Safety Study of Dantrolene to Treat Cerebral Vasospasm After Subarachnoid Hemorrhage
|ClinicalTrials.gov Identifier: NCT00964548|
Recruitment Status : Completed
First Posted : August 25, 2009
Results First Posted : May 25, 2012
Last Update Posted : May 25, 2012
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.
|Condition or disease||Intervention/treatment||Phase|
|Cerebral Vasospasm After Subarachnoid Hemorrhage||Drug: Dantrolene||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Dantrolene in the Treatment of Cerebral Vasospasm After Subarachnoid Hemorrhage - a Phase 1 Study|
|Study Start Date :||July 2007|
|Actual Primary Completion Date :||October 2009|
|Actual Study Completion Date :||October 2009|
|Experimental: Dantrolene (low dose)||
1.25 mg/kg IV once over 60 min
|Experimental: Dantrolene (high dose)||
2.5 mg/kg IV once over 60 min
- Hemodynamic Parameters (Change From Baseline Systolic Blood Pressure (Pre-infusion) Over Time Until 135 Minutes Post-infusion) [ Time Frame: baseline until 135 minutes post-infusion ]Systolic Blood Pressure (Change from baseline systolic blood pressure (pre-infusion) over time until 135 minutes post-infusion).
- Transcranial Doppler Peak Systolic Velocity (Change From Baseline Peak Systolic Velocity (Pre-infusion) Over Time Until 135 Minutes Post-infusion) [ Time Frame: baseline until 135 minutes post-infusion ]Peak Systolic Velocity of vessel in vasospasm (Change from baseline peak systolic velocity (pre-infusion) over time 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) [ Time Frame: baseline until 135 minutes post-infusion ]Mean flow velocities of vessel in vasospasm (Change from baseline mean flow velocity (pre-infusion) over time until 135 minutes post-infusion).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00964548
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|UMASS Memorial Medical Center/UMASS Medical School|
|Worcester, Massachusetts, United States, 01655|
|Principal Investigator:||Susanne Muehlschlegel, MD||UMASS Medical School|
|Study Director:||John R Sims, MD||Massachusetts General Hospital|