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

Study Overview
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Brief Summary
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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
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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

Official Title
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A Pilot Study Assessing the Safety and Efficacy of Pioglitazone as an Anti-inflammatory Agent for the Treatment of CF Lung Disease in Patients With Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female >= 28 years of age Confirmed diagnosis of cystic fibrosis Forced Expiratory Volume in 1 second (FEV1) >= 40% predicted Clinically stable Ability to reproduce spirometry Ability to understand and sign the informed consent 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

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pioglitazone<br>All subjects treated for 28 days with pioglitazone, 30 mg orally, once daily Other names: Actos, Takeda | Drug: pioglitazone<br>* All subjects treated for 28 days with pioglitazone, 30 mg orally, once daily.<br>* Other names: Takeda;|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prescription drugs, Administration, oral, Durable medical equipment, Kinetics