Evaluation of Rosiglitazone Anti-inflammatory Effect With FDG-PET Imaging

Study Overview
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Brief Summary
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The purpose of this research study is to gain understanding of the basic responses of the lung to inflammation and specifically if a certain medication can reduce the inflammation alone or in combination with another. Inflammation is the way our bodies react to irritation or injury, and involves red, warm, and often painful swelling of the affected tissue. Acute lung injury involves inflammation that is not specific to one area of the lung and is caused by any one of several conditions: infection, trauma, breathing toxic substances, etc. When lung injury is severe, not enough oxygen can get into the body; this can lead to the need for mechanical support of breathing (mechanical ventilation), problems with brain, heart or other organ function, and in some cases, death.

Official Title
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Noninvasive Quantification of the Pulmonary Anti-inflammatory Effect of Rosiglitazone

Conditions
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Lung Inflammation

Intervention / Treatment
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* Drug: Zileuton
* Drug: Pioglitazone placebo
* Drug: Zileuton placebo
* Drug: Pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy man or woman, any race or ethnicity, age 19 - 44 years old Screening FEV1 and FVC > 90% of predicted Screening oxygen saturation by pulse oximetry >97% on room air Capable of lying still and supine within the PET/CT scanner for  1.5 hours Capable of following instructions for breathing protocol during CT portion of PET/CT Able and willing to give informed consent BMI < 35 Exclusion Criteria: Pregnancy (confirmed by qualitative urine hCG pregnancy test) Lactation Active menstruation History of cardiopulmonary disease Currently taking any prescription medications History of tobacco use or illicit drug use within the past year Presence of implanted electronic medical device Enrollment in another research study of an investigational drug Known allergy to rosiglitazone or zileuton Known allergy to both trimethoprim/sulfamethoxazole and amoxicillin Known allergy to drugs routinely used during bronchoscopy History of chronic active liver disease or acute liver disease within the past 3 months SGOT >47 IU/L, SGPT > 53 IU/L, or bilirubin > 1.1 mg/dl Inability lie flat for 1.5 hours for PET/CT scans or follow breathing protocol instructions for the CT portion of the PET/CT Prior research-related radiation exposure within the past year such that participation in this study would result in exposures that exceed the limits as defined by the FDA RDRC regulations (21 CFR 361.1).

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 44 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pioglitazone+zileuton placebo<br>Pioglitazone 45 mg qD for 2 weeks plus Sugar pill q6hr for 5 days | Drug: Zileuton placebo<br>* Placebo tablets provided by manufacturer of Zyflo CR (Cornerstone Therapeutics), 2 tablets po bid x 5 days prior to endotoxin instillation until 24 hours after endotoxin.<br>Drug: Pioglitazone<br>* PPAR-gamma agonist<br>* Other names: Actos;|
| Experimental: Zileuton+pioglitazone placebo<br>Sugar pill qD for 2 weeks plus Zileuton 600 mg q6hr for 5 days | Drug: Zileuton<br>* 600 mg tablets po QID for 5 days prior to endotoxin, stopping 24 hours after endotoxin instillation<br>* Other names: Zyflo;Drug: Pioglitazone placebo<br>* Lactose filled gelatin capsule, size 00, 1 tablet po bid x 2 weeks prior to endotoxin instillation until 24 hours after endotoxin.<br>|
| Sham Comparator: Pioglitazone placebo+zileuton placebo<br>Sugar pill qD for 2 weeks plus Sugar pill q6hr for 5 days | Drug: Pioglitazone placebo<br>* Lactose filled gelatin capsule, size 00, 1 tablet po bid x 2 weeks prior to endotoxin instillation until 24 hours after endotoxin.<br>Drug: Zileuton placebo<br>* Placebo tablets provided by manufacturer of Zyflo CR (Cornerstone Therapeutics), 2 tablets po bid x 5 days prior to endotoxin instillation until 24 hours after endotoxin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ki, measure of FDG uptake | Ki will be measured before and after endotoxin. Primary outcome measure is change in Ki (post- minus pre-endotoxin value) and absolute Ki after endotoxin. | Before and after endotoxin | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bronchoalveolar lavage (BAL) fluid cell counts | Total and neutrophil cell counts obtained by bronchoalveolar lavage after endotoxin. | After endotoxin | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung inflammation, positron emission tomography, fluorodeoxyglucose, rosiglitazone, zileuton, lung anti-inflammatory therapy