Tetracycline-Derivatives for Treatment of Cerebral Arteriovenous Malformations and Aneurysms - Full Text View

Sponsors and Collaborators:	University of California, San Francisco National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by:	National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier:	NCT00243893

Purpose

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	Intervention	Phase
Aneurysms Arteriovenous Malformations	Drug: minocycline Drug: doxycycline	Phase I

MedlinePlus related topics: Aneurysms Arteriovenous Malformations

Drug Information available for: Doxycycline Doxycycline calcium Doxycycline hyclate Minocycline Minocycline hydrochloride Tetracycline Tetracycline hydrochloride BaseLine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment
Official Title:	Tetracycline-Derivatives for Treatment of Cerebral Arteriovenous Malformations and Aneurysms

Further study details as provided by National Institute of Neurological Disorders and Stroke (NINDS):

Primary Outcome Measures:

MRI will be done baseline and post treatment. [ Time Frame: 2 years ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: Yes ]

Enrollment:	26
Study Start Date:	July 2004
Estimated Study Completion Date:	October 2008
Estimated Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Brain AVMs: Active Comparator 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.
Aneurysms: Active Comparator	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.

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.

Eligibility

Ages Eligible for Study:	13 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00243893

Locations

United States, California
University of California
San Francisco, California, United States, 94143

Sponsors and Collaborators

University of California, San Francisco

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Principal Investigator:

William L. Young, MD

University of California, San Francisco

More Information

Responsible Party:	University of California, San Francisco ( William L. Young, M.D. )
Study ID Numbers:	R01NS027713, NS034949
Study First Received:	October 24, 2005
Last Updated:	January 3, 2008
ClinicalTrials.gov Identifier:	NCT00243893
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Neurological Disorders and Stroke (NINDS):

giant aneurysms
arteriovenous malformations
minocycline
doxycycline
BAVM

Study placed in the following topic categories:

Minocycline
Aneurysm
Cardiovascular Abnormalities
Intracranial Arteriovenous Malformations
Nervous System Malformations
Vascular Diseases
Central Nervous System Diseases
Tetracycline

Brain Diseases
Cerebrovascular Disorders
Intracranial Arterial Diseases
Vascular Malformations
Hemangioma
Arteriovenous Malformations
Congenital Abnormalities
Doxycycline

Additional relevant MeSH terms:

Anti-Infective Agents
Antiprotozoal Agents
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Central Nervous System Vascular Malformations
Nervous System Diseases
Enzyme Inhibitors
Pharmacologic Actions

Antimalarials
Protein Synthesis Inhibitors
Anti-Bacterial Agents
Antiparasitic Agents
Neoplasms
Therapeutic Uses
Neoplasms, Vascular Tissue
Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 13, 2009