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

Noninvasive Quantification of the Pulmonary Anti-inflammatory Effect of Rosiglitazone

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.

Study Overview

• Status: Completed
• Conditions: Lung Inflammation
• Intervention / Treatment: Drug: Zileuton placebo; Drug: Pioglitazone; Drug: Zileuton; Drug: Pioglitazone placebo

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University / Barnes Jewish Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 44 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pioglitazone+zileuton placebo; Pioglitazone 45 mg qD for 2 weeks plus Sugar pill q6hr for 5 days	Drug: Zileuton 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.; Drug: Pioglitazone; PPAR-gamma agonist; Other Names: Actos
Experimental: Zileuton+pioglitazone placebo; Sugar pill qD for 2 weeks plus Zileuton 600 mg q6hr for 5 days	Drug: Zileuton; 600 mg tablets po QID for 5 days prior to endotoxin, stopping 24 hours after endotoxin instillation; Other Names: Zyflo; Drug: Pioglitazone placebo; Lactose filled gelatin capsule, size 00, 1 tablet po bid x 2 weeks prior to endotoxin instillation until 24 hours after endotoxin.
Sham Comparator: Pioglitazone placebo+zileuton placebo; Sugar pill qD for 2 weeks plus Sugar pill q6hr for 5 days	Drug: Zileuton 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.; Drug: Pioglitazone placebo; Lactose filled gelatin capsule, size 00, 1 tablet po bid x 2 weeks prior to endotoxin instillation until 24 hours after endotoxin.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Doris Duke Charitable Foundation
• Investigators: Principal Investigator: Delphine L Chen, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• Chen DL, Huang HJ, Byers DE, Shifren A, Belikoff B, Engle JT, Arentson E, Kemp D, Phillips S, Scherrer DE, Fujiwara H, Spayd KJ, Brooks FJ, Pierce RA, Castro M, Isakow W. The peroxisome proliferator-activated receptor agonist pioglitazone and 5-lipoxygenase inhibitor zileuton have no effect on lung inflammation in healthy volunteers by positron emission tomography in a single-blind placebo-controlled cohort study. PLoS One. 2018 Feb 7;13(2):e0191783. doi: 10.1371/journal.pone.0191783. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: July 30, 2010
• First Submitted That Met QC Criteria: July 30, 2010
• First Posted (Estimate): August 3, 2010

Study Record Updates

• Last Update Posted (Estimate): April 23, 2014
• Last Update Submitted That Met QC Criteria: April 22, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: positron emission tomography; rosiglitazone; fluorodeoxyglucose; Lung inflammation; zileuton; lung anti-inflammatory therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Inflammation; Pneumonia; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Leukotriene Antagonists; Hormone Antagonists; Antisickling Agents; Lipoxygenase Inhibitors; Pioglitazone; Hydroxyurea; Zileuton
• Other Study ID Numbers: DDCF-2010060