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Canadian Biomarker Integration Network for Depression Study (CAN-BIND-1)

Primary Purpose

Major Depressive Disorder

Status

Completed

Phase

Phase 3

Locations

Canada

Study Type

Interventional

Intervention

escitalopram

aripiprazole

About this trial

This is an interventional diagnostic trial for Major Depressive Disorder focused on measuring major depression, major depressive disorder, biomarkers, escitalopram, aripiprazole, MDD, neuroimaging, proteomic, genomics

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

For Depressed patients:

Inclusion Criteria:

Outpatients who are 18-60 years of age
Meet DSM-IV-TR criteria for Major Depressive Episode in Major Depressive Disorder by the MINI
Episode duration ≥ 3 months
Free of psychotropic medications for at least 5 half-lives (i.e. 1 week for most antidepressants, 5 weeks for fluoxetine) before baseline Visit 1
MADRS ≥ 24
Fluency in English, sufficient to complete the interviews and self-report questionnaires

Exclusion Criteria:

Any Axis I 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 3 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 and patients at risk for hypomanic switch (i.e. with a history of antidepressant hypomania)

Inclusion criteria for Healthy Controls:

18 to 60 years of age
No history of Axis I or Axis II disorders, as determined by the MINI.
Fluency in English, sufficient to complete the interviews and self-report questionnaires.

Sites / Locations

University of Calgary
University of British Columbia
McMaster University
Queen's University
University Health Network
Centre for Addiction and Mental Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

escitalopram (10-20mg)

aripiprazole (2-10mg)

Arm Description

Patients are on escitalopram for 8 weeks. At Week 8, patients will be assessed as 'responders' or 'non-responders'. 'Responders' will continue on escitalopram until study endpoint.

At Week 8, patients assessed as 'non-responders' will be given aripiprazole as an add-on treatment to escitalopram.

Outcomes

Primary Outcome Measures

Change in MADRS (Montgomery-Asberg Depression Rating Scale) scores from baseline

Clinical response (≥ 50% reduction in MADRS scores from baseline)

Secondary Outcome Measures

Full Information

NCT ID

NCT01655706

First Posted

July 27, 2012

Last Updated

May 4, 2018

Sponsor

University Health Network, Toronto

Collaborators

University of Toronto, University of Calgary, University of British Columbia, McGill University, Queen's University, Centre for Addiction and Mental Health, McMaster University

1. Study Identification

Unique Protocol Identification Number

NCT01655706

Brief Title

Canadian Biomarker Integration Network for Depression Study

Acronym

CAN-BIND-1

Official Title

Integrated Biological Markers for the Prediction of Treatment Response in Depression

Study Type

Interventional

2. Study Status

Record Verification Date

May 2018

Overall Recruitment Status

Completed

Study Start Date

April 23, 2012 (Actual)

Primary Completion Date

January 2017 (Actual)

Study Completion Date

January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University Health Network, Toronto

Collaborators

University of Toronto, University of Calgary, University of British Columbia, McGill University, Queen's University, Centre for Addiction and Mental Health, McMaster University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study is a pilot to assess feasibility of the protocol in patients and controls across six participating sites. The goal is to identify biological markers (biomarkers)that can be measured at baseline or early in treatment to predict treatment outcome in individual patients with Major Depressive Disorder (MDD). Biomarkers of interest will be clinical (using interview and self-report measures), molecular (from blood samples) and neurobiological (using neuroimaging and EEG).

Detailed Description

This is a study to collect clinical and biomarker data which will be used to build models to predict treatment response. This is not a study to evaluate efficacy of medications, as medications in this study have been approved by Health Canada and are widely used for the treatment of MDD. This is an open label study involving MDD patients and healthy controls.Patients with a diagnosis of MDD and a current major depressive episode (MDE) will receive open-label standard of care treatment with escitalopram (10-20mg). Healthy controls will not receive medication; however, they will go through clinical assessments, blood collection and neuroimaging procedures. At week 8, patients will be assessed for medication response (response is defined as ≥ 50% reduction in MADRS scores from baseline). Responders will continue medication at their effective dose until study endpoint while non-responders will receive open label add-on treatment with aripiprazole (2-10mg). There are approximately 7 clinic visits over a 16 week period during which patients and healthy controls will undergo clinician administered scales and self reports, provide blood and urine samples (which will undergo proteomic and genomic analyses) as well as neuroimaging (fMRI and EEG). At the end of the study, mathematical modeling methods will be used to integrate the data from the various modalities to see which features best predict treatment outcome.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Major Depressive Disorder

Keywords

major depression, major depressive disorder, biomarkers, escitalopram, aripiprazole, MDD, neuroimaging, proteomic, genomics

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 3

Interventional Study Model

Factorial Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

211 (Actual)

8. Arms, Groups, and Interventions

Arm Title

escitalopram (10-20mg)

Arm Type

Active Comparator

Arm Description

Patients are on escitalopram for 8 weeks. At Week 8, patients will be assessed as 'responders' or 'non-responders'. 'Responders' will continue on escitalopram until study endpoint.

