Canadian Biomarker Integration Network for Depression Study

Study Overview
=================
Brief Summary
-----------------
This study is a pilot to assess feasibility of the protocol in patients and controls across six participating sites. The goal is to identify biological markers (biomarkers)that can be measured at baseline or early in treatment to predict treatment outcome in individual patients with Major Depressive Disorder (MDD). Biomarkers of interest will be clinical (using interview and self-report measures), molecular (from blood samples) and neurobiological (using neuroimaging and EEG).

Detailed Description
-----------------
This is a study to collect clinical and biomarker data which will be used to build models to predict treatment response. This is not a study to evaluate efficacy of medications, as medications in this study have been approved by Health Canada and are widely used for the treatment of MDD. This is an open label study involving MDD patients and healthy controls.Patients with a diagnosis of MDD and a current major depressive episode (MDE) will receive open-label standard of care treatment with escitalopram (10-20mg). Healthy controls will not receive medication; however, they will go through clinical assessments, blood collection and neuroimaging procedures. At week 8, patients will be assessed for medication response (response is defined as ≥ 50% reduction in MADRS scores from baseline). Responders will continue medication at their effective dose until study endpoint while non-responders will receive open label add-on treatment with aripiprazole (2-10mg). There are approximately 7 clinic visits over a 16 week period during which patients and healthy controls will undergo clinician administered scales and self reports, provide blood and urine samples (which will undergo proteomic and genomic analyses) as well as neuroimaging (fMRI and EEG). At the end of the study, mathematical modeling methods will be used to integrate the data from the various modalities to see which features best predict treatment outcome.

Official Title
-----------------
Integrated Biological Markers for the Prediction of Treatment Response in Depression

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Drug: escitalopram
* Drug: aripiprazole


Participation Criteria
=================
Eligibility Criteria
-----------------
For Depressed patients: Inclusion Criteria: Outpatients who are 18-60 years of age Meet DSM-IV-TR criteria for Major Depressive Episode in Major Depressive Disorder by the MINI Episode duration ≥ 3 months Free of psychotropic medications for at least 5 half-lives (i.e. 1 week for most antidepressants, 5 weeks for fluoxetine) before baseline Visit 1 MADRS ≥ 24 Fluency in English, sufficient to complete the interviews and self-report questionnaires Exclusion Criteria: Any Axis I 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 3 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 and patients at risk for hypomanic switch (i.e. with a history of antidepressant hypomania) Inclusion criteria for Healthy Controls: 18 to 60 years of age No history of Axis I or Axis II disorders, as determined by the MINI. Fluency in English, sufficient to complete the interviews and self-report questionnaires.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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 (10-20mg)<br>Patients are on escitalopram for 8 weeks. At Week 8, patients will be assessed as 'responders' or 'non-responders'. 'Responders' will continue on escitalopram until study endpoint. | Drug: escitalopram<br>* Patients will be given escitalopram for the first 8 weeks of the trial. At week 8, patients who are assessed as 'responders' will continue on escitalopram until study endpoint.<br>* Other names: Cipralex;|
| Active Comparator: aripiprazole (2-10mg)<br>At Week 8, patients assessed as 'non-responders' will be given aripiprazole as an add-on treatment to escitalopram. | Drug: escitalopram<br>* Patients will be given escitalopram for the first 8 weeks of the trial. At week 8, patients who are assessed as 'responders' will continue on escitalopram until study endpoint.<br>* Other names: Cipralex;Drug: aripiprazole<br>* At Week 8, patients assessed as 'non-responders' will be given aripiprazole as an add-on treatment to escitalopram.<br>* Other names: Abilify;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in MADRS (Montgomery-Asberg Depression Rating Scale) scores from baseline | Clinical response (≥ 50% reduction in MADRS scores from baseline) | Week 8, Week 16 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
major depression, major depressive disorder, biomarkers, escitalopram, aripiprazole, MDD, neuroimaging, proteomic, genomics