Tetracycline-Derivatives for Treatment of Cerebral Arteriovenous Malformations and Aneurysms

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00243893
First received: October 24, 2005
Last updated: October 8, 2013
Last verified: October 2013
  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 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Tetracycline-Derivatives for Treatment of Cerebral Arteriovenous Malformations and Aneurysms

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

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
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Principal Investigator: William L. Young, MD University of California, San Francisco
  More Information

Additional Information:
Publications:
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00243893     History of Changes
Obsolete Identifiers: NCT00305994
Other Study ID Numbers: R01NS027713, NS034949
Study First Received: October 24, 2005
Last Updated: October 8, 2013
Health Authority: United States: Federal Government

Keywords provided by University of California, San Francisco:
giant aneurysms
arteriovenous malformations
minocycline
doxycycline
BAVM

Additional relevant MeSH terms:
Congenital Abnormalities
Aneurysm
Arteriovenous Malformations
Hemangioma
Intracranial Arteriovenous Malformations
Vascular Diseases
Cardiovascular Diseases
Vascular Malformations
Cardiovascular Abnormalities
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Vascular Malformations
Nervous System Malformations
Intracranial Arterial Diseases
Tetracycline
Doxycycline
Doxycycline hyclate
Minocycline
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014