A Depression and Opioid Pragmatic Trial in Pharmacogenetics
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Duke University
- Enrollment
- 1,572
- Locations
- 24
- Primary Endpoint
- Change in Depression Symptom Control as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 8 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Outcomes
Primary Outcomes
Change in Depression Symptom Control as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)
Time Frame: 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 Outcomes
- Number of Participants With Drug-gene Concordance(3 months)
- Change in Depression Symptomatology as Measured by Patient Health Questionnaire (PHQ-8)(Baseline to 3 months)
- Side Effect Burden(3 months)
- Medication Non-Adherence as Measured by the Voils Medication Adherence Survey(3 months)
- Number of Participants With Depression Remission as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)(6 months)
- Number of Participants With Depression Remission as Measured by the Patient Health Questionnaire (PHQ-8)(6 months)
- Number of Participants With 50% Reduction in Patient Health Questionnaire (PHQ-8) Score(3 months)