Arm Title

aripiprazole (2-10mg)

Arm Type

Active Comparator

Arm Description

At Week 8, patients assessed as 'non-responders' will be given aripiprazole as an add-on treatment to escitalopram.

Intervention Type

Drug

Intervention Name(s)

escitalopram

Other Intervention Name(s)

Cipralex

Intervention Description

Patients will be given escitalopram for the first 8 weeks of the trial. At week 8, patients who are assessed as 'responders' will continue on escitalopram until study endpoint.

Intervention Type

Drug

Intervention Name(s)

aripiprazole

Other Intervention Name(s)

Abilify

Intervention Description

At Week 8, patients assessed as 'non-responders' will be given aripiprazole as an add-on treatment to escitalopram.

Primary Outcome Measure Information:

Title

Change in MADRS (Montgomery-Asberg Depression Rating Scale) scores from baseline

Description

Clinical response (≥ 50% reduction in MADRS scores from baseline)

Time Frame

Week 8, Week 16

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

For Depressed patients: Inclusion Criteria: Outpatients who are 18-60 years of age Meet DSM-IV-TR criteria for Major Depressive Episode in Major Depressive Disorder by the MINI Episode duration ≥ 3 months Free of psychotropic medications for at least 5 half-lives (i.e. 1 week for most antidepressants, 5 weeks for fluoxetine) before baseline Visit 1 MADRS ≥ 24 Fluency in English, sufficient to complete the interviews and self-report questionnaires Exclusion Criteria: Any Axis I 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 3 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 and patients at risk for hypomanic switch (i.e. with a history of antidepressant hypomania) Inclusion criteria for Healthy Controls: 18 to 60 years of age No history of Axis I or Axis II disorders, as determined by the MINI. Fluency in English, sufficient to complete the interviews and self-report questionnaires.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sidney Kennedy, MD

Organizational Affiliation

University Health Network, University of Toronto

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Calgary

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T2N 2T9

Country

Canada

Facility Name

University of British Columbia

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V6T 2A1

Country

Canada

Facility Name

McMaster University

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L8P 3B6

Country

Canada

Facility Name

Queen's University

City

Kingston

State/Province

Ontario

ZIP/Postal Code

K7L 4X3

Country

Canada

Facility Name

University Health Network

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2C4

Country

Canada

Facility Name

Centre for Addiction and Mental Health

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5T 1R8

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

Citations:

PubMed Identifier

22681173

Citation

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.

Results Reference

background

PubMed Identifier

27084692

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.

Results Reference

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PubMed Identifier

35546043

Citation

Espinola CW, Khoo Y, Parmar R, Demchenko I, Frey BN, Milev RV, Ravindran AV, Parikh SV, Ho K, Rotzinger S, Lou W, Lam RW, Kennedy SH, Bhat V. Males and females differ in reported sexual functioning with escitalopram treatment for major depressive disorder: A CAN-BIND-1 study report. J Psychopharmacol. 2022 May;36(5):604-613. doi: 10.1177/02698811221095832. Epub 2022 May 12.

Results Reference

derived

PubMed Identifier

35023065

Citation

Anteraper SA, Guell X, Lee YJ, Raya J, Demchenko I, Churchill NW, Frey BN, Hassel S, Lam RW, MacQueen GM, Milev R, Schweizer TA, Strother SC, Whitfield-Gabrieli S, Kennedy SH, Bhat V; CAN-BIND Investigator Team. Cerebello-cerebral Functional Connectivity Networks in Major Depressive Disorder: a CAN-BIND-1 Study Report. Cerebellum. 2023 Feb;22(1):26-36. doi: 10.1007/s12311-021-01353-5. Epub 2022 Jan 13.

Results Reference

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PubMed Identifier

34416758

Citation

van der Wijk G, Harris JK, Hassel S, Davis AD, Zamyadi M, Arnott SR, Milev R, Lam RW, Frey BN, Hall GB, Muller DJ, Rotzinger S, Kennedy SH, Strother SC, MacQueen GM, Protzner AB. Baseline Functional Connectivity in Resting State Networks Associated with Depression and Remission Status after 16 Weeks of Pharmacotherapy: A CAN-BIND Report. Cereb Cortex. 2022 Mar 4;32(6):1223-1243. doi: 10.1093/cercor/bhab286.

Results Reference

derived

PubMed Identifier

34229186

Citation

Suh JS, Fiori LM, Ali M, Harkness KL, Ramonas M, Minuzzi L, Hassel S, Strother SC, Zamyadi M, Arnott SR, Farzan F, Foster JA, Lam RW, MacQueen GM, Milev R, Muller DJ, Parikh SV, Rotzinger S, Sassi RB, Soares CN, Uher R, Kennedy SH, Turecki G, Frey BN. Hypothalamus volume and DNA methylation of stress axis genes in major depressive disorder: A CAN-BIND study report. Psychoneuroendocrinology. 2021 Oct;132:105348. doi: 10.1016/j.psyneuen.2021.105348. Epub 2021 Jun 29.

Results Reference

derived

PubMed Identifier

34008342

Citation

Allen TA, Harkness KL, Lam RW, Milev R, Frey BN, Mueller DJ, Uher R, Kennedy SH, Quilty LC. Interactions between neuroticism and stressful life events predict response to pharmacotherapy for major depression: A CAN-BIND 1 report. Personal Ment Health. 2021 Nov;15(4):273-282. doi: 10.1002/pmh.1514. Epub 2021 May 18.

Results Reference

derived

PubMed Identifier

33860922

Citation

Morton E, Bhat V, Giacobbe P, Lou W, Michalak EE, McInerney S, Chakrabarty T, Frey BN, Milev RV, Muller DJ, Parikh SV, Rotzinger S, Kennedy SH, Lam RW; CAN-BIND Investigator Team. Predictors of Quality of Life Improvement with Escitalopram and Adjunctive Aripiprazole in Patients with Major Depressive Disorder: A CAN-BIND Study Report. CNS Drugs. 2021 Apr;35(4):439-450. doi: 10.1007/s40263-021-00803-2. Epub 2021 Apr 16.

Results Reference

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PubMed Identifier

33683582

Citation

Chakrabarty T, McInerney SJ, Torres IJ, Frey BN, Milev RV, Muller DJ, Rotzinger S, Kennedy SH, Lam RW; CAN-BIND Investigator Team. Cognitive Outcomes with Sequential Escitalopram Monotherapy and Adjunctive Aripiprazole Treatment in Major Depressive Disorder: A Canadian Biomarker Integration Network in Depression (CAN-BIND-1) Report. CNS Drugs. 2021 Mar;35(3):291-304. doi: 10.1007/s40263-021-00793-1. Epub 2021 Mar 8.

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PubMed Identifier

33520402

Citation

Vaccarino AL, Kalali AH, Blier P, Gilbert Evans S, Engelhardt N, Foster JA, Frey BN, Greist JH, Kobak KA, Lam RW, MacQueen G, Milev R, Muller DJ, Parikh SV, Placenza FM, Rizvi SJ, Rotzinger S, Sheehan DV, Sills T, Soares CN, Turecki G, Uher R, Williams JBW, Kennedy SH, Evans KR. THE DEPRESSION INVENTORY DEVELOPMENT SCALE: Assessment of Psychometric Properties Using Classical and Modern Measurement Theory in a CAN-BIND Trial. Innov Clin Neurosci. 2020 Jul 1;17(7-9):30-40.

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PubMed Identifier

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Citation

Ge R, Hassel S, Arnott SR, Davis AD, Harris JK, Zamyadi M, Milev R, Frey BN, Strother SC, Muller DJ, Rotzinger S, MacQueen GM, Kennedy SH, Lam RW, Vila-Rodriguez F. Structural covariance pattern abnormalities of insula in major depressive disorder: A CAN-BIND study report. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Dec 20;111:110194. doi: 10.1016/j.pnpbp.2020.110194. Epub 2020 Dec 6.

Results Reference

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PubMed Identifier

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Citation

Uher R, Frey BN, Quilty LC, Rotzinger S, Blier P, Foster JA, Muller DJ, Ravindran AV, Soares CN, Turecki G, Parikh SV, Milev R, MacQueen G, Lam RW, Kennedy SH; CAN-BIND Investigator Team. Symptom Dimension of Interest-Activity Indicates Need for Aripiprazole Augmentation of Escitalopram in Major Depressive Disorder: A CAN-BIND-1 Report. J Clin Psychiatry. 2020 Jun 16;81(4):20m13229. doi: 10.4088/JCP.20m13229.

Results Reference

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PubMed Identifier

32349119

Citation

Dunlop K, Rizvi SJ, Kennedy SH, Hassel S, Strother SC, Harris JK, Zamyadi M, Arnott SR, Davis AD, Mansouri F, Schulze L, Ceniti AK, Lam RW, Milev R, Rotzinger S, Foster JA, Frey BN, Parikh SV, Soares CN, Uher R, Turecki G, MacQueen GM, Downar J. Clinical, behavioral, and neural measures of reward processing correlate with escitalopram response in depression: a Canadian Biomarker Integration Network in Depression (CAN-BIND-1) Report. Neuropsychopharmacology. 2020 Jul;45(8):1390-1397. doi: 10.1038/s41386-020-0688-x.

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Davis AD, Hassel S, Arnott SR, Harris J, Lam RW, Milev R, Rotzinger S, Zamyadi M, Frey BN, Minuzzi L, Strother SC, MacQueen GM, Kennedy SH, Hall GB. White Matter Indices of Medication Response in Major Depression: A Diffusion Tensor Imaging Study. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Oct;4(10):913-924. doi: 10.1016/j.bpsc.2019.05.016. Epub 2019 Jun 12.

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PubMed Identifier

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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.

Results Reference

derived

Links:

URL

http://www.albertahealthservices.ca/7297.asp

Description

A news article from the Calgary site promoting the CAN-BIND project.

URL

http://www.canbind.ca

Description

CAN-BIND study website

URL

https://www.youtube.com/watch?v=vtJJgxBToWk

Description

"Treating Depression Takes Too Long"

Learn more about this trial

Canadian Biomarker Integration Network for Depression Study

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