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

Not Applicable

Completed

Conditions: Depression

Registration Number: NCT05966155

Lead Sponsor: Duke University

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1572

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in Depression Symptom Control as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)	Baseline to 3 months	The 8-item PROMIS Emotional Distress Depression 8b and PROMIS Pediatric Depression Symptoms 8a questionnaire assess the extent to which participants experience depression symptoms over the past 7 days using a 5-point Likert scale. The responses to the 8 questions are converted to T-scores using the health measures assessment center scoring service. Pediatric T-scores are cross walked to adult T-scores using the cross walk published in Reeve et al 2016. Cross walked T-scores range from 37.1 to 80.9, higher scores correspond with higher levels of depression symptoms. Changes in T-scores from baseline to 3-months range from -43.8 to 43.8. Negative values of change in T-score correspond to symptom improvement, 0 corresponds to no change in depression T-scores, and positive change in depression T-scores correspond to symptom worsening at 3 months compared to baseline.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Drug-gene Concordance	3 months	Concordance defined as agreement between the PGx phenotype and SSRI medications reported.
Change in Depression Symptomatology as Measured by Patient Health Questionnaire (PHQ-8)	Baseline to 3 months	The 8-item PHQ-8 Questionnaire assesses severity of depression over the past 2 weeks using a 4-point scale indicating frequency of depression symptoms: not at all, several days, more than half the days, or nearly every day. The 8 questions are converted to a score ranging from 0 (not at all for all 8 symptoms) to 24 (nearly every day for all 8 symptoms). Changes in PHQ-8 scores from baseline to 3-months range from -24 to 24 and negative values of change in PHQ-8 correspond to improvement in depression at 3 months compared to baseline.
Side Effect Burden	3 months	An 8-item survey was developed to assess the severity of 8 depression medication side effects, using a 4-point scale for rating severity of the side effect: none, mild, moderate, severe. The 8 questions are converted to a side effect burden score ranging from 0 (none for all 8 side effects) to 24 (severe for all 8 side effects). Higher values correspond with more side effects and with higher severity.
Medication Non-Adherence as Measured by the Voils Medication Adherence Survey	3 months	Medication adherence level, non-adherent / adherent, derived from the Voils Medication Adherence survey. Reported as the number of participants who were non-adherent.
Number of Participants With Depression Remission as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)	6 months	Remission is defined as whether or not the summed raw responses to the PROMIS emotional distress depression survey is ≤ 16, corresponding to a participant respond "rarely" or "never" to most or all questions.
Number of Participants With Depression Remission as Measured by the Patient Health Questionnaire (PHQ-8)	6 months	The PHQ-8 scores range from 0 to 24 and remission is defined as having a PHQ-8 score of ≤ 4.
Number of Participants With 50% Reduction in Patient Health Questionnaire (PHQ-8) Score	3 months

Trial Locations

Locations (12): Nemours Children's Health System
🇺🇸
Orlando, Florida, United States
University of Florida - Gainesville
🇺🇸
Gainesville, Florida, United States
University of Florida - Jacksonville
🇺🇸
Jacksonville, 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
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Nemours Children's Health System
🇺🇸Orlando, Florida, United States