Pharmacogenomics for Antidepressant Guidance and Education 1 (PAGE-1_AG1)

Study Overview
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Brief Summary
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One-third or more of individuals treated for major depressive disorder (MDD) do not experience remission of symptoms despite at least two adequate antidepressant trials. Such treatment-resistant depression (TRD) contributes disproportionately to the tremendous costs of MDD, in terms of health care costs, functional impairment, and diminished quality of life. The promise of personalized medicine for individuals at high risk for TRD is apparent. If these individuals could be recognized early in their disease course, they could be triaged to more intensive or targeted interventions to improve their likelihood of remission. With the proliferation of treatment options in MDD, at present individuals can spend months or years in and out of treatment before receiving these next-step treatments. At present, no clinical or biomarker-based tool has been shown to assist in matching patients with treatments most likely to be effective for them. The Genecept Assay offers the possibility of Personalized Medicine in psychiatry. Clinicians may find this additional genetic information can lead to optimized treatment plans for individual patients. Before such an assay can be widely applied clinically, it is necessary to demonstrate that this tool usefully impacts treatment outcomes. This study will examine the potential impact of the assay in terms of depression severity at 3 months, with further follow-up out to 6 months. Secondary measures will allow an estimate of its potential to change clinician behavior and improve patient quality of life. Further measures will also allow for refinement of the assay to maximize patient and clinician satisfaction, and estimate the potential savings associated with deployment of this assay in real-world clinical settings.

Official Title
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A Six-month Study of the Genecept Assay vs. Treatment as Usual to Evaluate Efficacy of Using Assay Guided Treatment in Outpatient Adults With Treatment Resistant Depression

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Device: Genecept Assay


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-65 written informed consent diagnosis of non-psychotic major depression as determined by study clinician/current medical prescriber, and mood disorder diagnosis confirmed by PHQ-9 QIDS-SR score of at least 10 (i.e., moderate depression) at initial visit failure of at least 1 prior adequate trial of a standard antidepressant (by ATRQ criteria - i.e., 6 weeks at adequate dose) Exclusion Criteria: psychotic features in the current episode, based upon clinical assessment 4 or more failed pharmacologic interventions in the current major depressive episode [response rates for these subjects is likely to be extremely low and would require a substantially larger-scale study to identify treatment effects] current substance use disorder other than nicotine which based upon clinical assessment requires inpatient or outpatient detoxification pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy) women who are breastfeeding serious suicide or homicide risk, as assessed by evaluating clinician other unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease, based on review of medical history, physical examination, and screening laboratory tests patients who have taken an investigational psychotropic drug within the last 3 months

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Treatment as usual (TAU)<br>Subjects will give DNA sample for genetic testing but will not receive genetic results and will therefore receive treatment as usual. | |
| Experimental: Genecept Assay<br>Subjects donate DNA sample for genetic testing and treatment decisions take genetic results into account. | Device: Genecept Assay<br>* Genetic test which analyzes five pharmacodynamic and two pharmacokinetic genes important in psychiatric disorders<br>* Other names: Genetic Test;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Measured by Change in Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), Adjusted for Baseline Severity, at 6 Months | To determine the efficacy of assay-guided treatment (AGT) versus treatment-as-usual (TAU), in terms of depression severity as measured by change in Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), adjusted for baseline severity, at 6 months Add: highest score on any 1 of the 4 sleep items (items 1 to 4) highest score on any 1 of the 4 weight items (items 6 to 9) highest score on either of the 2 psychomotor items (15 and 16) scores for each of the 6 MDD symptom domains Total scores range from 0-27. 0 = no signs of depression; 27 = severe depression | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinician Behavior as Measured by Change in Recorded Treatment Choice Before and After the Assay Results Are Made Available. | Clinicians will rank first and alternative treatment choice and dosage prior to assay and first and two alternative treatment choices after receiving assay results (for AGT group). Clinician choices will be compared. | one week | 
| Quality of Life as Measured by Self Reported Assessment of Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ) | To determine the efficacy of assay-guided treatment (AGT) versus treatment-as-usual (TAU) in outpatient treatment of nonpsychotic major depressive disorder, in terms of patient quality of life (Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ)) The minimum raw score on the QLESQ is 14, and the maximum score is 70. | baseline, 3, 6 months | 
| Cost | To compare costs of AGT versus TAU in outpatient treatment of nonpsychotic major depressive disorder as measured by claims data. | 6 months | 
| Acceptability of the Use of AGT for Subjects and Clinicians as Measured by Satisfaction Survey | To determine the acceptability to patients and clinicians of assay-guided treatment (AGT) versus treatment-as-usual (TAU) in outpatient treatment of nonpsychotic major depressive disorder | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Treatment Resistant