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.

神经源性过度活跃的膀胱（NOAB），其特征是尿频率，紧急或紧迫性尿失禁 在膀胱的存储阶段发生的症状是多个尿液投诉 硬化症（MS）。 NOAB在MS中的当前管理选项的功效有限，而且不利 效果，这强调了我们研究的重要性，并强调了对更好，侵入性较小的需求 疗法。我们的小说研究调查了可能改变NOAB管理重点的大脑治疗靶标 从以膀胱为中心的焦点到大脑恢复的MS；专门调节我们在我们的大脑区域 先前的功能磁共振想象研究。重复的经颅磁刺激（RTMS）是一个 可以调节神经元（激发或抑制）以改善连通性的无创脑刺激 利益区域（ROI）。我们的初步数据首次证明了膀胱的显着改善 多灶经颅磁后，十名女性妇女的症状无效 没有任何与治疗相关的不良反应的刺激。 这项随机双盲，假手术单中心临床试验，可选开放标签扩展 （OLE）阶段旨在通过研究MS和NOAB的女性评估目标RTM的影响 脑功能的恢复重组和尿频，紧迫性和动荡的改善。 我们假设膀胱体积感测的皮质改变及其对刺激的反应有助于 在MS中出现NOAB症状，并改善对膀胱扩张的反应（电路1和2中的ROI） 使用神经宣传的RTM可以恢复大脑活动并改善症状（频率，紧迫性和 失禁）。我们将以特定目的检验我们的假设：目标1：确定 MS和NOAB女性的神经宣传和多灶性活动/假RTM；目标2：评估 神经模仿神经模仿的恢复作用在具有MS和NOAB的女性中活跃/假RTM；目标3：到 评估重复的RTM在MS和NOAB女性中的长期安全性和治疗作用 参加OLE阶段（两组的受试者将邀请在3个月的随访中输入）。 努力提高我们目前对大脑对降低尿路功能的贡献和发展的努力 大脑水平上的个性化，无创和有效的治疗方式将极大地影响 具有MS的个体以及随后患有OAB的个体的生活质量，无论是神经源或非神经源性的。