Tetracycline-Derivatives for Treatment of Cerebral Arteriovenous Malformations and Aneurysms

Phase 1

Completed

• Conditions: Aneurysms; Arteriovenous Malformations
• Interventions: Drug: minocycline; Drug: doxycycline

• Registration Number: NCT00243893
• Lead Sponsor: University of California, San Francisco

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2004-07
• Study First Submitted: 2005-10-24
• Study First Submitted QC: 2005-10-24
• Study First Posted: 2005-10-25
• Primary Completion: 2008-10
• Study Completion: 2008-10
• Status Verified: 2013-10
• Last Update Submitted: 2013-10-08
• Last Update Posted: 2013-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Brain AVMs	doxycycline	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.
Aneurysms	doxycycline	-
Brain AVMs	minocycline	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.
Aneurysms	minocycline	-

Primary Outcome Measures

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

Trial Locations

Locations (1)

University of California; 🇺🇸 San Francisco, California, United States