Canadian Biomarker Integration Network for Depression (CAN-BIND) - Validation Study

Integrated Biological Markers for the Prediction of Treatment Response in Depression: Validation Study

This is a validation study that will replicate a completed study designed to assess biomarkers of treatment response to standard antidepressant treatment. 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).

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Escitalopram; Drug: Brexpiprazole

Detailed Description

This is a multi-site study to replicate a previous multi-site, multi-platform study completed by the Canadian Biomarker Integration Network in Depression (CAN-BIND). This study aims to validate the integrated array of markers of response and non-response to first line antidepressant treatments that were previously identified in the original aforementioned study. This will be accomplished through collection of clinical, neurophysiological, and molecular measures. 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 treated with open-label escitalopram for 8 weeks. At week 8, participants will be assessed for treatment response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale score). Responders will continue on escitalopram for 8 more weeks. Non-responders will be given add-on brexpiprazole treatment, in addition to escitalopram, for 8 weeks.

Over the 16 weeks, pariticipants will attend 7 clinical 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
• Enrollment (Actual): 1
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Franca M Placenza, PhD; Phone Number: 8839 4166035800; Email: franca.placenza@uhn.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • University of Calgary
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T2A1
      • University of British Columbia
  • Ontario
    • Hamilton, Ontario, Canada, L8P3B6
      • McMaster University
    • Kingston, Ontario, Canada, K7L4X3
      • Queen's University
    • Toronto, Ontario, Canada, M5T2S8
      • University Health Network
    • Toronto, Ontario, Canada, M6J1H4
      • Centre for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: escitalopram (10-20 mg); Participants are given escitalopram for 8 weeks. At week 8, participants will be assessed and classified as "responders" or "non-responders". Responders will continue on escitalopram until the study endpoint (16 weeks).	Drug: Escitalopram; Participants are given escitalopram for 8 weeks. At week 8, those classified as responders will continue on escitalopram until the end of study.; Other Names: Cipralex
Active Comparator: brexpiprazole (0.5-2 mg); At week 8, participants classified as "non-responders" will be given 8 weeks of brexpiprazole as add-on treatment to escitalopram.	Drug: Brexpiprazole; Participants who are classified as non-responders are given 8 weeks add-on brexpiprazole, in addition to escitalopram, for the remainder of the study.; Other Names: Rexulti

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline	Measured as clinical response, defined as a decrease in Montgomery Asberg Depression Rating Scale (MADRS) score at the Week 8 and Week 16 visits, by 50% or greater, from MADRS score at Baseline visit (i.e., lower MADRS scores = better outcome)	Week 8, Week 16

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Kennedy SH, Downar J, Evans KR, Feilotter H, Lam RW, MacQueen GM, Milev R, Parikh SV, Rotzinger S, Soares C. The Canadian Biomarker Integration Network in Depression (CAN-BIND): advances in response prediction. Curr Pharm Des. 2012;18(36):5976-89. doi: 10.2174/138161212803523635.
• Lam RW, Milev R, Rotzinger S, Andreazza AC, Blier P, Brenner C, Daskalakis ZJ, Dharsee M, Downar J, Evans KR, Farzan F, Foster JA, Frey BN, Geraci J, Giacobbe P, Feilotter HE, Hall GB, Harkness KL, Hassel S, Ismail Z, Leri F, Liotti M, MacQueen GM, McAndrews MP, Minuzzi L, Muller DJ, Parikh SV, Placenza FM, Quilty LC, Ravindran AV, Salomons TV, Soares CN, Strother SC, Turecki G, Vaccarino AL, Vila-Rodriguez F, Kennedy SH; CAN-BIND Investigator Team. Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort. BMC Psychiatry. 2016 Apr 16;16:105. doi: 10.1186/s12888-016-0785-x.
• Kennedy SH, Lam RW, Rotzinger S, Milev RV, Blier P, Downar J, Evans KR, Farzan F, Foster JA, Frey BN, Giacobbe P, Hall GB, Harkness KL, Hassel S, Ismail Z, Leri F, McInerney S, MacQueen GM, Minuzzi L, Muller DJ, Parikh SV, Placenza FM, Quilty LC, Ravindran AV, Sassi RB, Soares CN, Strother SC, Turecki G, Vaccarino AL, Vila-Rodriguez F, Yu J, Uher R; CAN-BIND Investigator Team. Symptomatic and Functional Outcomes and Early Prediction of Response to Escitalopram Monotherapy and Sequential Adjunctive Aripiprazole Therapy in Patients With Major Depressive Disorder: A CAN-BIND-1 Report. J Clin Psychiatry. 2019 Feb 5;80(2):18m12202. doi: 10.4088/JCP.18m12202.

Helpful Links

• CAN-BIND study website
• Maclean's news article on suicide prediction and CAN-BIND research

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2019
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: November 11, 2019
• First Submitted That Met QC Criteria: November 11, 2019
• First Posted (Actual): November 14, 2019

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: neuroimaging; MDD; genomics; major depressive disorder; escitalopram; metabolomics; proteomics; major depression; brexpiprazole
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Antidepressive Agents, Second-Generation; Citalopram; Brexpiprazole
• Other Study ID Numbers: 19-5371

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No