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：
9898357
负责人：
Braden Kuo
金额：
$ 55.32万
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 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9898357
关键词：
Address Adverse effects Affect American Anus Brain Characteristics Development 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 Research Safety Sensorimotor functions Sensory Severities Signal Transduction Symptoms Testing Therapeutic Woman base care burden cost disability effective therapy evidence base gut-brain axis improved innovation nerve supply neurobiological mechanism neuroregulation novel pressure primary outcome psychosocial randomized trial rectal relating to nervous system 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.

经腰骶神经调节治疗大便失禁：随机试验项目摘要/摘要：大便失禁 (FI) 影响着 4000 万美国人，其中主要是女性和老年人。这是一个主要的医疗保健负担，严重损害生活质量和心理社会功能。 FI 的特点是由多因素功能障碍引起，包括腰骶神经病变、肛门直肠感觉运动功能障碍和适应不良的盆底脑神经支配。阻碍该领域进步的一个关键障碍 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，以及对治疗如何影响缺乏了解 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，大多数目前的补救措施仍然无效。我们的长期目标是解决缺乏资源的问题通过研究调节外周和中枢神经元的治疗方法来有效治疗 FI 扰动，从而改善感觉和内脏运动控制，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颖的、非侵入性的治疗包括经腰骶神经调节疗法 (TNT)，使用重复磁刺激，将通过增强短期和长期的 FI 显着改善神经兴奋性和诱导神经可塑性，从而提供多维治疗益处。我们的方法基于令人信服的初步研究，该研究表明 TNT 在 1 Hz 频率，通过增强双向肠道和大脑信号传导、肛门括约肌显着改善 FI 与 5 或 15 Hz 相比，强度和直肠感觉。我们的目标是 1) 调查在假手术对照、随机剂量中，新疗法 TNT 的功效、安全性和最佳剂量对 132 名 FI 患者进行的依赖性研究； 2) 通过评估确定 TNT 的机制基础传出脊髓-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 TNT 治疗反应和神经调节作用的持久性，以及强化 TNT 是否通过增强适应性来提供增强的改进神经可塑性，通过进行长期、假对照随机试验。我们的预期结果包括证明 TNT 是一种持久、有效、安全、基于机械的、 FI 的非侵入性、低风险治疗。我们项目的影响包括一种新的疾病修改 FI 的非侵入性治疗方法，开发该治疗方法的科学基础，以及加深对 FI 病理生理学及其神经生物学机制的了解 TNT 改变双向肠道和脑轴以及肛门直肠功能。最终，知识该项目产生的成果将为开发创新的、基于证据的 FI 的治疗。