Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D) (CAN-BIND-17)
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ClinicalTrials.gov Identifier: NCT05017311 |
Recruitment Status :
Not yet recruiting
First Posted : August 23, 2021
Last Update Posted : September 5, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Major Depressive Disorder | Drug: Escitalopram Drug: Brexpiprazole | Phase 4 |
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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 400 participants |
Allocation: | Randomized |
Intervention Model: | Factorial Assignment |
Masking: | Double (Participant, Care Provider) |
Primary Purpose: | Treatment |
Official Title: | Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D) |
Estimated Study Start Date : | September 1, 2021 |
Estimated Primary Completion Date : | December 31, 2023 |
Estimated Study Completion Date : | December 31, 2023 |

Arm | Intervention/treatment |
---|---|
Active Comparator: Allocation by Predictive Biomarker Algorithm; Escitalopram + Brexpiprazole
Patients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted as non-responders to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded.
|
Drug: Escitalopram
All patients will receive open-label escitalopram (10-20 mg/d) for the entire study duration (12 weeks).
Other Name: Cipralex Drug: Brexpiprazole Depending on the initial randomization process, patients will either receive blinded brexpiprazole (0.5-2 mg/d) for the entire study duration (12 weeks) or for the last 4 weeks of the study if they received the placebo during the first 8 weeks of the study and were non-responders.
Other Name: Rexulti |
Placebo Comparator: Allocation by Predictive Biomarker Algorithm; Placebo
Patients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted to respond to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded placebo for the first 8 weeks of the study. For the final 4 weeks of the study, responders will continue to receive open-label escitalopram without the placebo and non-responders will receive a combination of open-label escitalopram and open-label brexpiprazole.
|
Drug: Escitalopram
All patients will receive open-label escitalopram (10-20 mg/d) for the entire study duration (12 weeks).
Other Name: Cipralex |
Active Comparator: Random Allocation; Escitalopram + Brexpiprazole
Patients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded.
|
Drug: Escitalopram
All patients will receive open-label escitalopram (10-20 mg/d) for the entire study duration (12 weeks).
Other Name: Cipralex Drug: Brexpiprazole Depending on the initial randomization process, patients will either receive blinded brexpiprazole (0.5-2 mg/d) for the entire study duration (12 weeks) or for the last 4 weeks of the study if they received the placebo during the first 8 weeks of the study and were non-responders.
Other Name: Rexulti |
Placebo Comparator: Random Allocation; Placebo
Patients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded placebo for the first 8 weeks of the study. For the final 4 weeks of the study, responders will continue to receive open-label escitalopram without the placebo and non-responders will receive a combination of open-label escitalopram and open-label brexpiprazole.
|
Drug: Escitalopram
All patients will receive open-label escitalopram (10-20 mg/d) for the entire study duration (12 weeks).
Other Name: Cipralex |
- Change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline [ Time Frame: Baseline to Week 8 ]Measured as clinical response, defined as a decrease in Montgomery Asberg Depression Rating Scale (MADRS) score at the Week 8 visit, by 50% or greater, from MADRS score at Baseline visit (i.e., lower MADRS scores = better outcome)
- Clinical response [ Time Frame: Baseline to Week 8 ]Defined as a decrease in MADRS score at the Week 8 visit, by 50% or greater, from MADRS score at Baseline visit
- Time to clinical response [ Time Frame: Baseline to Week 8 ]Defined as time (i.e., number of weeks) to achieve clinical response (i.e., decrease in MADRS score at the Week 8 visit, by 50% or greater, from MADRS score at Baseline visit)
- Remission at Week 8 [ Time Frame: Week 8 ]Defined as MADRS score ≤10 at Week 8
- Week 12 clinical outcome - Response [ Time Frame: Baseline to Week 8 and Week 8 to Week 12 ]Response at Week 12 - defined as a decrease in MADRS score at the Week 12 visit, by 50% or greater, from MADRS score at Baseline visit and Week 8
- Week 12 clinical outcome - Remission [ Time Frame: Week 12 ]Defined as MADRS score ≤10 at Week 12

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Patients
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).
Healthy Comparison (HC) Participants
Inclusion Criteria:
- 18 to 60 years of age.
- No history of psychiatric disorders (as determined by the modified MINI v.6.0.) or significant physical conditions (e.g. arthritis, fibromyalgia).
- Fluency in English, sufficient to complete the interviews and self-report questionnaires.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05017311
Contact: Franca M Placenza, PhD | 4166035800 ext 8839 | franca.placenza@uhn.ca |
Canada, Alberta | |
University of Calgary | |
Calgary, Alberta, Canada, T2N 2T9 | |
Contact: Rachel Stone 403-210-8650 rnstone@ucalgary.ca | |
Principal Investigator: Valerie H Taylor, MD, PhD | |
Canada, British Columbia | |
University of British Columbia | |
Vancouver, British Columbia, Canada, V6T2A1 | |
Contact: Vanessa Evans 604-822-8012 vanessa.evans@ubc.ca | |
Principal Investigator: Raymond W Lam, MD | |
Canada, Ontario | |
McMaster University | |
Hamilton, Ontario, Canada, L8P3B6 | |
Contact: Patricia Lukas 905-522-1155 ext 39178 plukus@stjosham.on.ca | |
Principal Investigator: Benicio N Frey, MD, PhD | |
Queen's University | |
Kingston, Ontario, Canada, K7L4X3 | |
Contact: Evan Forth 14ef19@queensu.ca | |
Principal Investigator: Roumen Milev, MD, PhD | |
University Health Network | |
Toronto, Ontario, Canada, M5T2S8 | |
Contact: Franca M Placenza, PhD 416-603-5800 ext 8839 franca.placenza@uhn.ca | |
Principal Investigator: Sidney H Kennedy, MD | |
Centre for Addiction and Mental Health | |
Toronto, Ontario, Canada, M6J1H4 | |
Contact: Ilona Gorbovskaya 416-535-8501 ext 30231 ilona.gorbovskaya@camh.ca | |
Principal Investigator: Daniel J Mueller, MD |
Principal Investigator: | Sidney H Kennedy, MD | University Health Network, St. Michael's University, University of Toronto |
Responsible Party: | Sidney Kennedy, Professor of Psychiatry, University of Toronto, Arthur Sommer Rotenberg Chair in Suicide & Depression Studies, St. Michael's Hospital, Principal Investigator, Canadian Biomarker Integration Network for Depression, University Health Network, University Health Network, Toronto |
ClinicalTrials.gov Identifier: | NCT05017311 |
Other Study ID Numbers: |
Pending |
First Posted: | August 23, 2021 Key Record Dates |
Last Update Posted: | September 5, 2021 |
Last Verified: | September 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | This study is funded by the Ontario Brain Institute (OBI). Data collected from this study is entered into a research database called "Brain-CODE", deployed at a High Performance Computer Virtual Lab (HPCVL). The HPCVL supports the regulatory-compliant (e.g. 21 CRF Part 11, HIPPA, PIPEDA) processes for securing privacy of healthcare data. |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
major depression major depressive disorder MDD escitalopram brexpiprazole |
neuroimaging genomics proteomics metabolomics |
Depression Depressive Disorder Depressive Disorder, Major Behavioral Symptoms Mood Disorders Mental Disorders Citalopram Brexpiprazole Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors |
Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Serotonin Agents Physiological Effects of Drugs Antidepressive Agents, Second-Generation Antidepressive Agents Psychotropic Drugs Dopamine Agonists Dopamine Agents |