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

This study has been completed.
Sponsor:
Collaborators:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Brain & Behavior Research Foundation
Information provided by (Responsible Party):
Andre Brunoni, University of Sao Paulo
ClinicalTrials.gov Identifier:
NCT01894815
First received: July 3, 2013
Last updated: December 1, 2016
Last verified: December 2016
  Purpose
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.

Condition Intervention Phase
Major Depressive Disorder Major Depressive Disorder, Recurrent, Unspecified Major Depressive Disorder, Single Episode, Unspecified Drug: Escitalopram oxalate Device: transcranial direct current stimulation Other: Sham tDCS + Placebo Pill Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Escitalopram and Transcranial Direct Current Stimulation in Major Depressive Disorder: a Double-blind, Placebo-controlled, Randomized, Non-inferiority Trial

Resource links provided by NLM:


Further study details as provided by Andre Brunoni, University of Sao Paulo:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • Change in HDRS [ Time Frame: Weeks 0, 3, 6, 8, 10 ]
    Continuous measure (score changes).

  • Change in Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Weeks 0, 3, 6, 10 ]
    Continuous measure (score changes).

  • Change in Beck Depression Inventory (BDI) [ Time Frame: Weeks 0, 3, 6, 10 ]
  • Change in Positive and Negative Affect Scale (PANAS) [ Time Frame: Weeks 0, 3, 6, 10 ]
  • Change in State-Trait Anxiety Inventory (STAI) [ Time Frame: 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)

  • Hamilton Rating Scale for Depression, 17 items (HAMD17) [ Time Frame: Week 10 ]
    Remission (HAMD17 ≤7) at 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.

  • 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.

  • Young Manic Rating Scale (YMRS) [ Time Frame: Week 3 and Week 10. ]
    Assessment of treatment-emergent hypomania/mania, defined as YRMS>8.

  • Predictor of response [ Time Frame: Week 10 ]
    Age (years)

  • Predictor of response [ Time Frame: Week 10 ]
    Gender

  • Predictor of response [ Time Frame: Week 10 ]
    Low wage (less than 5 monthly wages in Brazil)

  • Predictor of response [ Time Frame: Week 10 ]
    Recurrent depression

  • Predictor of response [ Time Frame: Week 10 ]
    Chronic depression

  • Predictor of response [ Time Frame: Week 10 ]
    Refractory depression

  • Predictor of response [ Time Frame: Week 10 ]
    Severe depression

  • Predictor of response [ Time Frame: Week 10 ]
    Benzodiazepine use

  • Predictor of response [ Time Frame: Week 10 ]
    Higher education (>15 years of schooling)

  • Predictor of response [ Time Frame: Week 10 ]
    Age of onset of the depressive episode (years)

  • Predictor of response [ Time Frame: Week 10 ]
    Any anxiety disorder

  • Predictor of response [ Time Frame: Week 10 ]
    Physical activity

  • Predictor of response [ Time Frame: Week 10 ]
    melancholic depression

  • Predictor of response [ Time Frame: Week 10 ]
    atypical depression

  • Predictor of response [ Time Frame: Week 10 ]
    smoking status

  • Predictor of response [ Time Frame: Week 10 ]
    hypertension

  • Predictor of response [ Time Frame: Week 10 ]
    diabetes mellitus

  • Predictor of response [ Time Frame: Week 10 ]
    ethnicity

  • Predictor of response [ Time Frame: Week 10 ]
    marital status

  • Predictor of response [ Time Frame: Week 10 ]
    employment status

  • Predictor of response [ Time Frame: Week 10 ]
    obesity

  • Predictor of response [ Time Frame: Week 10 ]
    familial psychiatry history

  • Predictor of response [ Time Frame: Week 10 ]
    Temperament and Character Inventory - Novelty seeking

  • Predictor of response [ Time Frame: Week 10 ]
    Any tDCS related adverse event.

  • Predictor of response [ Time Frame: Week 10 ]
    Temperament and Character Inventory - Harm avoidance

  • Predictor of response [ Time Frame: Week 10 ]
    Temperament and Character Inventory - Reward Dependence

  • Predictor of response [ Time Frame: Week 10 ]
    Temperament and Character Inventory - Persistence

  • Predictor of response [ Time Frame: Week 10 ]
    Temperament and Character Inventory - Cooperativeness

  • Predictor of response [ Time Frame: Week 10 ]
    Temperament and Character Inventory - Self-transcendence

  • Predictor of response [ Time Frame: Week 10 ]
    Temperament and Character Inventory - Self-directedness

  • Predictor of response [ Time Frame: Week 10 ]
    FAS verbal fluency test

  • Predictor of response [ Time Frame: Week 10 ]
    Digit span forward

  • Predictor of response [ Time Frame: Week 10 ]
    Digit span backward

  • Predictor of response [ Time Frame: Week 10 ]
    Trail Making Test - A

  • Predictor of response [ Time Frame: Week 10 ]
    Trail Making Test - B

  • Predictor of response [ Time Frame: Week 10 ]
    Symbol digit

  • Predictor of response [ Time Frame: Week 10 ]
    Montreal Cognitive Assessment

  • Predictor of response [ Time Frame: Week 3 and 10 ]
    Motor Cortical Excitability - Cortical silent period (left and right hemispheres)

  • Predictor of response [ Time Frame: Week 3 and 10 ]
    Motor Cortical Excitability - Intracortical inhibition (left and right hemispheres)

  • Predictor of response [ Time Frame: Week 3 and 10 ]
    Motor Cortical Excitability - Intracortical facilitation (left and right hemispheres)

  • Predictor of response [ Time Frame: Week 3 and 10 ]
    Heart rate variability - HF

  • Predictor of response [ Time Frame: Week 3 and 10 ]
    Heart rate variability - LF

  • Predictor of response [ Time Frame: Week 3 and 10 ]
    Heart rate variability - RMSSD


Enrollment: 245
Study Start Date: October 2013
Study Completion Date: November 2016
Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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.

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.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01894815

Locations
Brazil
Institute of Psychiatry, HC-FMUSP
São Paulo, SP, Brazil
Hospital Universitário, Universidade de São Paulo
São Paulo, Brazil, 05508-000
Sponsors and Collaborators
University of Sao Paulo
Fundação de Amparo à Pesquisa do Estado de São Paulo
Brain & Behavior Research Foundation
Investigators
Principal Investigator: Andre R Brunoni, MD, PhD University of Sao Paulo
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Andre Brunoni, MD, PhD, University of Sao Paulo
ClinicalTrials.gov Identifier: NCT01894815     History of Changes
Other Study ID Numbers: ELECT-TDCS
FAPESP 2012/20911-5 ( Other Grant/Funding Number: FAPESP 2012/20911-5 )
Study First Received: July 3, 2013
Last Updated: December 1, 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Andre Brunoni, University of Sao Paulo:
major depressive disorder
major depression
depressive disorder
major depressive episode

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Disease
Recurrence
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Disease Attributes
Citalopram
Dexetimide
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on August 23, 2017