Doxycycline Effects on Inflammation in Cystic Fibrosis
Information source: University of Southern California
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cystic Fibrosis
Intervention: Doxycycline (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: University of Southern California Official(s) and/or principal investigator(s): Paul M Beringer, Pharm.D., Principal Investigator, Affiliation: University of Southern California
Summary
Doxycycline is known to exhibit immune modulatory activities beyond its antibacterial
effects. In particular, doxycycline is a potent inhibitor of matrix metalloproteinase 9,
which is a protease derived largely from neutrophils. Recent studies demonstrate a
significant correlation between pulmonary disease severity and sputum concentrations of
MMP-9 in patients with CF. In addition, sputum MMP-9 levels are associated with airway
remodeling in CF.
The goal of this study is to determine the therapeutic potential of doxycycline in
modulating host airway inflammation in patients with CF. Specifically, the study will
characterize the PK /PD of doxycycline, evaluate the safety of short term therapy, and
explore the concentration effect relationship between doxycycline exposure and sputum
biomarker levels.
Clinical Details
Official title: Effect of Doxycycline on Sputum Biomarkers of Inflammation and Lung Epithelial Repair in Patients With Cystic Fibrosis.
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: To determine the effect of doxycycline on inflammatory biomarkers
Secondary outcome: To characterize the pharmacokinetics, pharmacodynamics and safety of doxycycline in patients with cystic fibrosis
Detailed description:
This study will consist of a prospective, open-label, randomized, controlled trial conducted
in 24 patients with cystic fibrosis. Twenty subjects will be stratified in a 1: 2 ratio based
on baseline FEV1 into mild (> 70%) or moderate (40-70%) pulmonary disease in order to
control for disease severity within each dose level. The subjects will be randomized in
blocks of four to receive no drug, 40mg, 100mg, or 200mg daily for 28 days.
Sputum samples will be obtained in all groups by induction with hypertonic saline at
baseline, 8, 24, and 48 hours following the first dose and then weekly for 4 weeks. Sputum
will also be collected at two follow up visits after the treatment period at weeks 5 and 6.
In the doxycycline group, serial blood samples (5 mL) for determination of doxycycline
concentrations will be obtained before and at 0, 0. 5, 1, 2, 4, 12, 24, and 48 hours
following the 1-hr infusion of a single IV dose. Once daily dosing of doxycycline will
resume immediately following the 48-hour blood sample and will continue until day 28.
Additional levels will be obtained pre-dose, and 1, 2, and 3 hours after doses administered
on days 14 and 28. A sample of blood will be obtained at baseline, and at days 28 for
inflammatory marker analyses.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Age greater than 18 years
- Clinically stable (FEV1 within 10% of baseline)
- FEV1 > 40% predicted
Exclusion Criteria:
- Use of clinically significant concomitant drug therapy such as long-term use of
nonsteroidal anti-inflammatory drugs or corticosteroids
- Known hypersensitivity to doxycycline
- Pregnancy or attempting to conceive, breast feeding, initiation of or change in
hormonal method of contraception within 4 weeks of baseline or during the study
- Use of systemic antibiotics (except oral azithromycin) within 4 weeks of baseline
- Use of doxycycline within 60 days of baseline
- Known history of gastrointestinal bleeding or gastrointestinal ulceration.
Locations and Contacts
University of Southern California, Los Angeles, California 90089, United States
Additional Information
Starting date: April 2008
Last updated: June 13, 2012
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