Cystic Fibrosis
Conditions
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.
Interventions
DRUGPioglitazone
Treatment of pioglitazone will consist of 15 mg once daily for 28 days followed by 30 mg once daily for 28 days (N=12)
Sponsors
Paul Beringer
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the effect of pioglitazone on sputum biomarkers of lung inflammation and remodeling. | 83 days |
Secondary
| Measure | Time frame |
|---|---|
| To characterize the pharmacokinetics, pharmacodynamics and safety of pioglitazone in patients with cystic fibrosis. | 83 days |
Countries
United States
Outcome results
None listed