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.

本提案的目标是使用 Fecobionics 设备 在 SPARC OT2 程序中开发，以获得对神经生理学机制的更好理解 参与骶神经调节治疗严重大便失禁。相关机制 骶神经刺激（SNS）的功效尚不清楚。综合肛门直肠研究评估 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）和袋子几何形状（直肠感觉、肛门尺寸和排出速度） 新颖的 Fecobionics 设备将为 SNS 机制提供深入的见解。一项临床研究是 由于 Fecobionics 的新可能性，现阶段需要了解和推进神经调节 领域的技术。因此，具体目标是 1) 确定神经的疏散功效 对一组使用美敦力 Interstim SNS 成功治疗的 FI 患者进行刺激。里程碑： 评估开/关刺激对各部位（肛门括约肌、直肠括约肌）的即时神经调节作用 排便系统的敏感性（耻骨直肠肌）； 2) 阐明改变刺激参数对 了解对一组患有以下疾病的患者排便系统中各个组成部分的影响 植入 Interstim 刺激器。里程碑：比较刺激参数对神经调节作用的影响 排便系统中的上述成分； 3）应用数学建模工具 目标 1-2 中获得的数据可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。我们的提案旨在改变当前骶骨研究 通过使用先进的电子模拟粪便进行神经调节，多维地检查生理变化 （例如压力、变形性、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 疗法的改进。这可以改善预测和治疗方式 减少与治疗日益流行的肛门直肠疾病相关的医疗费用 人口老龄化。我们期望获得有关 SNS 神经调节功效的新知识和数据。这 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，其中更大范围的研究 将在 SNS 植入前后对患者组进行研究，以进一步表征和预测无反应者。 我们的工业合作伙伴美敦力（Medtronic）对拟议的研究和研究表示了极大的兴趣 支持 SPARC 概念范围内的后续研究。研究的影响是更好地理解 神经输入与肛门直肠功能之间的剂量反应关系以及治疗洞察力 机制。这可能有助于优化现有方法并带来新的治疗方式。