A Randomized Placebo-controlled Trial of Methylphenidate in Veterans With a Diagnosis of Post Traumatic Stress Disorder and Recent Cerebral Stroke
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in Modified Rankin Scale at 12 Weeks
研究概览
简要总结
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 can improve PTSD symptoms: avoidance behaviors, social withdrawal, hyperarousal, and working memory. 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.
详细描述
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 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. 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Study personnel and participants will be blinded to the treatment (placebo vs methylphenidate).
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female Veteran of US military; signed informed consent
- •Criterion A Index Trauma(s) resulting in PTSD occurred during adulthood prior to stroke
- •CAPS-5 past week total score =23 at baseline visit
- •Willing to refrain from antipsychotics, mood stabilizers, stimulants, and any formulation of MPH
- •First-ever symptomatic ischemic stroke radiologically verified, occurring within past 1-12 months
- •Females of child-bearing potential (i.e. not postmenopausal or surgically sterile) must be using a medically acceptable method of birth control and should not be pregnant nor have plans for pregnancy or breastfeeding during the study
排除标准
- •Moderate to severe cognitive impairment (Montreal Cognitive Assessment score <16/30)
- •Poor pre-stroke baseline function of a modified Rankin score >2
- •Presence of any standard MRI contraindications
- •Current diagnosis of DSM-5-defined bipolar disorder I, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, or major depressive disorder with psychotic features (MINI)
- •Diagnosis of moderate or severe substance use disorder (except for caffeine and nicotine) during the preceding 3 months
- •Patients who utilize alcohol or cannabis but do not meet criteria for moderate or severe disorder are permitted at the discretion of the investigator
- •Participants must agree to abstain from illicit drugs during the study
- •Increased risk of suicide that necessitates inpatient treatment or warrants additional therapy excluded by the protocol; and/or intensity of suicidal ideation (Type 4 or Type 5) or any suicidal behavior in the past 3 months on Columbia Suicide Severity Rating Scale (C-SSRS)
- •Use of any investigational drug, MPH formulation, antipsychotics, mood stabilizers, monoamine oxidase inhibitors, stimulants or any medication known to be a potent (strong) cytochrome P450 subtype 3A4 inhibitor within 2 weeks of baseline
- •Treatment with evidence-based trauma-focused therapy for PTSD within two weeks of baseline (if participant is receiving therapy, he/she must complete treatment prior to entering study)
- •Supportive psychotherapy in process at time of Screening may be continued during the study.
- •History of moderate or severe TBI as defined by the Ohio State University TBI Identification Method
- •Based on investigator's clinical judgment, history of mild TBI is not excluded
- •Any clinically significant, uncontrolled, or medical/surgical condition or laboratory abnormality that would contraindicate use of MPH (see Human Subjects section)
- •Severe allergic reaction, bronchospasm, or hypersensitivity to any MPH formulation.
- •Litigating for compensation for a psychiatric disorder. Veterans who are in the process of applying for or receiving VA service-connected disability are eligible
- •Current enrollment in another intervention trial for PTSD or stroke
- •Persons imprisoned, diagnosed with terminal illness, or require surrogate for consent
研究组 & 干预措施
Placebo
Patient with both PTSD and recent history of stroke. Placebo control arm. The frequency will be up to twice a day, with oral dosing.
干预措施: Placebo (Drug)
Methylphenidate
Patient with both PTSD and recent history of stroke. Methylphenidate active arm. The oral dosing maximum will be up to 20mg twice daily.
干预措施: Methylphenidate (Drug)
结局指标
主要结局
Change in Modified Rankin Scale at 12 Weeks
时间窗: From baseline to Week 12
The modified Ranking scale (mRS) is a single-item, global, Likert-type scale ranging from 0-6 (higher scores mean a worse outcome) to categorize level of functional independence with comparison to pre-stroke function, accounting for activities of daily living. Participants were scored at baseline, Week 4, Week 8, Week 12, and 30 days after tapering after methylphenidate/placebo. The mean change from baseline at Week 12 for each group is reported.
次要结局
未报告次要终点