Effect of Pioglitazone on Inflammation in Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

Effect of Pioglitazone on Sputum Biomarkers of Inflammation and Lung Epithelial Repair in Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00719381
• Other study ID #: HS-07-00308
• Secondary ID: IND #: 101989
• Status: Completed
• Phase: Phase 1
• First received: July 17, 2008
• Last updated: June 13, 2012
• Start date: January 2008
• Est. completion date: June 2009

Study information

• Verified date: June 2012
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

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)

Locations

Country	Name	City	State
United States	University of Southern California	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Paul Beringer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the effect of pioglitazone on sputum biomarkers of lung inflammation and remodeling.		83 days	No
Secondary	To characterize the pharmacokinetics, pharmacodynamics and safety of pioglitazone in patients with cystic fibrosis.		83 days	Yes