Pharmacogenomics Applied to Chronic Pain Treatment in Primary Care (PGx-ACT)

Pharmacogenomics (PGx) Applied to Chronic pain Treatment in primary care (PGx-ACT) is an open-label, prospective, randomized trial. Participants prescribed a relevant opioid and meet additional eligibility criteria will be randomized into either a PGx-guided care (intervention) arm or standard care (control) arm. The investigators will test the hypothesis that patients with intermediate or poor CYP2D6 metabolism assigned to PGx-guided care arm will experience improved pain control at 3 months compared to patients in the standard care arm. Additionally, the study investigators will be evaluating non-pain related uses of PGx information in the chronic pain population.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Pain
• Intervention / Treatment: Genetic: Pharmacogenetic Testing; Other: Pharmacist Consultation Note; Other: Delayed pharmacogenetic testing

Detailed Description

Chronic pain affects millions of Americans on an annual basis. Pharmacologic pain management strategies, which includes opioid analgesics, are widely used to treat chronic pain. The selection of an analagesic can be guided by pharmacogenomic (PGx) data via existing Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. The rationale for PGx-guided treatment is based upon the CYP2D6 bioactivation of tramadol, codeine, and hydrocodone, whereas patients with reduced CYP2D6 function may not activate these drugs and therefore may not experience the effective treatment from these drugs. A prior pragmatic proof-of-concept trial testing the effects of CYP2D6-guided opioid prescribing on pain control provides additional evidence for this study.

This study is designed to evaluate the impact of PGx-guided treatment on chronic pain score improvement compared to standard conventional treatment in a pragmatic setting. It will test for multiple genes to enable incorporation of CPIC guidelines for other drugs (e.g., antidepressants, nonsteroidal antiinflammatory drugs), account for drug-drug interactions, and utilize recently updated CYP2D6 phenotype translation thresholds.

Primary objective: Identify the effects of providing pharmacogenomic (PGx) results and recommendations for patients with chronic pain who are treated in primary care clinics versus standard care.

Secondary objective: Explore non-pain related uses of PGx information in a population with chronic pain.

• Study Type: Interventional
• Enrollment (Estimated): 315
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Max Smith, PharmD; Phone Number: 1-202-244-9831; Email: Max.Smith@medstar.net

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21239
      • MedStar Good Samaritan Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Any sex, 18 years of age or older
• Report chronic pain (i.e., pain for at least 3 months),
• Have a current prescription (prior to the enrollment visit) for either hydrocodone, tramadol, or codeine.
• This opioid is ordered by a provider associated with MedStar Health
• Treated at a participating primary care clinic (section 6)
• Willing and able to comply with scheduled visits, buccal sample collection, and other trial-related procedures.

Exclusion Criteria:

• Patients who have received a liver or bone marrow transplant.
• Patients with documented opioid use disorder (e.g., opioid use disorder on the problem list) or have current prescriptions for buprenorphine represent a level of complexity that are beyond the scope of this trial.
• Any surgical procedure that typically necessitates post-operative opioid (e.g., laparoscopic cholecystectomy, unilateral open and laparoscopic inguinal hernia repair, partial mastectomy with and without sentinel lymph node biopsy, uncomplicated cesarean delivery, minimally invasive hysterectomy, robotic retropubic prostatectomy, arthroscopic partial meniscectomy, and thyroidectomy) within the past 3 months or in the study period.
• Surgeries or procedures that would not typically require postoperative opioids are permissible (e.g., (uncomplicated vaginal delivery, cochlear implant, and cardiac catheterization).
• A urine drug screen at enrollment or during the study identifies the patient ingesting a narcotic medication that is not prescribed to them. It is not a study requirement that any patients have completed a urine drug screen as this will be considered part of clinical practice per the treating provider.
• Known to have previously received CYP2D6 testing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PGx-guided care; Pharmacogenetic results (e.g., CYP2D6, CYP2C9) and a pharmacist consultation will be provided to their primary care provider. This consultation note (PharmD consult) will aid primary care providers in the interpretation and application of PGx results in prescribing decisions. The ultimate prescribing decision is at the discretion of the primary care provider and patient.	Genetic: Pharmacogenetic Testing; Genetic results will be reported for CYP2D6, CYP2C19, CYP2C9, CYP2B6, CYP3A4, CYP3A5, SLCO1B1, TPMT, and VKORC1.; Other Names: pharmacogenomics; CYP2D6; CYP2C9; PGx; Other: Pharmacist Consultation Note; Recommendations will be based on phenotypes translated from genetic data in accordance with CPIC guidelines. Drug interactions will be incorporated into phenotype assignments when appropriate.
Active Comparator: Standard care; Care for study subjects will occur without PGx results at the discretion of the study subject, their primary care provider. After the active participation ends (i.e. after the three month follow up is complete), PGx results and a PharmD consult will be provided similar to the PGx-guided arm.	Other: Delayed pharmacogenetic testing; Pharmacogenetic testing and a pharmacist consultation note will be provided to participants provided to the standard care arm once 3 months have passed since their baseline visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pain Intensity	The change in composite pain intensity among CYP2D6 poor or intermediate metabolizers between the baseline visit and 3 months. The composite pain intensity is defined as the mean of current, worst, and average pain intensity. The PROMIS Scale v1.0 Pain Intensity 3a will be used to collected pain intensity data. The scale asks three separate questions regarding how intense the patient's pain is on average over the past 7 days, at it's worst over the past 7 days, and at that moment. Options range from 1 (had no pain) to 5 (very severe).	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Use	The change number of morphine milliequivalents (MMEs) prescribed between baseline and 3 months.	3 months
Recommendation Acceptance	Proportion of patients with prescribing decisions concordant with PGx with recommendations	first encounter (baseline visit), 3 months, 12 months
Significant Change in Pain Intensity	The proportion of patients with at least a 30% improvement in composite pain intensity.	3 months
Change in Physical Function	Using the PROMIS-29 Profile v2.0, assess the change in physical function between baseline and 3 months. The scale includes options that range from 1 (without any difficulty) to 5 (unable to do).	3 months
Change in Pain Interference Symptoms	Using the PROMIS-29 Profile v2.0, assess the change in symptoms between baseline and 3 months. The scale includes options that range from 1 (not at all) to 5 (very much).	3 months
Change in Pain Intensity Among Those with Therapy Concordant with PGx Recommendations	The subset of patients with actionable results (e.g., CYP2D6 poor or intermediate metabolism) will have pain intensity compared between those with therapy concordant and discordant with recommendations. The change in composite pain intensity between the baseline visit and 3 months. The composite pain intensity is defined as the mean of current, worst, and average pain intensity. The PROMIS Scale v1.0 Pain Intensity 3a will be used to collected pain intensity data. The scale asks three separate questions regarding how intense the patient's pain is on average over the past 7 days, at it's worst over the past 7 days, and at that moment. Options range from 1 (had no pain) to 5 (very severe).	3 months

Collaborators and Investigators

• Sponsor: Medstar Health Research Institute
• Collaborators: Kailos Genetics, Inc.
• Investigators: Principal Investigator: Max Smith, PharmD, MedStar Health

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2020
• Primary Completion (Actual): July 11, 2023
• Study Completion (Estimated): April 11, 2024

Study Registration Dates

• First Submitted: December 4, 2020
• First Submitted That Met QC Criteria: December 22, 2020
• First Posted (Actual): December 28, 2020

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: pharmacogenetics; CYP2C9; opioids; tramadol; pharmacogenomics; CYP2D6; codeine; hydrocodone; NSAIDs
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain
• Other Study ID Numbers: 00002751

Drug and device information, study documents

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