Influence of MMP on Brain AVM Hemorrhage - Full Text View

Sponsor:	University of California, San Francisco
Information provided by:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00783523

Purpose

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	Intervention
Brain Arteriovenous Malformations Brain Cavernous Malformations Brain Aneurysms	Drug: Doxycycline or Placebo

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Investigator), Placebo Control, Single Group Assignment
Official Title:	Influence of Matrix Metalloproteinase on Brain Arteriovenous Malformation Hemorrhage

Resource links provided by NLM:

MedlinePlus related topics: Aneurysms Arteriovenous Malformations Brain Diseases

Drug Information available for: Doxycycline Doxycycline hyclate Doxycycline calcium

U.S. FDA Resources

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	25
Study Start Date:	March 2008
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Doxycycline: Active Comparator 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 2-weeks preoperatively.
Placebo: Placebo Comparator 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 2-weeks preoperatively.

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.
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 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.

Eligibility

Ages Eligible for Study:	13 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00783523

Contacts

Contact: Nancy J. Quinnine, RN

415-476-2677

quinnine@anesthesia.ucsf.edu

Locations

United States, California
University of California	Recruiting
San Francisco, California, United States, 94143
Contact: Nancy J. Quinnine, RN 415-476-2677 quinnine@anesthesia.ucsf.edu
Principal Investigator: Chanhung Lee, MD

Sponsors and Collaborators

University of California, San Francisco

Investigators

Principal Investigator:

Chanhung Lee, MD

University of California, San Francisco

More Information

No publications provided

Responsible Party:	University of California, San Francisco ( Chanhung Lee, M.D. )
Study ID Numbers:	H42145-30334-02, AHA #0730360N
Study First Received:	October 30, 2008
Last Updated:	October 30, 2008
ClinicalTrials.gov Identifier:	NCT00783523 History of Changes
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Anti-Infective Agents
Antiprotozoal Agents
Hemorrhage
Brain Diseases
Intracranial Arterial Diseases
Cerebrovascular Disorders
Anti-Bacterial Agents
Antimalarials
Antiparasitic Agents
Pathologic Processes
Therapeutic Uses
Vascular Malformations
Neoplasms, Vascular Tissue
Hemangioma

Cardiovascular Diseases
Congenital Abnormalities
Neoplasms by Histologic Type
Cardiovascular Abnormalities
Aneurysm
Nervous System Diseases
Vascular Diseases
Central Nervous System Diseases
Pharmacologic Actions
Intracranial Aneurysm
Neoplasms
Arteriovenous Malformations
Doxycycline

ClinicalTrials.gov processed this record on November 05, 2009