TRANSLUMBOSACRAL NEUROMODULATION THERAPY FOR FECAL INCONTINENCE: RANDOMIZED TRIAL

经腰骶神经调节治疗大便失禁： 随机试验 项目总结/摘要： 粪便失禁（FI）影响着4000万美国人，主要是妇女和老年人。它是一个主要 卫生保健负担，严重损害生活质量和心理社会功能。FI的特点是 包括腰骶神经病变、肛门直肠感觉运动功能障碍 功能障碍和适应不良的骨盆底脑神经支配。这是在联合国取得进展的一个关键障碍， FI的治疗缺乏随机对照试验，缺乏基于机制的非 改变疾病的侵入性疗法，以及缺乏对治疗如何影响 FI的病理生理学，正如专家在最近的NIDDK研讨会上所强调的那样。因此，大多数 目前的补救办法仍然无效。我们的长期目标是解决缺乏 通过研究调节外周和中枢神经元的治疗， 扰动，从而改善感官和内脏控制，并了解 这些治疗的神经生物学基础。我们的中心假设是一种新型的非侵入性的 治疗包括经腰骶神经调节治疗（TNT），使用重复 磁刺激，将显着改善FI在短期和长期，通过提高 神经兴奋性和诱导神经可塑性，从而提供多维治疗 效益我们的方法是基于令人信服的初步研究，表明TNT在1赫兹 频率，显著改善FI，通过增强双向肠道和大脑信号，肛门括约肌 强度和直肠感觉相比，5或15赫兹。我们的目标是1）调查 一种新的治疗方法TNT的有效性、安全性和最佳剂量，采用假手术对照、随机剂量- 在132例FI患者中进行的依赖性研究; 2）通过评估 传出脊髓-肛门直肠和传入骨盆底-脑信号传导，以及肛门直肠感觉-运动 功能; 3）确定治疗反应的持久性和TNT的神经调节作用，以及 强化TNT是否通过增强适应性提供增强的改善 神经可塑性，通过进行长期，假对照随机试验。我们预期的 结果包括TNT作为一种持久、有效、安全、基于机械的， 非侵入性和低风险的治疗FI。我们项目的影响包括一种新颖的，疾病 改良的、非侵入性的FI治疗，开发这种治疗的科学依据，以及 提高对FI病理生理学和神经生物学机制的理解， TNT改变双向肠和脑轴和肛门直肠功能。最终，知识 该项目产生的将提供新的途径，为发展创新，循证 治疗FI。

TRANSLUMBOSACRAL NEUROMODULATION THERAPY FOR FECAL INCONTINENCE: RANDOMIZED TRIAL PROJECT SUMMARY/ABSTRACT: Fecal Incontinence (FI) affects 40 million Americans, predominantly women and elderly. It is a major health care burden, significantly impairs quality of life and psychosocial function. FI is characterized by multifactorial dysfunction that includes lumbosacral neuropathy, anorectal sensori-motor dysfunction, and maladaptive pelvic floor-brain innervation. A critical barrier to progress in the treatment of FI is the lack of randomized controlled trials, absence of mechanistically based non- invasive therapies that modify disease, and a lack of understanding on how treatments affect pathophysiology of FI, as highlighted by experts at a recent NIDDK workshop. Consequently, most current remedies remain ineffective. Our long-term goal is to address the problem of lack of effective treatments for FI by investigating treatments that modulate peripheral and central neuronal perturbations and thereby improve sensory and visceromotor control, and to understand the neurobiologic basis of these treatments. Our central hypothesis is that a novel, non-invasive treatment consisting of Translumbosacral Neuromodulation Therapy (TNT), using repetitive magnetic stimulation, will significantly improve FI in the short-term and long-term, by enhancing neural excitability and inducing neuroplasticity, and thereby provide a multidimensional therapeutic benefit. Our approach is based on compelling preliminary study which showed that TNT at 1 Hz frequency, significantly improved FI, by enhancing bidirectional gut and brain signaling, anal sphincter strength and rectal sensation compared to 5 or 15 Hz. Our objectives are to 1) investigate the efficacy, safety and optimal dose of a new treatment, TNT, in a sham controlled, randomized dose- dependent study in 132 FI patients; 2) determine the mechanistic basis for TNT by assessing the efferent spino-anorectal and afferent pelvic floor-brain signaling, and anorectal sensori-motor function; 3) identify the durability of treatment response and neuromodulatory effects of TNT, and whether reinforcement TNT provides augmented improvement through enhanced adaptive neuroplasticity, by performing a long-term, sham controlled randomized trial. Our expected outcomes include the demonstration of TNT as a durable, efficacious, safe, mechanistically based, non-invasive, and low risk treatment for FI. The impact of our project includes a novel, disease modifying, non-invasive treatment for FI, a scientific basis for the development of this treatment, and improved understanding of the pathophysiology of FI and the neurobiologic mechanism(s) of how TNT modifies bidirectional gut and brain axes and anorectal function. Ultimately, the knowledge generated by this project will provide new avenues for the development of innovative, evidence-based therapies for FI.