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: 10426264
• 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/10426264
• 关键词: Activities of Daily Living; Admission activity; Adverse event; Aerobic Exercise; Age; Brain; Caring; Central Nervous System Stimulants; Chronic; Clinical; Clinical Investigator; Clinical Trials; DSM-V; Data; Diagnosis; Dopamine; Eligibility Determination; Evidence based treatment; Exclusion; Exclusion Criteria; Exercise; Experimental Designs; Extinction; Face; Fright; Functional Magnetic Resonance Imaging; Genetic; Goals; Guidelines; High Prevalence; Intervention; Ischemic Stroke; Knowledge; Magnetic Resonance Imaging; Measures; Mediator; Mentors; Modeling; Moods; Motor; Multivariate Analysis; Neurology; Neurons; Neurosciences; Outcome; Outcomes Research; Pain; Participant; Pathogenesis; Patients; Persons; Phase; Placebo Control; 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; effective intervention; 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; psychiatric comorbidity; psychologic; randomized placebo controlled trial; reduce symptoms; resilience; screening; social; stressor; stroke clinical trials; stroke outcome; stroke recovery; stroke risk; success; symptom treatment; symptomatic improvement; 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 (PTSD) 的退伍军人在治疗后面临着管理其创伤后应激障碍 (PTSD) 严重程度的困难 患有中风。目前，PTSD 的临床试验排除了中风患者和患者 患有严重病前心理疾病（如创伤后应激障碍）的患者通常被排除在中风之外 临床试验。哌甲酯 (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蛋白，选择性增加前额皮质（PFC）活性。英里每小时可以 改善 PTSD 症状：回避行为、社交退缩、过度警觉和工作 记忆。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。 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 PTSD 或中风的临床试验中，MPH 已被证明可以 耐受性良好，不良事件最少。退伍军人中创伤后应激障碍（PTSD）患病率很高 中风为开发有效且有效的干预措施提供了强有力的理由 同时针对这两个条件。我们提案的总体目标是了解 MPH 如何改善患有中风共病的退伍军人的 PTSD 严重程度。 该提案是一项单中心、2 期、随机双盲安慰剂对照试验 MPH 治疗诊断为 PTSD 且在 1-12 个月内的退伍军人 脑中风。临床试验的目的是评估对 PTSD 的治疗效果 诊断患有以下疾病的退伍军人的症状和安慰剂对照 MPH 的中风后恢复 创伤后应激障碍和脑中风。拟议工作的成果预计将制定一个 对患有 PTSD 和中风的患者进行干预，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 将接受 MPH 方案与安慰剂方案的治疗，并治疗 12 周。他们被评估 每 4 周（4、8、12），然后是 2 周的减量期，最后以[最后的后续- 30 天后。] 50 名参与者将按 1:1 的比例随机分配到安慰剂或 MPH。 目标 1：确定比较 rTMS 和运动的功效研究设计的可行性 与假 rTMS 和运动相比，减轻慢性中风后疼痛患者的疼痛。 假设 1：我们的可行性试点提案将侧重于收集有限的功效数据 效果大小估计，使用经过验证的疼痛和功能进行更大规模的临床试验 使用 rTMS 和运动对慢性中风后疼痛患者进行治疗。 目标 2：评估 rTMS 联合有氧运动对有以下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的联合干预将具有较低的 不良事件的数量以及与有氧运动加假 rTMS 相似的发生率。 目标 3：评估前额皮质神经元连接与 退伍军人中 MPH 与安慰剂相比的 PTSD 结果和中风结果。 假设 3：与安慰剂相比，接受 MPH 的退伍军人将表现出增强 加强前额皮质与其他皮质的结构和功能连接 区域结构。这种加强的连通性将与创伤后应激障碍 (PTSD) 和 中风结果。