Evaluation of Pupillometry for cyp2d6 Phenotyping in Children Treated With Tramadol

Study Overview
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Brief Summary
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Pupillometry will be performed before administration of tramadol, at T0 and then 1 to twice per hour in children having received tramadol as a pain killer as part of his/her routine care. Pupillometry measurement will be correlate to CYP2D6 phenotype and CYP2D6 genetic score

Detailed Description
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The proposed study is a single-center, observational and prospective study which will be conducted at the Pediatric Emergency Department, Geneva Children's Hospital. This study will begin in January 2016 and will last one year. 53 patients are planned to be enrolled. Children receiving oral tramadol as a pain killer at the emergency department, as part of their routine care, will be informed of the current study. Patients willing to participate will be included in the study after signing the inform consent (or respectively his/her parents or legal guardians). A unique oral dose of dextromethorphan (0.15 mg/kg) will be given to the participant for CYP2D6 phenotyping (T0). Two hours later, capillary whole blood will be sampled to 1) measure the metabolic ratio dextrorphan/dextromethorphan (MRDOR/DEM) in order to determine CYP2D6 phenotype (validated metrics for CYP2D6 phenotyping), 2) measure tramadol and its active metabolite O-desmethyltramadol (M1), and 3) to genotype for CYP2D6. Saliva sample will also be performed to genotype for CYP2D6. Pupillometry will be performed before administration of tramadol, at T0 and then 1 to twice per hour, throughout the patient's stay at the emergency department.

Official Title
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Evaluation of Pupillometry for CYP2D6 Phenotyping in Children Treated With Tramadol

Conditions
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Drug Intolerance, Cytochrome P450 CYP2D6 Enzyme Deficiency, Drug Effect

Intervention / Treatment
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* Device: Pupillometry


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Age 1-15 year at time of inclusion Weight ≥ 10 kg Treatment with tramadol as a pain killer administrated as part of their routine care Parent/Legal guardian has been informed about the study and has signed Informed Consent Form Exclusion criteria Known kidney or liver disease Concomitant treatment with inhibitors/inducers of CYP2D6 and CYP3A Documented previous adverse reaction to tramadol or dextromethorphan Concomitant treatment with any opiate drug and/or any drug with a known impact on pupil size Any concomitant condition, which in the opinion of the investigator would preclude a subject's participation in the study

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single arm study<br>pupillometry, CYP2D6 genotyping and phenotyping | Device: Pupillometry<br>* Pupillometry performed before administration of tramadol, at T0 and then 1 to twice per hour, during the stay of the patient in the emergency department<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pupillometry parameters and CYP2D6 phenotype | Correlation between pupillometry parameters and CYP2D6 phenotype | 0-6hours after tramadol administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pupillometry parameters and CYP2D6 genotype | Correlation between pupillometry parameters and CYP2D6 genotype | 0-6hours after tramadol administration | 
| pupillometry parameters and tramadol concentration | Correlation between pupillometry parameters and blood levels of tramadol and its active metabolite M1 | 0-6hours after tramadol administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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children, pain, Cytochrome P450 CYP2D6 genotype, Cytochrome P450 CYP2D6 phenotype, Pupillometry