Background: Transcranial Magnetic Stimulation (TMS) is a technique based on the principles of electromagnetic induction. It applies pulses of magnetic radiation that penetrate the brain tissue, and it is a non-invasive, painless, and practically innocuous procedure. Previous studies advocate the therapeutic capacity of TMS in several neurodegenerative and psychiatric processes, both in animal models and in human studies. Its uses in Parkinson's disease, Alzheimer's disease and in Huntington's chorea have shown improvement in the symptomatology and in the molecular profile, and even in the cellular density of the brain. Consequently, the extrapolation of these TMS results in the aforementioned neurodegenerative disease to other entities with etiopathogenic and clinical analogy would raise the relevance and feasibility of its use in multiple sclerosis (MS). The overall objective will be to demonstrate the effectiveness of the TMS in terms of safety and clinical improvement, as well as to observe the molecular changes in relation to the treatment. Methods and Design: Phase II clinical trial, unicentric, controlled, randomized, single blind. A total of 90 patients diagnosed with relapsing-remitting multiple sclerosis (RRMS) who meet all the inclusion criteria and do not present any of the exclusion criteria that are established and from which clinically evaluable results can be obtained. The patients included will be assigned under the 1:1:1 randomization formula, constituting three groups for the present study: 30 patients treated with natalizumab + white (placebo) + 30 patients treated with natalizumab + TMS (1 Hz) + 30 patients treated with natalizumab + TMS (5 Hz). Discussion: Results of this study will inform on the efficiency of the TMS for the treatment of MS. The expected results are that TMS is a useful therapeutic resource to improve clinical status (main parameters) and neurochemical profile (surrogate parameters); both types of parameters will be checked. Ethics and Dissemination: The study is approved by the Local Ethics Committee and registered in https://clinicaltrials.gov (NCT04062331). Dissemination will include submission to a peer-reviewed journal, patients, associations of sick people and family members, healthcare magazines and congress presentations. Trial Registration: ClinicalTrials.gov ID: NCT04062331 (registration date: 19th/ August/2019). Version Identifier: EMTr-EMRR, ver-3, 21/11/2017.

中文翻译：

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经颅磁刺激（TMS）在多发性硬化症中的临床和神经化学作用：一项针对随机临床试验的研究方案。

背景：经颅磁刺激（TMS）是一种基于电磁感应原理的技术。它施加穿透脑组织的电磁辐射脉冲，这是一种无创，无痛且几乎无害的手术。先前的研究主张在动物模型和人体研究中，TMS在几种神经退行性和精神病学过程中的治疗能力。它在帕金森氏病，阿尔茨海默氏病和亨廷顿舞蹈病中的使用已显示出症状，分子分布甚至大脑细胞密度的改善。所以，这些TMS的外推导致上述神经退行性疾病与其他具有致病性和临床相似性的实体发生，将提高其在多发性硬化症（MS）中的应用的相关性和可行性。总体目标是证明TMS在安全性和临床改善方面的有效性，并观察与治疗有关的分子变化。方法和设计：II期临床试验，单中心，对照，随机，单盲。总共90例被诊断患有复发缓解型多发性硬化症（RRMS）的患者，符合所有纳入标准，但未提出已建立的任何排除标准，并且可以从中获得临床评价的结果。纳入的患者将按照1：1：1的随机分配方案进行分配，构成本研究的三组：30例接受那他珠单抗+白色（安慰剂）治疗的患者+ 30例接受那他珠单抗+ TMS（1 Hz）治疗的患者+ 30例那他珠单抗+ TMS（5 Hz）治疗的患者。讨论：这项研究的结果将为TMS治疗MS提供参考。预期结果是TMS是改善临床状态（主要参数）和神经化学特征（替代参数）的有用治疗资源；两种类型的参数都将被检查。道德与传播：该研究已由地方道德委员会批准，并在https://clinicaltrials.gov（NCT04062331）中注册。传播将包括提交给同行评审期刊，患者，病人和家庭成员协会，医疗杂志和国会报告。试验注册：ClinicalTrials。政府机关编号：NCT04062331（注册日期：2019年8月19日）。版本标识符：EMTr-EMRR，ver-3，21/11/2017。