Neurophysiological mechanism in sacral neuromodulation in patients suffering from fecal incontinence

大便失禁患者骶神经调节的神经生理机制

• 批准号: 10226390
• 负责人: Hans Gregersen
• 金额: $ 18.98万
• 依托单位: CALIFORNIA MEDICAL INNOVATIONS INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10226390
• 关键词: Anus; Behavior; Biomechanics; Clinical Research; Data; Devices; Dimensions; Dose; Epidemic; Esthesia; Fecal Incontinence; Feces; Follow-Up Studies; Geometry; Health Care Costs; Implant; Industrialization; Knowledge; Lead; Mathematics; Mechanical Stress; Modality; Motor; Nerve; Patients; Pattern; Physiological; Relaxation; Research; Sacral nerve; System; Technology; Testing; Therapeutic; aging population; anorectal disorder; design; falls; implantation; improved; insight; interest; mathematical model; neurophysiology; neuroregulation; novel; pressure; programs; prospective; rectal; relating to nervous system; response; sensory mechanism; simulation; sphincter ani muscle structure; tool; vector

The objective of the present proposal is to use the Fecobionics device developed within the SPARC OT2 program to obtain better understanding of the neurophysiological mechanism involved in sacral neuromodulation for treatment of severe fecal incontinence. The mechanism related to efficacy of sacral nerve stimulation (SNS) is not well understood. An integrated anorectal study evaluating pressure waveforms (rectal force, anal sphincter relaxation), orientation (anorectal angle and puborectalis relaxation) and bag geometry (rectal sensation, anal dimensions, and expulsion velocity) during evacuation of the novel Fecobionics device would provide tremendous insight into the mechanism of SNS. A clinical study is needed at this stage, due to the new possibilities with Fecobionics, to understand and advance neuromodulatory technologies in the field. Accordingly, the Specific aims are 1) To determine the evacuatory efficacy of nerve stimulation in a group of patients with FI with successful treatment with the Medtronic Interstim SNS. Milestone: To evaluate the immediate neuromodulatory effect of on/off stimulation on components (anal sphincter, rectal sensitivity, puborectalis) in the defecatory system; 2) To elucidate the effect of altered stimulation parameters to obtain knowledge of influence on various components in the defecatory system in a group of patients with implanted Interstim stimulator. Milestone: To compare stimulation parameters on the neuromodulatory effect on abovementioned components in the defecatory system; and 3) To apply a mathematical modeling tool to the data obtained in Aims 1-2 to provide deeper understanding of mechanical stresses in the defecatory system. Milestone: To use mathematical simulation of anorectal behavior to predict patterns and neuromodulatory mechanisms of sensory-motor action in SNS responders. Our proposal seeks to shift current research in sacral neuromodulation by using an advanced electronic simulated stool for examining the physiologic changes, multidimensionally (e.g., pressure, deformability, biomechanics, vectoral and topographic changes). The impact of our project is to test Fecobionics capabilities to provide new understanding of SNS mechanisms of action and thereby facilitate improvements in SNS therapies. This can improve predictive and therapeutic modalities and reduce healthcare costs associated with treatment of anorectal disorders that are growing epidemic with the aging population. We expect to gain new knowledge and data on the efficacy of SNS neuromodulation. The proposed studies will provide the basis for designing a prospective multi-center follow-up study where a larger patient group will be studied before and after SNS implantation for further characterizing and prediction of non-responders. Our industrial partner Medtronic has expressed great interest in the proposed studies and for supporting follow-up studies falling within the SPARC concept. The impact of the study is a better understanding of dose-response relationships between neural input and anorectal function and insight in therapeutic mechanisms. This may help optimization of existing approaches and lead to new treatment modalities.

本提案的目的是使用Fecobionics设备 在WITHOT 2程序中开发，以更好地了解神经生理学机制 参与骶骨神经调节以治疗严重大便失禁。机制涉及 骶神经刺激（SNS）的有效性尚未得到很好的理解。一项综合性肛门直肠研究， 压力波形（直肠力、肛门括约肌松弛）、方向（肛门直肠角和耻骨直肠肌 松弛）和袋的几何形状（直肠感觉，肛门尺寸和排出速度） 这种新颖的Fecobionics装置将为SNS的机制提供巨大的洞察力。一项临床研究是 由于Fecobionics的新可能性，在这个阶段需要了解和推进神经调节 技术在该领域。因此，本研究的具体目的是：（1）确定神经的排空效能 在一组使用Medtronic Interstim SNS成功治疗的FI患者中进行刺激。里程碑： 评价开/关刺激对组件（肛门括约肌、直肠）的即时神经调节作用 敏感性，耻骨直肠肌）在排便系统; 2）阐明改变刺激参数的影响， 了解对一组患者排便系统中各种成分的影响， 植入的Interstim刺激器。里程碑：比较刺激参数对神经调节的影响， 3）将数学建模工具应用于排便系统中的上述组件;以及 目标1-2中获得的数据，以更深入地了解排便系统中的机械应力。 里程碑：使用肛门直肠行为的数学模拟来预测模式和神经调节 SNS反应者的感觉-运动作用机制。我们的建议旨在改变目前的研究在骶骨 通过使用先进的电子模拟粪便来多维地检查生理变化的神经调节 (e.g.,压力、变形能力、生物力学、矢量和地形变化）。的影响 我们的项目是测试Fecobionics的能力，以提供对SNS作用机制的新理解， 从而促进SNS治疗的改进。这可以改善预测和治疗方式， 降低与治疗肛门直肠疾病相关的医疗保健费用， 人口老龄化我们期望获得关于SNS神经调节功效的新知识和数据。的 拟议的研究将为设计一项前瞻性多中心随访研究提供基础， 患者组将在SNS植入前后进行研究，以进一步表征和预测无应答者。 我们的工业合作伙伴美敦力对拟议的研究表示了极大的兴趣， 支持属于可持续发展概念的后续研究。这项研究的影响是更好地了解 神经输入和肛门直肠功能之间的剂量-反应关系以及治疗中的洞察力 机制等这可能有助于优化现有的方法，并导致新的治疗方式。