Ignite Creation Date:
2025-12-25 @ 12:13 AM
Ignite Modification Date:
2025-12-25 @ 10:15 PM
Study NCT ID:
NCT01452958
Status:
COMPLETED
Last Update Posted:
2013-01-30
First Post:
2011-09-22
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Endotoxin & Cytokines. Do Protein Loss and Metabolic Effects Depend on Central Nervous System (CNS) Activation of Stress Hormones or on Local Mechanisms in Muscle and Fat?
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007249', 'term': 'Inflammation'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D007333', 'term': 'Insulin Resistance'}], 'ancestors': [{'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D006946', 'term': 'Hyperinsulinism'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D014409', 'term': 'Tumor Necrosis Factor-alpha'}, {'id': 'D004731', 'term': 'Endotoxins'}], 'ancestors': [{'id': 'D006023', 'term': 'Glycoproteins'}, {'id': 'D006001', 'term': 'Glycoconjugates'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D015846', 'term': 'Monokines'}, {'id': 'D016207', 'term': 'Cytokines'}, {'id': 'D036341', 'term': 'Intercellular Signaling Peptides and Proteins'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D048069', 'term': 'Tumor Necrosis Factors'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D001685', 'term': 'Biological Factors'}, {'id': 'D001427', 'term': 'Bacterial Toxins'}, {'id': 'D014118', 'term': 'Toxins, Biological'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER']}, 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 24}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-06'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2013-01', 'completionDateStruct': {'date': '2013-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2013-01-29', 'studyFirstSubmitDate': '2011-09-22', 'studyFirstSubmitQcDate': '2011-10-13', 'lastUpdatePostDateStruct': {'date': '2013-01-30', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2011-10-17', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2013-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Acute metabolic effects of endotoxin and cytokine TNF-α (Study 2)', 'timeFrame': '2 hours', 'description': 'During a basal period.\n\nAcute metabolic effects: Glucose metabolism was quantified with raw arterio-venous differences and 3H3-Glucose tracer. Lactate was quantified with raw arterio-venous differences. Lipid metabolism was quantified with \\[9,10-3H\\]-Palmitate tracer and amino acid metabolism with 15N-Phenylalanine tracer and 13C-Urea tracer.'}, {'measure': 'Acute metabolic effects of endotoxin and cytokine TNF-α (Study 2)', 'timeFrame': '4 hours', 'description': 'During a hyperinsulinaemic euglycaemic clamp.\n\nAcute metabolic effects: Glucose metabolism was quantified with raw arterio-venous differences and 3H3-Glucose tracer. Lactate was quantified with raw arterio-venous differences. Lipid metabolism was quantified with \\[9,10-3H\\]-Palmitate tracer and amino acid metabolism with 15N-Phenylalanine tracer and 13C-Urea tracer.'}, {'measure': 'Acute metabolic effects of cytokine TNF-α (Study 1)', 'timeFrame': '3 hours', 'description': 'During a basal period.\n\nAcute metabolic effects: Glucose and lactate were quantified with raw arterio-venous differences; lipid metabolism was quantified with \\[9,10-3H\\]-palmitate and amino acid metabolism with 15N-phenylalanine.'}, {'measure': 'Acute metabolic effects of cytokine TNF-α (Study 1)', 'timeFrame': '3 hours', 'description': 'During a hyperinsulinaemic euglycaemic clamp.\n\nAcute metabolic effects: Glucose and lactate were quantified with raw arterio-venous differences; lipid metabolism was quantified with \\[9,10-3H\\]-palmitate and amino acid metabolism with 15N-phenylalanine.'}], 'secondaryOutcomes': [{'measure': 'Intracellular insulin signaling, growth hormone signalling and inflammatory signalling pathways.', 'timeFrame': '120 min.', 'description': 'Musle and fat biopsies during a basal period (120 min. from the beginning of a basal period)'}, {'measure': 'Intracellular insulin signaling, growth hormone signalling and inflammatory signalling pathways.', 'timeFrame': '30 min.', 'description': 'Musle and fat biopsies during a hyperinsulinaemic euglycaemic clamp (30 min. from the beginning of clamp)'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Endotoxin', 'LPS', 'TNF-α', 'insulin resistance', 'metabolism'], 'conditions': ['Inflammation', 'Glucose Metabolism Disorders']}, 'referencesModule': {'references': [{'pmid': '23835341', 'type': 'DERIVED', 'citation': 'Bach E, Nielsen RR, Vendelbo MH, Moller AB, Jessen N, Buhl M, K-Hafstrom T, Holm L, Pedersen SB, Pilegaard H, Bienso RS, Jorgensen JO, Moller N. Direct effects of TNF-alpha on local fuel metabolism and cytokine levels in the placebo-controlled, bilaterally infused human leg: increased insulin sensitivity, increased net protein breakdown, and increased IL-6 release. Diabetes. 2013 Dec;62(12):4023-9. doi: 10.2337/db13-0138. Epub 2013 Jul 8.'