Cystic Fibrosis
Conditions
Keywords
cystic fibrosis
Brief summary
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
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.
Interventions
DRUGDoxycycline
100 mg twice a day for 8 days
OTHERplacebo
placebo
Sponsors
Cystic Fibrosis Foundation
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events | 1 month from enrollment | Examines tolerability and safety with focus on adverse events (AEs) and serious adverse events (SAEs) |
| Matrix Metalloprotease-9 (MMP-9) Protein Levels in Sputum | 8 days past baseline | Mean sputum matrix metalloprotease-9 (MMP-9) levels measured at the end of therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Sputum Matrix Metalloprotease-9 (MMP-9) Activity End of Treatment | 8 days | Measurement of endogenous active matrix metalloprotease-9 (MMP-9) in the sputum |
| Mean Change in Pulmonary Function Over Treatment Duration | Baseline to end of inpatient clinical exacerbation (average 14 days) | Observe change in FEV1% predicted from beginning to end of study |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo: placebo | 19 |
| Doxycycline Doxycycline: 100 mg twice a day for 8 days | 20 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Doxycycline | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 19 Participants | 39 Participants |
| Age, Continuous | 29.1 years STANDARD_DEVIATION 8.9 | 27.3 years STANDARD_DEVIATION 9.4 | 28.2 years STANDARD_DEVIATION 9.1 |
| Gender Female | 8 Participants | 6 Participants | 14 Participants |
| Gender Male | 12 Participants | 13 Participants | 25 Participants |
| Region of Enrollment United States | 20 Participants | 19 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 19 | 5 / 20 |
| serious Total, serious adverse events | 0 / 19 | 0 / 20 |
Outcome results
Primary
Matrix Metalloprotease-9 (MMP-9) Protein Levels in Sputum
Mean sputum matrix metalloprotease-9 (MMP-9) levels measured at the end of therapy
Time frame: 8 days past baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Matrix Metalloprotease-9 (MMP-9) Protein Levels in Sputum | 4034 ng/mg total protein | Standard Deviation 3459 |
| Doxycycline | Matrix Metalloprotease-9 (MMP-9) Protein Levels in Sputum | 8837 ng/mg total protein | Standard Deviation 14752 |
p-value: <0.0595% CI: [0.128, 0.633]Wilcoxon (Mann-Whitney)
Primary
Number of Adverse Events
Examines tolerability and safety with focus on adverse events (AEs) and serious adverse events (SAEs)
Time frame: 1 month from enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Adverse Events | 5 adverse events |
| Doxycycline | Number of Adverse Events | 5 adverse events |
Secondary
Mean Change in Pulmonary Function Over Treatment Duration
Observe change in FEV1% predicted from beginning to end of study
Time frame: Baseline to end of inpatient clinical exacerbation (average 14 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in Pulmonary Function Over Treatment Duration | 6.9 Percentage of predicted FEV1 | Standard Deviation 10.4 |
| Doxycycline | Mean Change in Pulmonary Function Over Treatment Duration | 10.0 Percentage of predicted FEV1 | Standard Deviation 6.8 |
Secondary
Mean Sputum Matrix Metalloprotease-9 (MMP-9) Activity End of Treatment
Measurement of endogenous active matrix metalloprotease-9 (MMP-9) in the sputum
Time frame: 8 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Sputum Matrix Metalloprotease-9 (MMP-9) Activity End of Treatment | 12683 ng/mg total protein | Standard Deviation 35275 |
| Doxycycline | Mean Sputum Matrix Metalloprotease-9 (MMP-9) Activity End of Treatment | 3224 ng/mg total protein | Standard Deviation 2683 |