The Effect of Doxycycline on Matrix Metalloproteinase Expression and Activity in the Abdominal Aneurysm

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The matrix metalloproteinase-9 (MMP-9) is considered to play a central role in abdominal aortic aneurysm (AAA) initiation. Doxycycline has direct MMP-9 inhibiting properties in vitro, and it effectively suppresses AAA development in rodents. Observed inhibition of AAA progression, and contradictory findings in human studies evaluating the effect of doxycycline therapy on aortic wall MMP-9 suggest...

Brief Summary

Official Title: “The Effect of Doxycycline on Matrix Metalloproteinase Expression and Activity in the Abdominal Aneurysm”

The matrix metalloproteinase-9 (MMP-9) is considered to play a central role in abdominal aortic aneurysm (AAA) initiation. Doxycycline has direct MMP-9 inhibiting properties in vitro, and it effectively suppresses AAA development in rodents. Observed inhibition of AAA progression, and contradictory findings in human studies evaluating the effect of doxycycline therapy on aortic wall MMP-9 suggest that the effects of doxycycline extend beyond MMP-9 inhibition, and that the effect may be dose dependent.

  • Study Type: Interventional
  • Study Design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Basic Science

Detailed Clinical Trial Description

In this clinical trial, we evaluated the effect of two weeks of low (50 mg/day), medium (100 mg/day) or high dose (300 mg/day) doxycycline versus no medication in patients undergoing elective AAA repair. The effect of doxycycline treatment on MMP and cysteine proteases, and their respective inhibitors was evaluated in an integrative approach.

Intervention(s) in this Clinical Trial

  • Drug: doxycycline
    • 2 weeks once daily

Arms, Groups and Cohorts in this Clinical Trial

  • No Intervention: 1
  • Active Comparator: 2
    • doxycycline 50 mg/day
  • Active Comparator: 3
    • doxycycline 100 mg
  • Active Comparator: 4
    • doxycycline 300 mg

Outcome Measures for this Clinical Trial

Primary Measures

  • Collagenase mRNA and protein expression
    • Time Frame: 2 weeks

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

  • Elective open aneurysm repair

Exclusion Criteria:

  • Severe kidney and liver dysfunction

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Clinical Trial Investigator Information

Lead Investigator: Leiden University Medical Center Other

Overall Clinical Trial Officials and Contacts

Jan HN Lindeman, MD, PhD Principal Investigator Leiden University Medical Center  

Additional Information

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00538967

Study ID Number: P00.146

ClinicalTrials.gov Identifier: NCT00538967

Health Authority: Netherlands: Medical Ethics Review Committee (METC)

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http://clinicaltrialsfeeds.org/clinical-trials/show/NCT00538967