Safety and Efficacy of Pioglitazone as an Anti-inflammatory for the Treatment of Cystic Fibrosis (CF) Lung Disease

Not Applicable

Completed

Brief Summary: Study Hypothesis: Pioglitazone may decrease inflammation in cystic fibrosis lung disease.

Primary outcomes: Markers of inflammation (neutrophils, elastase, cytokines and bacteria)will be measured in induced sputum specimens before and after a 4 week treatment period with pioglitazone in clinically stable CF patients.

Detailed Description: * Single-center, open label study of pioglitazone in clinically stable patients with mild to moderate CF lung disease

* Induced sputum will be obtained from each subject at enrollment (Baseline) and again following 28 days of pioglitazone treatment (End of Treatment)

* Changes in markers of inflammation in the sputum samples will be assessed

* Safety measures, including complete blood count (CBC), serum chemistry, Erythrocyte sedimentation rate (ESR), C-Reactive Protein (CRP), urinalysis and spirometry, will also be assessed

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Use of an investigational agent within 4-week period prior to Visit 1
Chronic daily use of ibuprofen or other NSAIDS
Chronic daily use of insulin,oral diabetic agents or oral hypoglycemic agents
History of hypersensitivity to beta agonists
History of hypersensitivity to glitazones
Oxygen saturation<92%
Pregnant, breastfeeding or unwilling to practice acceptable birth control
History of hemoptysis >30cc per episode within 30 days prior to Visit 1
Significant history of hepatic, cardiovascular, renal,neurologic, hematologic or peptic ulcer disease
Serum Glutamic-Oxaloacetic Transaminase (SGOT)/(Serum Glutamic Pyruvic Transaminase (SGPT) >3 times the upper limit of normal at screening, documented biliary cirrhosis,or portal hypertension
Creatinine > 1.8 mg/dL at screening
Inability to swallow pills
Presence or abnormality that in the opinion of the investigator would compromise the safety or the quality of the data
Subjects who have routinely taken ibuprofen or other NSAIDS; prednisone or other systemic corticosteroids, or insulin, or oral diabetic agents within 4 weeks prior to visit 1 or who have taken these medications as needed within 72 hours prior to visit one will be excluded

Arm && Interventions

Group	Intervention	Description
Pioglitazone	pioglitazone	All subjects treated for 28 days with pioglitazone, 30 mg orally, once daily Other names: Actos, Takeda

Primary Outcome Measures

Name	Time	Method
Sputum TNFα	Day 0 and Day 29	The concentration of Tumor Necrosis Factor-α (TNFα) log 10 (pg/mL)
Sputum Neutrophil Count	Day 0 and Day 29	sputum neutrophils log 10 (cells/mL)
Sputum White Cell Count	Day 0 and Day 29	The total number of white cells log 10 cells/mL
Sputum Neutrophil Percent	Day 0 and Day 29	Neutrophils as a percent of the total white cells.
Sputum Active Elastase	Day 0 and Day 29	Log 10 of Concentration of active Elastase in mcg/mL
Sputum IL-8	Day 0 and Day 29	Concentration of Interleukin-8 log 10 (pg/mL)
Sputum IL-1ß	Day 0 and Day 29	The concentration of Interleukin-1ß (IL-1ß) log 10 (pg/mL)
Sputum IL-6	Day 0 and Day 29	The concentration of Interleukin-6 (IL-6) log 10 (pg/mL)