}]}, 'descriptionModule': {'briefSummary': 'Main objective :\n\nThe purpose of this study is to prove that the effects of bacterial endotoxin and cytokine TNF-α, on protein loss, fatty acid release, and glucose metabolism depend on two mechanisms:\n\n1. Direct local effects in muscle tissue.\n2. Activation of the hypothalamo-pituitary axis and a stress-hormone response\n\nStudy protocols:\n\n1. Acute metabolic effects of TNF-α(Beromun, Boehringer-Ingelheim Germany) vs placebo perfused into the femoral artery of the leg in 8 healthy subjects.\n2. Acute metabolic effects of\n\n * placebo(saline)\n * endotoxin(US standard reference E.Coli, endotoxin)\n * TNF-α(Beromun, Boehringer-Ingelheim Germany) given systemically\n * in 8 patients with hypopituitarism(to block stress hormone release) and in 8 healthy subjects all studied thrice.', 'detailedDescription': 'PURPOSE:\n\nKnowledge about the effects of bacterial endotoxin and cytokines (and inflammation in general) in humans on protein, glucose and lipid metabolism and intracellular signalling in muscle and fat is sporadic and it is uncertain whether endotoxin and cytokines act directly in fat and muscle tissue or indirectly via central nervous system (CNS) mediated stress hormone release.\n\nThe investigators hypothesize that the metabolic effects of endotoxin and cytokine TNF-α, including protein loss, fatty acid release and decreased glucose uptake depend on two mechanisms:\n\n1. Direct local effects in muscle tissue (Study protocol 1)\n2. Activation of the hypothalamo-pituitary axis and generalized stress hormone response (Study protocol 2)\n\nMETHODOLOGY:\n\nStudy protocol 1:\n\nAcute metabolic effects of TNF-α (Beromun, Boehringer-Ingelheim, Germany) versus placebo perfused into the femoral artery of the leg in 8 healthy subjects, studied once. Femoral vein sampling allows assessment of local metabolic events in the leg. The vessels were cannulated using the Seldinger technique. Each study comprises a 3 hour basal period and a 3 hour Hyperinsulinemic-Euglycemic Clamp. Muscle biopsies were obtained simultaneously from both lateral vastus muscles.\n\nStudy protocol 2:\n\nAcute metabolic effects of (i)placebo (saline), (ii)endotoxin (US standard reference E.Coli, endotoxin) and (iii)TNF-α (Beromun, Boehringer-Ingelheim, Germany) given systemically intravenously (i.v.) in 8 patients with hypopituitarism (to block stress hormone release) and in 8 healthy subjects all studied thrice. Every study comprises a 4 hour basal period and a 2 hour Hyperinsulinemic-Euglycemic Clamp. Muscle and fat biopsies were obtained.\n\nStudy protocol 1 and Study protocol 2:\n\nAssays: Mass spectrometry (15N-phenylalanine, 13C-urea), 3H-glucose, 3H-palmitate quantification, hormone and metabolite analysis, cytokine assays, intracellular signaling.'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria 1. group:\n\n* Male\n* 19 \\< BMI \\< 28\n* 18 ≤ Age ≤ 50\n* Healthy\n\nInclusion Criteria 2. group:\n\n* Male\n* 20 \\< BMI \\< 30\n* Age \\> 25\n* Healthy\n\nExclusion Criteria:\n\n* Diseases\n* Allergy'}, 'identificationModule': {'nctId': 'NCT01452958', 'briefTitle': 'Endotoxin & Cytokines. Do Protein Loss and Metabolic Effects Depend on Central Nervous System (CNS) Activation of Stress Hormones or on Local Mechanisms in Muscle and Fat?', 'organization': {'class': 'OTHER', 'fullName': 'Aarhus University Hospital'}, 'officialTitle': 'Endotoxin & Cytokines. Do Protein Loss and Metabolic Effects Depend on CNS Activation of Stress Hormones or on Local Mechanisms in Muscle and Fat?', 'orgStudyIdInfo': {'id': '2010/0604'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'TNF-α', 'description': 'Beromun, Boehringer-Ingelheim, Germany', 'interventionNames': ['Biological: TNF-alpha']}, {'type': 'EXPERIMENTAL', 'label': 'Endotoxin', 'interventionNames': ['Biological: Endotoxin']}], 'interventions': [{'name': 'TNF-alpha', 'type': 'BIOLOGICAL', 'otherNames': ['Beromun, Boehringer-Ingelheim, Germany'], 'description': 'Study protocol 1: 6 ng/kg/h intraarterial Study protocol 2: 18 ng/kg/h intravenous', 'armGroupLabels': ['TNF-α']}, {'name': 'Endotoxin', 'type': 'BIOLOGICAL', 'otherNames': ['E. coli endotoxin, US standard'], 'description': 'Study protocol 2:0,075 ng/kg/h intravenous', 'armGroupLabels': ['Endotoxin']}]}, 'contactsLocationsModule': {'locations': [{'zip': '8000', 'city': 'Aarhus', 'country': 'Denmark', 'facility': 'Medical Department MEA, NBG, Aarhus University Hospital', 'geoPoint': {'lat': 56.15674, 'lon': 10.21076}}], 'overallOfficials': [{'name': 'Niels Møller, Professor', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Aarhus University Hospital'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Aarhus University Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'University of Aarhus', 'class': 'OTHER'}, {'name': 'Lundbeck Foundation', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Medical Doctor, PhD student', 'investigatorFullName': 'Ermina Bosnjak', 'investigatorAffiliation': 'Aarhus University Hospital'}}}}