Effect of Pioglitazone on Inflammation in Cystic Fibrosis

Paul Beringer

Status and phase: Completed; Phase 1

Conditions: Cystic Fibrosis

Treatments: Drug: Pioglitazone

Study type: Interventional

Funder types: Other

Identifiers

NCT00719381

HS-07-00308

IND #: 101989

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

1

Active Comparator group

Description:

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

Treatment:

Drug: Pioglitazone

2

No Intervention group

Description:

Patients in this arm will receive no intervention