Trial of Doxycycline to Reduce Sputum MMP-9 Activity in Adult Cystic Fibrosis (CF) Patients (DOXY)

A Randomized Trial of Doxycycline to Reduce Sputum MMP-9 Activity in Adult CF Patients Hospitalized for Pulmonary Exacerbations

The purpose of this study is to examine the role of a well-known and well-tolerated antibiotic, doxycycline, in the treatment of cystic fibrosis patients who are hospitalized. This antibiotic does not effectively treat the bacteria in airways of cystic fibrosis patients, but may reduce the activity of inflammatory molecules in the disease.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Other: placebo; Drug: Doxycycline

Detailed Description

One molecule that is inhibited by doxycycline is matrix metalloprotease-9, which is emerging as an important mediator of lung inflammation and damage in cystic fibrosis. We hypothesize that the addition of treatment with doxycycline in CF inpatients will reduce MMP-9 activity and inflammatory markers in the sputum of cystic fibrosis patients compared to CF patients not treated with doxycycline.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cystic Fibrosis
• Hospitalization for Pulmonary exacerbation

Exclusion Criteria:

• Significant GI illness
• Participation in another Investigational Protocol
• Allergies to Doxycycline
• Sputum Culture only positive for Staphylococcus aureus,
• Pregnant or Nursing
• Unwilling to use effective birth control
• Elevated LFT's greater than 3x the upper limit of normal
• Creatinine greater than 1.5x the upper limit of normal
• Lung transplantation
• Substance abuse within 30 days of screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Patients given placebo twice a day for 8 days at beginning of inpatient CF exacerbation	Other: placebo; placebo
Active Comparator: doxycycline; Patients given doxycycline 100 mg tablet twice a day for 8 days at the beginning of inpatient CF exacerbation	Drug: Doxycycline; 100 mg twice a day for 8 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events	Examines tolerability and safety with focus on adverse events (AEs) and serious adverse events (SAEs)	1 month from enrollment
Matrix Metalloprotease-9 (MMP-9) Protein Levels in Sputum	Mean sputum matrix metalloprotease-9 (MMP-9) levels measured at the end of therapy	8 days past baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Sputum Matrix Metalloprotease-9 (MMP-9) Activity End of Treatment	Measurement of endogenous active matrix metalloprotease-9 (MMP-9) in the sputum	8 days
Mean Change in Pulmonary Function Over Treatment Duration	Observe change in FEV1% predicted from beginning to end of study	Baseline to end of inpatient clinical exacerbation (average 14 days)

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Amit Gaggar, MD, University of Alabama at Birmingham

Publications and helpful links

General Publications

• Xu X, Abdalla T, Bratcher PE, Jackson PL, Sabbatini G, Wells JM, Lou XY, Quinn R, Blalock JE, Clancy JP, Gaggar A. Doxycycline improves clinical outcomes during cystic fibrosis exacerbations. Eur Respir J. 2017 Apr 5;49(4):1601102. doi: 10.1183/13993003.01102-2016. Print 2017 Apr.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: April 20, 2010
• First Submitted That Met QC Criteria: April 27, 2010
• First Posted (Estimate): April 28, 2010

Study Record Updates

• Last Update Posted (Actual): March 6, 2017
• Last Update Submitted That Met QC Criteria: January 11, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: cystic fibrosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: F081024004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO