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Influence of MMP on Brain AVM Hemorrhage

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00783523
First received: October 30, 2008
Last updated: August 6, 2013
Last verified: August 2013
History of Changes
  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 Phase
Arteriovenous Malformations
Cavernous Angiomas
Brain Aneurysms
 Drug: Doxycycline or Placebo
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Influence of Matrix Metalloproteinase on Brain Arteriovenous Malformation Hemorrhage

Resource links provided by NLM:

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: 1 to 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: 1 to 2-week pre operative ] [ Designated as safety issue: No ]
Enrollment: 33
Study Start Date: March 2008
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00783523     History of Changes
Other Study ID Numbers: H42145-30334-02, AHA #0730360N
Study First Received: October 30, 2008
Last Updated: August 6, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Arteriovenous Malformations
Cardiovascular Abnormalities
Congenital Abnormalities
Vascular Malformations
Hemangioma
Cardiovascular Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Vascular Tissue
 Vascular Diseases
Doxycycline
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015