Abstract
In response to PA-20-272 Administrative Supplements to Existing NIH Grants and Cooperative Agreements
(Parent Admin Supp Clinical Trial Optional), we are requesting a supplement to parent cooperative agreement
UG3DA056892 (Sentanyl II: A Multi-State Analysis of Fentanyl/Analogs, Naloxone, and Clinical Features of
Non-Fatal Opioid Overdose). Although this notice cannot be used for this supplement request, Notice
Special
nevertheless
Aim
of
Interest (NOSI): Xylazine: Understanding its Use and the Consequences (NOT-DA-24-009),
encourages research on xylazine, and xylazine is the topic of the supplement request.
2 of the parent project, Sentanyl II (UG3DA056892), which is in progress, involves obtaining
demographic and clinical data and blood samples from University of Massachusetts Medical Center Emergency
Department (ED) opioid overdose patients. Blood samples undergo extensive assessment for opioids and other
substances by the Center for Forensic Science Research and Education (CFSRE). Highly relevant to the topic of
this supplement request, xylazine has been detected in the blood of 10 of 26 (38.5%) Sentanyl II participants
whose blood samples have been analyzed to date by CFSRE.
Xylazine has been used as an intentional adulterant in illicit opioids since approximately 2000. It
increasingly has been detected in the illicit opioid supply and the post-mortem specimens from people with
fentanyl-associated overdoses. Little is known about the pharmacokinetics of xylazine among humans since
xylazine has no approved therapeutic use in people. This absence of knowledge reduces our ability to
understand the expected clinical course of those who used xylazine, as well as the development of treatments to
mediate its effects. A human volunteer study to evaluate xylazine pharmacokinetics is not possible, given that
an investigational new drug application for human use of xylazine is unlikely, and subjecting participants to the
drug is hazardous. Sentanyl II provides a naturalistic and practical opportunity to study xylazine
pharmacokinetics. Furthermore, it provides a means to examine current point-of-care urine tests for xylazine
among recently exposed human participants.
For Supplement Aim 1, we will recruit twelve UMass ED patients who (1) present after opioid overdose via
injection use, and (2) whose initial blood sample obtained on arrival at the ED indicates a probable xylazine
exposure, per the Randox Laboratories Evidence MultiSTAT xylazine assay. Participants will provide additional
blood samples hourly for up to six hours. CFSRE will perform quantitative analyses of these samples to
produce xylazine pharmacokinetic profiles of these participants. For Supplement Aim 2, we will evaluate the
test performance characteristics (e.g., sensitivity, specificity, predictive value) of the ResponseTM Xylazine Test
Strip), as compared to the comparative “gold standard” of CFSRE blood sample testing.
