Feasibility of combination exercise and neuromodulation rehabilitation to improve post-stroke chronic pain

联合运动和神经调节康复改善中风后慢性疼痛的可行性

• 批准号: 10436215
• 负责人: Chen Lin
• 金额: --
• 依托单位: BIRMINGHAM VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10436215
• 关键词: Adverse event; Aerobic Exercise; Aftercare; American; American Stroke Association; Analgesics; Brain; Caring; Chronic; Classification; Clinical Trials; Cognition; Contralateral; Data; Development; Diagnosis; Double-Blind Method; Electromagnetics; European; Exercise; Fatigue; Future; Goals; Guidelines; Headache; Headache Disorders; Heart; Hospitalization; Hour; Inpatients; International; Intervention; Ischemic Stroke; Lead; Magnetism; Measurement; Measures; Medical center; Mental Depression; Meta-Analysis; Methods; Modification; Motor Cortex; Neurologic; Neurons; Opioid; Outcome; Pain; Participant; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Physical activity; Physical therapy; Pilot Projects; Precentral gyrus; Preparation; Procedures; Quality of life; Randomized; Recommendation; Recording of previous events; Recovery; Refractory; Regimen; Rehabilitation therapy; Reporting; Research Design; Safety; Site; Stroke; Stroke Belt; Suicide; Supervision; Symptoms; Syndrome; Techniques; Testing; Therapeutic Uses; Time; Treatment outcome; United States; Veterans; Work; acute stroke; arm; associated symptom; base; chronic pain; chronic pain management; cohort; craving; design; disability; efficacy study; efficacy trial; evidence based guidelines; exercise intervention; experience; functional outcomes; implementation intervention; improved; interest; military veteran; mortality; neuroimaging; neuroregulation; pain outcome; pain reduction; pain score; pain symptom; painful neuropathy; post stroke; post stroke pain; recruit; repetitive transcranial magnetic stimulation; safety and feasibility; screening; stroke incidence; stroke outcome; stroke survivor; tool; treatment effect

There are over 7 million stroke survivors in the United States. In the Veteran population, stroke is the leading cause of neurological disability, and one of leading causes of hospitalization. Chronic pain after stroke can occur between 10-50% of stroke survivors. Post- stroke pain (PSP) can lead to further complications in a stroke survivor’s recovery. Exercise has been shown to improve pain symptoms of patients with PSP. the American Heart/Stroke Association recommended that exercise should be incorporated into the management of stroke survivors. Repetitive transcranial magnetic stimulation (rTMS) uses noninvasive cortical neurostimulation to improve neuropathic pain. A European commission to establish guidelines on therapeutic use of rTMS stated the evidence of rTMS of the contralateral primary motor cortex as definite analgesic effect with few safety issues (Level A recommendation). However, the effects of the treatment are transient, usually lasting a few hours to days[20]. While non- invasive, as a practical therapy for chronic PSP, more sustained efficacy of rTMS would be needed to be demonstrated. We hypothesize that pairing rTMS with exercise may develop a complementary effect to enhance the duration of symptomatic relief. This proposal is a single-site, randomized sham-controlled trial of rTMS and exercise in the treatment of Veterans with a diagnosis of chronic PSP who are at least 6-months from their cerebral stroke. The purpose of the pilot study is to evaluate the feasibility and safety of rTMS+exercise in Veterans diagnosed with chronic PSP. We will gather data to plan for a larger efficacy trial to assess sustained rTMS effects with exercise on pain outcomes. The long-term goal of the proposed work is to develop a non-pharmacologic intervention that also increases physical activity for patients suffering from chronic PSP. Following successful screening and baseline randomization, eligible patients will be treated with a regimen of rTMS vs sham rTMS for 1 week. Participants return for assessments at the end of week 1 and continue the assigned rTMS arm while adding supervised aerobic exercise 3 times weekly from week 2 to 9. Final assessment is at 3 months. Aim 1: Evaluate the feasibility of an efficacy study design comparing rTMS and exercise versus sham rTMS and exercise to reduce pain in patients with chronic PSP. Hypothesis 1: The pace of recruitment will be acceptable. We will recruit 36 patients, 32 of whom will complete the study within 3 months. Aim 2: Evaluate the safety of rTMS combined with aerobic exercise in patients with a history of ischemic stroke and chronic PSP. Hypothesis 2: Less than 10% of patients randomized to combined intervention of aerobic exercise plus rTMS will have adverse events and the observed rate will be comparable to patients randomized to aerobic exercise plus sham rTMS. Aim 3: To assess the correlation between neuronal connectivity of the motor cortex with pain and stroke outcomes following rTMS stimulation and aerobic exercise intervention in Veterans. Hypothesis 3: The measured strengthening of the structural and functional connectivity in the motor cortex following rTMS stimulation with the default mode network, limbic, and sensorimotor regions will be higher for the exercise plus rTMS compared with exercise plus sham rTMS (estimate only, without statistical testing).

美国有超过700万中风幸存者。在退伍军人人口中， 中风是神经残疾的主要原因，是 住院。中风后的慢性疼痛可能发生在10-50％的中风幸存者之间。邮政- 中风疼痛（PSP）可能导致中风幸存者康复的进一步并发症。运动有 我们被证明可以改善PSP患者的疼痛症状。美国心脏/中风 协会建议将运动纳入中风管理 幸存者。重复的经颅磁刺激（RTMS）使用无创皮质 神经刺激以改善神经性疼痛。建立准则的欧洲委员会 理论上使用RTMS表示对侧原发电动机的RTMS的证据 皮质作为定义的镇痛作用，几乎没有安全问题（建议级）。然而， 治疗的作用是短暂的，通常持续几个小时到几天[20]。而不是 - 作为慢性PSP的一种实际疗法，RTMS的持续效率将是一种侵入性 需要证明。我们假设将RTM与运动配对可能会发展 完全效果以增强症状缓解的持续时间。 该提案是RTMS的单一站点，随机的假对照试验，并在 用慢性PSP的诊断对退伍军人的治疗，他们是至少6个月的 大脑中风。试点研究的目的是评估 RTMS+在被诊断为慢性PSP的退伍军人中运动。我们将收集数据以计划更大 效应试验，以通过运动对疼痛结果进行锻炼来评估持续的RTMS效应。长期 拟议的工作的目标是开发一种非药物干预措施，也会增加 患有慢性PSP的患者的体育活动。成功筛选之后 基线随机化，符合条件的患者将通过RTMS与假RTMS治疗 1周。参与者在第1周末返回评估，并继续分配 RTMS ARM在每周第2周至第9周增加3次监督有氧运动。 评估为3个月。 目标1：评估效率研究设计的可行性，比较RTMS和运动与运动 假RTMS和运动以减轻慢性PSP患者的疼痛。 假设1：招聘的步伐将是可以接受的。我们将招募36名患者，32例 谁将在3个月内完成研究。 目标2：评估RTMS与有氧运动的安全性 缺血性中风和慢性PSP。 假设2：少于10％ 练习加RTM会发生不良事件，观察到的速率将与 患者随机进行有氧运动和假RTMS。 目标3：评估运动皮层神经元连通性与疼痛和 RTMS刺激和有氧运动干预退伍军人后的中风结果。 假设3：测量的结构和功能连通性的增强 RTMS刺激后使用默认模式网络，边缘和 与运动相比，运动和RTM的感觉运动区域将更高 假RTMS（仅估计，没有统计测试）。