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

患有创伤后应激障碍(PTSD)的退伍军人患上创伤后应激障碍的风险增加 缺血性中风。患有创伤后应激障碍的退伍军人面临着管理其创伤后应激障碍严重程度的困难 罹患中风。目前，创伤后应激障碍的临床试验排除了中风患者和 严重的病前心理疾病，如创伤后应激障碍，通常被排除在中风之外 临床试验。哌醋甲酯(Mph)是一种中枢神经系统兴奋剂，可阻断多巴胺。 和去甲肾上腺素转运体，选择性地增加前额叶皮质(PFC)的活性。每小时英里数可以 改善创伤后应激障碍症状：回避行为、社交退缩、高度觉醒和工作 记忆。被怀疑的机制是mph激活PFC，增强恐惧消退[60]和 改善创伤后应激障碍症状。公共卫生还可以改善中风后的结局：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 耐受性好，不良事件最少。退伍军人创伤后应激障碍的高患病率 中风提供了强有力的理由来开发有效和 同时针对这两种情况。我们提案的首要目标是理解 公共卫生如何改善患有中风的退伍军人的创伤后应激障碍严重程度。 这项建议是一项单地点、2期、随机、双盲、安慰剂对照试验。 公共卫生对退伍军人创伤后应激障碍的治疗作用 脑中风。临床试验的目的是评估对创伤后应激障碍的治疗效果。 退伍军人接受安慰剂控制的公共卫生指数的症状和卒中后恢复 创伤后应激障碍和中风。拟议工作的结果预计将制定一项 对创伤后应激障碍和中风患者的干预，从而通过减少 症状严重程度。在成功的筛查和基线随机之后，符合条件的患者 将接受MPH与安慰剂的治疗方案，并治疗12周。对他们进行评估 每4周(4周、8周、12周)，然后是2周的锥化期，最后是[最终跟进- 最多30天。]50名参与者将按1：1的比例随机加入安慰剂或MPH。 目的1：比较rTMS和运动，确定有效性研究设计的可行性 对比假rTMS和运动以减轻慢性卒中后疼痛患者的疼痛。 假设1：我们的可行性试行方案将侧重于收集有限的疗效数据 使用验证的疼痛和功能性进行更大规模临床试验的效果-规模估计 应用rTMS和运动对慢性卒中后疼痛患者的测量。 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。 缺血性中风和慢性中风后疼痛。 假设2：有氧运动加rTMS的联合干预将会有一个低的 不良事件的数量以及与有氧运动加假rtms相似的发生率。 目的3：探讨前额叶皮质神经元连通性与 退伍军人在mph与安慰剂治疗后的创伤后应激障碍结果和卒中结果。 假设3：与安慰剂相比，接受公共卫生政策的退伍军人表现得更好 加强前额叶皮质与其他脑区的结构和功能连接 区域结构。这种加强的连接将与创伤后应激障碍和 中风的结果。

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.