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。在退伍军人中， 中风是导致神经功能障碍的主要原因，也是导致中风的主要原因之一。 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。后 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。演习 已被证明可以改善PSP患者的疼痛症状。美国心脏/中风 协会建议，运动应纳入中风的管理 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性疼痛。欧盟委员会将制定指导方针 关于rTMS的治疗应用，陈述了对侧初级运动的rTMS证据 皮质具有明确的镇痛作用，几乎没有安全性问题（A级推荐）。然而，在这方面， 治疗的效果是短暂的，通常持续数小时至数天[20]。虽然非- 作为一种实用的治疗慢性PSP的侵入性方法，rTMS更持久的疗效将是 需要被证明。我们假设，rTMS与运动配对可能会产生一种 相辅相成的效果，以提高症状缓解的持续时间。 本提案是一项单中心、随机化假对照试验，研究rTMS和运动在 治疗被诊断为慢性PSP的退伍军人，他们至少有6个月的时间， 脑中风试验研究的目的是评估 rTMS+运动在诊断为慢性PSP的退伍军人中的应用我们将收集数据， 疗效试验，以评估持续rTMS与运动对疼痛结局的影响。长期 拟议工作的目标是开发一种非药物干预， 慢性PSP患者的体力活动。在成功筛选后， 基线随机化，合格患者将接受rTMS与假rTMS方案治疗 1周。参与者在第1周结束时返回进行评估，并继续分配的 rTMS手臂，同时从第2周到第9周每周增加3次有监督的有氧运动。最终 评估是3个月。 目的1：评价比较rTMS和运动与 假rTMS和运动以减轻慢性PSP患者的疼痛。 假设1：征聘速度可以接受。我们将招募36名患者， 他们将在3个月内完成研究。 目的2：评估rTMS联合有氧运动治疗有以下病史患者的安全性： 缺血性中风和慢性PSP。 假设2：少于10%的患者随机接受有氧运动联合干预 运动加rTMS将有不良事件，观察到的发生率将与 患者随机分为有氧运动加假rTMS组。 目的3：评估运动皮层神经元连接与疼痛之间的相关性， 退伍军人接受rTMS刺激和有氧运动干预后的中风结局。 假设3：结构和功能连接的测量加强， 使用默认模式网络、边缘系统和 感觉运动区将更高的运动加rTMS相比，运动加 假rTMS（仅估计，无统计学检验）。