Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness - A Phase 1 Study
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events at Each Dose
研究概览
简要总结
Phase 1 of the STIMPACT trial is an open label,dose-escalation,safety study of intravenous (IV) methylphenidate (MPH) therapy in patients with disorders of consciousness (DoC) caused by severe brain injuries.
详细描述
To be classified as having a DoC, a patient must be in a coma, vegetative state (VS), or minimally conscious state (MCS), as determined by behavioral assessment using the Coma Recovery Scale-Revised (CRS-R). Patients with DoC admitted to the intensive care unit (ICU) will be eligible for the study. A total of 10 patients with DoC will be enrolled in the Phase 1 study. Patients will receive escalating daily doses of IV MPH starting at 0.5 mg/kg, increasing stepwise to 1.0mg/kg and 2.0 mg/kg unless an adverse event (AE) necessitates dose de-escalation or a serious adverse event (SAE) necessitates that the patient stop participation in the study. Pharmacokinetics will be evaluated in selected patients with indwelling venous catheters or arterial catheters via serial serum measurements of MPH at each dose. The pharmacodynamic properties of IV MPH at each dose will be assessed by comparison of pre-versus post-dose EEG-based measures. The pharmacodynamic properties of the maximum tolerated dose will also be assessed by comparison of pre-versus post-dose resting state functional MRI (rs-fMRI) connectivity measures. Finally, we will test the association between structural connectivity of the ventral tegmental area (VTA), a dopaminergic brainstem nucleus that is believed to mediate MPH activation of the cerebral cortex, and EEG and rs-fMRI pharmacodynamic measures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Severe, acute traumatic brain injury
- •Diagnosis of Coma, Vegetative State, or Minimally Conscious State
排除标准
- •Penetrating brain injury caused by a metallic missile/object (e.g. bullet)
- •Body metal contraindicating MRI
- •Prisoner or ward of the state
- •Neurological
- •Bilateral dilated unresponsive pupils
- •Intracranial hypertension (Intracranial Pressure [ICP] > 25 mmHg for > 5 min within past 24 hours with head-of-bed at standard clinical angle of 30-45 degrees)
- •Intracranial bolt
- •Status epilepticus or concern for post-ictal state
- •Cardiovascular
- •Poorly controlled hypertension (SBP > 200 mmHg of DBP > 120mmHg for 30 minutes, despite anti-hypertensive therapy, within the past 24 hours)
- •Coronary artery disease
- •ST elevation myocardial infarction
- •Acute coronary syndrome
- •Hemodynamically significant dysrhythmia
- •Congestive heart failure
- •Cardiomyopathy (including Takotsubo cardiomyopathy)
- •Other severe structural cardiac abnormalities
- •a. Renal failure requiring renal replacement therapy (e.g. CVVH or HD)
- •a. History of or clinical suspicion for thyrotoxicosis
- •Reproductive
- •a. Pregnancy
- •Ophthalmologic
- •a. History of glaucoma
- •Pharmacologic
- •a. Monoamine oxidase inhibitor therapy within past 14 days
- •Any condition or finding that in the judgment of the PI or treating clinical team significantly increases the risk or significantly decreases the likelihood of a response to IV MPH
研究组 & 干预措施
IV MPH
All patients will receive IV Methylphenidate (MPH). Patients will receive escalating daily doses of IV MPH starting at 0.5 mg/kg, increasing stepwise to 1.0mg/kg and 2.0 mg/kg unless an adverse event (AE) necessitates dose de-escalation or a serious adverse event (SAE) necessitates that the patient stop participation in the study.
干预措施: Methylphenidate (Drug)
结局指标
主要结局
Number of Participants With Adverse Events at Each Dose
时间窗: 4 Days
Adverse Events An AE is defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related (21 CFR 312.32 (a)). In the STIMPACT Trial an AE may include, but is not limited to: * Sustained hypertension = SBP \> 200 mmHg or DBP \> 120 mmHg for \> 30 min, refractory to medical therapy, or * Sustained tachycardia = HR \> 120 bpm for \> 30 min, refractory to medical therapy, or * Sustained intracranial hypertension = ICP \> 25 mmHg for \> 5 min, refractory to medical therapy Serious Adverse Events An AE or suspected adverse reaction is considered "serious" if, in the view of the investigator or the Independent Medical Monitor, it results in any of the following outcomes: * Death not related to withdrawal of life-sustaining therapy * A life-threatening event * Prolongation of existing hospitalization * Significant incapacity or substantial disruption of the ability to conduct normal life function
次要结局
- Time to Maximal Serum Concentration of IV Methylphenidate (MPH)(4 Days)
- Serum Half-life of IV Methylphenidate (MPH)(4 Days)
- Cerebral Cortical Connectivity as Measured by fMRI(4 Days)
- Cerebral Cortical Connectivity as Measured by EEG(4 Days)
研究者
Brian L. Edlow, M.D.
Director, Laboratory for NeuroImaging of Coma and Consciousness (NICC)
Massachusetts General Hospital