Feasibility of minocycline and doxycycline use as potential vasculostatic therapy for brain vascular malformations: pilot study of adverse events and tolerance.
BACKGROUND
Tetracyclines may be useful in preventing pathological vascular remodeling, thus decreasing the risk of spontaneous hemorrhage from brain vascular malformations.


METHODS
Arteriovenous malformation (AVM) and intracranial aneurysm patients undergoing noninvasive management were treated with minocycline or doxycycline (200 mg/day) up to 2 years in a prospective open-label safety pilot trial. The primary outcome was to compare dose-limiting intolerance, defined as treatment-related dose reduction or withdrawal between the agents.


RESULTS
Twenty-six patients with AVMs (n = 12) or aneurysms (n = 14) were recruited. Adverse event rates were similar to other reported trials of these agents; 4 of 13 (31%) minocycline and 3 of 13 (23%) doxycycline patients had dose-limiting intolerance (hazard ratio = 3.1, 95% CI = 0.52-18.11, log rank p = 0.70).


CONCLUSIONS
It is feasible to propose a long-term trial to assess the potential benefit of tetracycline therapy to decrease hemorrhagic risk in brain vascular malformations.
Frenzel
Tim
T
Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94110, USA.
Lee
Chanhung Z
CZ
Kim
Helen
H
Quinnine
Nancy J
NJ
Hashimoto
Tomoki
T
Lawton
Michael T
MT
Guglielmo
B Joseph
BJ
McCulloch
Charles E
CE
Young
William L
WL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000008:administration & dosage* / Q000009:adverse effects*; D005240:Feasibility Studies; D005500:Follow-Up Studies; D006801:Humans; D002532:Intracranial Aneurysm / Q000188:drug therapy; D002538:Intracranial Arteriovenous Malformations / Q000188:drug therapy; D008875:Middle Aged; D008911:Minocycline / Q000008:administration & dosage* / Q000009:adverse effects*; D010865:Pilot Projects; D011446:Prospective Studies; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D008911:Minocycline; D004318:Doxycycline