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Major Depressive DisorderPhase 3CAN-BIND-1NCT01655706

Canadian Biomarker Integration Network for Depression Study

A Phase 3 study testing escitalopram and aripiprazole in people with Major Depressive Disorder, run by University Health Network, Toronto at 6 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for
Major Depressive Disorder
What is being tested?
escitalopram and aripiprazole
Could I receive a placebo?
No, everyone receives an active treatment
How many people
211 participants
Where
6 sitesCanada
Study dates
23 Apr 2012to Jan 2017
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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.

Who cannot join

  • 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
Show all 10Show fewer
  • 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)

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Canada6 sites

  • University of Calgary

    Calgary, Alberta, T2N 2T9

  • McMaster University

    Hamilton, Ontario, L8P 3B6

  • Queen's University

    Kingston, Ontario, K7L 4X3

  • University Health Network

    Toronto, Ontario, M5G 2C4

  • Centre for Addiction and Mental Health

    Toronto, Ontario, M5T 1R8

  • University of British Columbia

    Vancouver, British Columbia, V6T 2A1

Other trials in Canada

About this study

Official title: Integrated Biological Markers for the Prediction of Treatment Response in Depression

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).

Read the 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.

Keywords
major depression, major depressive disorder, biomarkers, escitalopram, aripiprazole, MDD, neuroimaging, proteomic, genomics
Medical subject headings
Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • escitalopramDrug

    Also called Cipralex

    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.

  • aripiprazoleDrug

    Also called Abilify

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

Study groups in NCT01655706
Study groupRoleWhat they receive
escitalopram (10-20mg)Active comparatorPatients 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.
Receives: Drug: escitalopram
aripiprazole (2-10mg)Active comparatorAt Week 8, patients assessed as 'non-responders' will be given aripiprazole as an add-on treatment to escitalopram.
Receives: Drug: escitalopram; Drug: aripiprazole

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: Week 8, Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2012 (estimated)
  2. Study start23 Apr 2012
  3. Primary completionJan 2017
  4. Study completionJan 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
211 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01655706
Sponsor's protocol ID
11-0917-A
Acronym
CAN-BIND-1
Status last verified
May 2018
First submitted
27 Jul 2012
Last updated
11 May 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: 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.

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.

    PubMed 22681173

  • 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.

    PubMed 27084692

  • 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.

    PubMed 38128154

  • 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.

    PubMed 37967350

  • 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.

    PubMed 37796764

  • 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.

    PubMed 35546043

  • 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.

    PubMed 35023065

  • 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.

    PubMed 34416758

  • 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.

    PubMed 34229186

  • 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.

    PubMed 34008342

  • 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.

    PubMed 33860922

  • 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.

    PubMed 33683582

  • 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.

    PubMed 33520402

  • 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.

    PubMed 33296696

  • 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.

    PubMed 32558407

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing escitalopram and aripiprazole in people with Major Depressive Disorder, run by University Health Network, Toronto at 6 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in MADRS (Montgomery-Asberg Depression Rating Scale) scores from baseline (time frame: Week 8, Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01655706, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2018.

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CAN-BIND-1 Clinical Trial NCT01655706 | AzTrials