Tetracycline-Derivatives for Treatment of Cerebral Arteriovenous Malformations and Aneurysms

University of California San Francisco (UCSF)

Status and phase: Completed; Phase 1

Conditions: Arteriovenous Malformations; Aneurysms

Treatments: Drug: doxycycline; Drug: minocycline

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00243893

R01NS027713

NS034949

Details and patient eligibility

About

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.

Full 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.

Enrollment: 26 patients

Sex: All

Ages: 13 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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26 participants in 2 patient groups

Brain AVMs

Active Comparator group

Description:

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.

Treatment:

Drug: doxycycline

Drug: minocycline

Aneurysms

Active Comparator group

Treatment:

Drug: doxycycline

Drug: minocycline