Portable Transcranial Electrical Stimulation and Internet-Based Behavioral Therapy for Major Depression Study

NCT04889976 | Completed DMC

• 2 other identifiers: 13922419.1.0000.007619/06009-6
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 2

Brief Summary

First-line treatments for major depressive disorder (MDD), antidepressants and psychotherapy, are associated with refractoriness and discontinuation due to side effects, and logistical burdens, respectively. In this scenario, transcranial electrical stimulation (tES) is nowadays considered effective and safe for MDD, albeit with a modest effect size, and also prone to logistical burdens when performed in external facilities. In this regard, clinical investigation involving portable tES (ptES), and the potentiation of ptES with remotely-delivered psychological interventions, have shown positive, but preliminary, results. Here, the investigators present the design and rationale of a single-center, multi-arm, randomized, double-blind, sham-controlled clinical trial with digital features, using ptES (ptES) and internet-based behavioral therapy (iBT) for MDD (PSYLECT). This study will evaluate the efficacy, safety, tolerability and usability of (1) active ptES + active iBT ("double-active"), (2) active ptES + sham iBT ("ptES-only"), and (3) sham ptES + sham iBT ("double-sham"), in adults with MDD, with a Hamilton Depression Rating Scale - 17 item version (HDRS-17) score ≥ 17 at baseline, during 6 weeks. No antidepressant washouts will be performed during the trial. Three co-primary hypotheses are presented: changes in HDRS-17 will be greater in (1) "double-active" compared to "ptES-only", (2) "double-active" compared to "double-sham", and (3) "ptES-only" compared to "double-sham". The investigators aim to enroll 210 patients (70 per arm). The results of this trial should also offer new insights regarding the feasibility and scalability of combined ptES and iBT for MDD, in the area of digital mental health.

Conditions

Major Depressive Disorder; Unipolar Depression

Keywords

major depressive disorder; transcranial electrical stimulation; transcranial direct current stimulation; internet-based behavioral therapy; non-invasive brain stimulation; neuromodulation; home-use transcranial electrical stimulation

Outcome Measures

Primary Outcomes (3)

• Change in Hamilton Depression Rating Scale scores (17-item version) between "double active" and "ptES-only"

  Clinician-administered depression assessment scale. Score range = 0 - 52 (higher scores mean worse outcome).

  Week 0 (baseline) and Week 6.

• Change in Hamilton Depression Rating Scale scores (17-item version) between "double active" and "double-sham"

  Clinician-administered depression assessment scale. Score range = 0 - 52 (higher scores mean worse outcome).

  Week 0 (baseline) and Week 6.

• Change in Hamilton Depression Rating Scale scores (17-item version) between "ptES-only" and "double-sham"

  Clinician-administered depression assessment scale. Score range = 0 - 52 (higher scores mean worse outcome).

  Week 0 (baseline) and Week 6.

Secondary Outcomes (11)

• Change in Hamilton Depression Rating Scale scores (17-item version)

  Weeks 0, 2, 3, 4 and 6.

• Change in Montgomery-Asberg Depression Rating Scale scores (MADRS)

  Weeks 0, 2, 3, 4 and 6.

• Change in Beck Depression Inventory - II scores (BDI - II)

  Weeks 0, 2, 3, 4 and 6.

• Change in Hamilton Anxiety Rating Scale scores (HAM-A)

  Weeks 0, 3 and 6.

• Change in Clinical Global Impression Rating Scale (Severity of Illness) scores (CGI-S)

  Weeks 0 and 6.

Study Arms (3)

Double-active

EXPERIMENTAL

Active portable transcranial electrical stimulation (ptES) and active internet-based behavioral therapy (iBT).

Device: Double Active: Active portable transcranial stimulation (ptES) and active internet-based behavioral therapy (iBT)

ptES-only

ACTIVE COMPARATOR

Active portable transcranial electrical stimulation (ptES) and sham internet-based behavioral therapy (iBT).

Device: ptES-only: Active portable transcranial stimulation (ptES) and sham internet-based behavioral therapy (iBT)

Double-sham

SHAM COMPARATOR

Sham portable transcranial electrical stimulation (ptES) and sham internet-based behavioral therapy (iBT).

Device: Double-sham: Sham portable transcranial stimulation (ptES) and sham internet-based behavioral therapy (iBT)

Interventions

Double Active: Active portable transcranial stimulation (ptES) and active internet-based behavioral therapy (iBT) DEVICE

ptES is delivered by the Flow device (Flow Neuroscience, Malmö, Sweden), consisting of a one-size-fits-all, transcranial direct current stimulation (tDCS) headset with circular electrodes (area = 22.9cm2). The anode is positioned over the left prefrontal cortex, and the cathode over the right prefrontal cortex. Current strength is set at 2mA (current density = 0.087mA/cm2) for 30 minutes, daily for 5 continuous days (with a 2-day pause) for the first 3 weeks, with twice-weekly sessions for the following 3 weeks (total of 21 sessions in 6 weeks). Active iBT consists of a smartphone app with an electronic therapist-avatar. The iBT sessions are delivered concomitantly to the tDCS sessions (the tDCS device connects via bluetooth to the participant's smartphone app).

