Canadian Biomarker Integration Network for Depression Study

NCT ID: NCT01655706

Last Updated: 2018-05-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

211 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-04-23

Study Completion Date

2017-01-31

Brief Summary

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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

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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.

Conditions

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Major Depressive Disorder

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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escitalopram (10-20mg)

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.

Group Type ACTIVE_COMPARATOR

escitalopram

Intervention Type DRUG

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.

aripiprazole (2-10mg)

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

Group Type ACTIVE_COMPARATOR

escitalopram

Intervention Type DRUG

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.

aripiprazole

Intervention Type DRUG

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

Interventions

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escitalopram

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

aripiprazole

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

Intervention Type DRUG

Other Intervention Names

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Cipralex Abilify

Eligibility Criteria

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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


* 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.

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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Toronto

OTHER

Sponsor Role collaborator

University of Calgary

OTHER

Sponsor Role collaborator

University of British Columbia

OTHER

Sponsor Role collaborator

McGill University

OTHER

Sponsor Role collaborator

Queen's University

OTHER

Sponsor Role collaborator

Centre for Addiction and Mental Health

OTHER

Sponsor Role collaborator

McMaster University

OTHER

Sponsor Role collaborator

University Health Network, Toronto

OTHER

Sponsor Role lead

Responsible Party

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Sidney Kennedy

Psychiatrist, Pricipal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sidney Kennedy, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, University of Toronto

Locations

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University of Calgary

Calgary, Alberta, Canada

Site Status

University of British Columbia

Vancouver, British Columbia, Canada

Site Status

McMaster University

Hamilton, Ontario, Canada

Site Status

Queen's University

Kingston, Ontario, Canada

Site Status

University Health Network

Toronto, Ontario, Canada

Site Status

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Site Status

Countries

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Canada

References

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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.

Reference Type BACKGROUND
PMID: 22681173 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27084692 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38128154 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37967350 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37796764 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35546043 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35023065 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34416758 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34229186 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34008342 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33860922 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33683582 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33520402 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33296696 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32558407 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32349119 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31471185 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30840787 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

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

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

http://www.canbind.ca

CAN-BIND study website

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

"Treating Depression Takes Too Long"

Other Identifiers

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11-0917-A

Identifier Type: -

Identifier Source: org_study_id

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