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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Sao Paulo
Sponsor:
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
Andre Brunoni, University of Sao Paulo
ClinicalTrials.gov Identifier:
NCT01894815
First received: July 3, 2013
Last updated: August 13, 2014
Last verified: August 2014
  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
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 University of Sao Paulo:

Primary Outcome Measures:
  • Change in Hamilton Rating Scale for Depression, 17 items (HAMD17) [ Time Frame: Weeks 0, 3 and 10 ] [ Designated as safety issue: No ]
    Continuous measure (score changes).


Secondary Outcome Measures:
  • Change in Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Weeks 0, 3, 10 ] [ Designated as safety issue: No ]
    Continuous measure (score changes).

  • Change in Beck Depression Inventory (BDI) [ Time Frame: Weeks 0, 3, 10 ] [ Designated as safety issue: No ]
  • Hamilton Rating Scale for Depression, 17 items (HAMD17) [ Time Frame: Week 10 ] [ Designated as safety issue: No ]
    Response (≥50% improvement from week 0 to 10)

  • Hamilton Rating Scale for Depression, 17 items (HAMD17) [ Time Frame: Week 10 ] [ Designated as safety issue: No ]
    Remission (HAMD17 ≤7) at week 10.


Estimated Enrollment: 240
Study Start Date: October 2013
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: October 2017 (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, up-titrated from 5mg/day to 10mg/day, and then to 20mg/day, along two weeks.
Drug: Escitalopram oxalate
The investigators will use 5mg, 10mg and 20mg pills. The investigators will up-titrate escitalopram from 5 to 20mg/day according to the patient tolerability. The maximum dose (20mg/day) is sought to be achieved at week 2.
Other Names:
  • Lexapro
  • Cipralex
  • Reconter
  • Exodus
  • Escitalopram
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.


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
Genders Eligible for Study:   Both
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.

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

Contacts
Contact: Andre R Brunoni, MD, PhD brunowsky@gmail.com
Contact: Cibele Soares, MS pesquisacientificahu@gmail.com

Locations
Brazil
Hospital Universitário, Universidade de São Paulo Recruiting
São Paulo, Brazil, 05508-000
Contact: Cibele Soares, MS       pesquisacientificahu@gmail.com   
Principal Investigator: Andre R Brunoni, MD, PhD         
Sponsors and Collaborators
University of Sao Paulo
Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
Principal Investigator: Andre R Brunoni, MD, PhD University of Sao Paulo
  More Information

Additional Information:
No publications provided

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
Study First Received: July 3, 2013
Last Updated: August 13, 2014
Health Authority: Brazil: National Committee of Ethics in Research

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

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

ClinicalTrials.gov processed this record on August 28, 2014