Influence of MMP on Brain AVM Hemorrhage

NCT ID: NCT00783523

Last Updated: 2013-08-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

33 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-03-31

Study Completion Date

2010-12-31

Brief Summary

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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 Description

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* 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.

Conditions

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Arteriovenous Malformations Cavernous Angiomas Brain Aneurysms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Doxycycline or Placebo

Intervention Type DRUG

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

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

Group Type PLACEBO_COMPARATOR

Doxycycline or Placebo

Intervention Type DRUG

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

Interventions

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Doxycycline or Placebo

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

Intervention Type DRUG

Other Intervention Names

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Doxycycline Placebo

Eligibility Criteria

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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
Minimum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Chanhung Lee, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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University of California

San Francisco, California, United States

Site Status

Countries

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United States

Other Identifiers

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AHA #0730360N

Identifier Type: -

Identifier Source: secondary_id

H42145-30334-02

Identifier Type: -

Identifier Source: org_study_id