Influence of MMP on Brain AVM Hemorrhage

Arteriovenous Malformations Clinical Trial

Official title:

Influence of Matrix Metalloproteinase on Brain Arteriovenous Malformation Hemorrhage

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00783523
• Other study ID #: H42145-30334-02
• Secondary ID: AHA #0730360N
• Status: Completed
• Phase: Phase 1
• First received: October 30, 2008
• Last updated: August 6, 2013
• Start date: March 2008
• Est. completion date: December 2010

Study information

• Verified date: August 2013
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Description:

• 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Arteriovenous Malformations
• Brain Aneurysms
• Cavernous Angiomas
• Congenital Abnormalities
• Hemangioma

Intervention

Drug:
• Doxycycline or Placebo
Randomized to Doxycycline 100mg 2x/day or Placebo 2x/day for 1 or2-weeks pre-operatively.

Locations

Country	Name	City	State
United States	University of California	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		1 to 2-week pre-operative	No
Secondary	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		1 to 2-week pre operative	No