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Safety Study of Dantrolene to Treat Cerebral Vasospasm After Subarachnoid Hemorrhage

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ClinicalTrials.gov Identifier: NCT00964548
Recruitment Status : Completed
First Posted : August 25, 2009
Results First Posted : May 25, 2012
Last Update Posted : May 25, 2012
Sponsor:
Collaborator:
Massachusetts General Hospital
Information provided by (Responsible Party):
Susanne Muehlschlegel, University of Massachusetts, Worcester

Study Description
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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.


Condition or disease Intervention/treatment Phase
Cerebral Vasospasm After Subarachnoid Hemorrhage Drug: Dantrolene Phase 1 Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arms and Interventions
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Arm Intervention/treatment
Experimental: Dantrolene (low dose) Drug: Dantrolene
1.25 mg/kg IV once over 60 min
Experimental: Dantrolene (high dose) Drug: Dantrolene
2.5 mg/kg IV once over 60 min


Outcome Measures
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Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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).

  2. 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).


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00964548


Locations
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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
UMASS Memorial Medical Center/UMASS Medical School
Worcester, Massachusetts, United States, 01655
Sponsors and Collaborators
University of Massachusetts, Worcester
Massachusetts General Hospital
Investigators
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Principal Investigator: Susanne Muehlschlegel, MD UMASS Medical School
Study Director: John R Sims, MD Massachusetts General Hospital
More Information
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Publications of Results:

Other Publications:

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Responsible Party: Susanne Muehlschlegel, Study Principle Investigator, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier: NCT00964548    
Other Study ID Numbers: H-13076
First Posted: August 25, 2009    Key Record Dates
Results First Posted: May 25, 2012
Last Update Posted: May 25, 2012
Last Verified: April 2012
Keywords provided by Susanne Muehlschlegel, University of Massachusetts, Worcester:
vasospasm
subarachnoid hemorrhage
neurocritical care
dantrolene
vasorelaxation
Additional relevant MeSH terms:
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Subarachnoid Hemorrhage
Vasospasm, Intracranial
Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
 Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Dantrolene
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents