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.

具有创伤后应激障碍（PTSD）的退伍军人的发展风险增加 缺血性中风。持久PTSD的退伍军人在管理其PTSD严重性之后面临困难 患有中风。目前，PTSD的临床试验不包括中风患者和患者 诸如PTSD（PTSD）的重要前心理状况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刺激剂，可阻断多巴胺 和去甲肾上腺素转运蛋白，有选择地增加前额叶皮层（PFC）活性。 mph可以 改善PTSD症状：避免行为，社交戒断，高音和工作 记忆。可疑的机制是MPH激活PFC，增强了恐惧灭绝[60]和 改善PTSD症状。 MPH还可以改善势后结果：情绪，活动 日常生活和运动功能。在PTSD或中风的临床试验中，已显示MPH已显示为 对最小的不良事件进行良好的耐受性。在退伍军人中，PTSD的高龄 中风为开发干预措施提供了有效和有效的干预措施的理由 同时针对这两个条件。我们提议的总体目标是了解 MPH如何改善合并症的退伍军人的PTSD严重程度。 该提案是一个单点，第2阶段，随机的双盲安慰剂对照试验 MPH治疗退伍军人，并诊断为PTSD 大脑中风。临床试验的目的是评估对PTSD的治疗作用 在被诊断的退伍军人中，安慰剂控制的MPH的症状和势后恢复 PTSD和大脑中风。拟议工作的结果有望发展 对PTSD和中风患者的干预，从而通过减少来改善其结果 症状严重程度。成功筛查和基线随机分组后，符合条件的患者 将通过MPH与安慰剂的治疗治疗，并治疗12周。他们进行了评估 每4周（4、8、12），然后进行2周的锥度，并结束[最终后续时期 - 在30天后上升。] 50名参与者将以1：1的比例与安慰剂或MPH进行随机分配。 目标1：确定效能研究设计在比较RTM和锻炼中的可行性 相对于假RTMS和运动以减轻慢性冲程后疼痛患者的疼痛。 假设1：我们的可行性试点建议将集中于收集有限的效力数据 效应大小的估计，使用经过验证的疼痛和功能进行更大的临床试验 使用RTMS和运动的慢性冲程后疼痛患者的措施。 目标2：评估RTMS与有氧运动的安全性 缺血性中风和慢性势后疼痛。 假设2：有氧运动和RTM的综合干预措施将均具有较低的 不良事件的数量和类似于有氧运动加上假RTM的速度。 目标3：评估前额叶皮质的神经元连通性与 在退伍军人中，MPH与安慰剂之后的PTSD结果和中风结果。 假设3：与安慰剂相比，接收MPH的退伍军人将显示增强 加强前额叶皮层与其他的结构和功能连通性 区域结构。这种加强的连通性将与PTSD的变化和 中风结果。