Ignite Creation Date:
2025-12-24 @ 5:25 PM
Ignite Modification Date:
2026-03-27 @ 6:40 PM
Study NCT ID:
NCT02675868
Status:
COMPLETED
Last Update Posted:
2016-10-13
First Post:
2016-01-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effects of Vasopressors on Immune Response
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D019446', 'term': 'Endotoxemia'}, {'id': 'D003919', 'term': 'Diabetes Insipidus'}], 'ancestors': [{'id': 'D016470', 'term': 'Bacteremia'}, {'id': 'D018805', 'term': 'Sepsis'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D014115', 'term': 'Toxemia'}, {'id': 'D018746', 'term': 'Systemic Inflammatory Response Syndrome'}, {'id': 'D007249', 'term': 'Inflammation'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D010900', 'term': 'Pituitary Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D009638', 'term': 'Norepinephrine'}, {'id': 'D010656', 'term': 'Phenylephrine'}, {'id': 'D014667', 'term': 'Vasopressins'}, {'id': 'D001127', 'term': 'Arginine Vasopressin'}], 'ancestors': [{'id': 'D004983', 'term': 'Ethanolamines'}, {'id': 'D000605', 'term': 'Amino Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D015306', 'term': 'Biogenic Monoamines'}, {'id': 'D001679', 'term': 'Biogenic Amines'}, {'id': 'D002395', 'term': 'Catecholamines'}, {'id': 'D002396', 'term': 'Catechols'}, {'id': 'D010636', 'term': 'Phenols'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D010909', 'term': 'Pituitary Hormones, Posterior'}, {'id': 'D010907', 'term': 'Pituitary Hormones'}, {'id': 'D036361', 'term': 'Peptide Hormones'}, {'id': 'D006728', 'term': 'Hormones'}, {'id': 'D006730', 'term': 'Hormones, Hormone Substitutes, and Hormone Antagonists'}, {'id': 'D009479', 'term': 'Neuropeptides'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D009842', 'term': 'Oligopeptides'}, {'id': 'D009419', 'term': 'Nerve Tissue Proteins'}, {'id': 'D011506', 'term': 'Proteins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 40}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2016-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-04', 'completionDateStruct': {'date': '2016-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-10-12', 'studyFirstSubmitDate': '2016-01-25', 'studyFirstSubmitQcDate': '2016-02-02', 'lastUpdatePostDateStruct': {'date': '2016-10-13', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2016-02-05', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2016-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'concentration plasma TNFalpha (pg/ml) following endotoxemia between the noradrenaline and the placebo groups', 'timeFrame': '1 day', 'description': 'comparison of subjects treated with noradrenaline compared to subjects treated with placebo'}], 'secondaryOutcomes': [{'measure': 'concentration plasma IL-6 (pg/ml)', 'timeFrame': '1 day', 'description': 'Measured with Luminex assay'}, {'measure': 'concentration plasma IL-8 (pg/ml)', 'timeFrame': '1 day', 'description': 'Measured with Luminex assay'}, {'measure': 'Leucocyte counts and differentiation', 'timeFrame': '1 day', 'description': 'Measured with Luminex assay'}, {'measure': '-The phenotype of circulating leukocytes', 'timeFrame': '1 day', 'description': 'Measured with Luminex assay'}, {'measure': 'concentration plasma IL-10 (pg/ml)', 'timeFrame': '1 day', 'description': 'Measured with Luminex assay'}, {'measure': 'concentration plasma IL-1RA (pg/ml)', 'timeFrame': '1 day', 'description': 'Measured with Luminex assay'}, {'measure': 'concentration plasma IL-1beta (pg/ml)', 'timeFrame': '1 day', 'description': 'Measured with Luminex assay'}, {'measure': 'symptoms during endotoxin day', 'timeFrame': '1 day', 'description': '6 point likert scale'}, {'measure': 'blood pressure', 'timeFrame': '1 day', 'description': 'mmHg'}, {'measure': 'temperature', 'timeFrame': '1 day', 'description': 'tympanic temperature'}, {'measure': 'cytokine production after ex vivo stimulation of leukocytes', 'timeFrame': '1 day'}, {'measure': 