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

NCT ID: NCT01174056

Last Updated: 2014-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2014-03-31

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.

Conditions

Lung Inflammation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Pioglitazone+zileuton placebo

Pioglitazone 45 mg qD for 2 weeks plus Sugar pill q6hr for 5 days

Group Type: EXPERIMENTAL

Zileuton placebo

Intervention Type: DRUG

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.

Pioglitazone

Intervention Type: DRUG

PPAR-gamma agonist

Zileuton+pioglitazone placebo

Sugar pill qD for 2 weeks plus Zileuton 600 mg q6hr for 5 days

Group Type: EXPERIMENTAL

Zileuton

Intervention Type: DRUG

600 mg tablets po QID for 5 days prior to endotoxin, stopping 24 hours after endotoxin instillation

Pioglitazone placebo

Intervention Type: DRUG

Lactose filled gelatin capsule, size 00, 1 tablet po bid x 2 weeks prior to endotoxin instillation until 24 hours after endotoxin.

Pioglitazone placebo+zileuton placebo

Sugar pill qD for 2 weeks plus Sugar pill q6hr for 5 days

Group Type: SHAM_COMPARATOR

Pioglitazone placebo

Intervention Type: DRUG

Lactose filled gelatin capsule, size 00, 1 tablet po bid x 2 weeks prior to endotoxin instillation until 24 hours after endotoxin.

Zileuton placebo

Intervention Type: DRUG

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.

Interventions

Zileuton

600 mg tablets po QID for 5 days prior to endotoxin, stopping 24 hours after endotoxin instillation

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Pioglitazone

PPAR-gamma agonist

Intervention Type: DRUG

Other Intervention Names

Zyflo; Actos

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).

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 44 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Doris Duke Charitable Foundation

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Delphine L Chen, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University / Barnes Jewish Hospital

St Louis, Missouri, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29414995 (View on PubMed)

Other Identifiers

DDCF-2010060

Identifier Type: -

Identifier Source: org_study_id