Linking Epigenomics With Prescription Opioid Abuse and High Impact Musculoskeletal Pain (LEAP)

Genetic variability from epigenetic modification of genes related to pain physiology and opioid pharmacodynamics may influence susceptibility to high-impact chronic musculoskeletal pain, opioid efficacy, and vulnerability to opioid abuse. Exploring the role of epigenomics and opioid addiction may improve understanding and treatment of these complex multifactorial conditions and, potentially, reduce their development.

Study Overview

• Status: Completed
• Conditions: Pain, Chronic; Prescription Drug Abuse (Not Dependent)

Detailed Description

Over 19 million adults suffer with chronic pain, which frequently limits life or work activities. Many of these patients are chronic prescription opioid consumers and may be at risk for opioid use disorder. Genetic variability of genes related to pain physiology and opioid pharmacodynamics may influence susceptibility to high-impact chronic musculoskeletal pain (HICMP), opioid efficacy, and vulnerability to opioid abuse. There is a paucity of research on the epigenetic profile of patients with HICMP and of those who fall in the spectrum between opioid addicted and opioid naive. Exploring the role of epigenomics in HICMP and opioid addiction may improve understanding and treatment of these complex multifactorial conditions and, potentially, reduce development.

The long-term goal is to create a profile of genetic and psychosocial risk factors for identifying patients susceptible to HICMP and opioid abuse. The objective of this pilot study is to gather preliminary data on the association of epigenetic modification of genes with HICMP and prescription opioid abuse.The study team propose to compare COMT and OPRM1 DNA methylation patterns in patients with HICMP (Group 1) to those without HICMP (Group 2).The investigators will also correlate OPRM1 DNA methylation patterns with the likelihood of misuse and abuse in chronic opioid consumers. It is hypothesized: (1) the promoter region of the COMT and OPRM1 genes will be hypo- and hyper-methylated, respectively, in Group 1 compared to Group 2; and (2) the OPRM1 gene in patients at high risk for opioid misuse and abuse will be hyper-methylated.

• Study Type: Observational
• Enrollment (Actual): 275

Contacts and Locations

• Study Contact: Name: Sophia Sheikh, MD; Phone Number: 904-244-4986; Email: Sophia.Sheikh@jax.ufl.edu
• Study Contact Backup: Name: Phyllis Hendry, MD; Phone Number: 904-244-4986; Email: Phyllis.Hendry@jax.ufl.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • UF Health of University of Florida
    • Jacksonville, Florida, United States, 32008
      • UF Health - Jacksonville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population will be adult patients with chronic musculoskeletal pain (pain present for 3 or more months) treated with prescription opioids on most days in the past 3 months.

Description

Inclusion Criteria:

• Patients age ≥18 years with chronic musculoskeletal pain (pain present for 3 or more months) treated with prescription opioids on most days in the past 3 months.

Exclusion Criteria:

• Patients who are non-English speaking,
• Patients who are incarcerated
• Patients who are unable to provide consent will be excluded.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Patients with HICMP; Patients with PROMIS Pain Interference-6b scores one standard deviation above the national average will be categorized into this group.
Patients without HICMP; Patients without PROMIS Pain Interference-6b scores one standard deviation above the national average will be categorized will be categorized into this group.
Patients at risk for opioid abuse or misuse; The Opioid Risk Tool and PROMIS Short Form v1.0-Prescription Pain Medication Misuse will be used to categorize patients at risk.
Patients not at risk for opioid abuse or misuse; The Opioid Risk Tool and PROMIS Short Form v1.0-Prescription Pain Medication Misuse will be used to categorize patients at risk.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PROMIS Pain Interference 6b	Symptom assessment tool measures six items on 5-point scales for pain interference on aspects of daily life. The higher the total score, the more severe the symptom.	Baseline
Opioid Risk Tool	Prescription opioid abuse or misuse will be measured using the Opioid Risk Tool. This tool should be administered to patients upon an initial visit prior to beginning opioid therapy for pain management. A score of 3 or lower indicates low risk for future opioid abuse, a score of 4 to 7 indicates moderate risk for opioid abuse, and a score of 8 or higher indicates a high risk for opioid abuse.	Baseline
PROMIS Short Form v1.0-Prescription Pain Medication Misuse	Seven question survey concerning prescription pain medication use within the last 3 months. Self reported answers ranging 1-5; with 1 being 'never' to 5 being 'almost always.' Prescription opioid abuse or misuse will be measured using the PROMIS Short Form v1.0-Prescription Pain Medication Misuse. Patients with PPMM scores of 60 or more will be considered high risk for opioid misuse or abuse.	Baseline

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Florida Medical Malpractice Joint Underwriting Association
• Investigators: Principal Investigator: Sophia Sheikh, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2019
• Primary Completion (Actual): April 5, 2023
• Study Completion (Actual): April 6, 2023

Study Registration Dates

• First Submitted: May 9, 2019
• First Submitted That Met QC Criteria: May 9, 2019
• First Posted (Actual): May 13, 2019

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pain; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Narcotic-Related Disorders; Substance-Related Disorders; Chronic Pain; Opioid-Related Disorders; Musculoskeletal Pain
• Other Study ID Numbers: IRB201901297

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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