title: Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms: report of a prospective (Phase II) multicenter study.
abstract: BACKGROUND
  The primary purpose of this study was to evaluate compliance, side effects, and safety associated with prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms (AAAs). A secondary goal was to determine how treatment with doxycycline influences circulating levels of matrix metalloproteinase-9 (MMP-9) in this patient population.
  
  
  METHODS
  Thirty-six patients with AAAs (30 men and 6 women; mean age, 69 +/- 1 years) were enrolled into a 6-month phase II study to evaluate treatment with doxycycline (100 mg orally twice a day). Aneurysm size was measured before and after treatment, and compliance and side effects were monitored. Plasma levels of doxycycline were measured midway through the study, and plasma MMP-9 concentrations were measured at baseline, 3 months, and 6 months.
  
  
  RESULTS
  Thirty-three of the 36 patients (92%) completed 6 months of doxycycline treatment. Significant treatment-related side effects occurred in five patients (13.9%), including three with cutaneous photosensitivity reactions (8.3%), one with tooth discoloration (2.8%), and one with yeast infection (2.8%). A high rate of compliance with treatment was seen, despite minor but frequent side effects, including nonspecific gastrointestinal symptoms (25%), easily managed episodes of photosensitivity (22.2%), and reversible tooth discoloration (5.5%). The mean plasma doxycycline level after 3 months was 4.62 +/- 0.68 ug/mL (median, 3.64 microg/mL; range, 1.31 to 14.39 microg/mL; n = 23 patients). No significant change was seen in AAA diameter (42.7 +/- 1.3 mm at 6 months versus 41.0 +/- 0.9 mm at baseline), and the overall rate of AAA expansion was 0.63% +/- 0.25% per month. The mean plasma MMP-9 level (n = 19 patients) was elevated at baseline (118.9 +/- 37.9 ng/mL; upper limit of normal, 85 ng/mL) but subsequently decreased to 83.8 +/- 32.9 ng/mL at 3 months (not significant versus baseline) and to 66.4 +/- 24.2 ng/mL at 6 months (P =.022 versus baseline). Only 21% of patients had an elevated level of plasma MMP-9 after 6 months of treatment compared with 47% at baseline (P <.05).
  
  
  CONCLUSIONS
  Prolonged administration of doxycycline is safe and well tolerated by patients with small asymptomatic AAAs and is associated with a gradual reduction in plasma MMP-9 levels. Further studies are needed to evaluate the long-term effects of doxycycline on the rate and extent of aneurysm growth and the potential use of plasma MMP-9 levels as a biomarker of aneurysm disease progression.
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, USA.
authors.forename: B Timothy
authors.initials: BT
authors.lastname: Baxter
authors.forename: William H
authors.initials: WH
authors.lastname: Pearce
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Waltke
authors.forename: Fred N
authors.initials: FN
authors.lastname: Littooy
authors.forename: John W
authors.initials: JW
authors.lastname: Hallett
authors.forename: K Craig
authors.initials: KC
authors.lastname: Kent
authors.forename: Gilbert R
authors.initials: GR
authors.lastname: Upchurch
authors.forename: Elliot L
authors.initials: EL
authors.lastname: Chaikof
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Mills
authors.forename: Beverly
authors.initials: B
authors.lastname: Fleckten
authors.forename: G Matt
authors.initials: GM
authors.lastname: Longo
authors.forename: Jason K
authors.initials: JK
authors.lastname: Lee
authors.forename: Robert W
authors.initials: RW
authors.lastname: Thompson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D004318:Doxycycline / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000187:drug effects; D008875:Middle Aged; D010349:Patient Compliance; D011446:Prospective Studies; D013223:Statistics as Topic; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline