Escitalopram, Placebo and tDCS in Depression: a Non-inferiority Trial (ELECT-TDCS)

December 1, 2016 updated by: Andre Brunoni, University of Sao Paulo

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
245

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • São Paulo, Brazil, 05508-000
        • Hospital Universitário, Universidade de São Paulo
    • SP
      • São Paulo, SP, Brazil
        • Institute of Psychiatry, HC-FMUSP

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • 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).
  • 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Active tDCS / placebo pill
transcranial direct current stimulation, using the parameters specified in Interventions.
Device: transcranial direct current stimulation
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.
Other Names:
  • tDCS - Soterix Medical Device for Clinical Trials
Active Comparator: Sham tDCS / escitalopram
Escitalopram oxalate (Reconter), 10mg/day (first 3 weeks) and 20mg/day (week 3 to week 10).
Drug: Escitalopram oxalate
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.
Other Names:
  • Reconter
Placebo Comparator: Sham tDCS / placebo pill

For 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.
Other: Sham tDCS + Placebo Pill
This group receives sham tDCS and placebo pill.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes in Hamilton Rating Scale for Depression, 17 items (HAMD17)
Time Frame: Weeks 0 and 10
Continuous measure (score changes). Non-inferiority assessment: the difference between tDCS to escitalopram should be >50% of escitalopram to placebo efficacy.
Weeks 0 and 10

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in HDRS
Time Frame: Weeks 0, 3, 6, 8, 10
Continuous measure (score changes).
Weeks 0, 3, 6, 8, 10
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: Weeks 0, 3, 6, 10
Continuous measure (score changes).
Weeks 0, 3, 6, 10
Change in Beck Depression Inventory (BDI)
Time Frame: Weeks 0, 3, 6, 10
Weeks 0, 3, 6, 10
Change in Positive and Negative Affect Scale (PANAS)
Time Frame: Weeks 0, 3, 6, 10
Weeks 0, 3, 6, 10
Change in State-Trait Anxiety Inventory (STAI)
Time Frame: Weeks 0, 3, 6, 10
Weeks 0, 3, 6, 10
Hamilton Rating Scale for Depression, 17 items (HAMD17)
Time Frame: Week 10
Response (≥50% improvement from week 0 to 10)
Week 10
Hamilton Rating Scale for Depression, 17 items (HAMD17)
Time Frame: Week 10
Remission (HAMD17 ≤7) at week 10.
Week 10
Adverse events
Time Frame: Week 3 and Week 10.
Assessment and comparisons of tDCS and drug adverse events. We used a tDCS adverse events questionnaire (Brunoni et al., 2011) and the SAFTEE.
Week 3 and Week 10.
Serious adverse events
Time Frame: Up to Week 10.
Serious adverse events include treatment-emergent hypomania/mania (YMRS>8), suicide, psychiatric hospitalization and others life-threatening or incapacitant events.
Up to Week 10.
Young Manic Rating Scale (YMRS)
Time Frame: Week 3 and Week 10.
Assessment of treatment-emergent hypomania/mania, defined as YRMS>8.
Week 3 and Week 10.
Predictor of response
Time Frame: Week 10
Age (years)
Week 10
Predictor of response
Time Frame: Week 10
Gender
Week 10
Predictor of response
Time Frame: Week 10
Low wage (less than 5 monthly wages in Brazil)
Week 10
Predictor of response
Time Frame: Week 10
Recurrent depression
Week 10
Predictor of response
Time Frame: Week 10
Chronic depression
Week 10
Predictor of response
Time Frame: Week 10
Refractory depression
Week 10
Predictor of response
Time Frame: Week 10
Severe depression
Week 10
Predictor of response
Time Frame: Week 10
Benzodiazepine use
Week 10
Predictor of response
Time Frame: Week 10
Higher education (>15 years of schooling)
Week 10
Predictor of response
Time Frame: Week 10
Age of onset of the depressive episode (years)
Week 10
Predictor of response
Time Frame: Week 10
Any anxiety disorder
Week 10
Predictor of response
Time Frame: Week 10
Physical activity
Week 10
Predictor of response
Time Frame: Week 10
melancholic depression
Week 10
Predictor of response
Time Frame: Week 10
atypical depression
Week 10
Predictor of response
Time Frame: Week 10
smoking status
Week 10
Predictor of response
Time Frame: Week 10
hypertension
Week 10
Predictor of response
Time Frame: Week 10
diabetes mellitus
Week 10
Predictor of response
Time Frame: Week 10
ethnicity
Week 10
Predictor of response
Time Frame: Week 10
marital status
Week 10
Predictor of response
Time Frame: Week 10
employment status
Week 10
Predictor of response
Time Frame: Week 10
obesity
Week 10
Predictor of response
Time Frame: Week 10
familial psychiatry history
Week 10
Predictor of response
Time Frame: Week 10
Temperament and Character Inventory - Novelty seeking
Week 10
Predictor of response
Time Frame: Week 10
Any tDCS related adverse event.
Week 10
Predictor of response
Time Frame: Week 10
Temperament and Character Inventory - Harm avoidance
Week 10
Predictor of response
Time Frame: Week 10
Temperament and Character Inventory - Reward Dependence
Week 10
Predictor of response
Time Frame: Week 10
Temperament and Character Inventory - Persistence
Week 10
Predictor of response
Time Frame: Week 10
Temperament and Character Inventory - Cooperativeness
Week 10
Predictor of response
Time Frame: Week 10
Temperament and Character Inventory - Self-transcendence
Week 10
Predictor of response
Time Frame: Week 10
Temperament and Character Inventory - Self-directedness
Week 10
Predictor of response
Time Frame: Week 10
FAS verbal fluency test
Week 10
Predictor of response
Time Frame: Week 10
Digit span forward
Week 10
Predictor of response
Time Frame: Week 10
Digit span backward
Week 10
Predictor of response
Time Frame: Week 10
Trail Making Test - A
Week 10
Predictor of response
Time Frame: Week 10
Trail Making Test - B
Week 10
Predictor of response
Time Frame: Week 10
Symbol digit
Week 10
Predictor of response
Time Frame: Week 10
Montreal Cognitive Assessment
Week 10
Predictor of response
Time Frame: Week 3 and 10
Motor Cortical Excitability - Cortical silent period (left and right hemispheres)
Week 3 and 10
Predictor of response
Time Frame: Week 3 and 10
Motor Cortical Excitability - Intracortical inhibition (left and right hemispheres)
Week 3 and 10
Predictor of response
Time Frame: Week 3 and 10
Motor Cortical Excitability - Intracortical facilitation (left and right hemispheres)
Week 3 and 10
Predictor of response
Time Frame: Week 3 and 10
Heart rate variability - HF
Week 3 and 10
Predictor of response
Time Frame: Week 3 and 10
Heart rate variability - LF
Week 3 and 10
Predictor of response
Time Frame: Week 3 and 10
Heart rate variability - RMSSD
Week 3 and 10

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Sao Paulo

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Fundação de Amparo à Pesquisa do Estado de São Paulo
Brain & Behavior Research Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 3, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 9, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 10, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 5, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ELECT-TDCS
  • FAPESP 2012/20911-5 (Other Grant/Funding Number: FAPESP 2012/20911-5)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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