High-definition Endoscopic Ultrasound Navigation for Targeted Dual Neuromodulation Therapy

用于靶向双重神经调节治疗的高清内窥镜超声导航

• 批准号: 10817376
• 负责人: JON James WAATAJA
• 金额: $ 33.15万
• 依托单位: RESHAPE LIFESCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2024-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10817376
• 关键词: Acute; American; Amylases; Animals; Anterior; Area; Autonomic nervous system; Autopsy; Biological Assay; Biological Sciences; Biopsy; Blood Glucose; Blood Pressure; Celiac Plexus; Celiac ganglion; Cervical; Child; Chronic; Clinical; Clinical Treatment; Clinical Trials; Congestive Heart Failure; Development; Devices; Diabetes Mellitus; Disease; Distal; Doctor of Philosophy; Elderly; Electrodes; Endoscopes; Endoscopic Ultrasonography; Endoscopy; Esophagus; Family suidae; Fascicle; Fiber Optics; Fine needle aspiration biopsy; Forcep; Frequencies; Funding; Future; Gastroenterology; Gastroesophageal reflux disease; Glucagon; Goals; Grant; Head; Health; Heart Rate; Hepatic; Hormones; Hypertension; Image; Implant; Inferior esophageal sphincter structure; Insulin; Knowledge; Laparoscopy; Lead; Lipase; Liver; Location; Lung diseases; Measures; Medical Research; Medicine; Methods; Monitor; Needle biopsy procedure; Needles; Nerve; Nerve Block; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Operative Surgical Procedures; Organ; Outcome; Pancreas; Pancreatic Hormones; Pharmacologic Substance; Phase; Physiologic pulse; Physiological; Prediabetes syndrome; Procedures; Rattus; Relaxation; Research; Resolution; Risk; Shapes; Small Business Innovation Research Grant; Small Intestines; Stomach; Surgical sutures; System; Techniques; Therapeutic; Transillumination; Ultrasonography; United States National Institutes of Health; Vagus nerve structure; Venous Pressure level; bariatric surgery; bioelectronics; body system; compliance behavior; diabetic; glucagon-like peptide 1; glucose monitor; grasp; image guided; innovation; minimally invasive; nerve supply; neuroregulation; novel; optical fiber; phase 1 study; porcine model; pressure; professor; side effect; transmission process

Project Summary/Abstract 31 million Americans suffer from Type 2 Diabetes Mellitus (T2DM) with numbers growing in the elderly and children. An additional 84.1 million prediabetic Americans risk becoming diabetic. Current pharmaceutical therapies have poor patient compliance and, along with bariatric surgical approaches, are expensive and have negative side-effects. We have developed Targeted Dual Neuromodulation Therapy (TDN Therapy), an innovative approach to blood glucose reduction. The closed loop TDN system (implantable pulse generator (IPG), continuous blood glucose monitor (CGM) and bipolar nerve leads) senses elevated blood glucose levels and reduces those levels by blocking conduction of the hepatic branch of the vagus nerve with High Frequency Alternating Current (HFAC) while concurrently stimulating the celiac branch with Low Frequency Alternating Current (LFAC). We hypothesize that esophageal and, or gastric High-definition Endoscopic Ultrasound (EUS) will allow precise vagus branch identification and laparoscopic TDN nerve lead placement with reduced off target physiological effects. In Preliminary studies, EUS imaging of nerves within the celiac plexus and ganglion was successfully confirmed with a spyglass fiberoptic probe. These nerves were then manipulated with biopsy forceps under EUS guidance and stimulated to modify gastric physiological effects. This NIH-SBIR Phase I study will successfully demonstrate feasibility in swine as follows: Specific Aim 1: Identify celiac and hepatic branches of the vagus nerve using endoscopic ultrasound and or transillumination on endoscopy with feasibility confirmed by successful EUS guided imaging of the vagus celiac and hepatic branches with further confirmation by fiberoptic probe. Aim 2: Use laparoscopy with endoluminal EUS and endoscopy to place electrodes on the hepatic and celiac branching points of the vagus nerve in a consistent manner with feasibility demonstrated by confirmation of electrode placement by tracing the branches to the pancreas and liver during laparoscopy and necropsy. Aim 3: Minimize off target effects during stimulation of the hepatic and celiac branches with feasibility demonstrated by determination of the lowest current amplitudes to minimize off target effects while staying in a therapeutic current amplitude range. Evaluated off target effects will include non-GI effects of heart rate, blood pressure, & the GI related off target effects of pyloric contraction & relaxation, lower esophageal sphincter pressure, gastric & small intestinal contraction in the stomach. Liver effects will be assessed by hepatic hormones, & portal & hepatic venous pressures. Pancreas effects will be evaluated by assaying insulin, glucagon & GLP-1, amylase & lipase. Future Phase II efforts will incorporate EUS in TDN Therapy animal implants for future FDA submissions.

项目总结/摘要 3100万美国人患有2型糖尿病（T2 DM），老年人和 孩子另有8410万糖尿病前期美国人有患糖尿病的风险。Current pharmaceutical 治疗具有较差的患者依从性，并且沿着减肥手术方法，是昂贵的， 负面的副作用我们开发了靶向双重神经调节疗法（TDN疗法）， 降低血糖的创新方法。闭环TDN系统（植入式脉冲 发生器（IPG）、连续血糖监测仪（CGM）和双极神经电极导线）感测升高的血液 通过阻断迷走神经肝分支的传导， 高频交流电（HFAC），同时刺激腹腔分支， 频率交流（LFAC）。我们假设食管和/或胃的高清晰度 内镜超声（EUS）将允许精确的迷走神经分支识别和腹腔镜TDN神经 电极导线放置可减少偏离目标的生理影响。在初步研究中，神经EUS成像 在腹腔神经丛和神经节内，用望远镜光纤探针成功证实。这些神经 然后在EUS引导下用活检钳操作并刺激以改变胃生理 方面的影响.本NIH-SBIR I期研究将成功证明在猪中的可行性，具体如下： 目的1：使用内镜超声识别迷走神经的腹腔和肝分支， 或在内窥镜下透照，通过成功的EUS引导成像证实可行性， 腹腔迷走神经和肝支，并通过光纤探头进一步确认。目的2：使用腹腔镜 用腔内EUS和内窥镜将电极放置在肝和腹腔分支上 迷走神经点以一致的方式与通过确认 在腹腔镜检查和尸检过程中，通过追踪胰腺和肝脏的分支来放置电极。目的 3：在肝和腹腔分支刺激期间尽可能减少脱靶效应，具有可行性 通过确定最低电流幅度以最大限度地减少脱靶效应，同时保持在 治疗电流幅度范围。评价的脱靶效应将包括心率的非GI效应， 血压，胃肠道相关的幽门收缩和舒张的脱靶效应，下食管 括约肌压力，胃和小肠收缩。将通过以下方式评估肝脏影响： 肝激素、门静脉和肝静脉压力。胰腺效应将通过测定胰岛素进行评价， 胰高血糖素和GLP-1、淀粉酶和脂肪酶。未来的II期研究将在TDN治疗动物中纳入EUS 用于未来FDA提交的植入物。