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.

项目摘要/摘要 3100万美国人患有2型糖尿病(T2 DM)，老年人和 孩子们。另有8410万糖尿病前期美国人有患糖尿病的风险。现代药物 治疗方法的患者依从性很差，加上减肥手术方法，费用昂贵，而且 负面副作用。我们已经开发出有针对性的双重神经调节疗法(TDN疗法)， 一种创新的降血糖方法。闭环式TDN系统(植入式脉冲 发生器(IPG)、连续血糖监测仪(CGM)和双极神经导联)检测到血液升高 葡萄糖水平，并通过阻断迷走神经肝支的传导来降低这些水平 高频交流电(HFAC)，同时用低电流刺激腹部分支 频率交流(LFAC)。我们假设食道和/或胃的高清 内窥镜超声(EUS)将使准确的迷走神经分支识别和腹腔镜下TDN神经 铅的放置减少了偏离目标的生理影响。在初步研究中，EUS对神经的成像 在腹神经丛和神经节内，用望远镜光纤探头成功地确认了。这些神经 然后在EUS引导下用活组织检查钳操作，并刺激以改变胃生理 效果。这项NIH-SBIR第一阶段研究将成功地证明在猪身上的可行性如下： 目的1：使用内窥镜超声和超声识别迷走神经的腹支和肝支。 或在内窥镜下进行透光检查，并通过成功的EUS引导成像证实其可行性。 迷走神经、腹腔和肝脏分支，并通过光纤探头进一步证实。目标2：使用腹腔镜检查 腔内超声和内窥镜在肝和腹腔分支放置电极 迷走神经的穴位以一致的方式进行，通过确认 在腹腔镜术和尸检中追踪胰腺和肝脏分支的电极放置。目标 3：在可行的情况下，尽量减少刺激肝脏和腹部分支时的偏离目标的影响 通过确定最低电流幅度来最大限度地减少偏离目标的影响，同时留在 治疗性电流幅度范围。评估的目标外影响将包括心率的非GI影响， 血压和胃肠道相关的幽门收缩和松弛、食道下段的偏离目标的影响 括约肌压力，胃和胃内的小肠收缩。将通过以下方式评估对肝脏的影响 肝脏激素、门静脉和肝静脉压力。胰腺的作用将通过检测胰岛素来评估， 胰高血糖素和GLP-1，淀粉酶和脂肪酶。未来的第二阶段工作将在TDN治疗动物中纳入EUS 为未来FDA提交的植入物。