Identifying Biomarkers Related to Opioid Use and Pain Response Following Traumatic Injury and Surgery
Descripción general del estudio
Estado
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Rodney A Gabriel
- Número de teléfono: 858-663-7747
- Correo electrónico: ragabriel@health.ucsd.edu
Ubicaciones de estudio
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California
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La Jolla, California, Estados Unidos, 92037
- Reclutamiento
- University of California, San Diego
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Contacto:
- Rodney A Gabriel
- Número de teléfono: 858-663-7747
- Correo electrónico: ragabriel@health.ucsd.edu
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Investigador principal:
- Rodney A Gabriel
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Método de muestreo
Población de estudio
Descripción
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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)).
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
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Persistent Opioid Use Cohort
Patients who develop persistent opioid use after surgery (defined as any ongoing opioid use >3 months after admission for trauma injury)
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Non-persistent Opioid Use Cohort
Patients who do not develop persistent opioid use after surgery (defined as no ongoing opioid ≥ 3 months after surgery)
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Persistent Opioid Use
Periodo de tiempo: 3 months after trauma injury/surgery
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We will collect blood from participants (about 15mL total) for DNA, miRNA, and mRNA sequencing.
The blood draw for miRNA and mRNA sequencing, DNA genotyping, and bioinformatics analysis will be conducted at baseline and at subsequent in-person time points.
All biospecimens will be sequenced and analyzed at UCSD's Center for Computational Biology and Bioinformatics.
We will also collect baseline demographic, clinical and social data (including social determinants of health questionnaire, electronic health record data, demographic such as age, sex).
These markers will be assessed for association of persistent opioid use defined as ongoing opioid use for more than 3 months after trauma/surgical admission.
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3 months after trauma injury/surgery
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Pain via Brief Pain Inventory
Periodo de tiempo: Baseline, 1 week, 1 month, 3 months, and 6 months after surgery
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The Brief Pain Inventory (BPI) is well-validated in clinical populations and will measure participants' self-reported pain on a 0 ("no pain") to 10 ("most severe pain") scale.
We will use this survey to assess for average, minimal, and maximum pain and interference scores at multiple time points
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Baseline, 1 week, 1 month, 3 months, and 6 months after surgery
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Opioid Use Questionnaire
Periodo de tiempo: Baseline, 1 week, 1 month, 3 months, and 6 months after surgery
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Opioid use will be collected directly from the electronic health record data and ascertained by patient report at the follow-up time points.
At the 1-, 3-, and 6- month time point, we will elicit the average number of pain pills (name, dosing, frequency) over the last 7 days.
This will be converted to oral MME.
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Baseline, 1 week, 1 month, 3 months, and 6 months after surgery
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PROMIS-29 Questionnaire
Periodo de tiempo: Baseline, 1 week, 1 month, 3 months, and 6 months after surgery
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The PROMIS-29 questionnaire assesses a patient's physical and social well-being and measures pain intensity using a single 0-10 numeric rating item and seven health domains (physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance).
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Baseline, 1 week, 1 month, 3 months, and 6 months after surgery
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Rodney A Gabriel, University of California, San Diego
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Trastornos relacionados con narcóticos
- Dolor
- Manifestaciones neurológicas
- Desordenes mentales
- Complicaciones Postoperatorias
- Procesos Patológicos
- Trastornos relacionados con sustancias
- Trastornos inducidos químicamente
- Condiciones Patológicas, Signos y Síntomas
- Signos y síntomas
- Dolor Postoperatorio
- Trastornos relacionados con opioides
Otros números de identificación del estudio
- 814524
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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