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The Effects of the Anesthetic Ketamine in Young Children Undergoing Procedural Sedation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02650154
Recruitment Status : Completed
First Posted : January 8, 2016
Last Update Posted : October 18, 2016
Sponsor:
Collaborator:
University of Toronto
Information provided by (Responsible Party):
Yaron Finkelstein, The Hospital for Sick Children

Tracking Information
First Submitted Date January 5, 2016
First Posted Date January 8, 2016
Last Update Posted Date October 18, 2016
Study Start Date August 2013
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 6, 2016)
Increase in serum biomarkers of neurotoxicity (neuronal cell apoptosis) [ Time Frame: 1 to 24 hours from ketamine exposure ]
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: January 7, 2016)
  • Ketamine-induced mitochondrial damage [ Time Frame: 1-24 hours from ketamine exposure ]
    Peripheral blood cells we be tested for for mitochondrial damage (changes in biomass and mtDNA) post ketamine exposure. Isolated lymphocytes from pre- and post-ketamine exposure blood samples from each patient will be split into two pools analysed for changes to mitochondrial content and mtDNA damage. The first pool will be stained with mitochondrial membrane potential-specific dye (TMRM) and imaged to reveal changes in mitochondrial morphology and function. DNA will be isolated from the second pool and probed for both cellular mitochondrial content and mtDNA damage using quantitative PCR (Polymerase Chain Reaction).
  • Pharmacogenetics role in ketamine toxicity [ Time Frame: 1-24 hours from ketamine exposure ]
    In each patient we will determine the allele distribution (proportions/percentages) of polymorphic genes associated with the metabolism of ketamine.
Original Secondary Outcome Measures
 (submitted: January 6, 2016)
  • Ketamine-induced mitochondrial damage [ Time Frame: 1-24 hours from ketamine exposure ]
    Peripheral blood cells we be tested for for mitochondrial damage (changes in biomass and mtDNA) post ketamine exposure. Isolated lymphocytes from pre- and post-ketamine exposure blood samples from each patient will be split into two pools analysed for changes to mitochondrial content and mtDNA damage. The first pool will be stained with mitochondrial membrane potential-specific dye (TMRM) and imaged to reveal changes in mitochondrial morphology and function. DNA will be isolated from the second pool and probed for both cellular mitochondrial content and mtDNA damage using quantitative PCR.
  • Pharmacogenetics role in ketamine toxicity [ Time Frame: 1-24 hours from ketamine exposure ]
    In each patient we will determine the allele distribution (proportions/percentages) of polymorphic genes associated with the metabolism of ketamine.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title The Effects of the Anesthetic Ketamine in Young Children Undergoing Procedural Sedation
Official Title The Effects of the Anesthetic Ketamine in Young Children Undergoing Procedural Sedation
Brief Summary In the emergency department (ED), ketamine is a popular anesthetic agent during sedation of children for painful and other short procedures. Sedation for procedures is more commonly used in children than adults, to achieve motion control and cooperation. In children, ketamine offers an ideal choice due to the fact that it is short acting, a highly effective sedative, and preserves cardio-respiratory stability. In the United States, more than one million children per year up to four years of age undergo short procedures requiring anesthestic agents, including ketamine. However, there is mounting concern from animal studies and retrospective human research regarding the safety of ketamine when administered to infants and young children with respect to its potential toxic effects on the developing . Conversely, ketamine has also been suggested as a neuroprotective agent. Prompt investigation and resolution of this issue is urgently required.
Detailed Description

The objectives of this study are:

Primary Objective: In otherwise healthy children between 3 and 48 months of age who present to a tertiary care emergency department and receive procedural sedation with ketamine, to determine if there is at least a 50% increase, compared to baseline in the serum concentration of any of the neurotoxicity biomarkers S100B, glial fibrillary acidic protein (GFAP) or neuronal-specific enolase (NSE), 1 to 3 hours after intravenous ketamine administration. The cut-off of 50% is a benchmark value routinely quoted in both animal and human studies, which correlated neurotoxicity biomarker levels with functional outcomes.

Secondary Objectives: In the aforementioned population:

  1. To determine if at least a 50% increase in the serum concentration of S100B, GFAP or NSE compared to baseline at 6 to 12 hours after intravenous ketamine administration.
  2. To explore if genotypes relevant to ketamine metabolism and disposition are associated with increased vulnerability to the neurotoxic effects of ketamine.
  3. To determine the toxic effect of ketamine administration at the cellular level (evidence of sustainable cellular damage and mitochondrial DNA changes).
Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Blood and plasma samples
Sampling Method Probability Sample
Study Population All children between the ages of 3 and 48 months who receive intravenous ketamine for procedural sedation in the ED during study enrolment hours will be eligible for recruitment.
Condition Trauma
Intervention Not Provided
Study Groups/Cohorts
  • Pre-ketamine group
    Blood samples are taken prior to the administration of ketamine.
  • Post-ketamine group
    Blood samples are taken several hours after the administration of ketamine.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: January 6, 2016)
70
Original Estimated Enrollment Same as current
Actual Study Completion Date February 2016
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

1. All children between the ages of 3 and 48 months who receive intravenous ketamine for procedural sedation in the ED during study enrolment hours will be eligible for recruitment.

Exclusion Criteria:

  1. Children with contraindications to procedural sedation in the ED according to SickKids (the Hospital for Sick Children) practice guidelines or to ketamine administration will not be considered.
  2. Parents with an insurmountable language barrier (i.e. does not speak English and are not accompanied by another adult who cannot translate for the parent/caregiver), which prevents informed consent.
  3. Child who has received procedural sedation/ or surgery under general anesthesia in the past 30 days.
  4. A child who has received any central nervous system drugs (e.g. anticonvulsants, benzodiazepines) or a known neurotoxic drug (e.g., methotrexate, corticosteroids) concomitantly or in the 30 days preceding the sedation.
  5. A child who has suffered traumatic head injury concomitantly or in the previous 30 days
  6. A child who has CNS (Central Nervous System) illnesses or pathologies (e.g., meningitis, near drowning, hypoxic-ischemic brain injury, seizure disorder) in the 30 days prior to sedation, potentially leading to elevated baseline serum biomarkers.
  7. A child whose parents are considered to be in emotional distress due to the injury or illness of the child by the attending ED physician or where the attending ED physician does not believe it is appropriate to ask the parents for consent.
Sex/Gender
Sexes Eligible for Study: All
Ages 3 Months to 48 Months   (Child)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Canada
Removed Location Countries  
 
Administrative Information
NCT Number NCT02650154
Other Study ID Numbers REB1000033567
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Current Responsible Party Yaron Finkelstein, The Hospital for Sick Children
Original Responsible Party Same as current
Current Study Sponsor The Hospital for Sick Children
Original Study Sponsor Same as current
Collaborators University of Toronto
Investigators
Principal Investigator: Yaron Finkelstein, MD The Hospital for Sick Children
PRS Account The Hospital for Sick Children
Verification Date October 2016