Ignite Creation Date:
2025-12-25 @ 12:55 AM
Ignite Modification Date:
2026-02-24 @ 12:26 AM
Study NCT ID:
NCT02557867
Status:
UNKNOWN
Last Update Posted:
2016-10-12
First Post:
2015-09-06
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Effect of Obesity in Dexmedetomidine Metabolic Clearance
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009765', 'term': 'Obesity'}], 'ancestors': [{'id': 'D050177', 'term': 'Overweight'}, {'id': 'D044343', 'term': 'Overnutrition'}, {'id': 'D009748', 'term': 'Nutrition Disorders'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D001835', 'term': 'Body Weight'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D020927', 'term': 'Dexmedetomidine'}], 'ancestors': [{'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 40}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2015-08'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-10', 'completionDateStruct': {'date': '2017-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2016-10-10', 'studyFirstSubmitDate': '2015-09-06', 'studyFirstSubmitQcDate': '2015-09-21', 'lastUpdatePostDateStruct': {'date': '2016-10-12', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2015-09-23', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2016-10', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Dexmedetomidine plasmatic levels', 'timeFrame': 'From start of infusion (min): 5, 10, 20, 30, 45, 60, 90, 120, 150, 180; from end of infusion (min): 5, 10, 20, 30, 60, 90, 120, 240, 360, 720', 'description': 'Measured by high performance liquid chromatography'}], 'secondaryOutcomes': [{'measure': 'Steatohepatitis score', 'timeFrame': '3 months after liver biopsy specimen collection', 'description': 'Using liver biopsy, a score for steatohepatitis will be applied on samples from all patients'}, {'measure': 'Plasma disappearance rate of indocyanine', 'timeFrame': '2 hours after arrival to Post-Anesthesia Care Unit', 'description': 'Using indocyanine green and LiMON monitor (Pulsion Medical Systems) surrogate measures of liver blood flow will be registered.'}, {'measure': 'Enzyme expression', 'timeFrame': '3 months after liver biopsy specimen collection', 'description': 'Liver samples will be analyzed for UGT2B10 and UGT1A4 expression (involved in dexmedetomidine metabolization)'}, {'measure': 'Hemodynamics', 'timeFrame': 'Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia', 'description': 'Heart rate and arterial pressure will be recorded during anesthesia'}, {'measure': 'Anesthetic depth', 'timeFrame': 'Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia', 'description': 'Using a bispectral index monitor, anesthetic depth will be monitorized through out surgery.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['dexmedetomidine', 'pharmacokinetic', 'obesity'], 'conditions': ['Obesity']}, 'referencesModule': {'references': [{'pmid': '17952107', 'type': 'BACKGROUND', 'citation': 'Han PY, Duffull SB, Kirkpatrick CM, Green B. Dosing in obesity: a simple solution to a big problem. Clin Pharmacol Ther. 2007 Nov;82(5):505-8. doi: 10.1038/sj.clpt.6100381.'}, {'pmid': '15255794', 'type': 'BACKGROUND', 'citation': 'Green B, Duffull SB. What is the best size descriptor to use for pharmacokinetic studies in the obese? Br J Clin Pharmacol. 2004 Aug;58(2):119-33. doi: 10.1111/j.1365-2125.2004.02157.x.'}, {'pmid': '15809132', 'type': 'BACKGROUND', 'citation': 'Casati A, Putzu M. Anesthesia in the obese patient: pharmacokinetic considerations. J Clin Anesth. 2005 Mar;17(2):134-45. doi: 10.1016/j.jclinane.2004.01.009.'}, {'pmid': '10702460', 'type': 'BACKGROUND', 'citation': 'Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg. 2000 Mar;90(3):699-705. doi: 10.1097/00000539-200003000-00035.'}, {'pmid': '15505441', 'type': 'BACKGROUND', 'citation': 'Hsu YW, Cortinez LI, Robertson KM, Keifer JC, Sum-Ping ST, Moretti EW, Young CC, Wright DR, Macleod DB, Somma J. Dexmedetomidine pharmacodynamics: part I: crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology. 2004 Nov;101(5):1066-76. doi: 10.1097/00000542-200411000-00005.'}, {'pmid': '16803911', 'type': 'BACKGROUND', 'citation': 'Gurbet A, Basagan-Mogol E, Turker G, Ugun F, Kaya FN, Ozcan B. Intraoperative infusion of dexmedetomidine reduces perioperative analgesic requirements. Can J Anaesth. 2006 Jul;53(7):646-52. doi: 10.1007/BF03021622.'}, {'pmid': '18474681', 'type': 'BACKGROUND', 'citation': 'Kaivosaari S, Toivonen P, Aitio O, Sipila J, Koskinen M, Salonen JS, Finel M. Regio- and stereospecific N-glucuronidation of medetomidine: the differences between UDP glucuronosyltransferase (UGT) 1A4 and UGT2B10 account for the complex kinetics of human liver microsomes. Drug Metab Dispos. 2008 Aug;36(8):1529-37. doi: 10.1124/dmd.108.021709. Epub 2008 May 12.'}, {'pmid': '24022260', 'type': 'BACKGROUND', 'citation': 'Bedogni G, Agosti F, De Col A, Marazzi N, Tagliaferri A, Sartorio A. Comparison of dual-energy X-ray absorptiometry, air displacement plethysmography and bioelectrical impedance analysis for the assessment of body composition in morbidly obese women. Eur J Clin Nutr. 2013 Nov;67(11):1129-32. doi: 10.1038/ejcn.2013.159. Epub 2013 Sep 11.'}, {'pmid': '10484010', 'type': 'BACKGROUND', 'citation': 'Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999 Sep;94(9):2467-74. doi: 10.1111/j.1572-0241.1999.01377.x.'}, {'pmid': '19577876', 'type': 'BACKGROUND', 'citation': 'Li W, Zhang Z, Wu L, Tian Y, Feng S, Chen Y. Determination of dexmedetomidine in human plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection: application to a pharmacokinetic study. J Pharm Biomed Anal. 2009 Dec 5;50(5):897-904. doi: 10.1016/j.jpba.2009.06.012. Epub 2009 Jun 16.'}, {'pmid': '15282775', 'type': 'BACKGROUND', 'citation': 'Ji QC, Zhou JY, Gonzales RJ, Gage EM, El-Shourbagy TA. Simultaneous quantitation of dexmedetomidine and glucuronide metabolites (G-Dex-1 and G-Dex-2) in human plasma utilizing liquid chromatography with tandem mass spectrometric detection. Rapid Commun Mass Spectrom. 2004;18(15):1753-60. doi: 10.1002/rcm.1548.'}, {'pmid': '15568893', 'type': 'BACKGROUND', 'citation': 'Duffull SB, Dooley MJ, Green B, Poole SG, Kirkpatrick CM. A standard weight descriptor for dose adjustment in the obese patient. Clin Pharmacokinet. 2004;43(15):1167-78. doi: 10.2165/00003088-200443150-00007.'}, {'pmid': '29661414', 'type': 'DERIVED', 'citation': 'Rolle A, Paredes S, Cortinez LI, Anderson BJ, Quezada N, Solari S, Allende F, Torres J, Cabrera D, Contreras V, Carmona J, Ramirez C, Oliveros AM, Ibacache M. Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients. Br J Anaesth. 2018 May;120(5):969-977. doi: 10.1016/j.bja.2018.01.040. Epub 2018 Mar 28.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to study the effect of obesity in dexmedetomidine pharmacokinetics and pharmacodynamic profile.', 'detailedDescription': 'The investigators expect to find an inverse correlation between the amount of fat mass and liver blood flow or with the enzymatic metabolic capacity. Results will be based on a population pharmacokinetic modeling analysis performed in NONMEM program. The investigators will first account for the effect of different measured size scalars on volumes and clearances and then they will search for plausible covariates (liver blood flow, enzymatic capacity, degree of hepatic steatosis, etc) on dexmedetomidine metabolic clearance. A pharmacokinetic model capable of characterizing clearance changes in the obese using more plausible biological covariates will be tried to be defined.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '60 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria for obese patients:\n\n* American Society of Anesthesiology classification I-III patients.\n* Both genders.\n* Age between 18 - 60 years.\n* Body mass index higher than 40 Kg/m2.\n\nInclusion Criteria for non-obese patients:\n\n* American Society of Anesthesiology classification I-II patients\n* Both genders.\n* Age between 18 - 60 years\n* Body mass index lower than 30 Kg/m2.\n\nExclusion Criteria:\n\n* Known allergy to study drugs\n* Uncontrolled hypertension.\n* Heart block greater than first degree.\n* Chronic hepatic and kidney disease.\n* Patients taking any drug acting in the central nervous system within 24 hrs before surgery.\n* Patients taking drugs that induce overexpression of liver cytochrome P450-complex enzymes (Carbamazepine, Phenytoin, Phenobarbital, Rifampicin, Dexamethasone, Griseofulvin, Terbinafine, Prednisone, Hydrocortisone, Modafinil).)\n* Known addiction to illicit drugs.\n* Pregnancy.\n* Current or past oncologic disease.'}, 'identificationModule': {'nctId': 'NCT02557867', 'briefTitle': 'The Effect of Obesity in Dexmedetomidine Metabolic Clearance', 'organization': {'class': 'OTHER', 'fullName': 'Pontificia Universidad Catolica de Chile'}, 'officialTitle': 'The Effect of Obesity in Dexmedetomidine Metabolic Clearance', 'orgStudyIdInfo': {'id': '14-253'}, 'secondaryIdInfos': [{'id': '1150197', 'type': 'OTHER_GRANT', 'domain': 'FONDECYT'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Obese', 'description': 'Body composition measurement before surgery using Dual energy X-ray absorptiometry. Dexmedetomidine infusion during surgery. Venous blood sampling for dexmedetomidine plasmatic levels during and after surgery. Liver blood flow indirect non-invasive assessment after surgery using indocyanine. Liver biopsy during surgery.', 'interventionNames': ['Drug: Dexmedetomidine']}, {'type': 'EXPERIMENTAL', 'label': 'Non-obese', 'description': 'Body composition measurement before surgery using Dual energy X-ray absorptiometry. Dexmedetomidine infusion during surgery. Venous blood sampling for dexmedetomidine plasmatic levels during and after surgery. Liver blood flow indirect non-invasive assessment after surgery using indocyanine. Liver biopsy during surgery.', 'interventionNames': ['Drug: Dexmedetomidine']}], 'interventions': [{'name': 'Dexmedetomidine', 'type': 'DRUG', 'otherNames': ['Precedex'], 'description': 'Dexmedetomidine 0.5 μg/kg over 10 minutes and then, 0.5 mcg/kg/h throughout surgery.', 'armGroupLabels': ['Non-obese', 'Obese']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Santiago', 'state': 'Santiago Metropolitan', 'country': 'Chile', 'facility': 'Hospital Clinico Pontificia Universidad Catolica', 'geoPoint': {'lat': -33.45694, 'lon': -70.64827}}], 'overallOfficials': [{'name': 'Luis I Cortínez, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Associate Professor Ordinary Category'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Pontificia Universidad Catolica de Chile', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}