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Major Depressive DisorderPhase 3ELECT-TDCSNCT01894815

Escitalopram, Placebo and tDCS in Depression: a Non-inferiority Trial

A Phase 3 study testing Escitalopram oxalate and transcranial direct current stimulation in people with Major Depressive Disorder and Major Depressive Disorder, Recurrent, Unspecified, run by University of Sao Paulo at 2 sites in Brazil.

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

Major depressive disorder (MDD) is a common psychiatric condition, mostly treated with antidepressant drugs, which are limited for issues such as refractoriness and adverse effects. In this context, the investigators investigate a non-pharmacological treatment known as transcranial direct current stimulation (tDCS). Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Escitalopram oxalate and transcranial direct current stimulation
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
245 participants
Where
2 sitesBrazil
Study dates
Oct 2013to Nov 2016
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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • HAMD17>=17
  • more than 8 years of schooling OR able to read, speak and understand the Portuguese language.
  • Low suicide risk.

Who cannot join

  • Bipolar disorders.
  • Schizophrenia and other psychotic disorders.
  • Anxiety disorders, if it is the primary diagnosis (comorbidity with depression is not an exclusion disorder)
  • Substance abuse or dependence.
  • Depression symptoms better explained by medical conditions.
  • Neurologic conditions (e.g., stroke, multiple sclerosis, brain tumor).
Show all 14Show fewer
  • Severe medical conditions.
  • Pregnancy/breast-feeding.
  • Severe suicidal ideation, suicidal planning or recent (<4 weeks) suicide attempt.
  • Contra-indications to escitalopram.
  • Current use of escitalopram in the current depressive episode.
  • Use of escitalopram in a prior depressive episode that was not effective.
  • Contra-indications to tDCS.
  • Previous use of tDCS (current or previous depressive episode).

Trial locations and contacts

2 sites in 1 country.

Brazil2 sites

  • Hospital Universitário, Universidade de São Paulo

    São Paulo, São Paulo, 05508-000

  • Institute of Psychiatry, HC-FMUSP

    São Paulo, São Paulo

Other trials in Brazil

About this study

Official title: Escitalopram and Transcranial Direct Current Stimulation in Major Depressive Disorder: a Double-blind, Placebo-controlled, Randomized, Non-inferiority Trial

Major depressive disorder (MDD) is a common psychiatric condition, mostly treated with antidepressant drugs, which are limited for issues such as refractoriness and adverse effects. In this context, the investigators investigate a non-pharmacological treatment known as transcranial direct current stimulation (tDCS). To prove that tDCS is similarly effective than antidepressants would have a tremendous impact in clinical psychiatry, since tDCS is virtually absent of adverse effects. Its ease of use, portability and low price are also interesting characteristics for using in primary and secondary health care. Thus, our aim is to compare tDCS against a fully dosed, effective antidepressant. The study will be a non-inferiority, randomized, double-blinded, placebo-controlled, three-arm trial comparing active tDCS/placebo pill, sham tDCS/escitalopram 20mg/day and sham tDCS/placebo pill. Our primary aim is to show that tDCS is not inferior to escitalopram 20mg/day with a noninferiority margin of at least 50% of the escitalopram-placebo effect.

Read the detailed description

Major depressive disorder (MDD) is a common psychiatric condition, mostly treated with antidepressant drugs, which are limited for issues such as refractoriness and adverse effects. In this context, the researchers investigate a non-pharmacological treatment known as transcranial direct current stimulation (tDCS). In a prior clinical trial with 120 patients with MDD, the investigators demonstrated that the combination of tDCS with sertraline 50mg/day had increased, faster effects on depressive symptoms (Brunoni et al., JAMA Psychiatry, 2013). However, although the investigators suggested that tDCS vs. sertraline had similar efficacy, such comparison was compromised due to the low sertraline dose and also because the comparison of sertraline vs. placebo was not significant. To prove that tDCS is similarly effective than antidepressants would have a tremendous impact in clinical psychiatry, since tDCS is virtually absent of adverse effects. Its ease of use, portability and low price are also interesting characteristics for using in primary and secondary health care. Thus, our aim is to compare tDCS against a fully dosed, effective antidepressant. The study will be a non-inferiority, randomized, double-blinded, placebo-controlled, three-arm trial comparing active tDCS/placebo pill, sham tDCS/escitalopram 20mg/day and sham tDCS/placebo pill for ten weeks, randomizing 240 patients with MDD in a 3:3:2 ratio (less to placebo). Our primary aim is to show that tDCS is not inferior to escitalopram 20mg/day with a noninferiority margin of at least 50% of the escitalopram-placebo effect. As secondary aims, the researchers will investigate putative biomarkers for tDCS response. This is important considering the large sample size of this study and also the paucity of tDCS studies - therefore, the identification of such biomarkers could generate new hypothesis for future studies and for tDCS' mechanisms of action. The biomarkers will be: genetic polymorphisms (BDNF, SLC6A4, THP1, 5HT2A); serum markers (BDNF); motor cortical excitability (cortical silent period, intracortical inhibition, intracortical facilitation); heart rate variability; and neuroimaging (structural volume of the dorsolateral prefrontal and anterior cingulate cortex, white matter tracts of the prefrontal cortex and posterior cingulate cortex connectivity). This project represents a novel research line in our Institution, and the investigators thereby propose the onset of a new center denominated C.I.N.A. (Interdisciplinary Center for Applied Neuromodulation) that will foment the use and development of projects using neuromodulation techniques. This new center will also interact with other centers on the fields of clinical research, neurosciences and neuropsychiatry.

Being tested
Escitalopram oxalate, transcranial direct current stimulation, Sham tDCS + Placebo Pill
Keywords
major depressive disorder, major depression, depressive disorder, major depressive episode
Medical subject headings
Depressive Disorder, Major, Recurrence, Depressive Disorder

What participants receive

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

  • Escitalopram oxalateDrug

    Also called Reconter

    The investigators will use 10mg and 20mg pills. The investigators will up-titrate escitalopram from 10 to 20mg/day according to the patient tolerability. The maximum dose (20mg/day) is sought to be achieved at week 3.

  • transcranial direct current stimulationDevice

    Also called tDCS - Soterix Medical Device for Clinical Trials

    The anode will be applied over the F3 area and the cathode over the F4 area. The current dose is 2mA, current density is 0.8 A/m2. Electrodes will be 5x5cm in size. The investigators will apply 15 daily, consecutive tDCS sessions (excluding weekends) and after that one session per week until the primary endpoint.

  • Sham tDCS + Placebo PillOther

    This group receives sham tDCS and placebo pill.

Study groups in NCT01894815
Study groupRoleWhat they receive
Active tDCS / placebo pillExperimentaltranscranial direct current stimulation, using the parameters specified in Interventions.
Receives: Device: transcranial direct current stimulation
Sham tDCS / escitalopramActive comparatorEscitalopram oxalate (Reconter), 10mg/day (first 3 weeks) and 20mg/day (week 3 to week 10).
Receives: Drug: Escitalopram oxalate
Sham tDCS / placebo pillPlacebo comparatorFor sham tDCS, the device is automatically turned off after 30 second of stimulation and remains turned off during the 30-min session. For placebo pill, the pill has the same size, taste and color than escitalopram, and placebo and escitalopram will be provided in identical bottles, differing only according to a random-generated number placed in the label.
Receives: Other: Sham tDCS + Placebo Pill

What is being measured

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

  1. Changes in Hamilton Rating Scale for Depression, 17 items (HAMD17)

    Continuous measure (score changes). Non-inferiority assessment: the difference between tDCS to escitalopram should be >50% of escitalopram to placebo efficacy.

    Measured: Weeks 0 and 10

Secondary outcomes (53)

  1. Change in HDRS

    Continuous measure (score changes).

    Measured: Weeks 0, 3, 6, 8, 10

  2. Change in Montgomery-Asberg Depression Rating Scale (MADRS)

    Continuous measure (score changes).

