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: 10254914
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10254914
• 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; 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; Structure; Suicide; Supervision; Symptoms; Syndrome; Techniques; Testing; Therapeutic Uses; Time; Treatment outcome; United States; Veterans; Work; acute stroke; arm; associated symptom; base; chronic pain; 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700多万中风幸存者。在退伍军人群体中， 中风是导致神经功能障碍的主要原因之一，也是 住院治疗。中风后的慢性疼痛可能发生在10%-50%的中风幸存者之间。邮寄- 中风疼痛(PSP)可导致中风幸存者康复过程中的进一步并发症。锻炼有 已被证明能改善PSP患者的疼痛症状。美国人的心脏/中风 协会建议，应将运动纳入中风的管理 幸存者。重复经颅磁刺激(RTMS)使用非侵入性皮质 神经刺激以改善神经病理性疼痛。欧盟委员会将制定指导方针 论rTMS的治疗应用--兼论对侧初级运动rTMS的证据 皮质醇具有确切的止痛效果，安全性问题较少(A级推荐)。然而， 治疗的效果是短暂的，通常持续几个小时到几天[20]。而非- 作为一种治疗慢性PSP的实用方法，rTMS的疗效将更加持久。 需要被证明。我们假设rTMS与运动配对可能会发展成一种 补充作用，提高症状缓解的持续时间。 这项建议是一项关于rTMS和运动的单点随机假对照试验。 诊断为慢性PSP的退伍军人的治疗 脑中风。这项初步研究的目的是评估 退伍军人慢性PSP患者rTMS+运动的研究我们将收集数据以规划更大规模的 评估运动对疼痛结局的持续rTMS影响的有效性试验。长期的 这项拟议工作的目标是开发一种非药物干预，这种干预也可以增加 慢性PSP患者的体力活动。在成功进行筛查和 基线随机，符合条件的患者将接受rTMS和Sham rTMS方案的治疗 为期1周。参与者在第一周结束时返回进行评估，并继续分配的 RTMS手臂，同时增加监督有氧运动，每周3次，从第2周到第9周。最终 评估期限为3个月。 目的1：评价一项疗效研究设计的可行性，比较rTMS和运动与 假rTMS和运动可减轻慢性PSP患者的疼痛。 假设1：招聘的速度是可以接受的。我们将招募36名患者，其中32名 谁将在3个月内完成这项研究。 目的2：评价rTMS联合有氧运动治疗有高血压病史的患者的安全性。 缺血性卒中和慢性PSP。 假设2：不到10%的患者随机接受有氧联合干预 运动加rTMS将有不良事件，观察到的比率将与 患者被随机分为有氧运动加假rTMS组。 目的3：评估运动皮质神经元连接性与疼痛和 退伍军人rTMS刺激和有氧运动干预后的卒中结果。 假设3：测量到的结构和功能连接性的加强 RTMS刺激后的运动皮质以默认模式网络、边缘和 与运动加rTMS相比，运动加rTMS的感觉运动区更高 假rtms(仅供估计，不进行统计检验)。