Neurobiological and Cognitive Changes Following Exposure to Either Sevoflurane- or Propofol-based Anesthesia in Children

March 24, 2020 updated by: University of Calgary

Neurobiological, Cognitive-affective and Behavioral Changes Following Exposure to Either Sevoflurane- or Propofol-based Anesthesia in Children Undergoing MRI

The demand for magnetic resonance imaging (MRI) in pediatric patients is increasing due to its use in medical diagnosis and surveillance. Pediatric patients often require general anesthesia (GA) for MRI due to the need for prolonged immobility during the scanning process to obtain high quality images. Two widely used anesthetic techniques for pediatric MRIs are volatile-based anesthesia using sevoflurane and total intravenous anesthesia (TIVA) using propofol. Concerns have been raised regarding the potential neurotoxic effects of anesthetics on the developing brain. Within the animal literature, there is emerging evidence to suggest that both sevoflurane and propofol may cause inflammation, impacting brain cell survival and connections, thereby contributing to possible cognitive dysfunction. However, given the challenges in extrapolating the animal data to humans, and the relatively limited human cohort studies examining the long-term effects of anesthesia exposure, there is inadequate information available to make informed clinical decisions regarding the choice of optimal anesthetic agents for MRI in children. Therefore, this study will uniquely examine the mechanisms of two widely used anesthetics and their short and long-term impact on developmental outcomes in healthy children.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 1N4
        • University of Calgary

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 5 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Those between the ages 2 to 5 years who require general anesthesia for MRI Brain and have an American Society of Anesthesiologists' physical status of I to II

Exclusion Criteria:

  • Emergency cases
  • Intubated prior to MRI
  • Allergies/contraindication to anesthetics
  • Requirement of a painful procedure with MRI
  • Significant developmental delay
  • Autism or suspected autism
  • History of extreme prematurity <28 wks gestational age
  • Sedation or general anesthesia in the last 14 days
  • Receiving chemotherapy or radiation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: SUPPORTIVE_CARE
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Inhalational Technique
All patients will receive Ametop local anesthetic to the dorsum of both hands 30-45 minutes prior to induction. After inhalation induction of anesthesia with sevoflurane (in 100% O2), an IV will be obtained. Anesthesia will be maintained with sevoflurane (in a mixture of air:oxygen) with a minimum alveolar concentration of 1.0-1.3, titrated to effect. No long acting opioids or nitrous oxide will be used. Airway management will be at the discretion of the anesthesiologist. Each patient will receive the antiemetic ondansetron 0.1mg/kg IV.
Drug: Sevoflurane
The child will be randomized via a block design to receive either a volatile anesthetic (induction: sevoflurane), or total intravenous anesthetic technique (induction: propofol)
Drug: Ametop
Each patient will receive Ametop local anesthetic to the dorsum of both hands 30-45 minutes prior to induction.
Drug: Ondansetron
Each patient will receive the antiemetic ondansetron 0.1mg/kg IV.
EXPERIMENTAL: Total Intravenous Anesthetic Technique
All patients will receive Ametop local anesthetic to the dorsum of both hands 30-45 minutes prior to IV insertion. Once an IV is established, patients will receive an IV bolus of propofol (2-6mg/kg). Anesthesia will be maintained with a propofol infusion starting at 250 mcg/kg/min and titrated to effect. Airway management will be at the discretion of the anesthesiologist. Each patient will receive the antiemetic ondansetron 0.1mg/kg IV.
Drug: Ametop
Each patient will receive Ametop local anesthetic to the dorsum of both hands 30-45 minutes prior to induction.
Drug: Ondansetron
Each patient will receive the antiemetic ondansetron 0.1mg/kg IV.
Drug: Propofol
The child will be randomized via a block design to receive either a volatile anesthetic (induction: sevoflurane), or total intravenous anesthetic technique (induction: propofol)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV)
Time Frame: 12-15 weeks from date of randomization
The WPPSI - IV is designed for children aged 2.5 to 7.5 years, and is used to assess general intelligence.
12-15 weeks from date of randomization

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The Child Behavior Checklist (CBCL) 1.5 to 5 years
Time Frame: Change from baseline at 12-13 weeks after randomization
The CBCL is widely used for identifying problem behaviors in children ages 1.5 to 5 years
Change from baseline at 12-13 weeks after randomization

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P)
Time Frame: Change from baseline within 1 week after randomization
The BRIEF-P is the first standardized rating scale designed to specifically measure executive function in preschool-aged children (ages 2-5).
Change from baseline within 1 week after randomization
The Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P)
Time Frame: Change from baseline within 2-3 weeks after randomization
The BRIEF-P is the first standardized rating scale designed to specifically measure executive function in preschool-aged children (ages 2-5).
Change from baseline within 2-3 weeks after randomization
The Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P)
Time Frame: Change from baseline within 12-13 weeks after randomization
The BRIEF-P is the first standardized rating scale designed to specifically measure executive function in preschool-aged children (ages 2-5).
Change from baseline within 12-13 weeks after randomization
The Post Hospital Behavior Questionnaire (PHBQ)
Time Frame: Within 1 week after randomization
The PHBQ asks parents to rate their child's behavior on 27 items concerning sleep, eating, internalizing and externalizing behaviors. For each item parents must compare their child's current behavior with their behavior one week prior to hospitalization.
Within 1 week after randomization
The Post Hospital Behavior Questionnaire (PHBQ)
Time Frame: Within 2-3 weeks after randomization
The PHBQ asks parents to rate their child's behavior on 27 items concerning sleep, eating, internalizing and externalizing behaviors. For each item parents must compare their child's current behavior with their behavior one week prior to hospitalization.
Within 2-3 weeks after randomization
The Modified Yale Preoperative Anxiety Scale (mYPAS)
Time Frame: On the day of randomization, obtained just prior to the intervention
The mYPAS is the current "gold standard" for assessing anxiety during induction of anesthesia for children ages 2-16 years.
On the day of randomization, obtained just prior to the intervention
Pediatric Anesthesia Emergence Delirium (PAED) Scale
Time Frame: On the day or randomization, obtained immediately after the intervention
Validated tool to measure emergence delirium in children.
On the day or randomization, obtained immediately after the intervention
Nuclear Magnetic Resonance Spectroscopy (NMRS)
Time Frame: On the day of randomization, obtained during the intervention
Glucose, lactate, choline and NAA values will be obtained from the parietal cortex
On the day of randomization, obtained during the intervention
Resting State Functional Magnetic Resonance Imaging (rfMRI)
Time Frame: On the day of randomization, obtained during the intervention
Resting functional brain networks will be identified and compared between groups
On the day of randomization, obtained during the intervention
Inflammatory Markers
Time Frame: On the day of randomization, change from baseline, obtained immediately after the intervention
Concentrations of plasma IL-1b, TNF-a, IL-6, IL-10 will be quantified
On the day of randomization, change from baseline, obtained immediately after the intervention
Blood metabolites
Time Frame: On the day of randomization, change from baseline, obtained immediately after the intervention
Concentrations of plasma proteins, peptides and metabolites will be quantified
On the day of randomization, change from baseline, obtained immediately after the intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Calgary

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Tiffany Rice, PhD, MD, University of Calgary

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 21, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 11, 2017

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 16, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 26, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • REB16-0104

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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