Influence of MMP on Brain AVM Hemorrhage

NCT00783523 | Completed Phase 1

• 2 other identifiers: H42145-30334-02AHA #0730360N
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Arteriovenous Malformations; Cavernous Angiomas; Brain Aneurysms

Outcome Measures

Primary Outcomes (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.

  1 to 2-week pre-operative

Secondary Outcomes (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

  1 to 2-week pre operative

Study Arms (2)

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

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

Interventions

Doxycycline or Placebo DRUG

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

Also known as: Doxycycline, Placebo

Doxycycline; Placebo

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Arteriovenous Malformations; Hemangioma, Cavernous; Intracranial Aneurysm

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

Vascular Malformations; Cardiovascular Abnormalities; Cardiovascular Diseases; Vascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms; Cavernous Sinus Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hemostatic Disorders; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Intracranial Arterial Diseases; Cerebrovascular Disorders; Aneurysm

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Chanhung Lee, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2008
• First Posted: October 31, 2008
• Study Start: March 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: August 9, 2013

Record last verified: 2013-08

Locations

US (1)