Clinical Trial: Effects of Vasopressors on Immune Response
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: The Effects of Different Vasopressors on the Innate Immune Response During Experimental Human Endotoxemia, a Pilot Proof-of-principle Study
Brief Summary: Noradrenaline is a catecholamine and the cornerstone treatment for the improvement of hemodynamic parameters in septic shock. Catecholamines exert profound immunomodulatory effects. Noradrenaline in vitro inhibits LPS-induced pro-inflammatory cytokine production, however, the actions on immune function in vivo have not been assessed. Furthermore, effects on the immune system of viable vasopressor alternatives for the treatment of septic patients, namely phenylephrine and vasopressin, need to be established in humans in vivo.
Detailed Summary:
Rationale:
Septic shock is a major medical challenge associated with a high mortality rate and increasing incidence. It has become clear that the majority of septic patients do not succumb to an initial pro-inflammatory "hit", but at a later time-point in a pronounced immunosuppressive state, so called 'immunoparalysis'. Noradrenaline is a catecholamine and the cornerstone treatment for the improvement of hemodynamic parameters in septic shock. However, catecholamines exert profound immunomodulatory effects which have mainly been studied for adrenaline. It profoundly inhibits LPS-induced production of TNF-α, and enhances production of anti-inflammatory IL-10 in vitro, as well as in animal and human models of inflammation. Although in vitro studies have shown that noradrenaline inhibits LPS-induced pro-inflammatory cytokine production as potently as adrenaline, the effects of noradrenaline on the immune system in vivo have not yet been studied. Furthermore, effects on the immune system of viable vasopressor alternatives for the treatment of septic patients, namely phenylephrine and vasopressin, need to be established in humans in vivo.
Objective: To investigate whether noradrenaline exerts immunomodulatory effects in humans in vivo and to compare noradrenaline to other vasopressors (phenylephrine and vasopressin).
Study design: A randomized double-blind placebo-controlled study in healthy human volunteers during experimental endotoxemia.
Study population: 40 healthy male volunteers, aged 18-35 yrs.
Intervention:
- The noradrenaline group (n= 10): subjects that will receive intravenou
Sponsor: Radboud University
Current Primary Outcome: concentration plasma TNFalpha (pg/ml) following endotoxemia between the noradrenaline and the placebo groups [ Time Frame: 1 day ]
comparison of subjects treated with noradrenaline compared to subjects treated with placebo
Original Primary Outcome: Same as current
Current Secondary Outcome:
- concentration plasma IL-6 (pg/ml) [ Time Frame: 1 day ]Measured with Luminex assay
- concentration plasma IL-8 (pg/ml) [ Time Frame: 1 day ]Measured with Luminex assay
- Leucocyte counts and differentiation [ Time Frame: 1 day ]Measured with Luminex assay
- -The phenotype of circulating leukocytes [ Time Frame: 1 day ]Measured with Luminex assay
- concentration plasma IL-10 (pg/ml) [ Time Frame: 1 day ]Measured with Luminex assay
- concentration plasma IL-1RA (pg/ml) [ Time Frame: 1 day ]Measured with Luminex assay
- concentration plasma IL-1beta (pg/ml) [ Time Frame: 1 day ]Measured with Luminex assay
- symptoms during endotoxin day [ Time Frame: 1 day ]6 point likert scale
- blood pressure [ Time Frame: 1 day ]mmHg
- temperature [ Time Frame: 1 day ]tympanic temperature
- cytokine production after ex vivo stimulation of leukocytes [ Time Frame: 1 day ]
- phenotype of circulating leucocytes [ Time Frame: 1 day ]
- Heart rate variability [ Time Frame: 1 day ]Comparison between Holter and 2 phone applications
- Breathing frequency (breaths/ min) [ Time Frame: 1 day ]comparison between pulseoximeter and a health Patch device and VISI mobile device
- Stress Levels (in percentage based on heart rate and heart rate variability) [ Time Frame: 1 day ]Comparison between health patch device, and 2 phone applications and a subjective stress questionaire
- Mean flow velocity of the median cerebral artery [ Time Frame: 1 day ]As measured via Transcranial Doppler Ultrasound
- cerebral microcirculatory flow [ Time Frame: 1 day ]As measured via Near Infrared Spectroscopy
- Tranfer function analysis [ Time Frame: 1 day ]As derived from transcranial Doppler Ultrasound
- Cerebral vascular resistance [ Time Frame: 1 day ]As derived from transcranial Doppler Ultrasound
- Cerebral Critical closing pressure [ Time Frame: 1 day ]As derived from transcranial Doppler Ultrasound
- Microvascular flow (microvascular flow index) [ Time Frame: 1 day ]Measured via Sidestream Darkfield Imaging
- Pulsatility index of the median cerebral artery [ Time Frame: 1 day ]As measured via Transcranial Doppler Ultrasound
- Mean flow index [ Time Frame: via 1 day ]As measured via Transcranial Doppler Ultrasound
- cerebral oxygenation [ Time Frame: 1 day ]As measured via Near infrared spectroscopy
Original Secondary Outcome:
- concentration plasma IL-6 (pg/ml) [ Time Frame: 1 day ]Measured with Luminex assay
- concentration plasma IL-8 (pg/ml) [ Time Frame: 1 day ]Measured with Luminex assay
- Leucocyte counts and differentiation [ Time Frame: 1 day ]Measured with Luminex assay
- -The phenotype of circulating leukocytes [ Time Frame: 1 day ]Measured with Luminex assay
- concentration plasma IL-10 (pg/ml) [ Time Frame: 1 day ]Measured with Luminex assay
- concentration plasma IL-1RA (pg/ml) [ Time Frame: 1 day ]Measured with Luminex assay
- concentration plasma IL-1beta (pg/ml) [ Time Frame: 1 day ]Measured with Luminex assay
- symptoms during endotoxin day [ Time Frame: 1 day ]6 point likert scale
- blood pressure [ Time Frame: 1 day ]mmHg
- temperature [ Time Frame: 1 day ]tympanic temperature
- cytokine production after ex vivo stimulation of leukocytes [ Time Frame: 1 day ]
- phenotype of circulating leucocytes [ Time Frame: 1 day ]
Information By: Radboud University
Dates:
Date Received: January 25, 2016
Date Started: January 2016
Date Completion:
Last Updated: October 12, 2016
Last Verified: April 2016
- concentration plasma IL-6 (pg/ml) [ Time Frame: 1 day ]
