Clinical trial NCT05017311: Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D)
Official title: Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Major Depressive Disorder
Keywords: major depression
major depressive disorder
MDD
escitalopram
brexpiprazole
neuroimaging
genomics
proteomics
metabolomics
Lead sponsor: Nova Scotia Health Authority
Sponsor class: OTHER
Collaborators: name: Unity Health Toronto
name: Centre for Addiction and Mental Health
name: McMaster University
name: Queen's University
name: University of Ottawa
name: University of British Columbia
name: University of Calgary
name: McGill University
name: Dalhousie University
name: University of Michigan
name: Simon Fraser University
First posted: 2021-08-23
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: This is a study that will test a predictive biomarker algorithm based on results from a previous study. 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: This is a multi-site, randomized study with two treatment phases: a double-blind primary treatment phase of 8 weeks, and an open-label secondary extension phase of 4 weeks. This study aims to test a predictive biomarker algorithm to select medication treatment for patients with major depressive disorder (MDD) based on results from the recently completed Canadian Biomarker Integration Network in Depression (CAN-BIND)-1 study. This will be accomplished through collection of clinical, neurophysiological, and molecular measures from both MDD patients and healthy controls. 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 randomly assigned to one of the two treatment groups: Personalized Assignment group or Random Assignment group. Patients in the Random Assignment group will randomly receive open-label escitalopram with the addition of either blinded placebo or brexpiprazole for 8 weeks. Patients in the Personalized Assignment group will receive open-label escitalopram with the addition of either placebo or blinded brexpiprazole for 8 weeks depending on what the predictive biomarker algorithm suggests.

At Week 8, participants will be assessed for treatment response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale score). All patients who initially received both open-label escitalopram and blinded brexpiprazole (regardless of treatment group) will continue to receive these medications for another 4 weeks but the brexpiprazole will no longer be blinded. For those patients who initially received open-label escitalopram and blinded placebo (regardless of treatment group), nonresponders will receive open-label escitalopram and open-label brexpiprazole for another 4 weeks and responders will receive open-label escitalopram only for another 4 weeks.

Over the 12 weeks, participants will attend 7 study 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.

Eligibility criteria: Patients

Inclusion Criteria:

* Outpatients 18 to 65 years of age.
* Meet DSM-5 criteria for MDE in MDD as determined by SCID-5.
* 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 (exceptions: stable use of hypnotics; stable use of stimulants for attention-deficit/hyperactive disorder).
* 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).

Healthy Comparison (HC) Participants

Inclusion Criteria:

* 18 to 65 years of age.
* No history of psychiatric disorders (as determined by SCID-5) or significant physical conditions (e.g. arthritis, fibromyalgia).
* Fluency in English, sufficient to complete the interviews and self-report questionnaires.

Primary outcomes:
measure: Change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline
timeFrame: Baseline to Week 8
Secondary outcomes:
measure: Clinical response
timeFrame: Baseline to Week 8
measure: Time to clinical response
timeFrame: Baseline to Week 8
measure: Remission at Week 8
timeFrame: Week 8
Other outcomes:
measure: Week 12 clinical outcome - Response
timeFrame: Baseline to Week 8 and Week 8 to Week 12
measure: Week 12 clinical outcome - Remission
timeFrame: Week 12
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Halifax
country: Canada
facility: Nova Scotia Health Authority
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Kingston
country: Canada
facility: Queen's University
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Nova Scotia Health Authority
name: Rudolf Uher, MD
role: PRINCIPAL_INVESTIGATOR
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