Influence of MMP on Brain AVM Hemorrhage

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Arteriovenous Malformations; Cavernous Angiomas; Brain Aneurysms	Drug: Doxycycline or Placebo	Phase 1

Detailed 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.

Study Design

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	33 participants
Allocation:	Randomized
Intervention Model:	Single Group Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Prevention
Official Title:	Influence of Matrix Metalloproteinase on Brain Arteriovenous Malformation Hemorrhage
Study Start Date :	March 2008
Actual Primary Completion Date :	December 2010
Actual Study Completion Date :	December 2010

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Active Comparator: Doxycycline; Patients undergoing elective vascular malformation surgery will receive doxycycline100 mg twice a day, a dose shown to effectively decrease MMP or placebo, treatment for two weeks prior to surgery	Drug: Doxycycline or Placebo; Randomized to Doxycycline 100mg 2x/day or Placebo 2x/day for 1 or2-weeks pre-operatively.; Other Names: Doxycycline; Placebo
Placebo Comparator: Placebo; Patients undergoing elective vascular malformation surgery will receive doxycycline100 mg twice a day, a dose shown to effectively decrease MMP or placebo, treatment for two weeks prior to surgery	Drug: Doxycycline or Placebo; Randomized to Doxycycline 100mg 2x/day or Placebo 2x/day for 1 or2-weeks pre-operatively.; Other Names: Doxycycline; Placebo

Outcome Measures

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Primary Outcome Measures :

1. 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 ]

Secondary Outcome Measures :

1. 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 ]

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	13 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, California
University of California
San Francisco, California, United States, 94143

Sponsors and Collaborators

University of California, San Francisco

Investigators

Principal Investigator:	Chanhung Lee, MD	University of California, San Francisco

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00783523 History of Changes
Other Study ID Numbers:	H42145-30334-02; AHA #0730360N
First Posted:	October 31, 2008
Last Update Posted:	August 9, 2013
Last Verified:	August 2013

Additional relevant MeSH terms:

Congenital Abnormalities; Arteriovenous Malformations; Vascular Malformations; Cardiovascular Abnormalities; Hemorrhage; Aneurysm; Hemangioma; Intracranial Aneurysm; Hemangioma, Cavernous; Pathologic Processes; Vascular Diseases; Cardiovascular Diseases; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms	Intracranial Arterial Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hemostatic Disorders; Hemorrhagic Disorders; Hematologic Diseases; Doxycycline; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents