NCT03623022

Effects of 20,000 EU of Clinical Center Reference Endotoxin (CCRE) Versus Placebo(ENDOHEART)

Effects of 20,000 EU of Clinical Center Reference Endotoxin (CCRE) Versus Placebo on Systemic and Cardiovascular Inflammatory Responses in Mild Asthmatics and Healthy Volunteers

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: University of North Carolina, Chapel Hill · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

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.

Conditions

• Healthy

Interventions

Type	Name	Description
DRUG	Clinical Center Reference Endotoxin (CCRE)	subjects will undergo an exposure to inhaled endotoxin through a nebulizer for approximately 10 minutes.
DRUG	Normal saline	subjects will undergo an exposure to inhaled normal saline through a nebulizer for approximately 10 minutes

Timeline

• Start date: 2018-10-17
• Primary completion: 2019-09-17
• Completion: 2019-09-17
• First posted: 2018-08-09
• Last updated: 2019-09-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study