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

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ClinicalTrials.gov Identifier: NCT01894815
Recruitment Status : Completed
First Posted : July 10, 2013
Last Update Posted : December 5, 2016
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

Tracking Information
First Submitted Date  ICMJE July 3, 2013
First Posted Date  ICMJE July 10, 2013
Last Update Posted Date December 5, 2016
Study Start Date  ICMJE October 2013
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 22, 2016)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 9, 2013)
Changes in Hamilton Rating Scale for Depression, 17 items (HAMD17) [ Time Frame: Weeks 0, 3 and 10 ]
Continuous measure (score changes).
Change History Complete list of historical versions of study NCT01894815 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2016)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2013)
  • Change in Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Weeks 0, 3, 10 ]
    Continuous measure (score changes).
  • Change in Beck Depression Inventory (BDI) [ Time Frame: Weeks 0, 3, 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Escitalopram, Placebo and tDCS in Depression: a Non-inferiority Trial
Official Title  ICMJE Escitalopram and Transcranial Direct Current Stimulation in Major Depressive Disorder: a Double-blind, Placebo-controlled, Randomized, Non-inferiority Trial
Brief 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). 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Major Depressive Disorder
  • Major Depressive Disorder, Recurrent, Unspecified
  • Major Depressive Disorder, Single Episode, Unspecified
Intervention  ICMJE
  • 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
  • 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
  • Other: Sham tDCS + Placebo Pill
    This group receives sham tDCS and placebo pill.
Study Arms  ICMJE
  • Experimental: Active tDCS / placebo pill
    transcranial direct current stimulation, using the parameters specified in Interventions.
    Intervention: Device: transcranial direct current stimulation
  • Active Comparator: Sham tDCS / escitalopram
    Escitalopram oxalate (Reconter), 10mg/day (first 3 weeks) and 20mg/day (week 3 to week 10).
    Intervention: Drug: Escitalopram oxalate
  • 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.

    Intervention: Other: Sham tDCS + Placebo Pill
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 25, 2016)
245
Original Estimated Enrollment  ICMJE
 (submitted: July 9, 2013)
240
Actual Study Completion Date  ICMJE November 2016
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01894815
Other Study ID Numbers  ICMJE ELECT-TDCS
FAPESP 2012/20911-5 ( Other Grant/Funding Number: FAPESP 2012/20911-5 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Andre Brunoni, University of Sao Paulo
Study Sponsor  ICMJE University of Sao Paulo
Collaborators  ICMJE
  • Fundação de Amparo à Pesquisa do Estado de São Paulo
  • Brain & Behavior Research Foundation
Investigators  ICMJE
Principal Investigator: Andre R Brunoni, MD, PhD University of Sao Paulo
PRS Account University of Sao Paulo
Verification Date December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP