Official Title: “Effect of Pioglitazone on Sputum Biomarkers of Inflammation and Lung Epithelial Repair in Cystic Fibrosis”

The purpose of this study is to determine the effect of pioglitazone on reducing airway inflammation in cystic fibrosis and characterize the amount and timecourse of pioglitazone elimination from the body.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Placebo Control, Single Group Assignment, Pharmacokinetics/Dynamics Study

Study Primary Completion Date: June 2009

Progressive loss of lung function due to chronic infection and inflammation is the primary cause of morbidity and mortality in patients with CF. Current therapies directed at treatment of chronic P. aeruginosa infection (e.g. aerosolized tobramycin, azithromycin) provide short-term improvement in pulmonary function; however, persistence of the infection/inflammation causes the inevitable loss of lung function. PPARgamma is a nuclear transcription factor which is known to reduce activation of NFKB, a central mediator of airway inflammation in CF. Recent studies demonstrate that PPARgamma expression is reduced in patients with CF and may offer a potential therapeutic target to combat airway inflammation in CF. Pioglitazone is a thiazolidinedione whose principal pharmacological target it PPARgamma. The purpose of this pilot study is to determine the pharmacokinetics/pharmacodynamics of pioglitazone and effect on reducing airway inflammation in cystic fibrosis.

Intervention(s) in this Clinical Trial

• Drug: Pioglitazone
  • Treatment of pioglitazone will consist of 15 mg once daily for 28 days followed by 30 mg once daily for 28 days (N=12)

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Treatment of pioglitazone will consist of 15 mg once daily for 28 days followed by 30 mg once daily for 28 days (N=12)
• No Intervention: 2
  • Patients in this arm will receive no intervention

Primary Measures

• To determine the effect of pioglitazone on sputum biomarkers of lung inflammation and remodeling.
  • Time Frame: 83 days
    Safety Issue?: No

Secondary Measures

• To characterize the pharmacokinetics, pharmacodynamics and safety of pioglitazone in patients with cystic fibrosis.
  • Time Frame: 83 days
    Safety Issue?: Yes

Inclusion Criteria:

• Age greater than 18 years
• Clinically stable (FEV1 within 10% of baseline)
• FEV1 > 40% predicted

Exclusion Criteria:

• History of hypoglycemic events
• Hepatic disease (AST, ALT > 2.5x ULN)
• Renal disease (GFR < 60 ml/min - 1.73m2)
• Currently receiving beta-blocker, oral corticosteroids, statin, angiotensin receptor blocker, trimethoprim-sulfamethoxazole, gemfibrozil, or rifampin therapies.
• Allergy to thiazolidinediones
• Pregnancy or attempting to conceive, breast feeding
• Hematocrit < 30
• Congestive heart failure
• Pulmonary hypertension

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Southern California

Overall Clinical Trial Officials and Contacts

Paul M Beringer, Pharm.D. Principal Investigator University of Southern California  

Overall Contact: Paul M Beringer, Pharm.D. 323-442-1402 beringer@usc.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00719381

Study ID Number: HS-07-00308

ClinicalTrials.gov Identifier: NCT00719381

Health Authority: United States: Food and Drug Administration