Safety Study of Dantrolene to Treat Cerebral Vasospasm After Subarachnoid Hemorrhage

Dantrolene in the Treatment of Cerebral Vasospasm After Subarachnoid Hemorrhage - a Phase 1 Study

Sponsors

Lead Sponsor: University of Massachusetts, Worcester

Collaborator: Massachusetts General Hospital

Source University of Massachusetts, Worcester
Brief Summary

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.

Detailed Description

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.

Overall Status Completed
Start Date 2007-07-01
Completion Date 2009-10-01
Primary Completion Date 2009-10-01
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Hemodynamic Parameters (Change From Baseline Systolic Blood Pressure (Pre-infusion) Over Time Until 135 Minutes Post-infusion) baseline until 135 minutes post-infusion
Secondary Outcome
Measure Time Frame
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
Enrollment 10
Condition
Intervention

Intervention Type: Drug

Intervention Name: Dantrolene

Description: 1.25 mg/kg IV once over 60 min

Arm Group Label: Dantrolene (low dose)

Intervention Type: Drug

Intervention Name: Dantrolene

Description: 2.5 mg/kg IV once over 60 min

Arm Group Label: Dantrolene (high dose)

Eligibility

Criteria:

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Location
Facility:
Massachusetts General Hospital | Boston, Massachusetts, 02114, United States
UMASS Memorial Medical Center/UMASS Medical School | Worcester, Massachusetts, 01655, United States
Location Countries

United States

Verification Date

2012-04-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University of Massachusetts, Worcester

Investigator Full Name: Susanne Muehlschlegel

Investigator Title: Study Principle Investigator

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Dantrolene (low dose)

Type: Experimental

Label: Dantrolene (high dose)

Type: Experimental

Study Design Info

Allocation: Non-Randomized

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News