Double-active

ptES-only: Active portable transcranial stimulation (ptES) and sham internet-based behavioral therapy (iBT) DEVICE

ptES is delivered by the Flow device (Flow Neuroscience, Malmö, Sweden), consisting of a one-size-fits-all, transcranial direct current stimulation (tDCS) headset with circular electrodes (area = 22.9cm2). The anode is positioned over the left prefrontal cortex, and the cathode over the right prefrontal cortex. Current strength is set at 2mA (current density = 0.087mA/cm2) for 30 minutes, daily for 5 continuous days (with a 2-day pause) for the first 3 weeks, with twice-weekly sessions for the following 3 weeks (total of 21 sessions in 6 weeks). The sham iBT sessions are delivered concomitantly to the active ptES sessions (the ptES device connects via bluetooth to the participant's smartphone app).

ptES-only

Double-sham: Sham portable transcranial stimulation (ptES) and sham internet-based behavioral therapy (iBT) DEVICE

Sham ptES for this trial is delivered by the Flow device (Flow Neuroscience, Malmö, Sweden), consisting of a one-size-fits-all transcranial direct current stimulation (tDCS) headset, with circular electrodes (area = 22.9cm2). The anode is positioned over the left prefrontal cortex, and the cathode over the right prefrontal cortex. The sham protocol consists of a fade-in and fade-out phases of 1mA for 45 seconds, followed by a silent period in between for the remaining 28 1/2 minutes. The sham iBT sessions are delivered concomitantly to the sham ptES sessions (the ptES device connects via bluetooth to the participant's smartphone app).

Double-sham

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of major depressive disorder (MDD) per DSM-5 criteria
• Hamilton Rating Scale (17-item version)-HDRS score ≥ 17 at baseline
• Years of education ≥ 8
• Having access to a smartphone with internet access at home
• Treatment refractoriness ≤ 3 antidepressants, at optimal doses and for appropriate duration
• No contraindications for tDCS (i.e., metallic plates on the head, brain devices, cochlear implants, cardiac pacemakers)
• No suicidal ideation with planning, or attempted suicide, in the 4 weeks prior to baseline

You may not qualify if:

• Suspected or confirmed pregnancy
• Lactation
• Severe clinical or neurological conditions, including Post-Acute Sequelae of COVID-19
• Depressive symptoms better explained by other clinical conditions (i.e., hypothyroidism, anemia) or other psychiatric disorders.
• Use of benzodiazepines \> 10mg diazepam or diazepam-equivalent per day

Sponsors & Collaborators

• University of Sao Paulo: lead
• Fundação de Amparo à Pesquisa do Estado de São Paulo: collaborator

Study Sites (2)

Institute of Psychiatry, HC-FMUSP

São Paulo, São Paulo, Brazil

Location

Hospital Universitário - USP

São Paulo, 05508000, Brazil

Location

Related Publications (12)

• Sathappan AV, Luber BM, Lisanby SH. The Dynamic Duo: Combining noninvasive brain stimulation with cognitive interventions. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 8;89:347-360. doi: 10.1016/j.pnpbp.2018.10.006. Epub 2018 Oct 9.

  PMID: 30312634 BACKGROUND

• 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.

  PMID: 28657871 BACKGROUND

• Brunoni AR, Valiengo L, Baccaro A, Zanao TA, de Oliveira JF, Goulart A, Boggio PS, Lotufo PA, Bensenor IM, Fregni F. The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial. JAMA Psychiatry. 2013 Apr;70(4):383-91. doi: 10.1001/2013.jamapsychiatry.32.

  PMID: 23389323 BACKGROUND

• Segrave RA, Arnold S, Hoy K, Fitzgerald PB. Concurrent cognitive control training augments the antidepressant efficacy of tDCS: a pilot study. Brain Stimul. 2014 Mar-Apr;7(2):325-31. doi: 10.1016/j.brs.2013.12.008. Epub 2013 Dec 19.

  PMID: 24486425 BACKGROUND

• Brunoni AR, Boggio PS, De Raedt R, Bensenor IM, Lotufo PA, Namur V, Valiengo LC, Vanderhasselt MA. Cognitive control therapy and transcranial direct current stimulation for depression: a randomized, double-blinded, controlled trial. J Affect Disord. 2014 Jun;162:43-9. doi: 10.1016/j.jad.2014.03.026. Epub 2014 Mar 27.

  PMID: 24767004 BACKGROUND

• Razza LB, Afonso Dos Santos L, Borrione L, Bellini H, Branco LC, Cretaz E, Duarte D, Ferrao Y, Galhardoni R, Quevedo J, Simis M, Fregni F, Correll CU, Padberg F, Trevizol A, Daskalakis ZJ, Carvalho AF, Solmi M, Brunoni AR. Appraising the effectiveness of electrical and magnetic brain stimulation techniques in acute major depressive episodes: an umbrella review of meta-analyses of randomized controlled trials. Braz J Psychiatry. 2021 Sep-Oct;43(5):514-524. doi: 10.1590/1516-4446-2020-1169.

  PMID: 33111776 BACKGROUND

• Borrione L, Suen PJC, Razza LB, Santos LAD, Sudbrack-Oliveira P, Brunoni AR. The Flow brain stimulation headset for the treatment of depression: overview of its safety, efficacy and portable design. Expert Rev Med Devices. 2020 Sep;17(9):867-878. doi: 10.1080/17434440.2020.1813565. Epub 2020 Sep 7.

  PMID: 32820677 BACKGROUND

• Charvet LE, Shaw MT, Bikson M, Woods AJ, Knotkova H. Supervised transcranial direct current stimulation (tDCS) at home: A guide for clinical research and practice. Brain Stimul. 2020 May-Jun;13(3):686-693. doi: 10.1016/j.brs.2020.02.011. Epub 2020 Feb 10.

  PMID: 32289698 BACKGROUND

• Alonzo A, Fong J, Ball N, Martin D, Chand N, Loo C. Pilot trial of home-administered transcranial direct current stimulation for the treatment of depression. J Affect Disord. 2019 Jun 1;252:475-483. doi: 10.1016/j.jad.2019.04.041. Epub 2019 Apr 10.

  PMID: 31005790 BACKGROUND

• Brunoni AR, Sampaio-Junior B, Moffa AH, Aparicio LV, Gordon P, Klein I, Rios RM, Razza LB, Loo C, Padberg F, Valiengo L. Noninvasive brain stimulation in psychiatric disorders: a primer. Braz J Psychiatry. 2019 Jan-Feb;41(1):70-81. doi: 10.1590/1516-4446-2017-0018. Epub 2018 Oct 11.

  PMID: 30328957 BACKGROUND

• Borrione L, Cavendish BA, Aparicio LVM, Luethi MS, Goerigk S, Ramos MRF, Moran NKS, Carneiro AM, Valiengo L, Moura DO, de Souza JP, Batista MP, Aparecida da Silva V, Klein I, Suen P, Gallucci-Neto J, Padberg F, Razza LB, Vanderhasselt MA, Lotufo PA, Bensenor IM, Fregni F, Brunoni AR. Home-Use Transcranial Direct Current Stimulation for the Treatment of a Major Depressive Episode: A Randomized Clinical Trial. JAMA Psychiatry. 2024 Apr 1;81(4):329-337. doi: 10.1001/jamapsychiatry.2023.4948.

  PMID: 38170541 DERIVED

• Borrione L, Cirillo PC, Aparicio LV, Cavendish BA, Valiengo L, Moura DO, de Souza JP, Luethi MS, Klein I, Bariani B, Gallucci-Neto J, Suen P, Padberg F, Goerigk S, Vanderhasselt MA, De Deng Z, O'Shea J, Lotufo PA, Bensenor IM, Brunoni AR. A study protocol for an ongoing multi-arm, randomized, double-blind, sham-controlled clinical trial with digital features, using portable transcranial electrical stimulation and internet-based behavioral therapy for major depression disorders: The PSYLECT study. Expert Rev Neurother. 2022 Jun;22(6):513-523. doi: 10.1080/14737175.2022.2083959. Epub 2022 Jun 8.

  PMID: 35642516 DERIVED

Related Links

• Information site of the Interdisciplinary Service of Neuromodulation Department of the Institute of Psychiatry of the University of Sao Paulo Medical School (research and assistance)

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Study Officials

• Andre R Brunoni, MD, PhD

  University of Sao Paulo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The iBT intervention is performed concomitantly to the ptES session, and consists of an app-based interactive protocol (with a chatbot and online videos), synchronized via bluetooth, to the ptES device. For PSYLECT, the chatbot iBT protocol has been translated from English to Portuguese, and all iBT videos are either presented with Portuguese subtitles, or in the case of meditation videos (which allow participants to close their eyes), have been dubbed to Portuguese. Further details about active and sham iBT sessions are not described in this platform to avoid breaking the blinding of future participants enrolled in this study, with means of access to this platform. The complete details will be provided when the study results are published or upon reasonable request.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of the Medical School of the University of Sao Paulo (FMUSP), Principal Investigator

Model Details: This is a multi-arm, randomized, double-blind, sham-controlled clinical trial with digital features, using portable transcranial electrical stimulation (ptES) and internet-based behavioral therapy (iBT) for major depressive disorder (MDD). The aims of this study are to evaluate the efficacy, safety, tolerability and usability of (1) active ptES + active iBT ("double-active"), (2) active ptES + sham iBT ("ptES-only"), and (3) sham ptES + sham iBT ("double-sham"), in adults with MDD, with a Hamilton Depression Rating Scale - 17 item version (HDRS-17) score ≥ 17 at baseline, during 6 weeks.

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 17, 2021
• Study Start: May 22, 2021
• Primary Completion: October 21, 2022
• Study Completion: October 21, 2022
• Last Updated: November 1, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

BR (2)