Cerebral Vasospasm After Subarachnoid Hemorrhage Clinical Trial
Official title:
Dantrolene in the Treatment of Cerebral Vasospasm After Subarachnoid Hemorrhage - a Phase 1 Study
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.
| Status | Completed |
| Enrollment | 10 |
| Est. completion date | October 2009 |
| Est. primary completion date | October 2009 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - 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 Exclusion Criteria: - 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 |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | UMASS Memorial Medical Center/UMASS Medical School | Worcester | Massachusetts |
| Lead Sponsor | Collaborator |
|---|---|
| University of Massachusetts, Worcester | Massachusetts General Hospital |
United States,
Muehlschlegel S, Rordorf G, Bodock M, Sims JR. Dantrolene mediates vasorelaxation in cerebral vasoconstriction: a case series. Neurocrit Care. 2009;10(1):116-21. doi: 10.1007/s12028-008-9132-5. Epub 2008 Aug 12. — View Citation
Muehlschlegel S, Rordorf G, Sims J. Effects of a single dose of dantrolene in patients with cerebral vasospasm after subarachnoid hemorrhage: a prospective pilot study. Stroke. 2011 May;42(5):1301-6. doi: 10.1161/STROKEAHA.110.603159. Epub 2011 Mar 31. — View Citation
Muehlschlegel S, Sims JR. Dantrolene: mechanisms of neuroprotection and possible clinical applications in the neurointensive care unit. Neurocrit Care. 2009;10(1):103-15. doi: 10.1007/s12028-008-9133-4. Epub 2008 Aug 12. Review. — View Citation
Salomone S, Soydan G, Moskowitz MA, Sims JR. Inhibition of cerebral vasoconstriction by dantrolene and nimodipine. Neurocrit Care. 2009;10(1):93-102. doi: 10.1007/s12028-008-9153-0. Epub 2008 Oct 16. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Hemodynamic Parameters (Change From Baseline Systolic Blood Pressure (Pre-infusion) Over Time Until 135 Minutes Post-infusion) | Systolic Blood Pressure (Change from baseline systolic blood pressure (pre-infusion) over time until 135 minutes post-infusion). | baseline until 135 minutes post-infusion | Yes |
| Secondary | Transcranial Doppler Peak Systolic Velocity (Change From Baseline Peak Systolic Velocity (Pre-infusion) Over Time 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). | baseline until 135 minutes post-infusion | No |
| Secondary | Transcranial Doppler Mean Flow Velocity (Change From Baseline Mean Flow Velocity (Pre-infusion) Over Time 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). | baseline until 135 minutes post-infusion | No |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT01400360 -
Invasive Diagnostic and Therapeutic Management of Cerebral Vasospasm After Aneurysmatic Subarachnoid Hemorrhage
|
N/A |