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

基本信息

批准号：
10609483
负责人：
Braden Kuo
金额：
$ 40.61万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10609483
关键词：
Address Adverse effects Affect American Anus Brain Characteristics Development Dimensions Disease Dose Educational workshop Elderly Esthesia Evoked Potentials Fecal Incontinence Feces Frequencies Functional disorder Goals Healthcare Impairment Intestines Investigation Knowledge Magnetism Mission Modality Monitor Motor Evoked Potentials National Institute of Diabetes and Digestive and Kidney Diseases Neurobiology Neuronal Plasticity Neurons Neuropathy Outcome Outcome Measure Patients Pelvic floor structure Peripheral Placebos Psychological reinforcement Quality of life Randomized Randomized, Controlled Trials Rectum Research Safety Sensorimotor functions Sensory Severities Signal Transduction Symptoms Testing Therapeutic Woman care burden cost disability effective therapy evidence base improved innovation nerve supply neural neurobiological mechanism neuroregulation novel pressure primary outcome psychosocial randomized trial rectal response safety assessment secondary outcome sphincter ani muscle structure symptomatic improvement therapy development treatment arm treatment response treatment risk

项目摘要

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.

易屈尿液尿液尿液尿液的神经调节疗法：随机试验项目摘要/摘要：粪便尿失禁（FI）影响了4000万美国人，主要是妇女和老年人。这是一个专业医疗保健负担，严重损害生活质量和社会心理功能。 FI是特征的通过包括腰椎神经病，厌食直肠感觉运动运动的多因素功能障碍功能障碍和适应不良的骨盆脑脑神经支配。进步的关键障碍 FI的处理是缺乏随机对照试验，没有机械基于机械的非基础改变疾病的侵入性疗法，以及对治疗方式的了解 FI的病理生理学，正如最近的NIDDK研讨会上的专家所强调的那样。因此，大多数当前的疗法仍然无效。我们的长期目标是解决缺乏的问题通过调查调节周围和中枢神经元的治疗方法，对FI进行有效治疗扰动，从而改善感觉和内脏控制，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小说，无创的使用重复性磁刺激将通过增强在短期和长期内显着改善FI 神经兴奋性和诱导神经可塑性，从而提供多维治疗益处。我们的方法基于引人注目的初步研究，该研究表明TNT在1 Hz处通过增强双向肠道和大脑信号传导，频率显着改善了FI，肛门括约肌强度和直肠感觉与5或15 Hz相比。我们的目标是1）调查在虚假控制的，随机的剂量中，新处理的功效，安全性和最佳剂量TNT 对132名FI患者的依赖研究； 2）通过评估TNT确定TNT的机械基础传出的SPINO-anor直肠和传入的骨盆底脑信号传导以及厌食直肠传感器运动器功能; 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是否通过增强的适应性提供增强的改进神经可塑性，通过进行长期的假控制随机试验。我们的期望结果包括将TNT作为耐用，有效，安全，基于机械机械的示范，非侵入性和低风险治疗FI。我们项目的影响包括一种新颖的疾病修改FI的修改，无创的治疗方法，该处理的发展的科学依据，对FI的病理生理学和神经生物学机制的理解有了改善 TNT修饰双向肠道和脑轴以及厌食函数。最终，知识该项目产生的将为开发创新的，循证的途径提供新的途径 FI的疗法。