Evaluation of Inhaled Antibiotics on Bacterial Diversity and Richness in the Cystic Fibrosis Lung

Study Overview
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Brief Summary
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The purpose of this study is to characterize bacterial diversity and richness in the sputum of cystic fibrosis patients treated with every-other-month TOBI™ Podhaler™ and continuous alternating therapy with TOBI™ Podhaler and colistimethate (Colistin).

Official Title
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Comparative Evaluation of Bacterial Diversity and Richness in CF Lung in Patients Who Use Cycled Every Other Month Tobramycin Inhalation Powder (TOBI™ Podhaler™) Or Continuous Alternating Therapy With Tobramycin Inhalation Powder (TOBI™ Podhaler™) and Inhaled Colistimethate

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: TOBI™ Podhaler™ 112 mg inhaled twice daily
* Drug: Colistimethate 75 mg inhaled two times daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of cystic fibrosis confirmed by mutation analysis of the cystic fibrosis transmembrane conductance regulator gene Sputum or throat swab culture positive for Pseudomonas aeruginosa at or within 6 months of enrollment Age ≥12 years Forced expiratory volume in one second (FEV1) 25-90 percent-predicted Exclusion Criteria: Age <18 years Inability to routinely expectorate sputum without induction by hypertonic saline Inability to provide or withdrawal of written informed consent History of aminoglycoside sensitivity or adverse reaction to inhaled antibiotics Serum creatinine ≥ 2.0 mg/dl Serum blood urea nitrogen (BUN) ≥40 mg/dl Pregnancy or lactating at screening History of systemic intravenous anti-Pseudomonal antibiotics within 28 days of enrollment

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 75 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Continuous Therapy<br>TOBI™ Podhaler™ 112 mg inhaled by mouth twice daily for 30 days followed by a 30-day cycle colistimethate 75 mg inhaled two times daily. Repeat cycle. | Drug: TOBI™ Podhaler™ 112 mg inhaled twice daily<br> <br> * Other names: Tobramycin inhalation powder;Drug: Colistimethate 75 mg inhaled two times daily<br> <br> |
| Cyclic therapy<br>TOBI™ Podhaler™ 112 mg inhaled by mouth twice daily for 30 days followed by a 30-day period during which no inhaled antibiotics are used. Repeat cycle. | Drug: TOBI™ Podhaler™ 112 mg inhaled twice daily<br> <br> * Other names: Tobramycin inhalation powder;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Simpson Diversity Index | The primary estimate in our study is the mean effects of Continuous Alternating Therapy compared to Cyclic therapy on Simpson Diversity Index (SDI) averaged at month 6 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bacterial Relative Abundance | Using 454 pyrosequencing and quantitative polymerase chain reaction (qPCR) techniques, the relative abundance of various bacterial genera will be determined. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic fibrosis, Microbiome, Sputum, Tobramycin, Colistimethate