Doxycycline Effects on Inflammation in Cystic Fibrosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Paul Beringer, University of Southern California
ClinicalTrials.gov Identifier:
NCT01323101
First received: February 15, 2011
Last updated: June 13, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis
Drug: Doxycycline
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Doxycycline on Sputum Biomarkers of Inflammation and Lung Epithelial Repair in Patients With Cystic Fibrosis.

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • To determine the effect of doxycycline on inflammatory biomarkers [ Time Frame: Within 42 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To characterize the pharmacokinetics, pharmacodynamics and safety of doxycycline in patients with cystic fibrosis [ Time Frame: Within 42 days ] [ Designated as safety issue: Yes ]

Enrollment: 21
Study Start Date: April 2008
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Doxycycline
    Doxycycline 40mg, 100mg, 200mg tablet once daily, or no drug for 28 days.
    Other Names:
    • Doryx
    • Vibramycin
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01323101

Locations
United States, California
University of Southern California
Los Angeles, California, United States, 90089
Sponsors and Collaborators
University of Southern California
Investigators
Principal Investigator: Paul M Beringer, Pharm.D. University of Southern California
  More Information

Publications:
Responsible Party: Paul Beringer, Associate Professor, University of Southern California
ClinicalTrials.gov Identifier: NCT01323101     History of Changes
Other Study ID Numbers: HS-08-00017
Study First Received: February 15, 2011
Last Updated: June 13, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Inflammation
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Doxycycline
Doxycycline hyclate
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on July 10, 2014