Official Title: “Tetracycline-Derivatives for Treatment of Cerebral Arteriovenous Malformations and Aneurysms”

The purpose of this pilot study is to investigate the use of minocycline and doxycycline as medical therapy for inoperable or partially treated arteriovenous malformations (AVMs) and giant aneurysms.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Parallel Assignment

Study Primary Completion Date: October 2008

Arteriovenous malformations (AVMs) are a treatable cause of stroke in young adults. The processes by which AVMs and giant aneurysms grow in size and spontaneously bleed are unknown.

The primary reason to treat AVMs and aneurysms is to guard against intracranial bleeding.

This pilot study will examine the use of two common antibiotics—minocycline and doxycycline—as medical therapy for inoperable or partially treated AVMs and giant aneurysms.

These drugs, which are tetracycline derivatives, can reduce the levels of a family of enzymes, called matrix metalloproteases, that degrade tissue and thereby cause a reduction in the risk of spontaneous bleeding from AVMs or aneurysm—which is the main cause of stroke associated with these disorders. The enzymes can contribute to weaknesses in the wall of blood vessels and may increase the risk of the vessel wall rupturing and causing spontaneous bleeding.

This trial also will show that taking minocycline and doxycycline over an extended period in this patient population is safe and well tolerated. Results from this study could help plan future studies to benefit patients with abnormal blood vessels prone to bleeding in their brains.

Intervention(s) in this Clinical Trial

• Drug: minocycline
  • Take minocycline 50mg BID x2 years. Labs drawn at baseline, then every-6 months. MRI is done at baseline and completion of study.
• Drug: doxycycline
  • Take doxycycline 50mg BID x2 years. Labs drawn at baseline, then every-6 months. MRI is done at baseline and completion of study.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Brain AVMs
  • This trial is to investigate the use of minocycline or doxycycline as medical therapy, can minocycline or doxycycline induce biologically significant changes in the enzyme system thought to be related to spontaneous growth/rupture of these malformations. Finally, can patients safely tolerate these medications over an extended period of time.
• Active Comparator: Aneurysms

Primary Measures

• MRI will be done baseline and post treatment.
  • Time Frame: 2 years
    Safety Issue?: Yes
• MMP levels are being followed q 6-mos.
  • Time Frame: Patients called weekly for 1st-3 months, then every 6-months until completion of study
    Safety Issue?: Yes
• Drug levels are being followed q 6-mos.
  • Time Frame: Patients called weekly for 1st-3 months, then every 6-months until completion of study
    Safety Issue?: Yes

Inclusion Criteria:

• Giant aneurysms or brain arteriovenous malformations (BAVM)
• Female patients of child bearing age using effective birth control, males
• Creatinine no greater than 2.0 mg/dl
• ALT no greater than 2 times upper limit of control

Exclusion Criteria:

• Unstable medical illness
• Contraindications to Tetracycline
• History of vestibular disease, (except benign positional vertigo)
• Prior tetracycline use within 2 mos of baseline visit.
• History of noncompliance with treatment or other protocols
• History of systemic lupus
• Patients not eligible for MRI

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 13 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of California, San Francisco

Overall Clinical Trial Officials and Contacts

William L. Young, MD Principal Investigator University of California, San Francisco  

Information obtained from ClinicalTrials.gov on October 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00243893

Study ID Number: R01NS027713

ClinicalTrials.gov Identifier: NCT00243893

Health Authority: United States: Federal Government