Tetracycline-Derivatives for Treatment of Cerebral Arteriovenous Malformations and Aneurysms

Arteriovenous Malformations Clinical Trial

Official title:

Tetracycline-Derivatives for Treatment of Cerebral Arteriovenous Malformations and Aneurysms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00243893
• Other study ID #: R01NS027713
• Secondary ID: NS034949
• Status: Completed
• Phase: Phase 1
• First received: October 24, 2005
• Last updated: October 8, 2013
• Start date: July 2004
• Est. completion date: October 2008

Study information

• Verified date: October 2013
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00305994

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years to 80 Years

Eligibility

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

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aneurysm
• Aneurysms
• Arteriovenous Malformations
• Congenital Abnormalities
• Hemangioma
• Intracranial Arteriovenous Malformations

Intervention

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

Locations

Country	Name	City	State
United States	University of California	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Frenzel T, Lee CZ, Kim H, Quinnine NJ, Hashimoto T, Lawton MT, Guglielmo BJ, McCulloch CE, Young WL. Feasibility of minocycline and doxycycline use as potential vasculostatic therapy for brain vascular malformations: pilot study of adverse events and tole — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MRI will be done baseline and post treatment.		2 years	Yes
Primary	MMP levels are being followed q 6-mos.		Patients called weekly for 1st-3 months, then every 6-months until completion of study	Yes
Primary	Drug levels are being followed q 6-mos.		Patients called weekly for 1st-3 months, then every 6-months until completion of study	Yes

External Links

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