A Phase 1 interventional study of Clinical Center Reference Endotoxin (CCRE) and Normal saline in Healthy, sponsored by University of North Carolina, Chapel Hill. Completed at 1 site in United States. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-09-20.
Sponsored by University of North Carolina, Chapel Hill · Phase 1, Interventional, and Other
To determine the systemic inflammatory effects of inhaled endotoxin and associated alterations in cardiovascular function. Subjects will undergo an exposure to inhaled endotoxin in a crossover fashion with normal saline inhalation. Blood samples and sputum samples will be taken before and after inhalation challenge to measure markers of systemic inflammation. Cardiovascular measures, including a heart rate variability monitor, flow mediated dilation of the brachial artery and left ventricular stain will also be measured.
The purpose of this study is to determine the systemic inflammatory effects of inhaled endotoxin and associated alterations in cardiovascular function. The investigators have previously found that inhalation of 20,000 Endotoxin Units (EU) of CCRE increases the neutrophil content of the blood; this dose can then be employed to screen populations for enhanced susceptibility to the systemic and cardiovascular inflammatory effect of inhaled endotoxin. Endotoxin is a commonly encountered bioaerosol and component of particulate matter (PM), a prevalent indoor and outdoor air pollutant [1-3]. For reasons that remain unclear, some individuals appear to be more susceptible to the inflammatory effects of inhaled endotoxin than are others, possibly owing to single nucleotide polymorphisms in the Toll-like receptor 4 (TLR4) gene that influence TLR4 signaling and function [4-6]. Exposure to PM is associated with increased cardiovascular morbidity and mortality [7]. PM exposure has been specifically linked with increases in blood pressure [8,9]. Susceptible individuals represent a population of particular interest for further mechanistic studies of the effects of endotoxin and for therapeutic trials. Systemic inflammatory response to inhaled endotoxin will be determined by measuring change in peripheral blood neutrophil counts, a biomarker of systemic inflammation, following inhaled CCRE vs placebo. Blood pressure, heart rate variability (HRV), vascular stiffness (by flow mediated dilation, or FMD) and left ventricular strain (LVS) will be measured before and after CCRE or placebo exposure to investigate the effect of endotoxin-induced systemic inflammation on cardiovascular function.
University of North Carolina, Chapel Hill is the lead sponsor of 1,340 studies on the registry; 133 are open to participants now.
Of its 155 completed or terminated interventional studies of FDA-regulated products, 136 (88%) have results posted.
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Normal lung function, defined as (NHanes III predicted set):
Exclusion Criteria:
Endotoxin challenge: Subjects will undergo inhalation of 20,000 EU CCRE. The Clinical Center Reference Endotoxin (CCRE) will be inhaled by subjects as a nebulized preparation using an ultrasonic nebulizer until the challenge solution is completely spent (generally 10 minutes). Following a washout of 2 weeks to 3 months the participant will undergo a Saline Challenge: Subjects will undergo inhalation of 0.9% sodium chloride. The Normal saline will be inhaled by subjects as a nebulized preparation using an ultrasonic nebulizer until the challenge solution is completely spent (generally 10 minutes).
Drug: Clinical Center Reference Endotoxin (CCRE) · Drug: Normal saline
Saline Challenge: Subjects will undergo inhalation of 0.9% sodium chloride. The Normal saline will be inhaled by subjects as a nebulized preparation using an ultrasonic nebulizer until the challenge solution is completely spent (generally 10 minutes). Following a washout of 2 weeks to 3 months the participant will undergo an Endotoxin challenge: Subjects will undergo inhalation of 20,000 EU CCRE. The CCRE will be inhaled by subjects as a nebulized preparation using an ultrasonic nebulizer until the challenge solution is completely spent (generally 10 minutes).
Drug: Clinical Center Reference Endotoxin (CCRE) · Drug: Normal saline
subjects will undergo an exposure to inhaled endotoxin through a nebulizer for approximately 10 minutes.
Also known as: Endotoxin
subjects will undergo an exposure to inhaled normal saline through a nebulizer for approximately 10 minutes
Also known as: 0.9% sodium Chloride (NACL)
Change in Left Ventricular Strain
Comparing pre and post results before and after endotoxin vs normal saline inhalations
Time frame: 15 minutes and 4 hrs after inhalation
Change in Flow Mediated Dilation
Comparing pre and post results before and after endotoxin vs normal saline inhalations
Time frame: 15 minutes and 4 hrs after inhalation
Percent Change in sputum Polymorphonuclear Neutrophils (PMNs)
post differences in % change comparing saline to endotoxin
Time frame: 6 hrs after inhalation
Percent Change in Blood Polymorphonuclear Neutrophils (PMNs)
post differences in % change comparing saline to endotoxin
Time frame: 5 hours and 30 minutes after inhalation
Plan to share: No
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This study is completed, as verified in Sep 2019. You cannot join it, but the record below documents what was studied.
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University of North Carolina, Chapel Hill