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

Opioid Use, Unspecified Clinical Trial

Official title:

Evaluation of Opioids and Metabolites in Hair and Sweat of Pediatric Patients in a Monitored Clinical Context, by Means of Targeted Liquid Chromatography-tandem Mass Spectrometry

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05740657
• Other study ID #: 2022-01693
• Status: Recruiting
• Start date: December 6, 2022
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: University of Zurich
• Contact: Tina M. Binz, Dr.
• Phone: +41 44 635 7614
• Email: TinaMaria.Binz[@]irm.uzh.ch
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 225
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 13 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Opioid Use, Unspecified

Intervention

Drug:
• Fentanyl
The drugs were administered in the course of a surgery or for pain management.

Locations

Country	Name	City	State
Switzerland	University's Children Hospital	Zurich

Sponsors (2)

Lead Sponsor	Collaborator
University of Zurich	University Children's Hospital, Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Normative opioid concetration values and metabolite reatios in pediatric hair.	This data will be analyzed by using descriptive statistics (box plots) including the median, mean, 10th percentile, and 90th percentile values and for their distribution (normal or non-normal) by Shapiro-Wilks Test. Thus, opioid specific concentration values and metabolite ratios in hair of children will be established.	after data evaluation, 3 months after end of study