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Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D) (CAN-BIND-17)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05017311
Recruitment Status : Not yet recruiting
First Posted : August 23, 2021
Last Update Posted : September 5, 2021
Sponsor:
Collaborators:
Unity Health Toronto
Baycrest
Centre for Addiction and Mental Health
McMaster University
Queen's University
University of Ottawa
University of British Columbia
University of Calgary
McGill University
Dalhousie University
University of Michigan
Simon Fraser University
Information provided by (Responsible Party):
Sidney Kennedy, University Health Network, Toronto

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).

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: Escitalopram Drug: Brexpiprazole Phase 4

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.

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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

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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

  2. 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)

  3. Remission at Week 8 [ Time Frame: Week 8 ]
    Defined as MADRS score ≤10 at Week 8


Other Outcome Measures:
  1. 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

  2. Week 12 clinical outcome - Remission [ Time Frame: Week 12 ]
    Defined as MADRS score ≤10 at Week 12



Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

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


Contacts
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Contact: Franca M Placenza, PhD 4166035800 ext 8839 franca.placenza@uhn.ca

Locations
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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         
Sponsors and Collaborators
University Health Network, Toronto
Unity Health Toronto
Baycrest
Centre for Addiction and Mental Health
McMaster University
Queen's University
University of Ottawa
University of British Columbia
University of Calgary
McGill University
Dalhousie University
University of Michigan
Simon Fraser University
Investigators
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Principal Investigator: Sidney H Kennedy, MD University Health Network, St. Michael's University, University of Toronto
Publications:

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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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sidney Kennedy, University Health Network, Toronto:
major depression
major depressive disorder
MDD
escitalopram
brexpiprazole
neuroimaging
genomics
proteomics
metabolomics
Additional relevant MeSH terms:
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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