Clinical trial NCT05966155: A Depression and Opioid Pragmatic Trial in Pharmacogenetics (Depression Trial)
Official title: A Depression and Opioid Pragmatic Trial in Pharmacogenetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depression
Keywords: Pharmacogenetic
CYP2D6
CYP2C19
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Human Genome Research Institute (NHGRI)
name: University of Florida
name: Vanderbilt University Medical Center
name: Indiana University School of Medicine
name: Icahn School of Medicine at Mount Sinai
First posted: 2023-07-28
Enrollment: 1461
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Immediate vs. delayed pharmacogenetic testing and genotype-guided pain or depression therapy
Primary purpose: TREATMENT

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.

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
* Have cognitive developmental delay and/or cognitive disability, including autism spectrum disorders (Note: ADHD is not an exclusion criteria)
* Has a seizure disorder
* Have bipolar disorder

Primary outcomes:
measure: 3 Month Depression Symptom Control Change from Baseline
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: 3 Month Change in PHQ of Depression Symptomatology Change from Baseline Scores
timeFrame: baseline and 3 months
measure: 3 Month Medication Side Effect Burden Change from Baseline
timeFrame: 3 months
measure: 3 Month Medication Adherence Change from Baseline
timeFrame: 3 months
measure: 6 Month Depression Remission Change from Baseline
timeFrame: 6 months
Other outcomes:
Locations:
city: Wilmington
country: United States
facility: Nemours Children's Health System
state: Delaware
city: Gainesville
country: United States
facility: University of Florida - Gainesville
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Health System
state: Florida
city: Jacksonville
country: United States
facility: University of Florida - Jacksonville
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Health System
state: Florida
city: Indianapolis
country: United States
facility: Eskenazi Health
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: The Institute for Family Health
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Fargo
country: United States
facility: Sanford Health
state: North Dakota
city: Nashville
country: United States
facility: Meharry Medical College
state: Tennessee
city: Nashville
country: United States
facility: Nashville General Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Duke University
name: Hrishikesh Chakraborty
role: STUDY_DIRECTOR
affiliation: Vanderbilt University Medical Center
name: Josh F. Peterson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.