A Depression and Opioid Pragmatic Trial in Pharmacogenetics (Chronic Pain Trial) (ADOPT PGx)

A Depression and Opioid Pragmatic Trial in Pharmacogenetics

This study is comprised of three separate pharmacogenetic trials grouped into a single protocol due to similarities in the intervention, the hypotheses, and the trial design. The three trials are the Acute Pain Trial, the Chronic Pain Trial, and the Depression Trial. Participants can enroll in only one of the three trials. All three trials were registered on ClinicalTrials.gov under NCT04445792. In July 2023 each of the three treatment trials was registered under a separate NCT# and NCT04445792 was converted to a screening record per recent guidance on master protocol research programs (MPRPs). This record is specific to the Chronic Pain Trial within the ADOPT-PGx protocol.

The Chronic Pain Trial is a prospective, multicenter, two arm randomized pragmatic trial. Participants meeting eligibility criteria will be randomly assigned to either immediate pharmacogenetic testing and genotype-guided opioid therapy (Intervention arm) or standard care with 6-month delayed pharmacogenetic testing (Control arm). The investigators will test the hypothesis that pharmacogenetic testing and genotype guided pain therapy improves pain control after surgery in participants who's body processes some pain medicines slower than normal.

Study Overview

• Status: Completed
• Conditions: Chronic Pain
• Intervention / Treatment: Other: Pharmacogenetic testing; Other: Clinical decisions support

Detailed Description

Pain and depression are conditions that impact substantial proportions of the US population. Finding safe and effective drug therapies for both conditions is challenging. In the case of treatment for acute and chronic pain, the challenge is finding effective therapy while minimizing adverse effects or opioid addiction (and the ensuing consequences). For depression, there are few clinically relevant predictors of successful treatment leading to multiple trials of inadequate therapy for some patients. Both opioid and antidepressant prescriptions can be guided by pharmacogenetics (PGx) data based on existing guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC).

This study is designed to evaluate the impact of pharmacogenetic testing and genotype-guided pain or anti-depressant therapy on pain control or depression symptoms in a pragmatic setting.

The rationale for examining a genotype-guided approach to acute and chronic pain management is based on the importance of CYP2D6 for the bioactivation of tramadol, codeine, and hydrocodone and data from a pilot study supporting improved pain control in intermediate and poor CYP2D6 metabolizers in the genotype-guided arm who are taking these drugs at baseline. Similarly, the rationale for examining a genotype-guided approach to depression medication therapy is based on the demonstrated role of CYP2D6 in the bio inactivation and CYP2C19 oxidation of select, commonly used SSRIs. Secondly, data from industry sponsored trials support the hypothesis of improved depression symptom control in a genotype-guided arm.

Study objectives:

Determine if a genotype-guided approach to pain therapy in participants with at least 3 months of chronic pain leads to improved pain control compared to usual care.

• Study Type: Interventional
• Enrollment (Actual): 1048
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida - Gainesville
    • Jacksonville, Florida, United States, 32209
      • University of Florida - Jacksonville
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
    • Indianapolis, Indiana, United States, 46202
      • Eskenazi Health
  • New York
    • New York, New York, United States, 10029
      • ICAHN School of Medicine at Mount Sinai
    • New York, New York, United States, 10035
      • The Institute for Family Health
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37208
      • Meharry Medical College
    • Nashville, Tennessee, United States, 37208
      • Nashville General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Chronic Pain Trial

• Age ≥ 18 years
• English speaking or Spanish speaking
• Seen at primary care clinics (such as, but not limited to, Internal Medicine, Family Medicine or Pediatrics) or patients seen in pain-relevant specialty clinics
• History of pain for at least the last 3 months
• Currently treated or being considered for treatment with tramadol, hydrocodone, or codeine to improve pain management

Exclusion Criteria

Trial-wide:

• Life expectancy less than 12 months
• Are too cognitively impaired to provide informed consent and/or complete study protocol
• Are institutionalized or too ill to participate (i.e. mental or nursing home facility or incarcerated)
• Have a history of allogeneic stem cell transplant or liver transplant
• People with prior clinical pharmacogenetic test results for genes relevant for the study in which they will enroll (CYP2D6 for the pain studies and CYP2D6 or CYP2C19 for depression) or already enrolled in an ADOPT PGx trial

