Clinical Trial: Influence of MMP on Brain AVM Hemorrhage

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Influence of Matrix Metalloproteinase on Brain Arteriovenous Malformation Hemorrhage

Brief Summary:

Brain vascular malformations, including arteriovenous malformations (AVM), cavernous malformations (CVM) and aneurysms, are a source of life-threatening risk of intracranial hemorrhage. The etiology and pathogenesis are unknown. There is no medical therapy presently available. Prevention of spontaneous intracerebral hemorrhage (ICH) is the primary reason to treat brain vascular malformations. The goal of this study is to: begin pilot studies to lay the groundwork for future clinical trials to develop medical therapy to decrease ICH risk.

Matrix metalloproteinases (MMPs) regulate the extracellular matrix in association with various hemorrhagic brain disorders. MMP-9 has been most consistently associated with vascular wall instability and hemorrhagic brain disorders. Doxycycline, a non-specific MMP inhibitor, may enhance vascular stability, thus reducing the risk of spontaneous hemorrhage in brain vascular malformations by decreasing MMP-9 activity.


Detailed Summary:

  • Doses will be randomized by the Pharmacy Department at UCSF for Doxycycline 100 mg/BID and Placebo BID. These will be prepared in blister-packs.
  • Depending on enrollment/surgery date, patients will take medication either one to two weeks before surgery. Patients will be assigned to a treatment group according to a random table.
  • Each patient will be initially provided with a 1 or 2-week supply of drug in blister packs. The patient will take the final dose of study drug on the morning of surgery.

Baseline labs will be obtained and then again at time of surgery along with a piece of surgical tissue.


Sponsor: University of California, San Francisco

Current Primary Outcome: Our primary aim is to perform a pilot study to document the effect of doxycycline therapy to decrease MMP expression in the vascular malformation tissue. [ Time Frame: 1 to 2-week pre-operative ]

Original Primary Outcome: Our primary aim is to perform a pilot study to document the effect of doxycycline therapy to decrease MMP expression in the vascular malformation tissue. [ Time Frame: 2-week pre-operative ]

Current Secondary Outcome: Our secondary aims are: (1) To explore whether plasma MMP-9 levels can be used as a marker for MMP-9 inhibition in the vascular malformation lesional tissue [ Time Frame: 1 to 2-week pre operative ]

Original Secondary Outcome: Our secondary aims are: (1) To explore whether plasma MMP-9 levels can be used as a marker for MMP-9 inhibition in the vascular malformation lesional tissue [ Time Frame: 2-week pre operative ]

Information By: University of California, San Francisco

Dates:
Date Received: October 30, 2008
Date Started: March 2008
Date Completion:
Last Updated: August 6, 2013
Last Verified: August 2013