Doxycycline Effects on Inflammation in Cystic Fibrosis

March 28, 2017 updated by: Paul Beringer, University of Southern California

Effect of Doxycycline on Sputum Biomarkers of Inflammation and Lung Epithelial Repair in Patients With Cystic Fibrosis.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90089
        • University of Southern California

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Doxycycline
Drug: Doxycycline
Doxycycline 40mg, 100mg, 200mg tablet once daily, or no drug for 28 days.
Other Names:
  • Vibramycin
  • Doryx
Sham Comparator: Control
No doxycycline
Other: No doxycycline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine the effect of doxycycline on inflammatory biomarkers
Time Frame: Within 42 days
Within 42 days

Secondary Outcome Measures

Outcome Measure
Time Frame
To characterize the pharmacokinetics, pharmacodynamics and safety of doxycycline in patients with cystic fibrosis
Time Frame: Within 42 days
Within 42 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Southern California

Investigators

  • Principal Investigator: Paul M Beringer, Pharm.D., University of Southern California

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2008

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

February 15, 2011

First Submitted That Met QC Criteria

March 23, 2011

First Posted (Estimate)

March 25, 2011

Study Record Updates

Last Update Posted (Actual)

March 30, 2017

Last Update Submitted That Met QC Criteria

March 28, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HS-08-00017

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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