Combinatorial Pharmacogenomics Testing in Treatment-Naïve Major Depressive Disorder

Study Overview
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Brief Summary
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This study aims to determine whether the GeneSight Psychotropic test can result in better treatment outcomes for patients with treatment-naive major depressive disorder

Detailed Description
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Major Depressive Disorder is a chronic psychiatric illness that leads to devastating consequences at the individual and societal levels. Today, the choice of treatment continues to be largely based on subjective factors, primarily the clinician and/or patient's preferences, as well as the individual's history of response to treatment, often tainted by recall bias. Psychiatric medication decisions are even more arbitrary when the subject in question has not had past treatment trials. This often leads to a trial and error process and an increasingly resistant disease with each failed trial. Early implementation of an objective tool designed for tailoring medication choice to an individual may prove highly beneficial in decreasing illness chronicity, individual suffering, and economic burden. GeneSight Psychotropic test is a pharmacogenomic decision support tool, developed to help clinicians make informed, evidence-based decisions about proper drug selection. Therefore, we propose conducting a randomized, double blind, controlled trial to evaluate the impact of the GeneSight Psychotropic test to guide treatment decisions in patients with treatment-naïve (never having taken medication for depression) Major Depressive Disorder. This study will involve 6 visits over about 24 weeks where participants will be randomized to have their study clinician have access to their pharmacogenetic report in order to make treatment decisions, or to not have access to their report for the first 12 weeks. At Visit 5, Week 12, all participants will receive a copy of their pharmacogenetics report and all clinicians will be unblinded to be able to use the results to guide treatment options for an additional 12 weeks.

Official Title
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Combinatorial Pharmacogenomics Testing in Treatment-Naïve Major Depressive Disorder

Conditions
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Major Depressive Disorder, Depression, Depressive Disorder, Depressive Episode, Depression, Unipolar

Intervention / Treatment
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* Other: GeneSight Psychotropic test
* Drug: FDA-approved antidepressant or antipsychotic treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults 18-65 years of age Treatment-naïve major depressive disorder meeting Diagnostic and Statistical Manual 4th Edition (DSM-IV) criteria, without psychosis Total baseline score on the Quick Inventory Of Depressive Symptomatology Clinician-rated (QIDS-C16) and the Quick Inventory Of Depressive Symptomatology Self-Report (QIDS-SR16) rating scale ≥11 Good command of the English language Exclusion Criteria: Patients with a current diagnosis of schizophrenia Patients with a current diagnosis of schizoaffective disorder Patients with a current diagnosis of bipolar disorder (any type) Currently meeting DSM-IV criteria for significant substance use disorder (exception: nicotine use disorder) A diagnosis of personality disorder that may interfere with the patient's ability to improve on pharmacologic treatment, as determined by study investigator Patients currently receiving electroconvulsive therapy(ECT), deep brain stimulation (DBS) or transcranial magnetic stimulation (TMS) treatment History of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic or euthyroid for 6 months Significant unstable medical condition; life threatening disease; hepatic insufficiency; liver transplant recipient; cirrhosis of the liver; need for therapies that may obscure the results of treatment and/or of the study; malignancy (except basal cell carcinoma) and/or chemotherapy within 1 year prior to screening; malignancy more than 1 year prior to screening must have been local and without metastasis and/or recurrence, and if treated with chemotherapy, without nervous system complications History of gastric bypass surgery Acute suicidal intention and/or in need of immediate hospitalization as judged by the investigator Active psychotic symptoms Currently in an inpatient facility History of prior pharmacogenomic testing Currently pregnant or lactating Inability to provide informed consent Any other factor that in the investigators' judgment may affect patient safety or compliance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized to have their study clinician have access to their pharmacogenetic report (provide through the GeneSight Psychotropic tool) in order to make treatment decisions, or to not have access to their report for the first 12 weeks. At Visit 5, Week 12, all participants will receive a copy of their pharmacogenetics report and all clinicians will be unblinded for 'open label' to be able to use the results to guide treatment options for an additional 12 weeks.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GeneSight Psychotropic test<br>Participants randomized to have their study clinician have access to their pharmacogenetic report (provided through the GeneSight Psychotropic tool) in order to make treatment decisions for the first 12 weeks. At Visit 5, Week 12, participants will receive a copy of their pharmacogenetics report and clinicians will continue to be able to use the results to guide treatment options for an additional 12 weeks. | Other: GeneSight Psychotropic test<br>* GeneSight Psychotropic test, developed by AssureRx Health, is a genetic test that analyses pre-selected pharmacokinetics and pharmacodynamics genes and results in a composite phenotype and interpretive report, addressing both safety and efficacy of psychiatric medications.<br>* Other names: GeneSight test;Drug: FDA-approved antidepressant or antipsychotic treatment<br>* Participant is treated with medications included in the GeneSight Psychotropic product.<br>|
| Active Comparator: Treatment As Usual<br>Participants randomized to treatment as usual will receive treatment from study clinicians who do not have access to the participant's report for the first 12 weeks. At Visit 5, Week 12, participants will receive a copy of their pharmacogenetics report and clinicians will be unblinded to be able to use the results to guide treatment options for an additional 12 weeks. | Drug: FDA-approved antidepressant or antipsychotic treatment<br>* Participant is treated with medications included in the GeneSight Psychotropic product.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Rating Scale for Depression change score- Week 8 | 17-item Hamilton Rating Scale for Depression (HAM-D17) to assess mean change in depressive symptoms severity. Total range of the Hamilton Rating Scale for Depression is 0 to 52, with a greater score being an indication of more severe depressive symptoms. | Baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Rating Scale for Depression change score- Week 4 | 17-item Hamilton Rating Scale for Depression (HAM-D17) to assess mean change in depressive symptoms severity. Total range of the Hamilton Rating Scale for Depression is 0 to 52, with a greater score being an indication of more severe depressive symptoms. | Baseline to end of week 4 | 
| Hamilton Rating Scale for Depression change score- Week 12 | 17-item Hamilton Rating Scale for Depression (HAM-D17) to assess mean change in depressive symptoms severity. 17-item Hamilton Rating Scale for Depression (HAM-D17) to assess mean change in depressive symptoms severity. Total range of the Hamilton Rating Scale for Depression is 0 to 52, with a greater score being an indication of more severe depressive symptoms. | Baseline to end of week 12 | 
| Hamilton Rating Scale for Depression change score- Week 24 | 17-item Hamilton Rating Scale for Depression (HAM-D17) to assess mean change in depressive symptoms severity. 17-item Hamilton Rating Scale for Depression (HAM-D17) to assess mean change in depressive symptoms severity. Total range of the Hamilton Rating Scale for Depression is 0 to 52, with a greater score being an indication of more severe depressive symptoms. | Baseline to end of week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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treatment naive, major depression, pharmacotherapy, pharmacogenomic, genomics