Lung Inflammation
Conditions
Keywords
Lung inflammation, positron emission tomography, fluorodeoxyglucose, rosiglitazone, zileuton, lung anti-inflammatory therapy
Brief summary
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.
Interventions
DRUGZileuton
600 mg tablets po QID for 5 days prior to endotoxin, stopping 24 hours after endotoxin instillation
Lactose filled gelatin capsule, size 00, 1 tablet po bid x 2 weeks prior to endotoxin instillation until 24 hours after endotoxin.
DRUGZileuton placebo
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.
DRUGPioglitazone
PPAR-gamma agonist
Sponsors
Doris Duke Charitable Foundation
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
19 Years to 44 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ki, measure of FDG uptake | Before and after endotoxin | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bronchoalveolar lavage (BAL) fluid cell counts | After endotoxin | Total and neutrophil cell counts obtained by bronchoalveolar lavage after endotoxin. |
Countries
United States
Outcome results
None listed