Noninvasive Quantification of the Pulmonary Anti-inflammatory Effect of Rosiglitazone
Overview
- Phase
- Early Phase 1
- Intervention
- Zileuton placebo
- Conditions
- Lung Inflammation
- Sponsor
- Washington University School of Medicine
- Enrollment
- 39
- Locations
- 1
- Primary Endpoint
- Ki, measure of FDG uptake
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Pioglitazone+zileuton placebo
Pioglitazone 45 mg qD for 2 weeks plus Sugar pill q6hr for 5 days
Intervention: Zileuton placebo
Pioglitazone+zileuton placebo
Pioglitazone 45 mg qD for 2 weeks plus Sugar pill q6hr for 5 days
Intervention: Pioglitazone
Zileuton+pioglitazone placebo
Sugar pill qD for 2 weeks plus Zileuton 600 mg q6hr for 5 days
Intervention: Zileuton
Zileuton+pioglitazone placebo
Sugar pill qD for 2 weeks plus Zileuton 600 mg q6hr for 5 days
Intervention: Pioglitazone placebo
Pioglitazone placebo+zileuton placebo
Sugar pill qD for 2 weeks plus Sugar pill q6hr for 5 days
Intervention: Pioglitazone placebo
Pioglitazone placebo+zileuton placebo
Sugar pill qD for 2 weeks plus Sugar pill q6hr for 5 days
Intervention: Zileuton placebo
Outcomes
Primary Outcomes
Ki, measure of FDG uptake
Time Frame: 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 Outcomes
- Bronchoalveolar lavage (BAL) fluid cell counts(After endotoxin)