Influence of MMP on Brain AVM Hemorrhage

• Status: Completed
• Trial end date: 2010-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Treatments: Doxycycline

Criteria

Inclusion Criteria:

• 13 years or older

• Female patients of child bearing age using barrier-type birth control

• Creatinine no greater than 2.0 mg/di

• Alanine aminotransferase (ALT) no greater than 2 times upper limit of normal

• WBC count at least 3,800/mm3

• BMI within 50% of normal

Exclusion Criteria:

• Allergy to tetracycline

• Unstable medical illness (unstable angina, advanced cancer, etc) over the last 30 days

• Female patients of child-bearing age not using effective birth control (barrier)

• History of vestibular disease (except benign positional vertigo)

• History of noncompliance with treatment or other experimental protocols

• Patients taking other antibiotics

• History of systemic lupus erythematosis

• Patients who are immunocompromised Patients with clinically significant hepatic dysfunction