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Tetracycline-Derivatives for Treatment of Cerebral Arteriovenous Malformations and Aneurysms

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ClinicalTrials.gov Identifier: NCT00243893
Recruitment Status : Completed
First Posted : October 25, 2005
Last Update Posted : October 9, 2013
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE October 24, 2005
First Posted Date  ICMJE October 25, 2005
Last Update Posted Date October 9, 2013
Study Start Date  ICMJE July 2004
Actual Primary Completion Date October 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2008)
  • MRI will be done baseline and post treatment. [ Time Frame: 2 years ]
  • 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 ]
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 24, 2005)
  • MRI will be done baseline and post treatment (2 years).
  • MMP levels are being followed q 6-mos.
  • Drug levels are being followed q 6-mos.
Change History Complete list of historical versions of study NCT00243893 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tetracycline-Derivatives for Treatment of Cerebral Arteriovenous Malformations and Aneurysms
Official Title  ICMJE Tetracycline-Derivatives for Treatment of Cerebral Arteriovenous Malformations and Aneurysms
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Aneurysms
  • Arteriovenous Malformations
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: minocycline
    • Drug: doxycycline
  • Active Comparator: Aneurysms
    Interventions:
    • Drug: minocycline
    • Drug: doxycycline
Publications * 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 tolerance. Cerebrovasc Dis. 2008;25(1-2):157-63. doi: 10.1159/000113733. Epub 2008 Jan 23.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 3, 2008)
26
Original Enrollment  ICMJE
 (submitted: October 24, 2005)
122
Actual Study Completion Date  ICMJE October 2008
Actual Primary Completion Date October 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 13 Years to 80 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00243893
Other Study ID Numbers  ICMJE R01NS027713( U.S. NIH Grant/Contract )
NS034949
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE National Institute of Neurological Disorders and Stroke (NINDS)
Investigators  ICMJE
Principal Investigator: William L. Young, MD University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP