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The Effect of Obesity in Dexmedetomidine Metabolic Clearance

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ClinicalTrials.gov Identifier: NCT02557867
Recruitment Status : Active, not recruiting
First Posted : September 23, 2015
Last Update Posted : October 12, 2016
Sponsor:
Information provided by (Responsible Party):
Pontificia Universidad Catolica de Chile

Brief Summary:
The purpose of this study is to study the effect of obesity in dexmedetomidine pharmacokinetics and pharmacodynamic profile.

Condition or disease Intervention/treatment Phase
Obesity Drug: Dexmedetomidine Phase 4

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: The Effect of Obesity in Dexmedetomidine Metabolic Clearance
Study Start Date : August 2015
Estimated Primary Completion Date : October 2016
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Obese
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.
Drug: Dexmedetomidine
Dexmedetomidine 0.5 μg/kg over 10 minutes and then, 0.5 mcg/kg/h throughout surgery.
Other Name: Precedex

Experimental: Non-obese
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.
Drug: Dexmedetomidine
Dexmedetomidine 0.5 μg/kg over 10 minutes and then, 0.5 mcg/kg/h throughout surgery.
Other Name: Precedex




Primary Outcome Measures :
  1. Dexmedetomidine plasmatic levels [ Time Frame: 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 ]
    Measured by high performance liquid chromatography


Secondary Outcome Measures :
  1. Steatohepatitis score [ Time Frame: 3 months after liver biopsy specimen collection ]
    Using liver biopsy, a score for steatohepatitis will be applied on samples from all patients

  2. Plasma disappearance rate of indocyanine [ Time Frame: 2 hours after arrival to Post-Anesthesia Care Unit ]
    Using indocyanine green and LiMON monitor (Pulsion Medical Systems) surrogate measures of liver blood flow will be registered.

  3. Enzyme expression [ Time Frame: 3 months after liver biopsy specimen collection ]
    Liver samples will be analyzed for UGT2B10 and UGT1A4 expression (involved in dexmedetomidine metabolization)

  4. Hemodynamics [ Time Frame: Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia ]
    Heart rate and arterial pressure will be recorded during anesthesia

  5. Anesthetic depth [ Time Frame: Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia ]
    Using a bispectral index monitor, anesthetic depth will be monitorized through out surgery.



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria for obese patients:

  • American Society of Anesthesiology classification I-III patients.
  • Both genders.
  • Age between 18 - 60 years.
  • Body mass index higher than 40 Kg/m2.

Inclusion Criteria for non-obese patients:

  • American Society of Anesthesiology classification I-II patients
  • Both genders.
  • Age between 18 - 60 years
  • Body mass index lower than 30 Kg/m2.

Exclusion Criteria:

  • Known allergy to study drugs
  • Uncontrolled hypertension.
  • Heart block greater than first degree.
  • Chronic hepatic and kidney disease.
  • Patients taking any drug acting in the central nervous system within 24 hrs before surgery.
  • Patients taking drugs that induce overexpression of liver cytochrome P450-complex enzymes (Carbamazepine, Phenytoin, Phenobarbital, Rifampicin, Dexamethasone, Griseofulvin, Terbinafine, Prednisone, Hydrocortisone, Modafinil).)
  • Known addiction to illicit drugs.
  • Pregnancy.
  • Current or past oncologic disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02557867


Locations
Chile
Hospital Clinico Pontificia Universidad Catolica
Santiago, Región metropolitana, Chile
Sponsors and Collaborators
Pontificia Universidad Catolica de Chile
Investigators
Principal Investigator: Luis I Cortínez, MD Associate Professor Ordinary Category

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pontificia Universidad Catolica de Chile
ClinicalTrials.gov Identifier: NCT02557867     History of Changes
Other Study ID Numbers: 14-253
1150197 ( Other Grant/Funding Number: FONDECYT )
First Posted: September 23, 2015    Key Record Dates
Last Update Posted: October 12, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Pontificia Universidad Catolica de Chile:
dexmedetomidine
pharmacokinetic
obesity

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Dexmedetomidine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action