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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Doxycycline
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cystic fibrosis