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

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

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).

Study Overview

• Status: Terminated
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: TOBI™ Podhaler™ 112 mg inhaled twice daily; Drug: Colistimethate 75 mg inhaled two times daily

• Study Type: Observational
• Enrollment (Actual): 1

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with cystic fibrosis who are followed at Dartmouth-Hitchcock Medical Center

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Continuous Therapy; 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; Other Names: Tobramycin inhalation powder; Drug: Colistimethate 75 mg inhaled two times daily
Cyclic therapy; 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; Other Names: Tobramycin inhalation powder

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborators: Novartis Pharmaceuticals

Publications and helpful links

General 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.
• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: April 9, 2014
• First Submitted That Met QC Criteria: April 10, 2014
• First Posted (Estimate): April 14, 2014

Study Record Updates

• Last Update Posted (Actual): March 12, 2018
• Last Update Submitted That Met QC Criteria: March 8, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Microbiome; Cystic fibrosis; Sputum; Tobramycin; Colistimethate
• 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; Tobramycin
• Other Study ID Numbers: D14010; CTBM100DUS02T (Other Grant/Funding Number: Novartis Pharmaceuticals)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No