A Phase 4 interventional study of Norepinephrine and Phenylephrine in Endotoxemia, sponsored by Radboud University Medical Center. Completed at 1 site in Netherlands. Open to male participants aged 18 Years to 35 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-10-13.
Sponsored by Radboud University Medical Center · Phase 4, Interventional, and Basic science
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.
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:
Main parameters/endpoints:
The difference of LPS-induced TNF-α plasma concentrations following endotoxemia between the noradrenaline and the placebo groups
81 studies on the registry are indexed under Endotoxemia; 7 are open to participants now.
This study's enrollment of 40 is above the median of 31 across 70 interventional studies indexed under Endotoxemia.
Browse Endotoxemia studies →Radboud University Medical Center is the lead sponsor of 986 studies on the registry; 136 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The noradrenaline group: a group of 10 subjects that will receive noradrenaline 0.05 μg/kg/min infusion for 5 hours, starting 60 minutes before endotoxin administration.
Drug: Norepinephrine
The vasopressin group: a group of 10 subjects that will receive vasopressin 0.04 IU/min infusion for 5 hours, starting 60 minutes before endotoxin administration.
Drug: Vasopressins
The phenylephrine group: a group of 10 subjects that will receive phenylephrine 0.5 μg/kg/min infusion for 5 hours, starting 60 minutes before endotoxin administration.
Drug: Phenylephrine
The placebo group: a group of 10 subjects that will receive NaCl 0.9% infusion for 5 hours, starting 60 minutes before endotoxin administration.
Drug: Placebo
Noradrenaline is an endogenous catecholamine with sympathomimetic effects. It has mainly α-adrenergic receptor selectivity but also β-effects in higher concentrations. It will be administered at 0.05 μg/kg/min, a clinical relevant dose on the low end of the scale.
Also known as: Noradrenaline
Phenylephrine is a selective α-adrenergic receptor agonist. It will be administered at 0.5 μg/kg/min, based on its relative vasopressor potency in comparison with noradrenaline.
Vasopressin is 8-arginine-vasopressin, a synthetic analogue of endogenous nonapeptide hormone. It exerts its action via V1 receptors (ubiquitous vasoconstriction) and V2 receptors (renal water resorption). It will be administered at 0.04 IU/min, a clinically relevant dose.
Also known as: Argipressin
NaCl 0.9% infusion
Also known as: NaCl 0,9%
concentration plasma TNFalpha (pg/ml) following endotoxemia between the noradrenaline and the placebo groups
comparison of subjects treated with noradrenaline compared to subjects treated with placebo
Time frame: 1 day
concentration plasma IL-6 (pg/ml)
Measured with Luminex assay
Time frame: 1 day
concentration plasma IL-8 (pg/ml)
Measured with Luminex assay
Time frame: 1 day
Leucocyte counts and differentiation
Measured with Luminex assay
Time frame: 1 day
-The phenotype of circulating leukocytes
Measured with Luminex assay
Time frame: 1 day
concentration plasma IL-10 (pg/ml)
Measured with Luminex assay
Time frame: 1 day
concentration plasma IL-1RA (pg/ml)
Measured with Luminex assay
Time frame: 1 day
concentration plasma IL-1beta (pg/ml)
Measured with Luminex assay
Time frame: 1 day
symptoms during endotoxin day
6 point likert scale
Time frame: 1 day
blood pressure
mmHg
Time frame: 1 day
temperature
tympanic temperature
Time frame: 1 day
cytokine production after ex vivo stimulation of leukocytes
Time frame: 1 day
phenotype of circulating leucocytes
Time frame: 1 day
Heart rate variability
Comparison between Holter and 2 phone applications
Time frame: 1 day
Breathing frequency (breaths/ min)
comparison between pulseoximeter and a health Patch device and VISI mobile device
Time frame: 1 day
Stress Levels (in percentage based on heart rate and heart rate variability)
Comparison between health patch device, and 2 phone applications and a subjective stress questionaire
Time frame: 1 day
Mean flow velocity of the median cerebral artery
As measured via Transcranial Doppler Ultrasound
Time frame: 1 day
cerebral microcirculatory flow
As measured via Near Infrared Spectroscopy
Time frame: 1 day
Tranfer function analysis
As derived from transcranial Doppler Ultrasound
Time frame: 1 day
Cerebral vascular resistance
As derived from transcranial Doppler Ultrasound
Time frame: 1 day
Cerebral Critical closing pressure
As derived from transcranial Doppler Ultrasound
Time frame: 1 day
Microvascular flow (microvascular flow index)
Measured via Sidestream Darkfield Imaging
Time frame: 1 day
Pulsatility index of the median cerebral artery
As measured via Transcranial Doppler Ultrasound
Time frame: 1 day
Mean flow index
As measured via Transcranial Doppler Ultrasound
Time frame: via 1 day
cerebral oxygenation
As measured via Near infrared spectroscopy
Time frame: 1 day
Plan to share: No
The record gives a start of Jan 2016, a primary completion of Jul 2016 and a completion of Oct 2016. It does not say whether these dates are actual or estimated.
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This study is completed, as verified in Apr 2016. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Norepinephrine
Radboud University Medical Center →