A Depression and Opioid Pragmatic Trial in Pharmacogenetics (Acute 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 Acute Pain Trial within the ADOPT-PGx protocol.

The Acute 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 post-surgical opioid therapy (Intervention arm) or standard care and pharmacogenetic testing after 6 months (Control arm). The investigators will test the hypothesis that pharmacogenetic testing and genotype guided pain management therapy improves pain control after surgery in participants who's body processes some pain medicines slower than normal.

Study Overview

• Status: Completed
• Conditions: Acute 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 acute post-surgical pain therapy leads to improved pain control compared to usual care, as defined by a decrease in the SIA score. Secondarily, The investigators will evaluate whether this approach leads to reduced use of DEA Schedule II opioids and reduced pain intensity.

• Study Type: Interventional
• Enrollment (Actual): 1602
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours Children's Health System
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida - Gainesville
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Health System
    • Orlando, Florida, United States, 32827
      • Nemours Children's Health System
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Sanford Health
  • 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: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Acute Pain Trial

• Age ≥ 8 years
• English speaking or Spanish speaking
• Elective/planned surgery types with planned or anticipated to be treated with tramadol, hydrocodone, or codeine pain management at an enrolling site, which may include orthopedic surgeries (e.g. arthroplasty, spine, etc.), open abdominal surgery, or cardiothoracic surgery and others

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

Acute Pain Trial

• Undergoing a laparoscopic surgery
• Receiving chronic opioid therapy, defined as use of opioids on most days for >3 months

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: Acute 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: Acute 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
10 Day Silverman Integrated Analgesic Assessment (SIA) Score	A composite measure of pain and opioid usage, the Silverman Integrated Analgesic Assessment (SIA) score, at 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75. The SIA has a total score range of -200 to 200, where a higher score corresponds with higher pain and opioid use.	Day of surgery (baseline) to 10 days post surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
10 Day Pain Intensity as Measured by the PROMIS Numeric Pain Rating Scale	PROMIS (Patient-Reported Outcomes Measurement Information System) Numeric Pain Rating Scale Pain intensity at 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75. Pain was measured on a scale of 0-10, where higher scores correspond to higher levels of pain.	10 days post-surgery
Post-surgery Opioid Usage, Measured in Milligrams of Morphine Equivalents (MME) Per Day	Opioid usage from surgery to 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.	Day of surgery (baseline) to 10 days post surgery
3 Month Prescription Pain Medication Misuse	The 7-item PROMIS Prescription Pain Medication Misuse questionnaire assesses the extent to which participants experience medication misuse symptoms over the past 3 months using a 5-point Likert scale. The 7 questions are converted to a raw score, ranging from 7 to 35. Raw scores are converted to T-scores using the PROMIS conversion tables and range from 36.3 to 55.8. Higher scores reflect greater medication misuse.	3 months post surgery
1 Month PROMIS Mobility Score	PROMIS mobility score at 1 month post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75 in the adult population only. The score ranges from 15 to 75, where a higher score corresponds to higher mobility.	1 month post surgery
Number of Participants With Opioid Persistence	Opioid persistence defined as a filled prescription for an opioid medication 3-6 months post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.	3-6 months post-surgery, assessed at 6 months
Participants With Drug-Gene Concordance	Drug-Gene Concordance defined as an agreement between the Pharmacogenomics (PGx) Test and the prescribed opioids post surgery for pain management in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75	Within 10 days post-surgery

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: Larisa H. Cavallari, PharmD, University of Florida; Principal Investigator: Julie A. Johnson, PharmD, Ohio State University

Publications and helpful links

General Publications

• Cavallari LH, Cicali E, Wiisanen K, Fillingim RB, Chakraborty H, Myers RA, Blake KV, Asiyanbola B, Baye JF, Bronson WH, Cook KJ, Elwood EN, Gray CF, Gong Y, Hines L, Kannry J, Kucher N, Lynch S, Nguyen KA, Obeng AO, Pratt VM, Prieto HA, Ramos M, Sadeghpour A, Singh R, Rosenman M, Starostik P, Thomas CD, Tillman E, Dexter PR, Horowitz CR, Orlando LA, Peterson JF, Skaar TC, Van Driest SL, Volpi S, Voora D, Parvataneni HK, Johnson JA; IGNITE Pragmatic Trials Network. Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators. Clin Transl Sci. 2022 Oct;15(10):2479-2492. doi: 10.1111/cts.13376. Epub 2022 Aug 4.
• Cavallari LH, Myers RA, Chakraborty H, Skaar TC, Gray CF, Baye JF, Volpi S, Rider R, Cicali EJ, Elwood EN, Harris EC, Hines LJ, Nahid NA, Nguyen KA, Obeng AO, Parr JA, Ramos MA, Orlando LA, Prieto HA, Sadeghpour A, Singh R, Starostik P, Tillman EM, Wyatt C, Horowitz CR, Voora D, Blake KV, Parvataneni HK, Fillingim RB, Dexter PR, Peterson JF, Johnson JA; IGNITE Pragmatic Trials Network. CYP2D6-Guided Opioid Management and Postoperative Pain Control: A Randomized Clinical Trial. JAMA Netw Open. 2026 Feb 2;9(2):e2558299. doi: 10.1001/jamanetworkopen.2025.58299.

Helpful Links

• Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators
• CYP2D6-Guided Opioid Management and Postoperative Pain Control: A Randomized Clinical Trial

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2021
• Primary Completion (Actual): March 25, 2024
• Study Completion (Actual): March 25, 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): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: CYP2D6; CYP2C19; Pharmacogenetic
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Acute Pain; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Health Services; Health Care Facilities Workforce and Services; Preventive Health Services; Genetic Testing; Genetic Techniques; Genetic Services; Diagnostic Services; Pharmacogenomic Testing
• Other Study ID Numbers: PRO00104948_A; 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