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

NCT ID: NCT05966155

Last Updated: 2025-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1572 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-10
• Study Completion Date: 2024-04-27

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 Depression Trial within the ADOPT-PGx protocol.

The Depression 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 anti-depressant 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 anti-depressant therapy will reduce depression symptoms in participants who's body processes some anti-depressants faster or 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 genotype-guided dosing or selection of antidepressants among participants with at least 3 months of depressive symptoms who require new or revised antidepressant therapy leads to improved control of depression, compared to usual care.

Conditions

Depression

Study Design

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

Study Groups

Depression - Immediate PGx Testing

Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant 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

Depression - Delayed PGx Testing

Delayed genetic testing of CYP2D6 and CYP2C19 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

Depression Trial

• Age ≥ 8 years
• English speaking or Spanish speaking
• Patients followed at psychiatry clinics or primary care clinics at an enrolling site (such as, but not limited to, Internal Medicine, Family Medicine, or Pediatrics)
• Documentation of depression and/or provider report of depression
• Evidence of depressive symptoms for at least 3 months based on patient interview or documentation in electronic health records
• Recent initiation of SSRI therapy, recent revised SSRI therapy, or anticipated need for revised or new SSRI therapy per health care provider

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

Depression Trial

• Plan to move out of the area within 6 months of enrollment
• Have active psychosis or diagnosed psychotic disorders (schizophrenia, schizoaffective disorder, delusional disorder, psychotic depression, substance induced psychosis, schizophreniform disorder)
• Have dementia or other neurocognitive disorders due to any cause, such as Alzheimer's disease, vascular/subcortical, lewy body disease, frontotemporal lobar degeneration
• Has a seizure disorder
• Have bipolar disorder

• 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

Josh F. Peterson, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

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

University of Florida - Jacksonville

Jacksonville, Florida, United States

Nemours Children's Health System

Orlando, Florida, United States

Eskenazi Health

Indianapolis, Indiana, United States

Indiana University

Indianapolis, Indiana, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

The Institute for Family Health

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

Hines LJ, Wilke RA, Myers R, Mathews CA, Liu M, Baye JF, Petry N, Cicali EJ, Duong BQ, Elwood E, Hulvershorn L, Nguyen K, Ramos M, Sadeghpour A, Wu RR, Williamson L, Wiisanen K, Voora D, Singh R, Blake KV, Murrough JW, Volpi S, Ginsburg GS, Horowitz CR, Orlando L, Chakraborty H, Dexter P, Johnson JA, Skaar TC, Cavallari LH, Van Driest SL, Peterson JF; IGNITE Pragmatic Trials Network. Rationale and design for a pragmatic randomized trial to assess gene-based prescribing for SSRIs in the treatment of depression. Clin Transl Sci. 2024 Jun;17(6):e13822. doi: 10.1111/cts.13822.

Reference Type: BACKGROUND

PMID: 38860639 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://pubmed.ncbi.nlm.nih.gov/38860639/

Rationale and design for a pragmatic randomized trial to assess gene-based prescribing for SSRIs in the treatment of depression

Other Identifiers

U01HG010225

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PRO00104948_C

Identifier Type: -

Identifier Source: org_study_id