NCT01655706

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
211

participants targeted

Target at P25-P50 for phase_3 major-depressive-disorder

Timeline
Completed

Started Apr 2012

Longer than P75 for phase_3 major-depressive-disorder

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 23, 2012

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

July 27, 2012

Completed
6 days until next milestone

First Posted

Study publicly available on registry

August 2, 2012

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2017

Completed
Last Updated

May 11, 2018

Status Verified

May 1, 2018

Enrollment Period

4.7 years

First QC Date

July 27, 2012

Last Update Submit

May 4, 2018

Conditions

Major Depressive Disorder

Keywords

major depressionmajor depressive disorderbiomarkersescitalopramaripiprazoleMDDneuroimagingproteomicgenomics

Outcome Measures

Primary Outcomes (1)

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

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

    Week 8, Week 16

Study Arms (2)

escitalopram (10-20mg)

ACTIVE COMPARATOR

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.

Drug: escitalopram

aripiprazole (2-10mg)

ACTIVE COMPARATOR

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

Drug: escitalopramDrug: aripiprazole

Interventions

escitalopramDRUG

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.

Also known as: Cipralex
aripiprazole (2-10mg)escitalopram (10-20mg)
aripiprazoleDRUG

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

Also known as: Abilify
aripiprazole (2-10mg)

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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)
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

University of Calgary

Calgary, Alberta, T2N 2T9, Canada

Location

University of British Columbia

Vancouver, British Columbia, V6T 2A1, Canada

Location

McMaster University

Hamilton, Ontario, L8P 3B6, Canada

Location

Queen's University

Kingston, Ontario, K7L 4X3, Canada

Location

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1R8, Canada

Location

Related Publications (18)

  • 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.

    PMID: 22681173BACKGROUND

  • 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.

    PMID: 27084692BACKGROUND

  • Mazurka R, Cunningham S, Hassel S, Foster JA, Nogovitsyn N, Fiori LM, Strother SC, Arnott SR, Frey BN, Lam RW, MacQueen GM, Milev RV, Rotzinger S, Turecki G, Kennedy SH, Harkness KL. Relation of hippocampal volume and SGK1 gene expression to treatment remission in major depression is moderated by childhood maltreatment: A CAN-BIND-1 report. Eur Neuropsychopharmacol. 2024 Jan;78:71-80. doi: 10.1016/j.euroneuro.2023.12.003. Epub 2023 Dec 20.

    PMID: 38128154DERIVED

  • Phaterpekar T, Nunez JJ, Morton E, Liu YS, Cao B, Frey BN, Milev RV, Muller DJ, Rotzinger S, Soares CN, Taylor VH, Uher R, Kennedy SH, Lam RW. Machine Learning Prediction of Quality of Life Improvement During Antidepressant Treatment of Patients With Major Depressive Disorder: A STAR*D and CAN-BIND-1 Report. J Clin Psychiatry. 2023 Nov 15;85(1):23m14864. doi: 10.4088/JCP.23m14864.

    PMID: 37967350DERIVED

  • Islam F, Magarbeh L, Elsheikh SSM, Kloiber S, Espinola CW, Bhat V, Frey BN, Milev R, Soares CN, Parikh SV, Placenza F, Hassel S, Taylor VH, Leri F, Blier P, Uher R, Farzan F, Lam RW, Turecki G, Foster JA, Rotzinger S, Kennedy SH, Muller DJ. Influence of CYP2C19, CYP2D6, and ABCB1 Gene Variants and Serum Levels of Escitalopram and Aripiprazole on Treatment-Emergent Sexual Dysfunction: A Canadian Biomarker Integration Network in Depression 1 (CAN-BIND 1) Study. Can J Psychiatry. 2024 Mar;69(3):183-195. doi: 10.1177/07067437231203433. Epub 2023 Oct 5.

    PMID: 37796764DERIVED

  • 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.

    PMID: 35546043DERIVED

  • 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.

    PMID: 35023065DERIVED

  • 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.

    PMID: 34416758DERIVED

  • 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.

    PMID: 34229186DERIVED

  • 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.

    PMID: 34008342DERIVED

  • 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.

    PMID: 33860922DERIVED

  • 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.

    PMID: 33683582DERIVED

  • 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.

    PMID: 33520402DERIVED

  • 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.

    PMID: 33296696DERIVED

  • 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.

    PMID: 32558407DERIVED

  • 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.

    PMID: 32349119DERIVED

  • 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.

    PMID: 31471185DERIVED

  • 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.

    PMID: 30840787DERIVED

Related Links

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

EscitalopramDexetimideAripiprazole

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

PropylaminesAminesOrganic ChemicalsNitrilesBenzofuransHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsPiperidonesPiperidinesHeterocyclic Compounds, 1-RingPiperazinesQuinolonesQuinolines

Study Officials

  • Sidney Kennedy, MD

    University Health Network, University of Toronto

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Psychiatrist, Pricipal Investigator

Study Record Dates

First Submitted

July 27, 2012

First Posted

August 2, 2012

Study Start

April 23, 2012

Primary Completion

January 1, 2017

Study Completion

January 1, 2017

Last Updated

May 11, 2018

Record last verified: 2018-05

Data Sharing

IPD Sharing
Will share

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.

Locations

CA(6)