Low frequency rTMS and fluoxetine for motor recovery after ischemic stroke

低频 rTMS 和氟西汀用于缺血性中风后运动恢复

• 批准号: 8918015
• 负责人: Felipe Fregni
• 金额: $ 24.13万
• 依托单位: SPAULDING REHABILITATION HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8918015
• 关键词: Accounting; Activities of Daily Living; Affect; Age; American Heart Association; Area; Biological Neural Networks; Brain; Clinical; Combined Modality Therapy; Control Groups; Evaluation; Fluoxetine; Frequencies; Future; Goals; Health; Intervention; Ischemic Stroke; Knowledge; Long-Term Potentiation; Measurement; Mental Depression; Motor; Motor Cortex; Motor Evoked Potentials; Motor Skills; Multicenter Trials; Neuronal Plasticity; Occupational Therapy; Patients; Pattern; Performance; Pharmacotherapy; Physical therapy; Physiologic pulse; Placebo Control; Placebos; Population; Process; Property; Recovery; Recruitment Activity; Rehabilitation therapy; Research; Research Project Grants; Role; Selective Serotonin Reuptake Inhibitor; Sertraline; Stroke; System; Testing; Therapeutic; Treatment Protocols; United States; base; disability; experience; functional outcomes; improved; indexing; motor function improvement; motor learning; motor recovery; neurophysiology; neuroregulation; post intervention; post stroke; repetitive transcranial magnetic stimulation; restoration; skill acquisition; stroke recovery; stroke rehabilitation; success

DESCRIPTION (provided by applicant): The goal of this proposal is to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) combined with pharmacotherapy (fluoxetine) in the rehabilitation of post-stroke subjects. This research will help to reveal the relationship between function restorations via pharmacological intervention when combined with noninvasive neuromodulation in patients after ischemic stroke. Stroke is the leading cause of disability in the United States (Nowak et al., 2009) According to the American Heart Association, over 795,000 people experience stroke annually in the USA (Lloyd-Jones et al., 2009). Unfortunately, restitution of post-stroke motor function is frequently incomplete, with the majorit of stroke patients unable to perform professional duties or activities of daily living by six month after their stroke (Hummel and Cohen, 2006). Currently, there are only a few treatments available to improve motor function in stroke; most of them are based on motor learning strategies. Although these treatments may improve motor function significantly, their effects are often limited. The general objective of this research project is to assess the clinical and neurophysiological properties of rTMS and fluoxetine to promote motor recovery in post-stroke subjects as indexed by clinical motor function scales. This will be done by delivering low-frequency rTMS over the brain primary motor cortex (M1) in the unaffected hemisphere while the subjects are receiving fluoxetine treatment, subjects will be assessed at one and three months post intervention. Finally, we will investigate the mechanisms of this treatment by studying the induced neurophysiological and functional changes. This will be indexed by motor evoked potentials, cortical excitability/inhibition measurements, transcallosal inhibition evaluation, and paired associative stimulation. Regarding assurance of success, this proposal has two main specific aims: Aim 1: To determine whether low-frequency rTMS associated with fluoxetine offers additional benefits on motor rehabilitation and retention of motor skills, than pharmacotherapy alone. Aim 2: To determine the effects on cortical excitability when rTMS is combined with pharmacotherapy, whether fluoxetine is capable to induce positive or negative effects in M1 neuromodulation.

描述（由申请人提供）：本提案的目的是研究重复经颅磁刺激（rTMS）联合药物治疗（氟西汀）对中风后受试者康复的影响。这项研究将有助于揭示缺血性中风患者通过药物干预与无创神经调节相结合恢复功能之间的关系。中风是美国致残的主要原因（Nowak 等，2009）。根据美国心脏协会的统计，美国每年有超过 795,000 人中风（Lloyd-Jones 等，2009）。不幸的是，中风后运动功能的恢复通常是不完全的，大多数中风患者在中风后六个月内无法履行专业职责或日常生活活动（Hummel 和 Cohen，2006）。目前，只有少数治疗方法可以改善中风的运动功能；其中大多数都是基于运动学习策略。尽管这些治疗可以显着改善运动功能，但其效果往往有限。该研究项目的总体目标是评估 rTMS 和氟西汀的临床和神经生理学特性，以促进中风后受试者的运动恢复（以临床运动功能量表为索引）。这将通过在受试者接受氟西汀治疗时向未受影响的半球的大脑初级运动皮层 (M1) 提供低频 rTMS 来完成，受试者将在干预后 1 个月和 3 个月进行评估。最后，我们将通过研究引起的神经生理和功能变化来研究这种治疗的机制。这将通过运动诱发电位、皮质兴奋性/抑制测量、经胼胝体抑制评估和配对联想刺激来索引。关于成功的保证，该提案有两个主要的具体目标： 目标 1：确定与单独的药物治疗相比，与氟西汀相关的低频 rTMS 是否对运动康复和运动技能的保留具有额外的益处。目标 2：确定 rTMS 与药物治疗相结合时对皮质兴奋性的影响，氟西汀是否能够对 M1 神经调节产生积极或消极的影响。

项目成果

Combining Fluoxetine and rTMS in Poststroke Motor Recovery: A Placebo-Controlled Double-Blind Randomized Phase 2 Clinical Trial.

氟西汀和 rTMS 联合用于中风后运动恢复：安慰剂对照双盲随机 2 期临床试验。

• 发表时间: 2019
• 影响因子: 4.2
• 作者: Bonin Pinto, Camila;Morales;de Toledo Piza, Polyana Vulcano;Zeng, Dian;Saleh Vélez, Faddi Ghassan;Ferreira, Isadora Santos;Lucena, Pedro Henrique;Duarte, Dante;Lopes, Fernanda;El;Rizzo, Luiz Vicente;Camargo, Eri
• 通讯作者: Camargo, Eri

Neurophysiologic predictors of motor function in stroke.

中风运动功能的神经生理学预测因素。

• 发表时间: 2016
• 影响因子: 2.8
• 作者: Simis, Marcel;Doruk, Deniz;Imamura, Marta;Anghinah, Renato;Morales;Fregni, Felipe;Battistella, Linamara Rizzo
• 通讯作者: Battistella, Linamara Rizzo

SSRI and Motor Recovery in Stroke: Reestablishment of Inhibitory Neural Network Tonus.

SSRI 和中风中的运动恢复：抑制性神经网络张力的重建。

• 发表时间: 2017
• 作者: Pinto, Camila B;Saleh Velez, Faddi G;Lopes, Fernanda;de Toledo Piza, Polyana V;Dipietro, Laura;Wang, Qing M;Mazwi, Nicole L;Camargo, Erica C;Black;Fregni, Felipe
• 通讯作者: Fregni, Felipe

A combined therapeutic approach in stroke rehabilitation: A review on non-invasive brain stimulation plus pharmacotherapy.

中风康复的综合治疗方法：非侵入性脑刺激加药物治疗的回顾。

• 发表时间: 2014-11
• 作者: Perez, Carolina;Morales;Fregni, Felipe
• 通讯作者: Fregni, Felipe

Recruitment challenges in stroke neurorecovery clinical trials.

中风神经恢复临床试验中的招募挑战。

• 发表时间: 2019-09
• 影响因子: 1.5
• 作者: Ferreira, Isadora Santos;Pinto, Camila Bonin;Saleh Velez, Faddi Ghassan;Leffa, Douglas Teixeira;Vulcano de Toledo Piza, Polyana;Fregni, Felipe
• 通讯作者: Fregni, Felipe