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），以尿频、尿急或尿急性尿失禁为特征 症状发生在储存阶段的膀胱，是最常见的泌尿投诉，在多个 硬化症（MS）。MS中NOAB的当前管理选项具有有限的疗效和相当大的不良反应。 这强调了我们研究的重要性，并强调了需要更好，更少的侵入性 治疗我们的新研究调查了可能转移NOAB管理重点的大脑治疗靶点 在MS中，从以膀胱为中心的焦点到大脑恢复;特别是调节我们在 之前的功能性磁共振成像研究重复经颅磁刺激（rTMS）是一种 非侵入性脑刺激，可以调节神经元（兴奋或抑制），以改善大脑的连通性。 感兴趣区域（ROI）。我们的初步数据表明，第一次，膀胱的显着改善 10名患有MS的女性患者在多焦经颅磁共振成像后出现排尿功能障碍的症状 没有任何治疗相关的副作用。 这项随机、双盲、假手术对照、单中心临床试验（可选开放标签扩展） (OLE)阶段的目的是评估有针对性的rTMS在MS和NOAB妇女的影响，通过调查 脑功能的恢复性重组和改善尿频、尿急和尿失禁。 我们假设，膀胱容量感知的皮质改变及其对刺激的反应有助于 MS中NOAB症状，以及改善对膀胱扩张的反应（回路1和回路2内的ROI） 神经导航rTMS可以恢复大脑活动，改善症状（频率，紧迫性， 失禁）。我们将测试我们的假设与这些具体的目标：目标1：确定的临床效果 MS和NOAB女性患者的神经导航和多灶主动/假rTMS;目的2：评估 神经导航主动/假rTMS在MS和NOAB女性中的神经影像学恢复作用;目的3： 评估重复rTMS在MS和NOAB女性中的长期安全性和治疗效果， 参与OLE期（3个月随访时将邀请两组受试者入组）。 努力提高我们目前对脑对下尿路功能的贡献的认识， 在大脑水平上的个性化，非侵入性和有效的治疗方式将极大地影响 MS患者和随后的OAB患者的生活质量，无论是神经源性还是非神经源性。