Chronic Pain

• Plan to move out of the area within 6 months of enrollment
• Undergoing treatment for an active cancer diagnosis
• Currently taking daily opioids other than tramadol, codeine or hydrocodone

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: Chronic Pain - Immediate PGx Testing; Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider	Other: Pharmacogenetic testing; Genetic testing of CYP2D6 and CYP2C19; Other: Clinical decisions support; Prescribing recommendations to the provider based on the pharmacogenetic testing results
Other: Chronic Pain - Delayed PGx Testing; Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period	Other: Pharmacogenetic testing; Genetic testing of CYP2D6 and CYP2C19

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pain Intensity	The composite pain intensity score is derived from the 3-time PROMIS (Patient-Reported Outcomes Measurement Information System) pain intensity scale. Composite pain intensity score is the sum of the 3 questions and ranges from 3 (no pain) to 15 (intense pain). Change in composite pain intensity score ranges from -12 (change from the highest level of pain to the lowest level of pain) to 12 (change from the lowest level of pain to the highest level of pain).	Baseline to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Reduction Magnitude	Ratio of Composite Pain Score at 3 months relative to baseline. Composite pain intensity scores were shifted to range 0-12 and the pain reduction magnitude is reported as the ratio of pain at 3 months relative to pain at baseline using this adjusted scale. Statistical analyses were conducted using the log ratio pain at 3 months relative to pain at baseline. Due to the presence of 0 values in the ratios, the log ratios include a +.5 offset, i.e. log(3-month pain +.5 / baseline pain + 0.5).	Baseline to 3 months
Number of Participants With Clinically Significant Pain Reduction	Clinically significant pain reduction defined as ratio of 3-month composite pain score relative to baseline is < 0.7, corresponding to a 30% or more improvement in pain scores.	Baseline to 3 months
Prescription Pain Medication Misuse as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)	The 7-item PROMIS questionnaire assesses the extent to which participant experience prescription pain medication misuse symptoms in the past 3 months using a 5-point Likert scale. Participants are asked if they have had a prescription for pain medication in the last 3 months. If no, the questionnaire is not administered, if yes, the questionnaire is administered. For the completed questionnaires. Raw scores ranging from 7 to 35. Raw scores are converted to T-scores using the PROMIS conversion table, with T-scores ranging 36.3 to 54.1. Higher T-scores reflect greater symptom severity.	3 months
Number of Participants With Drug-Gene Concordance	Concordance between the participant reported opioid medications at 3 months and CYP2D6 phenotype.	3 months

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Icahn School of Medicine at Mount Sinai; University of Florida; Vanderbilt University Medical Center; National Human Genome Research Institute (NHGRI); Indiana University School of Medicine
• Investigators: Study Director: Hrishikesh Chakraborty, Duke University; Principal Investigator: Todd Skaar, PhD, Indiana University

Publications and helpful links

General Publications

• Skaar TC, Myers RA, Fillingim RB, Callaghan JT, Cicali E, Eadon MT, Elwood EN, Ginsburg GS, Lynch S, Nguyen KA, Obeng AO, Park H, Pratt VM, Rosenman M, Sadeghpour A, Shuman S, Singh R, Tillman EM, Volpi S, Wiisanen K, Winterstein AG, Horowitz CR, Voora D, Orlando L, Chakraborty H, Van Driest S, Peterson JF, Cavallari LA, Johnson JA, Dexter PR; IGNITE Pragmatic Trials Network. Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators. Clin Transl Sci. 2024 Aug;17(8):e70005. doi: 10.1111/cts.70005.

Helpful Links

• Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Actual): May 10, 2024
• Study Completion (Actual): May 10, 2024

Study Registration Dates

• First Submitted: July 21, 2023
• First Submitted That Met QC Criteria: July 21, 2023
• First Posted (Actual): July 28, 2023

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 9, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: CYP2D6; CYP2C19; Pharmacogenetic
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain
• Other Study ID Numbers: PRO00104948_B; U01HG010225 (U.S. NIH Grant/Contract)

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