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

NCT02113397 — Terminated, 1 participants, Dartmouth-Hitchcock Medical Center

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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

Registry	NCT02113397
Status	Terminated - Insufficient enrollment
Study type	Observational
Enrollment	1 (Actual)
Sponsor	Dartmouth-Hitchcock Medical Center (Other); collaborators: Novartis Pharmaceuticals
Conditions	Cystic Fibrosis
Interventions	TOBI™ Podhaler™ 112 mg inhaled twice daily, Colistimethate 75 mg inhaled two times daily (Drug)
Dates	start 2014-04-01, primary completion 2016-08-01, completion 2016-08-01, first posted 2014-04-14, last updated 2018-03-12
Locations	1 site in United States

-Summary

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).

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+Arms and interventions

Arm	Type	Interventions	Description
Continuous Therapy		Drug: TOBI™ Podhaler™ 112 mg inhaled twice daily; Drug: Colistimethate 75 mg inhaled two times daily	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.
Cyclic therapy		Drug: TOBI™ Podhaler™ 112 mg inhaled twice daily	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.

TOBI™ Podhaler™ 112 mg inhaled twice daily (Drug), also known as Tobramycin inhalation powder
Colistimethate 75 mg inhaled two times daily (Drug)

+Outcome measures

Primary outcomes

Simpson Diversity Index [6 months]: 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

Secondary outcomes

Bacterial Relative Abundance [6 months]: Using 454 pyrosequencing and quantitative polymerase chain reaction (qPCR) techniques, the relative abundance of various bacterial genera will be determined.

+Eligibility

Sex: All, ages: 12 Years to 75 Years

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

+Locations (1)

Facility	City	Country	Status
Dartmouth-Hitchcock Medical Center	Lebanon, New Hampshire	United States

+Publications

Filkins LM, Hampton TH, Gifford AH, Gross MJ, Hogan DA, Sogin ML, Morrison HG, Paster BJ, O'Toole GA. Prevalence of streptococci and increased polymicrobial diversity associated with cystic fibrosis patient stability. J Bacteriol. 2012 Sep;194(17):4709-17. doi: 10.1128/JB.00566-12. Epub 2012 Jun 29. PMID 22753064
Price KE, Hampton TH, Gifford AH, Dolben EL, Hogan DA, Morrison HG, Sogin ML, O'Toole GA. Unique microbial communities persist in individual cystic fibrosis patients throughout a clinical exacerbation. Microbiome. 2013 Nov 1;1(1):27. doi: 10.1186/2049-2618-1-27. PMID 24451123