Subarachnoid Hemorrhage and Soluble Epoxide Hydrolase Inhibition Trial
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
- Participants With Adverse Events
研究概览
简要总结
Soluble epoxide hydrolase (sEH) is the metabolizing enzyme of epoxyeicosatrienoic acids (EETs), which may play a role in reducing neuroinflammation and regulating cerebral blood flow after subarachnoid hemorrhage (SAH). Hypotheses: Pharmacologic inhibition of the sEH enzyme is safe and will result in increased EETs availability in the blood and cerebrospinal fluid. This study is a double-blind, placebo-controlled, phase 1b randomized trial to evaluate the safety and efficacy of GSK2256294, a novel soluble epoxide hydrolase inhibitor in patients with aneurysmal SAH.
详细描述
Study Description: Soluble epoxide hydrolase (sEH) is the metabolizing enzyme of epoxyeicosatrienoic acids (EETs), which may play a role in reducing neuroinflammation and regulating cerebral blood flow after subarachnoid hemorrhage (SAH).
Hypothesis: Pharmacologic inhibition of the sEH enzyme is safe and will result in increased EETs availability at the neurovascular unit, and a measured increase in the EET/DHET ratio in the serum and cerebrospinal fluid. This study is a double-blind, placebo-controlled, phase 1b randomized trial to evaluate the safety and of GSK2256294, an inhibitor of soluble epoxide hydrolase, in patients with aneurysmal SAH.
Objectives:
Primary Objective:
Determine the safety of administration of GSK2256294 in patients with aneurysmal SAH.
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
Investigational pharmacy staff will maintain the randomization list and study/drug placebo assignment. Participants, care providers, the investigators and outcomes assessors will be blinded to the grouping.
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
- •Head CT evidence of subarachnoid hemorrhage
- •Digital subtraction cerebral angiography or CT angiogram documenting the presence of a cerebral aneurysm.
排除标准
- •Symptom onset compatible with SAH of > 3 days prior to admission to OHSU
- •Absence of an indwelling external ventricular drain
- •Administration of any of the following inducers/inhibitors of CYP3A4: ritonavir, indinavir, nelfinavir, saquinavir, clarithromycin, telithromycin, chloramphenicol, ketoconazole, itraconazole, nefazodone, cobicistat or enzalutamide.
- •Suspected or confirmed pregnancy
- •Preexisting severe neurologic deficit or condition
- •Chronic renal failure requiring dialysis
- •Severe terminal disease with life expectancy <6 months
- •Unable to read or understand written or spoken English or Spanish
- •Refusal of informed consent
研究组 & 干预措施
GSK2256294
10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days.
干预措施: GSK2256294 (Drug)
Placebo
10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Participants With Adverse Events
时间窗: 90 days
Summary tables and listings will be provided for all reported adverse events, defined as adverse events that start on or after the first administration of study drug. The reported adverse event term will be assigned a standardized preferred term. Adverse events will be summarized based on the number and percentage of patients experiencing the event. In the event a patient experiences repeat episodes of the same adverse event, then the event with the highest severity grade and strongest causal relationship to study treatment will be used for purposes of incidence tabulations. All deaths will be reported in a patient listing, which will include the primary cause of death and the number of days between the date of the last dose of study drug and death.
次要结局
- Study Day 7 and Study Day 10 Serum and CSF EET/ Dihyroxyeicosatrienoic (DHET) Ratio, by Mass Spectroscopic Analysis (ng/mL)(10 days)
- Study Day 7 and Study Day 10 Serum Epoxyoctadecenoic Acid (EPOME) to Dihydroxyoctadec-12-enoic Acid (DPOME) Ratio, by Mass Spectroscopic Analysis (ng/mL)(10 days)
- Serum Biomarkers of Endothelial Injury From Blood Samples Obtained on Study Day 7 and Study Day 10(10 days)
- CSF Biomarkers of Neuroinflammation, From Blood Samples Obtained on Study Day 7 and Study Day 10(10 days)
研究者
Ross Martini, MD
Principal Investigator
Oregon Health and Science University