Tetracycline-Derivatives for Treatment of Cerebral Arteriovenous Malformations and Aneurysms

Sponsor

University of California, San Francisco (Other)

Overall Status

Completed

CT.gov ID

NCT00243893

Collaborator

National Institute of Neurological Disorders and Stroke (NINDS) (NIH)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Aneurysms Arteriovenous Malformations	Drug: minocycline Drug: doxycycline	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

26 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Tetracycline-Derivatives for Treatment of Cerebral Arteriovenous Malformations and Aneurysms

Study Start Date :

Jul 1, 2004

Actual Primary Completion Date :

Oct 1, 2008

Actual Study Completion Date :

Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
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.	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.
Active Comparator: Aneurysms	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.

Arm

Intervention/Treatment

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.

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.

Active Comparator: Aneurysms

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.

Outcome Measures

Primary Outcome Measures

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