Effect of Pioglitazone on Inflammation in Cystic Fibrosis

Phase 1

Completed

• Conditions: Cystic Fibrosis
• Interventions: Drug: Pioglitazone

• Registration Number: NCT00719381
• Lead Sponsor: Paul Beringer

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2008-01
• Study First Submitted: 2008-07-17
• Study First Submitted QC: 2008-07-17
• Study First Posted: 2008-07-21
• Primary Completion: 2009-06
• Study Completion: 2009-06
• Status Verified: 2012-06
• Last Update Submitted: 2012-06-13
• Last Update Posted: 2012-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	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)

Primary Outcome Measures

Name	Time	Method
To determine the effect of pioglitazone on sputum biomarkers of lung inflammation and remodeling.	83 days

Secondary Outcome Measures

Name	Time	Method
To characterize the pharmacokinetics, pharmacodynamics and safety of pioglitazone in patients with cystic fibrosis.	83 days

Trial Locations

Locations (1)

University of Southern California; 🇺🇸 Los Angeles, California, United States