A PK/PD Genetic Variation Treatment Algorithm Versus Treatment As Usual for Adolescent Management Of Depression

Study Overview
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Brief Summary
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The overall goal of this investigator-initiated trial is to evaluate the impact of platform algorithm products designed to rapidly identify pharmacokinetic (PK) and/or pharmacodynamic (PD) genomic variation on treatment outcome of depression in adolescents. This new technology may have the potential to optimize treatment selection by improving response, minimizing unfavorable adverse events / side effects and increasing treatment adherence

Detailed Description
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Treatment seeking adolescent patients with a moderate to severe major depressive episode defined as a 40 or greater on Childhood Depression Rating Scale-Revised (CDRS-R) will be invited to participate in this study evaluating the GeneSight® platform. This new technology can rapidly assess PK and PD genetic variation that can potentially impact antidepressant, anti-psychotic, and stimulant treatment selection. These patients will have GeneSight® testing and will be randomized to one of two groups. In Group 1 (n=138), GeneSight® testing results will be available to the patient's treating clinician prior to treatment selection. In Group 2 (n=138), testing results will not be available to the patient's research treating clinician. However, all testing results will be made available to all participants and clinicians after the 8-week trial (upon completion of blinded assessments at week 8). The patients and the clinical raters will be blinded to group assignment.

Official Title
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A Pharmacokinetic/Pharmacodynamic Genetic Variation Treatment Algorithm Versus Treatment As Usual for Adolescent Management Of Depression (Abbreviation Assurex AMOD)

Conditions
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Depression

Intervention / Treatment
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* Other: AssureRx GeneSight genotyping results
* Other: Treatment as usual


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 13-18, male or female, any race/ethnicity Treating clinician, patient, and family feel that pharmacotherapy is indicated as part of a comprehensive treatment plan. Major depressive episode diagnosis or bipolar disorder based on KSADS-PL semi-structured psychiatric interview with a severity criteria-40 or greater on Childhood Depression Rating Scale-Revised (CDRS-R) Ability to provide informed consent Exclusion Criteria: Inability to speak English Inability or lack of willingness to provide informed consent and assent. Axis I diagnoses: Autism Spectrum Disorder, Anorexia Nervosa, Schizophreniform, and Schizophrenia. Psychotropic medication change (including dosage) between screening & randomization visits. Patients who meet DSM 5 criteria for any significant current substance use disorder other than nicotine, caffeine, or cannabis. Must have at least early, partial or full, remission X 3 months Serious suicidal risk and/or in need of immediate hospitalization as judged by the investigator. Significant unstable medical condition. Anticipated inability to attend scheduled study visits. Patients who in the judgment of the Investigator may be unreliable or uncooperative with the evaluation procedure outlined in this protocol. Cytochrome (CYP) & serotonin transporter genomic testing within 5 years.

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 18 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GeneSight guided treatment<br>GeneSight guided group will have their research psychiatrist make treatment recommendations based on test results | Other: AssureRx GeneSight genotyping results<br> <br> |
| Active Comparator: Treatment as usual group<br>Treatment as usual group will have treatment recommendations based on clinical judgment | Other: Treatment as usual<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline to endpoint change in depression | The primary outcome measure is the baseline to endpoint change in the Children's Depression Rating Scale, Revised (CDRS-R). | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of depressive symptoms | Quick Inventory of Depressive Symptomatology Adolescent Clinician Rated Form (QIDS-A17 CR) | 8 weeks | 
| Improvement of depressive symptoms | Quick Inventory of Depressive Symptomatology Adolescent Self-Report (QIDS-A17 SR) | 8 weeks | 
| Improvement of depressive symptoms | Quick Inventory of Depressive Symptomatology Adolescent Self-Report - Parent [(QIDS-A17 SR (P) | 8 weeks | 
| Improvement of depressive symptoms | Clinical Global Impression (CGI) scale | 8 weeks | 
| Improvement of depressive symptoms | Global Assessment Scale (CGAS) | 8 weeks | 
| Improvement of depressive symptoms | General Behavior Inventory Parent Version (P-GBI) (subscales mania and sleep) Short Form | 8 weeks | 
| Improvement of depressive symptoms | Treatment adherence based on concordance vs. non-concordance of gene test results and clinical intervention | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Genotyping, Pharmacokinetic, Pharmacodynamic