Evaluation of Rosiglitazone Anti-inflammatory Effect With FDG-PET Imaging
Primary Purpose
Lung Inflammation
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Zileuton
Pioglitazone placebo
Zileuton placebo
Pioglitazone
Sponsored by
About this trial
This is an interventional basic science trial for Lung Inflammation focused on measuring Lung inflammation, positron emission tomography, fluorodeoxyglucose, rosiglitazone, zileuton, lung anti-inflammatory therapy
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
- 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).
Sites / Locations
- Washington University / Barnes Jewish Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Sham Comparator
Arm Label
Pioglitazone+zileuton placebo
Zileuton+pioglitazone placebo
Pioglitazone placebo+zileuton placebo
Arm Description
Pioglitazone 45 mg qD for 2 weeks plus Sugar pill q6hr for 5 days
Sugar pill qD for 2 weeks plus Zileuton 600 mg q6hr for 5 days
Sugar pill qD for 2 weeks plus Sugar pill q6hr for 5 days
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Bronchoalveolar lavage (BAL) fluid cell counts
Total and neutrophil cell counts obtained by bronchoalveolar lavage after endotoxin.
Full Information
NCT ID
NCT01174056
First Posted
July 30, 2010
Last Updated
April 22, 2014
Sponsor
Washington University School of Medicine
Collaborators
Doris Duke Charitable Foundation
1. Study Identification
Unique Protocol Identification Number
NCT01174056
Brief Title
Evaluation of Rosiglitazone Anti-inflammatory Effect With FDG-PET Imaging
Official Title
Noninvasive Quantification of the Pulmonary Anti-inflammatory Effect of Rosiglitazone
Study Type
Interventional
2. Study Status
Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
Doris Duke Charitable Foundation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Inflammation
Keywords
Lung inflammation, positron emission tomography, fluorodeoxyglucose, rosiglitazone, zileuton, lung anti-inflammatory therapy
7. Study Design
Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Factorial Assignment
Masking
Participant
Allocation
Non-Randomized
Enrollment
39 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pioglitazone+zileuton placebo
Arm Type
Experimental
Arm Description
Pioglitazone 45 mg qD for 2 weeks plus Sugar pill q6hr for 5 days
Arm Title
Zileuton+pioglitazone placebo
Arm Type
Experimental
Arm Description
Sugar pill qD for 2 weeks plus Zileuton 600 mg q6hr for 5 days
Arm Title
Pioglitazone placebo+zileuton placebo
Arm Type
Sham Comparator
Arm Description
Sugar pill qD for 2 weeks plus Sugar pill q6hr for 5 days
Intervention Type
Drug
Intervention Name(s)
Zileuton
Other Intervention Name(s)
Zyflo
Intervention Description
600 mg tablets po QID for 5 days prior to endotoxin, stopping 24 hours after endotoxin instillation
Intervention Type
Drug
Intervention Name(s)
Pioglitazone placebo
Intervention Description
Lactose filled gelatin capsule, size 00, 1 tablet po bid x 2 weeks prior to endotoxin instillation until 24 hours after endotoxin.
Intervention Type
Drug
Intervention Name(s)
Zileuton placebo
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Pioglitazone
Other Intervention Name(s)
Actos
Intervention Description
PPAR-gamma agonist
Primary Outcome Measure Information:
Title
Ki, measure of FDG uptake
Description
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.
Time Frame
Before and after endotoxin
Secondary Outcome Measure Information:
Title
Bronchoalveolar lavage (BAL) fluid cell counts
Description
Total and neutrophil cell counts obtained by bronchoalveolar lavage after endotoxin.
Time Frame
After endotoxin
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
44 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Delphine L Chen, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University / Barnes Jewish Hospital
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
29414995
Citation
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.
Results Reference
derived
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Evaluation of Rosiglitazone Anti-inflammatory Effect With FDG-PET Imaging
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