Predicting Chronic Opioid Use Following Lower Extremity Joint Arthroplasty

Using Genomics and Gut Microbiome Data to Predict Postoperative Opioid Use in Patients Undergoing Lower Extremity Joint Replacement

Personalized medicine is a concept in which medical care is individualized to a patient based on their unique characteristics, including comorbidities, demographics, genetics, and microbiome. After major surgery, some patients are at increased risk of opioid dependence. By identifying unique genetic and microbiome markers, clinicians may potentially identify individual risk factors for opioid dependence. By identifying these high risk patients early-on, personalized interventions may be applied to these patients in order to reduce the incidence of opioid-dependence.

Study Overview

• Status: Recruiting
• Conditions: Joint Pain; Chronic Pain; Opioid Use

Detailed Description

The primary objective of this study is to identify associations with genetic variants, gut microbiome, and metabolomics (i.e. exosome profiling) with postoperative opioid use in surgical patients. Patients will be recruited preoperatively who underwent lower extremity joint replacement. The following tests will be performed: 1) genome-wide single nucleotide polymorphisms and structural variation, with a particular focus on the following genes: COMT, BDNF, SCN11a, OPRM1, ACBC1, CYPD26, CYP34A, ANKK1, OPRD1, OPRK1,NGFB, UGT2B7, FFAR2, FFAR3, GABRG2, SLCO1B1, DRD4; 2) longitudinal gut microbiome sampling; and 3) exosome profiling - blood will be collecting for RNAseq and plasma for metabolomics and extracellular vesicle characterization with ultimate impact on in vitro cell function. These genes were selected because they have been shown to be associated with opioid use, opioid metabolism, and pain. Furthermore, subjects will fill out surveys preoperatively, including: pain catastrophizing scale, brief pain inventory, PROMIS-29, and fibromyalgia survey criteria. Other data collected will include body mass index, age, sex, comorbidities, lifestyle habits, and medication use.

The hypothesis is that there will be clinically significant associations with patient genetics, microbiome, exosome profiles with their postoperative opioid use. Such findings will help personalize pain interventions for high-risk patients undergoing knee or hip arthroplasty in order to help improve postoperative pain control and reduce incidence of chronic opioid use.

Specific Aim #1. To validate and identify pharmacogenomic associations with acute postoperative opioid use (during the first 48 postoperative hours) and chronic opioid use (at >3-4 months after surgery) in patients who underwent lower extremity joint replacement.

Specific Aim #2. To identify gut microbiome and metabolomics associations with acute postoperative opioid use (during the first 48 postoperative hours) and chronic opioid use (at >3-4 months after surgery) in patients underwent lower extremity joint replacement.

Specific Aim #3. To identify blood RNAseq patterns, plasma metabolic markers, extracellular vesicles, and impact of plasma on in vitro cell metabolism associated with acute postoperative opioid use (during the first 48 postoperative hours) and chronic opioid use (at >3-4 months after surgery) in patients underwent lower extremity joint replacement.

Machine learning approaches will be used to combine all data to improve prediction of the primary outcomes.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Rodney A Gabriel, MD, MAS; Phone Number: 858-663-7747; Email: ragabriel@health.ucsd.edu

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • University of California San Diego
      • Contact: Rodney A Gabriel, MD; Phone Number: 858-663-7747; Email: ragabriel@health.ucsd.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

patients undergoing lower extremity joint replacement (i.e. total knee arthroplasty, total hip arthroplasty, hemiarthroplasty, unicompartmental knee replacement)

Description

Inclusion Criteria:

• patient undergoing unilateral knee or hip arthroplasty

Exclusion Criteria:

• refusal to consent
• lack of independent decision-making capacity
• inability to communicate effectively with research personnel
• if patient received antibiotics within the last 3 months prior to surgery

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Persistent Opioid Use at 3 months; Patients who continue to use opioids about 3 months after their joint replacement surgery
No Persistent Opioid Use at 3 months; Patients who do not use opioids after about 3 months following joint replacement surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-month persistent opioid use	continual opioid use 3 months after surgery	3 months
3-month persistent post-surgical pain	continual pain at surgical site at 3 months	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute postoperative opioid use	opioid use during the first 48 hours after surgery	48 hours
Acute postoperative pain	pain scores during the first 48 hours after surgery	48 hours

Collaborators and Investigators

• Sponsor: University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2021
• Primary Completion (Estimated): October 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 23, 2021

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Arthralgia; Chronic Pain
• Other Study ID Numbers: 210132

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No