    Measured: Weeks 0, 3, 6, 10

  3. Change in Beck Depression Inventory (BDI)

    Measured: Weeks 0, 3, 6, 10

  4. Change in Positive and Negative Affect Scale (PANAS)

    Measured: Weeks 0, 3, 6, 10

  5. Change in State-Trait Anxiety Inventory (STAI)

    Measured: Weeks 0, 3, 6, 10

  6. Hamilton Rating Scale for Depression, 17 items (HAMD17)

    Response (≥50% improvement from week 0 to 10)

    Measured: Week 10

  7. Hamilton Rating Scale for Depression, 17 items (HAMD17)

    Remission (HAMD17 ≤7) at week 10.

    Measured: Week 10

  8. Adverse events

    Assessment and comparisons of tDCS and drug adverse events. We used a tDCS adverse events questionnaire (Brunoni et al., 2011) and the SAFTEE.

    Measured: Week 3 and Week 10.

  9. Serious adverse events

    Serious adverse events include treatment-emergent hypomania/mania (YMRS>8), suicide, psychiatric hospitalization and others life-threatening or incapacitant events.

    Measured: Up to Week 10.

  10. Young Manic Rating Scale (YMRS)

    Assessment of treatment-emergent hypomania/mania, defined as YRMS>8.

    Measured: Week 3 and Week 10.

  11. Predictor of response

    Age (years)

    Measured: Week 10

  12. Predictor of response

    Gender

    Measured: Week 10

  13. Predictor of response

    Low wage (less than 5 monthly wages in Brazil)

    Measured: Week 10

  14. Predictor of response

    Recurrent depression

    Measured: Week 10

  15. Predictor of response

    Chronic depression

    Measured: Week 10

  16. Predictor of response

    Refractory depression

    Measured: Week 10

  17. Predictor of response

    Severe depression

    Measured: Week 10

  18. Predictor of response

    Benzodiazepine use

    Measured: Week 10

  19. Predictor of response

    Higher education (>15 years of schooling)

    Measured: Week 10

  20. Predictor of response

    Age of onset of the depressive episode (years)

    Measured: Week 10

  21. Predictor of response

    Any anxiety disorder

    Measured: Week 10

  22. Predictor of response

    Physical activity

    Measured: Week 10

  23. Predictor of response

    melancholic depression

    Measured: Week 10

  24. Predictor of response

    atypical depression

    Measured: Week 10

  25. Predictor of response

    smoking status

    Measured: Week 10

  26. Predictor of response

    hypertension

    Measured: Week 10

  27. Predictor of response

    diabetes mellitus

    Measured: Week 10

  28. Predictor of response

    ethnicity

    Measured: Week 10

  29. Predictor of response

    marital status

    Measured: Week 10

  30. Predictor of response

    employment status

    Measured: Week 10

  31. Predictor of response

    obesity

    Measured: Week 10

  32. Predictor of response

    familial psychiatry history

    Measured: Week 10

  33. Predictor of response

    Temperament and Character Inventory - Novelty seeking

    Measured: Week 10

  34. Predictor of response

    Any tDCS related adverse event.

    Measured: Week 10

  35. Predictor of response

    Temperament and Character Inventory - Harm avoidance

    Measured: Week 10

  36. Predictor of response

    Temperament and Character Inventory - Reward Dependence

    Measured: Week 10

  37. Predictor of response

    Temperament and Character Inventory - Persistence

    Measured: Week 10

  38. Predictor of response

    Temperament and Character Inventory - Cooperativeness

    Measured: Week 10

  39. Predictor of response

    Temperament and Character Inventory - Self-transcendence

    Measured: Week 10

  40. Predictor of response

    Temperament and Character Inventory - Self-directedness

    Measured: Week 10

  41. Predictor of response

    FAS verbal fluency test

    Measured: Week 10

  42. Predictor of response

    Digit span forward

    Measured: Week 10

  43. Predictor of response

    Digit span backward

    Measured: Week 10

  44. Predictor of response

    Trail Making Test - A

    Measured: Week 10

  45. Predictor of response

    Trail Making Test - B

    Measured: Week 10

  46. Predictor of response

    Symbol digit

    Measured: Week 10

  47. Predictor of response

    Montreal Cognitive Assessment

    Measured: Week 10

  48. Predictor of response

    Motor Cortical Excitability - Cortical silent period (left and right hemispheres)

