Identifying Biomarkers Related to Opioid Use and Pain Response Following Traumatic Injury and Surgery

Обзор

The mechanisms leading to opioid tolerance or dependence are not well understood and there are currently no biomarkers for predicting who is at risk for development of OUD. The purpose of this project is to support the feasibility of detecting a miRNA bio-behavioral signature of opioid misuse risk that will demonstrate improved predictive precision compared to current tools such as polygenic risk scores (PRS). Specifically, the study will address key goals of the Wellcome Leap program to develop scalable measures assessing individual addiction susceptibility and quantifying addiction risk and progression during prescription drug use. The study will utilize behavioral, genomics, and bioinformatics pipelines to characterize opioid-induced miRNA expression dynamics among trauma and surgical patients prescribed opioids at discharge. Based on results from this study, the research will develop a high-throughput screening assay to predict risk for opioid use disorder (OUD). The hypothesis is that miRNAs will serve as powerful bio-signatures for predicting long-term clinical outcomes in patients treated with opioids for pain management following trauma injury and/or surgery.

Подробное описание

The mechanisms leading to opioid tolerance or dependence are not well understood and there are currently no biomarkers for predicting who is at risk for development of OUD. The purpose of this project is to support the feasibility of detecting a miRNA bio-behavioral signature of opioid misuse risk that will demonstrate improved predictive precision compared to current tools such as polygenic risk scores (PRS). Specifically, the study will address key goals of the Wellcome Leap program to develop scalable measures assessing individual addiction susceptibility and quantifying addiction risk and progression during prescription drug use. The study will utilize behavioral, genomics, and bioinformatics pipelines to characterize opioid-induced miRNA expression dynamics among trauma and surgical patients prescribed opioids at discharge. Based on results from this study, the research will develop a high-throughput screening assay to predict risk for opioid use disorder (OUD). The hypothesis is that miRNAs will serve as powerful bio-signatures for predicting long-term clinical outcomes in patients treated with opioids for pain management following trauma injury and/or surgery.

The specific aim is to develop a new conceptual framework to validate DNA\< mRNA, and miRNAs as biomarkers of persistent opioid use among patients after traumatic injury and/or surgery.

The primary goal is to correlate patterns in miRNA sequencing with persistent opioid use after trauma/surgery.

The study will recruit up to 100 adult (\>18 yo) participants prospectively from UC Health sites, including Jacobs Medical Center, Hillcrest Hospital, McGrath Outpatient Pavilion, and Koman Outpatient Pavilion. Eligible participants will be identified by reviewing newly admitted patients in the trauma service and/or surgical suite (same day as surgery preoperatively).

The study will collect baseline data including baseline clinical and demographic data, pain/opioid use from surveys/questions, social determinants of health (from survey), and biospecimens (blood for DNA and miRNA sequencing). Data will be collected initially near estimated hospital discharge (baseline), at 7 days post-discharge, 1 month post-discharge, 3 months post-discharge and 6 months post-discharge.

The proposed project will identify a miRNA signature associated with risk for persistent opioid use (defined as ongoing opioid use at 1, 3 and 6 months after index time point) in patients following exposure to opiate medication after traumatic injury/surgery. It is expected to demonstrate improved predictive precision with the miRNA signature compared to current tools alone (PRS, ORT). Success of this project will provide the go signal for a subsequent implementation study to develop a miRNA test kit and optimize the use of this screening tool and its potential to inform targeted interventions to prevent persistent opioid use and OUD after traumatic injury/surgery.

Первичные конечные точки

• Persistent Opioid Use [Срок оценки: 3 months after trauma injury/surgery]

Вторичные конечные точки (3)

• Pain via Brief Pain Inventory [Срок оценки: Baseline, 1 week, 1 month, 3 months, and 6 months after surgery]
• Opioid Use Questionnaire [Срок оценки: Baseline, 1 week, 1 month, 3 months, and 6 months after surgery]
• PROMIS-29 Questionnaire [Срок оценки: Baseline, 1 week, 1 month, 3 months, and 6 months after surgery]

Критерии участия

Критерии включения

• Patients 18 years of age or older
• Patients admitted for traumatic injury at Hillcrest or Jacobs Medical Center or patients who will undergo the orthopedic (e.g., joint, spine), abdominal, breast, vascular (e.g., amputation), or thoracic surgery.

Критерии исключения

• Patients with a prior history of opioid use disorder or dependence
• Pregnant women
• Prisoners
• Patients with an inability to independently provide informed consent to participate in the study due to lack of capacity. This lack of capacity can be from either a chronic/continuous condition (i.e. dementia), or can be temporary (i.e. clear signs of intoxication at the time of the visit (not alert or oriented, slurring words \[and confirmed not to be baseline\], unsteady gait \[and confirmed not to be baseline\], or appears impaired based on clinical judgement by PI/Co-I)).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• University of California, San Diego — La Jolla

Публикации

• Jones J, Correll DJ, Lechner SM, Jazic I, Miao X, Shaw D, Simard C, Osteen JD, Hare B, Beaton A, Bertoch T, Buvanendran A, Habib AS, Pizzi LJ, Pollak RA, Weiner SG, Bozic C, Negulescu P, White PF; VX21-548-101 and VX21-548-102 Trial Groups. Selective Inhibition of NaV1.8 with VX-548 for Acute Pain. N Engl J Med. 2023 Aug 3;389(5):393-405. doi: 10.1056/NEJMoa2209870. PMID 37530822
• Zhang Z, Wang JJ, Ping ZG, Jin XG, Yang JJ, Wang Y, Chu QJ; Pain Group of the Chinese Society of Anesthesiology. The Impact of Opioid-Sparing Analgesia on Postoperative Pain and Recovery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Pain Ther. 2025 Oct;14(5):1473-1497. doi: 10.1007/s40122-025-00762-2. Epub 2025 Jul 25. PMID 40711665
• Gabriel RA, Swisher MW, Sztain JF, Furnish TJ, Ilfeld BM, Said ET. State of the art opioid-sparing strategies for post-operative pain in adult surgical patients. Expert Opin Pharmacother. 2019 Jun;20(8):949-961. doi: 10.1080/14656566.2019.1583743. Epub 2019 Feb 27. PMID 30810425
• Barocas JA, Savinkina A, Adams J, Jawa R, Weinstein ZM, Samet JH, Linas BP. Clinical impact, costs, and cost-effectiveness of hospital-based strategies for addressing the US opioid epidemic: a modelling study. Lancet Public Health. 2022 Jan;7(1):e56-e64. doi: 10.1016/S2468-2667(21)00248-6. Epub 2021 Nov 30. PMID 34861189
• Jivraj NK, Raghavji F, Bethell J, Wijeysundera DN, Ladha KS, Bateman BT, Neuman MD, Wunsch H. Persistent Postoperative Opioid Use: A Systematic Literature Search of Definitions and Population-based Cohort Study. Anesthesiology. 2020 Jun;132(6):1528-1539. doi: 10.1097/ALN.0000000000003265. PMID 32243330
• Brummett CM, Waljee JF, Goesling J, Moser S, Lin P, Englesbe MJ, Bohnert ASB, Kheterpal S, Nallamothu BK. New Persistent Opioid Use After Minor and Major Surgical Procedures in US Adults. JAMA Surg. 2017 Jun 21;152(6):e170504. doi: 10.1001/jamasurg.2017.0504. Epub 2017 Jun 21. PMID 28403427

Идентификаторы

NCT: NCT07693270 · 814524

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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