Dantrolene in the Treatment of Cerebral Vasospasm After Subarachnoid Hemorrhage - a Phase 1 Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Hemodynamic Parameters (Change From Baseline Systolic Blood Pressure (Pre-infusion) Over Time Until 135 Minutes Post-infusion)
研究概览
简要总结
Subarachnoid hemorrhage (SAH) is a devastating acute brain injury due to bleeding onto the brain surface from a ruptured aneurysm. Cerebral vasospasm (cVSP; critical narrowing of brain arteries) is a known complication after SAH and significantly increases disability and death after SAH. Vasospasm is difficult to treat and can lead to stroke. Animal studies have shown that the muscles in the artery wall play a role in cVSP.
Dantrolene has been FDA approved and extensively used in clinical practice as a muscle relaxant for more than 30 years. It has been shown to provide some benefit in animal studies of cVSP, as well as in a small number of humans. Therefore, we plan to undertake this study to evaluate the safety and tolerability of treatment with dantrolene in patients with cVSP after SAH, and to determine the maximal tolerated dose to be used in future studies to determine if treatment with Dantrolene can improve the outcome of patients with cVSP after SAH.
详细描述
Our main objectives are: 1) to evaluate the safety and tolerability of varying doses of dantrolene, by determining the treatment related adverse events, in participants with cVSP after SAH; and 2) to determine the maximal tolerated dose to be adopted in subsequent studies and 3) to determine efficacy trends of dantrolene on brain vessels as assessed by ultrasound of brain vessels (transcranial Doppler).
We hypothesize that dantrolene is well-tolerated and has minimal serious adverse effects in patients with cVSP after SAH. The results can potentially bring a new treatment to patients with SAH. cVPS after SAH is a frequent cause of disability and death. A successful study demonstrating the safety of dantrolene in would be of considerable public health significance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Participants with aneurysmal SAH admitted to the Massachusetts General Hospital NeuroICU (Blake 12) and undergoing standard-of-care daily transcranial doppler (TCD).
- •Participants with unilateral or bilateral anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA), or basilar artery vasospasm as defined by the following TCD criteria
- •a >50% mean velocity increase from the baseline mean TCD velocity (baseline is the first TCD measurement, usually within 24hrs of admission), or
- •peak systolic TCD velocities of 200 cm/s or higher in the MCA or ACA (for MCA with a concurrent ipsilateral LR of 3.0 or higher), or peak systolic TCD velocities of 120 cm/s or higher in the PCA or basilar artery, or
- •any daily 100 cm/s peak systolic TCD velocity increase from the previous day, or
- •any longitudinal mean TCD velocity increase of 80 cm/s or more
排除标准
- •Inability to obtain consent from patient or health care proxy
- •Age < 18 years
- •Pregnancy
- •Traumatic SAH
- •Known allergy to dantrolene
- •Prior history of cirrhosis or hepatitis B/C, or any two of the following three liver enzymes elevated to greater than: ALT >165 Units/L, AST >120 Units/L, alkaline phosphatase >345 Units/L (three times upper limit of normal)
- •Participants on verapamil
研究组 & 干预措施
Dantrolene (low dose)
干预措施: Dantrolene (Drug)
Dantrolene (high dose)
干预措施: Dantrolene (Drug)
结局指标
主要结局
Hemodynamic Parameters (Change From Baseline Systolic Blood Pressure (Pre-infusion) Over Time Until 135 Minutes Post-infusion)
时间窗: baseline until 135 minutes post-infusion
Systolic Blood Pressure (Change from baseline systolic blood pressure (pre-infusion) over time until 135 minutes post-infusion).
次要结局
- Transcranial Doppler Peak Systolic Velocity (Change From Baseline Peak Systolic Velocity (Pre-infusion) Over Time Until 135 Minutes Post-infusion)(baseline until 135 minutes post-infusion)
- Transcranial Doppler Mean Flow Velocity (Change From Baseline Mean Flow Velocity (Pre-infusion) Over Time Until 135 Minutes Post-infusion)(baseline until 135 minutes post-infusion)
研究者
Susanne Muehlschlegel
Study Principle Investigator
University of Massachusetts, Worcester