    Measured: Week 3 and 10

  49. Predictor of response

    Motor Cortical Excitability - Intracortical inhibition (left and right hemispheres)

    Measured: Week 3 and 10

  50. Predictor of response

    Motor Cortical Excitability - Intracortical facilitation (left and right hemispheres)

    Measured: Week 3 and 10

  51. Predictor of response

    Heart rate variability - HF

    Measured: Week 3 and 10

  52. Predictor of response

    Heart rate variability - LF

    Measured: Week 3 and 10

  53. Predictor of response

    Heart rate variability - RMSSD

    Measured: Week 3 and 10

Timeline

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

  1. First posted10 Jul 2013 (estimated)
  2. Study startOct 2013
  3. Primary completionJul 2016
  4. Study completionNov 2016

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
245 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01894815
Sponsor's protocol ID
ELECT-TDCS
Other IDs
FAPESP 2012/20911-5
Acronym
ELECT-TDCS
Status last verified
Dec 2016
First submitted
3 Jul 2013
Last updated
5 Dec 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Goerigk SA, Padberg F, Chekroud A, Kambeitz J, Buhner M, Brunoni AR. Parsing the antidepressant effects of non-invasive brain stimulation and pharmacotherapy: A symptom clustering approach on ELECT-TDCS. Brain Stimul. 2021 Jul-Aug;14(4):906-912. doi: 10.1016/j.brs.2021.05.008. Epub 2021 May 26.

    PubMed 34048940

  • Bulubas L, Padberg F, Bueno PV, Duran F, Busatto G, Amaro E Jr, Bensenor IM, Lotufo PA, Goerigk S, Gattaz W, Keeser D, Brunoni AR. Antidepressant effects of tDCS are associated with prefrontal gray matter volumes at baseline: Evidence from the ELECT-TDCS trial. Brain Stimul. 2019 Sep-Oct;12(5):1197-1204. doi: 10.1016/j.brs.2019.05.006. Epub 2019 May 8.

    PubMed 31105027

  • Brunoni AR, Moffa AH, Sampaio-Junior B, Borrione L, Moreno ML, Fernandes RA, Veronezi BP, Nogueira BS, Aparicio LVM, Razza LB, Chamorro R, Tort LC, Fraguas R, Lotufo PA, Gattaz WF, Fregni F, Bensenor IM; ELECT-TDCS Investigators. Trial of Electrical Direct-Current Therapy versus Escitalopram for Depression. N Engl J Med. 2017 Jun 29;376(26):2523-2533. doi: 10.1056/NEJMoa1612999.

    PubMed 28657871

  • Brunoni AR, Sampaio-Junior B, Moffa AH, Borrione L, Nogueira BS, Aparicio LV, Veronezi B, Moreno M, Fernandes RA, Tavares D, Bueno PV, Seibt O, Bikson M, Fraguas R, Bensenor IM. The Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS): rationale and study design of a non-inferiority, triple-arm, placebo-controlled clinical trial. Sao Paulo Med J. 2015 May-Jun;133(3):252-63. doi: 10.1590/1516-3180.2014.00351712. Epub 2015 Jun 1.

    PubMed 26176930

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Escitalopram oxalate and transcranial direct current stimulation in people with Major Depressive Disorder and Major Depressive Disorder, Recurrent, Unspecified, run by University of Sao Paulo at 2 sites in Brazil.

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 3 inclusion and 14 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 5 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Brazil. 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. Some participants in this study may receive a placebo. 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?

Changes in Hamilton Rating Scale for Depression, 17 items (HAMD17) (time frame: Weeks 0 and 10). 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 NCT01894815, which also lists 4 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 5 Dec 2016.

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