A randomized, sham-controlled clinical trial evaluating individualized neuromodulation of cortical regions involved in neurogenic overactive bladder in Multiple Sclerosis

一项随机、假对照临床试验，评估多发性硬化症患者神经源性膀胱过度活动症相关皮质区域的个体化神经调节

• 批准号: 10560461
• 负责人: Rose Khavari
• 金额: $ 40.12万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-24 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10560461
• 关键词: Address; Adverse effects; Aftercare; Bladder; Bladder Control; Bladder Dysfunction; Brain; Brain region; Clinical; Clinical Data; Clinical Trials; Controlled Clinical Trials; Data; Development; Double-Blind Method; Effectiveness; Electromagnetic Fields; Frequencies; Functional disorder; Health; Incontinence; Increased frequency of micturition; Individual; Knowledge; Location; Lower urinary tract; Magnetic Resonance; Maintenance; Modality; Multiple Sclerosis; Multiple Sclerosis Lesions; National Institute of Diabetes and Digestive and Kidney Diseases; Neuronal Plasticity; Neuronavigation; Neurons; Outcome; Overactive Bladder; Participant; Patients; Pattern; Phase; Phenotype; Prediction of Response to Therapy; Prevalence; Quality of life; Randomized; Research; Residual state; Rest; Role; Safety; Symptoms; Testing; Therapeutic Effect; Time; Transcranial magnetic stimulation; Woman; active method; clinical center; clinical effect; cost; design; effective therapy; follow-up; gray matter; improved; incontinence symptom; interest; nervous system disorder; neural; neuroimaging; neuroregulation; noninvasive brain stimulation; novel; open label; pilot trial; placebo group; repetitive transcranial magnetic stimulation; responders and non-responders; response; restoration; symptomatic improvement; therapeutic target; treatment group; urinary; urologic; white matter

Neurogenic overactive bladder (NOAB), characterized by urinary frequency, urgency or urgency incontinence symptoms occurring during the storage phase of the bladder, is the most common urinary complaint in multiple sclerosis (MS). Current management options for NOAB in MS have limited efficacy and considerable adverse effects, which underscores the significance of our study and highlights the need for better, less invasive therapies. Our novel study investigates brain therapeutic targets that could shift the focus of NOAB management in MS from a bladder-centric focus to brain restoration; specifically modulating the brain regions identified in our prior functional magnetic resonance imagining studies. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation that can modulate neurons (excite or inhibit) to improve the connectivity of the regions of interest (ROI). Our preliminary data demonstrate, for the first time, significant improvement in bladder symptoms in ten women with MS who have voiding dysfunction following multifocal transcranial magnetic stimulation without any treatment-related adverse effects. This randomized double-blind, sham-controlled single center clinical trial with an optional open-label extension (OLE) phase is designed to evaluate the effects of targeted rTMS in women with MS and NOAB by investigating restorative reorganization of brain function and improvement of urinary frequency, urgency and incontinence. We hypothesize that cortical alterations in bladder volume sensing and their response to stimulation contribute to NOAB symptoms in MS, and that improving the response to bladder distention (ROI within circuits 1 and 2) with neuronavigated rTMS can restore brain activity and improve symptoms (frequency, urgency, and incontinence). We will test our hypothesis with thses specific aims: Aim 1: To determine the clinical effects of neuronavigated and multifocal active/sham rTMS in women with MS and NOAB; Aim 2: To assess the neuroimaging restorative effects of neuronavigated active/sham rTMS in women with MS and NOAB; Aim 3: To assess the long-term safety and therapeutic effects of repeated rTMS in women with MS and NOAB who participate in the OLE phase (which subjects from both groups will be invited to enter at the 3-month follow up). Efforts to improve our current knowledge of brain contribution to lower urinary tract function and the development of an individualized, noninvasive, and effective treatment modality at the level of the brain will greatly impact the quality of life for individuals with MS and subsequently others with OAB, whether neurogenic or non-neurogenic.

神经源性膀胱过度活动症 (NOAB)，其特征是尿频、尿急或急迫性尿失禁 发生在膀胱储存期的症状是多种疾病中最常见的泌尿系统疾病 硬化症（MS）。目前针对多发性硬化症的 NOAB 治疗方案疗效有限，且不良反应相当大 效应，这强调了我们研究的重要性，并强调需要更好、侵入性更小的方法 疗法。我们的新研究调查了可能改变 NOAB 管理焦点的大脑治疗靶点 在多发性硬化症中，从以膀胱为中心的焦点转向大脑恢复；专门调节我们识别的大脑区域 先前的功能磁共振成像研究。重复经颅磁刺激（rTMS）是一种 无创脑刺激可以调节神经元（兴奋或抑制）以改善神经元的连接性 感兴趣的区域（ROI）。我们的初步数据首次证明膀胱功能显着改善 十名患有多发性硬化症的女性​​在多灶性经颅磁力检查后出现排尿功能障碍的症状 刺激，没有任何治疗相关的副作用。 这项随机双盲、假对照单中心临床试验，具有可选的开放标签扩展 (OLE) 阶段旨在通过调查评估靶向 rTMS 对患有 MS 和 NOAB 的女性的影响 大脑功能的恢复性重组和尿频、尿急和尿失禁的改善。 我们假设膀胱容量感知的皮质变化及其对刺激的反应有助于 改善 MS 中的 NOAB 症状，并改善对膀胱扩张的反应（回路 1 和 2 内的 ROI） 神经导航 rTMS 可以恢复大脑活动并改善症状（频率、紧迫性和 失禁）。我们将通过以下具体目标来检验我们的假设： 目标 1：确定临床效果 对患有 MS 和 NOAB 的女性进行神经导航和多灶主动/假 rTMS；目标 2：评估 神经导航主动/假 rTMS 对患有 MS 和 NOAB 的女性的神经影像恢复作用；目标 3： 评估重复 rTMS 对患有 MS 和 NOAB 的女性的长期安全性和治疗效果 参加 OLE 阶段（两组受试者将被邀请在 3 个月的随访中进入）。 努力提高我们目前对大脑对下尿路功能和发育的贡献的认识 在大脑层面上个体化、无创且有效的治疗方式将极大地影响 多发性硬化症患者以及随后的其他OAB患者（无论是神经源性还是非神经源性）的生活质量。