Canadian Biomarker Integration Network for Depression (CAN-BIND) - Validation Study

Study Overview
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Brief Summary
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This is a validation study that will replicate a completed study designed to assess biomarkers of treatment response to standard antidepressant treatment. The goal of this study is to integrate clinical, imaging, EEG, and molecular data across 8 sites to predict treatment outcome for patients experiencing a major depressive episode (MDE).

Detailed Description
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This is a multi-site study to replicate a previous multi-site, multi-platform study completed by the Canadian Biomarker Integration Network in Depression (CAN-BIND). This study aims to validate the integrated array of markers of response and non-response to first line antidepressant treatments that were previously identified in the original aforementioned study. This will be accomplished through collection of clinical, neurophysiological, and molecular measures. This is not a study to evaluate efficacy of medications; medications in this study have been approved by Health Canada and are widely used for the treatment of MDD. In this study, individuals diagnosed with MDD in a current major depressive episode (MDE) will be treated with open-label escitalopram for 8 weeks. At week 8, participants will be assessed for treatment response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale score). Responders will continue on escitalopram for 8 more weeks. Non-responders will be given add-on brexpiprazole treatment, in addition to escitalopram, for 8 weeks. Over the 16 weeks, pariticipants will attend 7 clinical visits where they will complete clinical assessments (clinician administered and self-report) and cognitive tests; provide blood, urine, and stool samples; undergo neuroimaging procedures (MRI and EEG); and provide speech samples. At the end of the study, modeling methods will be used to integrate data from these measures to determine the features that best predict treatment outcome.

Official Title
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Integrated Biological Markers for the Prediction of Treatment Response in Depression: Validation Study

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Escitalopram
* Drug: Brexpiprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients 18 to 60 years of age. Meet DSM-5 criteria for MDE in MDD as determined by the MINI. Episode duration > 3 months. Free of psychotropic medications for at least 5 half-lives (e.g. 1 week for most antidepressants, 5 weeks for fluoxetine) before baseline Visit 1. MADRS score ≥ 24. Fluency in English, sufficient to complete the interviews and self-report questionnaires. Exclusion Criteria: Any diagnosis, other than MDD, that is considered the primary diagnosis. Bipolar I or Bipolar-II diagnosis. Presence of a significant Axis II diagnosis (borderline, antisocial). High suicidal risk, defined by clinician judgment. Substance dependence/abuse in the past 6 months. Presence of significant neurological disorders, head trauma, or other unstable medical conditions. Pregnant or breastfeeding. Failure of 4 or more adequate pharmacologic interventions (as determined by the Antidepressant Treatment History Form). Started psychological treatment within the past 3 months with the intent of continuing treatment. Patients who have previously failed escitalopram or showed intolerance to escitalopram or brexpiprazole, and patients at risk for hypomanic switch (i.e. with a history of antidepressant induced hypomania).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: escitalopram (10-20 mg)<br>Participants are given escitalopram for 8 weeks. At week 8, participants will be assessed and classified as responders or non-responders. Responders will continue on escitalopram until the study endpoint (16 weeks). | Drug: Escitalopram<br>* Participants are given escitalopram for 8 weeks. At week 8, those classified as responders will continue on escitalopram until the end of study.<br>* Other names: Cipralex;|
| Active Comparator: brexpiprazole (0.5-2 mg)<br>At week 8, participants classified as non-responders will be given 8 weeks of brexpiprazole as add-on treatment to escitalopram. | Drug: Brexpiprazole<br>* Participants who are classified as non-responders are given 8 weeks add-on brexpiprazole, in addition to escitalopram, for the remainder of the study.<br>* Other names: Rexulti;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline | Measured as clinical response, defined as a decrease in Montgomery Asberg Depression Rating Scale (MADRS) score at the Week 8 and Week 16 visits, by 50% or greater, from MADRS score at Baseline visit (i.e., lower MADRS scores = better outcome) | Week 8, Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDD, escitalopram, brexpiprazole, genomics, proteomics, major depression, major depressive disorder, neuroimaging, metabolomics