A randomized placebo-controlled trial of methylphenidate in Veterans with a diagnosis of post traumatic stress disorder and recent cerebral stroke.

在诊断为创伤后应激障碍和近期脑卒中的退伍军人中进行哌甲酯的随机安慰剂对照试验。

• 批准号: 10257285
• 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: 2021-10-01 至 2026-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10257285
• 关键词: Activities of Daily Living; Adverse event; Aerobic Exercise; Age; Brain; Caring; Central Nervous System Stimulants; Chronic; Clinical; Clinical Investigator; Clinical Trials; DSM-V; Data; Diagnosis; Dopamine; Evidence based treatment; Exclusion Criteria; Exercise; Experimental Designs; Extinction (Psychology); Face; Fright; Functional Magnetic Resonance Imaging; Genetic; Goals; Guidelines; High Prevalence; Intervention; Ischemic Stroke; Knowledge; Lead; Magnetic Resonance Imaging; Measures; Mediator of activation protein; Mentors; Modeling; Moods; Motor; Multivariate Analysis; Neurology; Neurons; Neurosciences; Outcome; Outcomes Research; Pain; Participant; Pathogenesis; Patients; Phase; Placebos; Play; Post-Traumatic Stress Disorders; Prefrontal Cortex; Psychiatry; Randomized; Recording of previous events; Recurrence; Regimen; Research; Research Design; Risk; Ritalin; Role; Safety; Services; Severities; Short-Term Memory; Signal Transduction; Site; Stroke; Stroke Belt; Structure; Symptoms; System; Therapeutic Effect; Training; United States; Veterans; Vietnam; Withdrawal; Work; acute stroke; avoidance behavior; comorbidity; dopamine transporter; double-blind placebo controlled trial; efficacy study; fear memory; follow-up; functional outcomes; high risk; improved; memory consolidation; military veteran; mood symptom; noradrenaline transporter; novel therapeutics; pain reduction; post stroke; post stroke pain; psychologic; randomized placebo controlled trial; reduce symptoms; resilience; screening; social; stress related disorder; stressor; stroke clinical trials; stroke outcome; stroke patient; stroke recovery; stroke risk; success; symptom treatment; therapy development; vascular risk factor

Veterans with post-traumatic stress disorder (PTSD) have an increased risk of developing ischemic stroke. Veterans enduring PTSD face difficulties in managing their PTSD severity after suffering from a stroke. Currently, clinical trials in PTSD exclude patients with stroke and patients with significant premorbid psychological conditions like PTSD are usually excluded from stroke clinical trials. Methylphenidate (MPH) is a central nervous system stimulant that blocks dopamine and norepinephrine transporters, selectively increasing prefrontal cortex (PFC) activity. MPH can improve PTSD symptoms: avoidance behaviors, social withdrawal, hyperarousal, and working memory. The suspected mechanism is MPH activates PFC, enhancing fear extinction [60] and improving PTSD symptoms. MPH can also improve post-stroke outcomes: mood, activities of daily living, and motor functioning. In clinical trials for PTSD or stroke, MPH has been shown to be well-tolerated with minimal adverse events. The high prevalence of PTSD in Veterans with stroke provides strong justification for development of interventions that effectively and simultaneously target both conditions. The overarching goal of our proposal is to understand how MPH improves PTSD severity in Veterans with comorbid stroke. This proposal is a single-site, phase 2, randomized double-blind placebo-controlled trial of MPH in the treatment of Veterans with a diagnosis of PTSD who are within 1-12 months of cerebral stroke. The purpose of the clinical trial is to evaluate the therapeutic effects on PTSD symptoms and post-stroke recovery of placebo-controlled MPH in Veterans diagnosed with PTSD and cerebral stroke. The outcome of the proposed work is expected to develop an intervention for patients with PTSD and stroke, thus improving their outcome by reducing symptom severity. Following successful screening and baseline randomization, eligible patients will be treated with a regimen of MPH vs placebo and treated for 12 weeks. They are assessed every 4 weeks (4, 8, 12) followed by a 2-week taper period and concluding with a [final follow- up at 30 days.] 50 participants will be randomized in a 1:1 ratio to placebo or MPH. Aim 1: Determine the feasibility of the efficacy study design in comparing rTMS and exercise versus sham rTMS and exercise to reduce pain in patients with chronic post-stroke pain. Hypothesis 1: Our feasibility pilot proposal will focus on collecting limited efficacy data for effect-size estimation to conduct a larger clinical trial using validated pain and functional measures in patients with chronic post-stroke pain using rTMS and exercise. Aim 2: Evaluate the safety of rTMS combined with aerobic exercise in patients with a history of ischemic stroke and chronic post-stroke pain. Hypothesis 2: The combined intervention of aerobic exercise plus rTMS will have both a low number of adverse events and a similar rate as aerobic exercise plus sham rTMS. Aim 3: To assess the correlation between the neuronal connectivity of the prefrontal cortex with PTSD outcomes and stroke outcomes following MPH vs Placebo in Veterans. Hypothesis 3: Compared to placebo, Veterans receiving MPH will show enhanced strengthening of the structural and functional connectivity of the prefrontal cortex with other regional structures. This strengthened connectivity will correlate to changes in PTSD and Stroke outcomes.

患有创伤后应激障碍（PTSD）的退伍军人患上 缺血性中风经历创伤后应激障碍的退伍军人在管理他们的创伤后应激障碍严重程度方面面临困难， 患有中风。目前，创伤后应激障碍的临床试验排除了中风患者和 有明显的病前心理状况，如创伤后应激障碍， 临床试验哌醋甲酯（MPH）是一种中枢神经系统兴奋剂， 和去甲肾上腺素转运蛋白，选择性地增加前额叶皮层（PFC）的活动。MPH可以 改善PTSD症状：回避行为、社交退缩、过度觉醒和工作 记忆怀疑的机制是MPH激活PFC，增强恐惧消退[60]， 改善创伤后应激障碍症状MPH还可以改善中风后的结果：情绪，活动， 日常生活和运动功能。在创伤后应激障碍或中风的临床试验中，MPH已被证明 耐受性良好，不良事件最少。创伤后应激障碍在退伍军人中的高患病率 中风为开发有效的干预措施提供了有力的理由， 同时针对这两种情况。我们提案的首要目标是了解 MPH如何改善患有共病卒中的退伍军人的PTSD严重程度 本提案是一项单中心、II期、随机、双盲、安慰剂对照试验， 公共卫生硕士学位用于治疗1-12个月内诊断出创伤后应激障碍的退伍军人 脑中风临床试验的目的是评估治疗PTSD的效果 在诊断患有MPH的退伍军人中安慰剂对照MPH的症状和卒中后恢复 创伤后应激障碍和脑中风。拟议工作的成果预计将制定一项 对创伤后应激障碍和中风患者进行干预，从而通过减少 症状严重程度。成功筛选和基线随机化后，符合条件的患者 将用MPH与安慰剂的方案治疗，并治疗12周。被评估 每4周（4，8，12）一次，随后是2周的减量期，并以[最终随访- 在30天内）。50名参与者将以1：1的比例随机分配至安慰剂组或MPH组。 目的1：确定比较rTMS和运动的有效性研究设计的可行性 与假rTMS和运动相比，以减轻慢性卒中后疼痛患者的疼痛。 假设1：我们的可行性试点提案将侧重于收集有限的疗效数据， 使用经验证的疼痛和功能进行更大规模临床试验的效应量估计 使用rTMS和运动对慢性卒中后疼痛患者进行测量。 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： 缺血性中风和慢性中风后疼痛。 假设2：有氧运动+rTMS的联合干预， 不良事件的数量和相似的比率为有氧运动加假rTMS。 目的3：评估前额叶皮层神经元连通性与 退伍军人中MPH与安慰剂治疗后的PTSD结局和卒中结局 假设3：与安慰剂相比，接受MPH的退伍军人将表现出增强的 加强前额叶皮层与其他神经元的结构和功能连接， 区域结构。这种加强的连接将与PTSD的变化相关， 卒中结局。