Observational Study on the Incorporation of Opioids and Their Metabolites Into Hair of Pediatric Patients

NCT05740657 | Completed

• 1 other identifier: 2022-01693
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Hair analysis is a well-established and important tool in both forensic and clinical context. When it comes to the interpretation of positive hair analysis results, reliable and comprehensive reference data is essential. Such data on opioids, especially novel synthetic ones (such as fentanyl and its analogues (fentalogs)) is currently highly limited. This applies especially to hair with pediatric origin, due to differences in the metabolism and hair anatomy in children compared to adults. Investigators hypothesize that opioids, both traditional and novel synthetic ones exhibit detectable concentrations and distinct metabolite ratios within the hair matrices of pediatric patients. Thus, this observational, prospective research study provides 150 hair and sweat samples from children who received opioids as part of surgery or pain management. The samples will be consecutively extracted and analyzed using a sensitive targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, enabling the quantitative determination of the opioid and metabolite concentrations. The study thereby contributes valuable reference data for both forensic and clinical applications, addressing challenges in interpreting hair analysis results in especially pediatric populations. Further, a deeper understanding of the mechanisms (e.g. via sweat) and pharmacokinetic processes involved in the opioid incorporation to hair will be achieved. The study has received ethical approval from the Swiss Ethics Board (approval number: 2022-01693 / amendment approval date: 09.01.2024).

Conditions

Opioid Use, Unspecified

Keywords

hair analysis; fentanyl; fentalogs; new synthetic opioids; opioids

Outcome Measures

Primary Outcomes (2)

• Evaluation of the opioid and metabolite concentrations (pg/mg: units of picograms of opioid per milligram hair) in the hair samples of the study population.

  For the collected hair samples, a two-stage extraction is performed, using methanol and a buffered methanol-water mixture for 90 minutes each. The extracts are then evaporated, resuspended in a 3:7 mixture of methanol and eluent A (20 mM ammonium formate with 0.1% (v/v) formic acid in water). The hair sample extracts will then be measured on an the LC-MS/MS system (SCIEX Triple Quad™ 7500 LC-MS/MS (QTRAP) System). A validated analysis method will be used for the analysis of the following opiates, opioids or their metabolites: hydromorphone, 4-ANPP, acetylcodeine, acetylmorphine, alfenanil, betahydroxyfentanyl, codeine, dihydrocodeine, fentanyl, hydrocodone, methadone, morphine, naloxone, norfentanyl, norsufentanil, omegahydroxyfentanyl, oxycodone, oxymorphone, pethidine, remifentanil, remifentanil-acid, sufentanil and tramadol. The data is processed with the software SciexOS version 1.6.7.

  Through study completion, an average of two years

• Evaluation of the opioid and metabolite concentrations (ng/mL: units of nanograms of opioid per milliliter) in the sweat extracts of the study population.

  The extraction procedure of the sweat swabs looks as follows: the cotton ends of the forensic swabs will be cut and extracted with methanol. The methanol extracts will then be diluted to avoid detector saturation and mixed in a 3:7 ratio with eluent A. The sweat sample extracts will then be measured on an the LC-MS/MS system (SCIEX Triple Quad™ 7500 LC-MS/MS (QTRAP) System). A validated analysis method will be used for the analysis of the following opiates, opioids or their metabolites: hydromorphone, 4-ANPP, acetylcodeine, acetylmorphine, alfenanil, betahydroxyfentanyl, codeine, dihydrocodeine, fentanyl, hydrocodone, methadone, morphine, naloxone, norfentanyl, norsufentanil, omegahydroxyfentanyl, oxycodone, oxymorphone, pethidine, remifentanil, remifentanil-acid, sufentanil and tramadol. The data is processed with the software SciexOS version 1.6.7.

  Through study completion, an average of two years

Secondary Outcomes (1)

• Normative opioid concetration values and metabolite reatios in pediatric hair.

  after data evaluation, 3 months after end of study

Study Arms (1)

KISPI 000

Patients of the group received one or multiple clinically approved opioids, namely; Fentanyl, Remifentanil, Sufentanil, Alfentanil, Oxycodone, Morphine, Nalbuphine, Hydromorphone and Methadon. The drugs were administered in the course of a surgery or for pain management.

Drug: Fentanyl

Interventions

Fentanyl DRUG

The drugs were administered in the course of a surgery or for pain management.

Also known as: Remifentanil, Sufentanil, Hydromorphone, Oxycodone, Morphine, Alfentanil, Nalbuphine, Methadon

KISPI 000

Eligibility Criteria

• Age: 1 Day - 13 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients (newborns, infants, children and adolescents up to 13 years of age) from the pediatric intensive care unit from the Children's Hospital Zurich. Patients in focus are exposed to fentanyl and fentalogs (remifentanil, sufentanil and alfentanil) or other more traditional opioids (such as morphine, oxycodone and methadone) either during surgery or as part of post-operative pain management for up to three months prior to study inclusion.

You may qualify if:

• Obtained written informed-consent from legal representatives (and oral consent from the patient).
• Patient's age must be within date of birth irrespective of gestational age to completed 13th year of life
• Patients that received single or multiple treatment (either with single doses or continuous infusion) of fentanyl, remifentanil or sufentanil either during surgery or during stay in the pediatric intensive care unit

You may not qualify if:

• Patient's age of 14 or older
• Inability to understand the study procedure due to language or cognitive reasons (applies to legal representatives and elder children)
• Denied or missing informed consent
• Insufficient amount of head hair to obtain hair sample
• Cosmetic hair treatment, like coloring, bleaching and dying

Sponsors & Collaborators

• University of Zurich: lead
• University Children's Hospital, Zurich: collaborator

Study Sites (1)

University's Children Hospital

Zurich, Canton of Zurich, 8032, Switzerland

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Hair samples (without hair root) Sweat Samples

MeSH Terms

Interventions

Fentanyl; Remifentanil; Sufentanil; Hydromorphone; Oxycodone; Morphine; Alfentanil; Nalbuphine

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Propionates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Codeine

Study Officials

• Tina Binz

  University Zürich

  PRINCIPAL INVESTIGATOR

• Florian Zapf, Dr.

  University's Children Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Week
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2023
• First Posted: February 23, 2023
• Study Start: December 6, 2022
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: starting after publication
• Access Criteria: upon request via e-mail

Locations

CH (1)