Safety Study of Dantrolene to Treat Cerebral Vasospasm After Subarachnoid Hemorrhage

April 25, 2012 updated by: Susanne Muehlschlegel, University of Massachusetts, Worcester

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Worcester, Massachusetts, United States, 01655
        • UMASS Memorial Medical Center/UMASS Medical School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dantrolene (low dose)
Drug: Dantrolene
1.25 mg/kg IV once over 60 min
Drug: Dantrolene
2.5 mg/kg IV once over 60 min
Experimental: Dantrolene (high dose)
Drug: Dantrolene
1.25 mg/kg IV once over 60 min
Drug: Dantrolene
2.5 mg/kg IV once over 60 min

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
baseline until 135 minutes post-infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
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)
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).
baseline until 135 minutes post-infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Massachusetts, Worcester

Collaborators

Massachusetts General Hospital

Investigators

  • Principal Investigator: Susanne Muehlschlegel, MD, UMass Medical School
  • Study Director: John R Sims, MD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Actual)

October 1, 2009

Study Completion (Actual)

October 1, 2009

Study Registration Dates

First Submitted

August 23, 2009

First Submitted That Met QC Criteria

August 23, 2009

First Posted (Estimate)

August 25, 2009

Study Record Updates

Last Update Posted (Estimate)

May 25, 2012

Last Update Submitted That Met QC Criteria

April 25, 2012

Last Verified

April 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-13076

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 register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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