Influence of MMP on Brain AVM Hemorrhage - Full Text View

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:

Genetics Home Reference related topics: Parkes Weber syndrome capillary malformation-arteriovenous malformation syndrome cerebral cavernous malformation

MedlinePlus related topics: Aneurysms Arteriovenous Malformations Bleeding

Drug Information available for: Doxycycline Doxycycline monohydrate Doxycycline hyclate Doxycycline calcium

Genetic and Rare Diseases Information Center resources: Cerebral Cavernous Malformation

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 (Child, Adult, Senior)
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


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:


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

ClinicalTrials.gov processed this record on September 26, 2016