'phenotype of circulating leucocytes', 'timeFrame': '1 day'}, {'measure': 'Heart rate variability', 'timeFrame': '1 day', 'description': 'Comparison between Holter and 2 phone applications'}, {'measure': 'Breathing frequency (breaths/ min)', 'timeFrame': '1 day', 'description': 'comparison between pulseoximeter and a health Patch device and VISI mobile device'}, {'measure': 'Stress Levels (in percentage based on heart rate and heart rate variability)', 'timeFrame': '1 day', 'description': 'Comparison between health patch device, and 2 phone applications and a subjective stress questionaire'}, {'measure': 'Mean flow velocity of the median cerebral artery', 'timeFrame': '1 day', 'description': 'As measured via Transcranial Doppler Ultrasound'}, {'measure': 'cerebral microcirculatory flow', 'timeFrame': '1 day', 'description': 'As measured via Near Infrared Spectroscopy'}, {'measure': 'Tranfer function analysis', 'timeFrame': '1 day', 'description': 'As derived from transcranial Doppler Ultrasound'}, {'measure': 'Cerebral vascular resistance', 'timeFrame': '1 day', 'description': 'As derived from transcranial Doppler Ultrasound'}, {'measure': 'Cerebral Critical closing pressure', 'timeFrame': '1 day', 'description': 'As derived from transcranial Doppler Ultrasound'}, {'measure': 'Microvascular flow (microvascular flow index)', 'timeFrame': '1 day', 'description': 'Measured via Sidestream Darkfield Imaging'}, {'measure': 'Pulsatility index of the median cerebral artery', 'timeFrame': '1 day', 'description': 'As measured via Transcranial Doppler Ultrasound'}, {'measure': 'Mean flow index', 'timeFrame': 'via 1 day', 'description': 'As measured via Transcranial Doppler Ultrasound'}, {'measure': 'cerebral oxygenation', 'timeFrame': '1 day', 'description': 'As measured via Near infrared spectroscopy'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['noradrenaline', 'vasopressin', 'phenylephrine', 'endotoxemia', 'Lipopolysaccharide', 'vasopressor'], 'conditions': ['Endotoxemia']}, 'referencesModule': {'references': [{'pmid': '33483132', 'type': 'DERIVED', 'citation': 'Stolk RF, Reinema F, van der Pasch E, Schouwstra J, Bressers S, van Herwaarden AE, Gerretsen J, Schambergen R, Ruth M, van der Hoeven HG, van Leeuwen HJ, Pickkers P, Kox M. Phenylephrine impairs host defence mechanisms to infection: a combined laboratory study in mice and translational human study. Br J Anaesth. 2021 Mar;126(3):652-664. doi: 10.1016/j.bja.2020.11.040. Epub 2021 Jan 20.'}, {'pmid': '31008870', 'type': 'DERIVED', 'citation': 'van Loon LM, Stolk RF, van der Hoeven JG, Veltink PH, Pickkers P, Lemson J, Kox M. Effect of Vasopressors on the Macro- and Microcirculation During Systemic Inflammation in Humans In Vivo. Shock. 2020 Feb;53(2):171-174. doi: 10.1097/SHK.0000000000001357.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': 'Rationale:\n\nSeptic 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.\n\nObjective: To investigate whether noradrenaline exerts immunomodulatory effects in humans in vivo and to compare noradrenaline to other vasopressors (phenylephrine and vasopressin).\n\nStudy design: A randomized double-blind placebo-controlled study in healthy human volunteers during experimental endotoxemia.\n\nStudy population: 40 healthy male volunteers, aged 18-35 yrs.\n\nIntervention:\n\n1. The noradrenaline group (n= 10): subjects that will receive intravenous infusion of noradrenaline 0.05 μg/kg/min for 5 hours, starting 60 minutes before intravenous administration of 2 ng/kg LPS.\n2. The phenylephrine group (n=10): subjects that will receive intravenous infusion of phenylephrine 0.5 μg/kg/min for 5 hours, starting 60 minutes before intravenous administration of 2 ng/kg LPS. .\n3. The vasopressin group (n = 10): subjects that will receive intravenous infusion of vasopressin 0.04 IU/min for 5 hours, starting 60 minutes before intravenous administration of 2 ng/kg LPS.