Predicting Chronic Opioid Use Following Lower Extremity Joint Arthroplasty

Chronic Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04974463
• Other study ID #: 210132
• Status: Recruiting
• Start date: July 19, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: July 2023
• Source: University of California, San Diego
• Contact: Rodney A Gabriel, MD, MAS
• Phone: 858-663-7747
• Email: ragabriel[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 31, 2023
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthralgia
• Chronic Pain
• Joint Pain
• Opioid Use

Locations

Country	Name	City	State
United States	University of California San Diego	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3-month persistent opioid use	continual opioid use 3 months after surgery	3 months
Primary	3-month persistent post-surgical pain	continual pain at surgical site at 3 months	3 months
Secondary	Acute postoperative opioid use	opioid use during the first 48 hours after surgery	48 hours
Secondary	Acute postoperative pain	pain scores during the first 48 hours after surgery	48 hours