Pharmacogenetics of Ketamine in Children

March 31, 2023 updated by: IRCCS Burlo Garofolo

Pharmacogenetics of Ketamine in Children Presenting Emesis and Recovery Agitation During Procedural Analgesia and Sedation Outside of the Operating Room

The need to treat the children with painful diagnostic-therapeutic procedures has increased in the last years. There is evidence from a wide scientific literature that drugs available in the setting of procedural sedation and analgesia such as midazolam, fentanyl, nitrous oxide, ketamine and propofol are absolutely safe without a significant incidence of adverse effects, if administered by anaesthesiologists and also trained pediatricians outside the operating room. Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that blocks glutamate excitatory effects. Ketamine's molecular mechanism is not restricted to the NMDA receptor. Several studies indicate interactions with a series of receptor systems, including opioid, cholinergic and dopaminergic receptors. Ketamine is a safe and effective drug during procedural analgesia and sedation applied to children outside the operating room. A recent multicenter study, showed that ketamine, without being associated with other analgesic or sedative drugs, is the drug regimen with the lowest risk of adverse effects during this procedures. Even though being safe, ketamine may cause some adverse effects. When ketamine is administered for procedural sedation outside the operating room, adverse effects more frequently recorded are emesis and recovery agitation, each with a prevalence of around 8%. Recovery agitation, defined as any abnormal behavioural response such as any combination of agitation, crying, hallucinations or nightmares after sedation, in some cases (around 1%) may be severe and leads to specific treatment, mainly benzodiazepines. Emesis and recovery agitation are minor adverse events, but both may be very unpleasant for the patient and may play a role in the perception of patients and their parents of the quality of sedation, especially in children who need repeated procedures. Identifying patients, particularly children with chronic illnesses and leukemia, at risk of emesis and recovery agitation may facilitate the choice of different drugs regimens, improving the quality of care. The aim of this study is the identification of genetic and epigenetic biomarkers useful to predict emesis and recovery agitation related to administration of ketamine for procedural sedation and analgesia applied to children and to correlate them with the pharmacokinetic profile.

Study Overview

Status

Status

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

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.

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.
Observational

Enrollment (Anticipated)

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.
250

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Italy
      • Trieste, Italy, 34137
        • Recruiting
        • IRCCS Burlo Garofolo

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

1 year to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

children between 1 and 17 years of age needing sedation and analgesia for painful procedures

Description

Inclusion Criteria:

  1. Any child between 1 and 17 years of age needing sedation and analgesia for painful procedures, such as suture laceration, fracture reductions, burn medications, bone marrow aspiration, lumbar puncture, arthrocentesis, colonoscopy and others.
  2. Use of intravenous ketamine as the sole sedative agent for the procedure.

Exclusion Criteria:

  1. Children needing drugs other that ketamine for sedation, such as fentanyl, propofol, midazolam and dexmedetomidine .
  2. Children with intellectual disability or with non typical neurodevelopment, such as children with autism.
  3. Children with a history of allergy or hypersensibility to ketamine.
  4. Parents limitations in language and understanding informed consent forms and procedures.

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

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
To identify genetic variants associated with the development of emesis and recovery agitation after intravenous administration of ketamine
Time Frame: 10 minutes before procedural sedation
Genotyping will be performed using Illumina Omni 2.5 + exome array. Biomarker identification will be performed considering the genetic contribution of variants focusing on 10 candidate genes relevant for the biotransformation (CYP2B6, CYP2C9, CYP3A4, CYP3A5, CYP2A6) and for pharmacodynamics (genes encoding for the NMDA receptor subunits: GRIN1 e GRIN2A-D) of ketamine, selected on the basis of literature. The independent variable associated with ketamine induced adverse effects will be the presence or not of functional variants in the candidate genes.
10 minutes before procedural sedation

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
To assess the maximum plasmatic concentration (Cmax) after intravenous administration of ketamine
Time Frame: 10 minutes before procedural sedation
Ketamine and its main metabolite norketamine will be quantified in plasma through a method of liquid chromatography / tandem mass spectrometry. The pharmacokinetic parameters will be calculated using WinNonlin software.
10 minutes before procedural sedation
To assess the area under the concentration curve from time 0 (AUC 0-last) after intravenous administration of ketamine
Time Frame: 10 minutes before procedural sedation
Ketamine and its main metabolite norketamine will be quantified in plasma through a method of liquid chromatography / tandem mass spectrometry. The pharmacokinetic parameters will be calculated using WinNonlin software.
10 minutes before procedural sedation
To assess the plasmatic half-life after intravenous administration of ketamine
Time Frame: 10 minutes before procedural sedation
Ketamine and its main metabolite norketamine will be quantified in plasma through a method of liquid chromatography / tandem mass spectrometry. The pharmacokinetic parameters will be calculated using WinNonlin software.
10 minutes before procedural sedation
To assess the plasmatic clearance defined as dose/AUC after intravenous administration of ketamine
Time Frame: 10 minutes before procedural sedation
Ketamine and its main metabolite norketamine will be quantified in plasma through a method of liquid chromatography / tandem mass spectrometry. The pharmacokinetic parameters will be calculated using WinNonlin software.
10 minutes before procedural sedation
To identify exosomal miRNAs linked to the development of emesis and recovery agitation after intravenous administration of ketamine
Time Frame: 10 minutes before procedural sedation
Neuronal-derived exosomes will be isolated and miRNAs will be sequenced. miRNAs contained in neuronal-derived exosomes and associated with ketamine induced adverse effects will be quantified through next generation sequencing.
10 minutes before procedural sedation

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.
IRCCS Burlo Garofolo

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.
  • Study Director: Egidio Barbi, MD, IRCCS materno infantile Burlo Garofolo

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 (Actual)

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.
June 26, 2020

Primary Completion (Anticipated)

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.
May 15, 2024

Study Completion (Anticipated)

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.
May 15, 2024

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).
March 20, 2023

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.
March 31, 2023

First Posted (Actual)

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.
April 3, 2023

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.
April 3, 2023

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 31, 2023

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.
March 1, 2023

More Information

Terms related to this study

Keywords

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.
  • RC 16/19

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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