\n4. The placebo group (n = 10): subjects that will receive intravenous infusion of NaCl 0.9% for 5 hours, starting 60 minutes before intravenous administration of 2 ng/kg LPS.\n\nMain parameters/endpoints:\n\nThe difference of LPS-induced TNF-α plasma concentrations following endotoxemia between the noradrenaline and the placebo groups'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['ADULT'], 'maximumAge': '35 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Written informed consent\n* Age ≥18 and ≤35 yrs\n* Male\n* Healthy\n\nExclusion Criteria:\n\n* Use of any medication\n* Smoking\n* Previous spontaneous vagal collapse\n* History of atrial or ventricular arrhythmia\n* (Family) history of myocardial infarction or stroke under the age of 65 years\n* Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complex bundle branch block\n* Hypertension (defined as RR systolic \\> 160 or RR diastolic \\> 90)\n* Hypotension (defined as RR systolic \\< 100 or RR diastolic \\< 50)\n* Renal impairment (defined as plasma creatinin \\>120 μmol/l)\n* Liver enzyme abnormalities\n* Medical history of any disease associated with immune deficiency\n* CRP \\> 20 mg/L, WBC \\> 12x109/L, or clinically significant acute illness, including infections, within 4 weeks before endotoxin administration\n* Participation in a drug trial or donation of blood 3 months prior to the LPS challenge\n* Use of recreational drugs within 7 days prior to experiment day\n* Recent hospital admission or surgery with general anaesthesia (\\<3 months)\n* Known anaphylaxis or hypersensitivity to the study drugs or their excipients\n* Recent anaesthesia with halogenated agents\n* Known cardiovascular disease (coronary artery disease)\n* Known chronic nephritis'}, 'identificationModule': {'nctId': 'NCT02675868', 'briefTitle': 'Effects of Vasopressors on Immune Response', 'organization': {'class': 'OTHER', 'fullName': 'Radboud University Medical Center'}, 'officialTitle': 'The Effects of Different Vasopressors on the Innate Immune Response During Experimental Human Endotoxemia, a Pilot Proof-of-principle Study', 'orgStudyIdInfo': {'id': 'NL53411.091.015'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Norepinephrine', 'description': '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.', 'interventionNames': ['Drug: Norepinephrine']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Vasopressins', 'description': '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.', 'interventionNames': ['Drug: Vasopressins']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Phenylephrine', 'description': '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.', 'interventionNames': ['Drug: Phenylephrine']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'The placebo group: a group of 10 subjects that will receive NaCl 0.9% infusion for 5 hours, starting 60 minutes before endotoxin administration.', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Norepinephrine', 'type': 'DRUG', 'otherNames': ['Noradrenaline'], 'description': '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.', 'armGroupLabels': ['Norepinephrine']}, {'name': 'Phenylephrine', 'type': 'DRUG', 'description': '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.', 'armGroupLabels': ['Phenylephrine']}, {'name': 'Vasopressins', 'type': 'DRUG', 'otherNames': ['Argipressin'], 'description': '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.', 'armGroupLabels': ['Vasopressins']}, {'name': 'Placebo', 'type': 'DRUG', 'otherNames': ['NaCl 0,9%'], 'description': 'NaCl 0.9% infusion', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '6500HB', 'city': 'Nijmegen', 'state': 'Gelderland', 'country': 'Netherlands', 'facility': 'Radboudumc', 'geoPoint': {'lat': 51.8425, 'lon': 5.85278}}], 'overallOfficials': [{'name': 'Roeland Stolk, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Radboudumc, Intensive Care'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Radboud University Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}