Effects of 20,000 EU of Clinical Center Reference Endotoxin (CCRE) Versus Placebo(ENDOHEART)
Condition: Healthy
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Clinical Center Reference Endotoxin (CCRE); Normal saline
Intervention type(s): Drug; Drug
Intervention description(s): subjects will undergo an exposure to inhaled endotoxin through a nebulizer for approximately 10 minutes.; subjects will undergo an exposure to inhaled normal saline through a nebulizer for approximately 10 minutes
Other intervention name(s): Endotoxin; 0.9% sodium Chloride (NACL)
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Subjects will undergo an exposure to inhaled endotoxin in a crossover fashion with normal saline inhalation.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: healthy