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

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04162522
• Other study ID #: 19-5371
• Status: Completed
• Phase: Phase 3
• Start date: December 23, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: February 2023
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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).

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	McMaster University	Hamilton	Ontario
Canada	Queen's University	Kingston	Ontario
Canada	Centre for Addiction and Mental Health	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	University of British Columbia	Vancouver	British Columbia

Sponsors (13)

Lead Sponsor	Collaborator
University Health Network, Toronto	Baycrest, Centre for Addiction and Mental Health, Dalhousie University, McGill University, McMaster University, Queen's University, Simon Fraser University, Unity Health Toronto, University of British Columbia, University of Calgary, University of Michigan, University of Ottawa

Country where clinical trial is conducted

Canada, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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

External Links

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