A Depression and Opioid Pragmatic Trial in Pharmacogenetics (Acute Pain Trial)

NCT ID: NCT05966129

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1602 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-10
• Study Completion Date: 2024-03-25

Brief Summary

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.

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.

Conditions

Acute Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Acute Pain - Immediate PGx Testing

Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider

Group Type: EXPERIMENTAL

Pharmacogenetic testing

Intervention Type: OTHER

Genetic testing of CYP2D6 and CYP2C19

Clinical decisions support

Intervention Type: OTHER

Prescribing recommendations to the provider based on the pharmacogenetic testing results

Acute Pain - Delayed PGx Testing

Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period

Group Type: OTHER

Pharmacogenetic testing

Intervention Type: OTHER

Genetic testing of CYP2D6 and CYP2C19

Interventions

Pharmacogenetic testing

Genetic testing of CYP2D6 and CYP2C19

Intervention Type: OTHER

Clinical decisions support

Prescribing recommendations to the provider based on the pharmacogenetic testing results

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 8 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Human Genome Research Institute (NHGRI)

NIH

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: collaborator

Indiana University School of Medicine

OTHER

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hrishikesh Chakraborty

Role: STUDY_DIRECTOR

Duke University

Larisa H. Cavallari, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Julie A. Johnson, PharmD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Nemours Children's Health System

Wilmington, Delaware, United States

University of Florida - Gainesville

Gainesville, Florida, United States

Nemours Children's Health System

Jacksonville, Florida, United States

Nemours Children's Health System

Orlando, Florida, United States

Indiana University

Indianapolis, Indiana, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Sanford Health

Fargo, North Dakota, United States

Meharry Medical College

Nashville, Tennessee, United States

Nashville General Hospital

Nashville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 35899435 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

https://pubmed.ncbi.nlm.nih.gov/35899435/

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

Other Identifiers

U01HG010225

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PRO00104948_A

Identifier Type: -

Identifier Source: org_study_id