需进餐触发的VNS方法与常规VNS方法进行比较，以开发一种算法，并用它来检测食物摄入量，并在进食时自动启动 VNS。它将根据食物摄入时自主功能的变化进行设计。将使用光谱分析来评估自主功能。该团队还组建了一支具有神经调节、软件和设备开发、肥胖和手术方面专业知识的综合性、有竞争力的团队。项目将证明所提出的治疗肥胖方法的可行性。