Adiponectin Polymorphisms, Insulin Resistance, and Pharmacokinetics in Obesity

Phase 1

Completed

• Conditions: Obesity
• Interventions: Drug: Propofol and Fentanyl administration

• Registration Number: NCT01593397
• Lead Sponsor: Stanford University

Brief Summary

The primary objective of this study is to determine the influence of insulin resistance on drug metabolism and response in obese subjects. The investigators hypothesize that expression of adiponectin (a hormone secreted by fat tissue), and specific variants in the adiponectin gene can predict the insulin resistance and drug response among obese subjects.

Detailed Description

The following study will hypothesizes that insulin resistance causes changes in drug metabolism, elimination, and effect. We will differentiate the insulin resistant phenotype amongst obese individuals on the basis of both laboratory (fasting insulin, triglycerides, fasting glucose) analysis, and quantitative and qualitative adiponectin expression. We will determine the effect of insulin resistance on the pharmacokinetics and pharmacodynamics of anesthetic induction agents and opioids, using propofol and fentanyl as examples.

Study Timeline

• Study Start: 2011-11
• Study First Submitted: 2012-04-30
• Study First Submitted QC: 2012-05-04
• Study First Posted: 2012-05-08
• Primary Completion: 2017-09
• Study Completion: 2017-09
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-27
• Last Update Posted: 2017-12-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Inclusion criteria include patients of adult age
• American Society of Anesthesiologists Class I, II, or III, and undergoing elective surgical procedures requiring general anesthesia
• Body mass index greater than 35

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Exclusion Criteria

• Patients with evidence of hepatic, renal, or cardiovascular dysfunction
• History of difficult tracheal intubation, or adverse reaction to anesthesia shall be excluded from the study
• Patients taking prescribed or over-the-counter anxiolytics, narcotics, or sleeping aids, will also be excluded

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Propofol and Fentanyl administration	Propofol and Fentanyl administration	Propofol and Fentanyl will be administered to all subjects. All subjects will have blood drawn to determine pharmacokinetic variables. Processed EEG will be used to determine pharmacodynamics. Plasma samples will be used to ascertain adiponectin levels and for DNA sampling for analysis of adiponectin single nucleotide polymorphisms.

Primary Outcome Measures

Name	Time	Method
plasma concentration of drugs fentanyl and propofol	measured for 12 hours (beginning of anesthesia to 12 hours after)	Plasma concentration over time will be measured and modeled in order to calculate drug clearance, volume of distribution, area under the curve, and micro rate constants.; Knowledge of these variables will allow safer administration of anesthetic drug administration in the obese population.

Secondary Outcome Measures

Name	Time	Method
Adiponectin plasma protein levels	measured once (immediately before the operation)	The investigators will measure specific levels of the protein adiponectin in the blood, to determine if quantitative expression of adiponectin can predict insulin resistance in obesity and drug metabolism and response.
Adiponectin gene polymorphisms	measured once per study (immediately before the operation)	The investigators will look at specific genetic variants of the adiponectin gene to determine if expression of specific variants can predict insulin resistance and changed in drug response and metabolism.

Trial Locations

Locations (1)

Stanford University School of Medicine, Department of Anesthesia; 🇺🇸 Stanford, California, United States