Canadian Biomarker Integration Network for Depression Study

Phase 3

Completed

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
escitalopram (10-20mg)	escitalopram	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.
aripiprazole (2-10mg)	escitalopram	At Week 8, patients assessed as 'non-responders' will be given aripiprazole as an add-on treatment to escitalopram.
aripiprazole (2-10mg)	aripiprazole	At Week 8, patients assessed as 'non-responders' will be given aripiprazole as an add-on treatment to escitalopram.

Primary Outcome Measures

Name	Time	Method
Change in MADRS (Montgomery-Asberg Depression Rating Scale) scores from baseline	Week 8, Week 16	Clinical response (≥ 50% reduction in MADRS scores from baseline)

Secondary Outcome Measures

Name	Time	Method

Locations (6): University of British Columbia
🇨🇦
Vancouver, British Columbia, Canada
University Health Network
🇨🇦
Toronto, Ontario, Canada
University of Calgary
🇨🇦
Calgary, Alberta, Canada
Centre for Addiction and Mental Health
🇨🇦
Toronto, Ontario, Canada
Queen's University
🇨🇦
Kingston, Ontario, Canada
McMaster University
🇨🇦
Hamilton, Ontario, Canada