Home-Based Randomized Trial of Spaced Transcranial Direct Current Stimulation for Treatment-Resistant Depression

NCT07834762 | Not Yet Recruiting DMC FDA Device

• 2 other identifiers: 8147321K23MH144148-01
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the clinical efficacy and neurophysiological mechanisms of home-based spaced tDCS in TRD through a randomized, double-blind, sham-controlled trial conducted under remote supervision. Specifically, this trial will: (1) compare the efficacy of active versus sham spaced tDCS on depressive symptom severity in individuals with TRD and (2) characterize neurophysiological changes associated with spaced tDCS using TMS-EEG, TMS-EMG and resting state EEG.

Conditions

Treatment Resistant Depression (TRD); Major Depressive Disorder (MDD)

Keywords

tDCS; Treatment Resistant Depression; Major Depressive Disorder; MDD; transcranial direct current stimulation

Outcome Measures

Primary Outcomes (1)

• Active vs Sham spaced tDCS Efficacy as measured by the Montgomery-Åsberg Depression Rating Scale

  To compare the efficacy of active versus sham spaced tDCS in reducing depressive symptom severity in TRD. Symptom severity will be measured using the MADRS score at four weeks post-treatment.

  Baseline to 4-weeks post treatment

Secondary Outcomes (10)

• Changes in MADRS with active versus sham spaced tDCS during all post treatment visits

  1-week post treatment to 10-week post treatment

• Changes in Hamilton Depression Rating Scale, 17-item version scores

  1-week post treatment to 10-week post treatment

• Changes in Patient Health Questionnaire-9

  1-week post treatment to 10-week post treatment

• Changes in General Anxiety Disorder-7

  1-week post treatment to 10-week post treatment

• Changes in The Modified Scale for Suicidal Ideation

  1-week post treatment to 10-week post treatment

Other Outcomes (5)

• Biomarker Discovery: Short-Interval Intracortical Inhibition (SICI) and Long-Interval Intracortical Inhibition (LICI) via TMS-EMG

  Baseline to 4-weeks post treatment

• Biomarker Discovery: Intracortical Facilitation (ICF) via TMS-EMG

  Baseline to 4-weeks post treatment

• Biomarker Discovery: Cortical Silent Period (CSP) via Transcranial Magnetic Stimulation-Electromyography (TMS-EMG)

  Baseline to 4-weeks post treatment

Study Arms (2)

Active spaced-tDCS

ACTIVE COMPARATOR

Active tDCS applies low-intensity electrical current to the scalp to modulate cortical excitability through subthreshold shifts in neuronal membrane potentials, influencing synaptic plasticity

Device: Spaced Transcranial Direct Current Stimulation (tDCS)

Sham spaced-tDCS

SHAM COMPARATOR

Sham tDCS is a placebo control that simulates the physical sensations of tDCS but does not deliver any actual, prolonged electrical current to the brain.

Device: Sham Spaced tDCS

Interventions

Spaced Transcranial Direct Current Stimulation (tDCS) DEVICE

Spaced-tDCS will be self-administered at home under the supervision of a trained clinical research coordinator using the Soterix Medical mini-CT device with remote monitoring via a secure videoconferencing platform (e.g., Microsoft Teams).

Active spaced-tDCS

Sham Spaced tDCS DEVICE

Soterix Medical mini-CT device sham protocol that match real stimulation parameters will be used.

Sham spaced-tDCS

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• People between the ages of 18 and 70 at the time of screening.
• Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
• Currently diagnosed with Major Depressive Disorder (MDD) and meets criteria for a Major Depressive Episode, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
• Medical records confirming a history of at least moderate treatment-resistance as defined on Antidepressant Treatment History Form (ATHF) score for that antidepressant trial of \> 2 in the current episode OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF score of 1 or 2 on those 2 separate antidepressants) OR have a combination of one failed trial and one not tolerated trial, per the definitions above.
• MADRS score of ≥20 at screening.
• Existing relationship with mental health provider and access to ongoing psychiatric care before and after completion of the study.
• Must be on a stable antidepressant therapeutic regimen for at least 4 weeks prior to study enrollment and agree to continue this regimen throughout the study period. Participants who are not currently on antidepressant treatment are eligible, provided that no discontinuation occurred within the 4 weeks preceding study enrollment.
• For persons of child-bearing potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.
• Agreement to adhere to Lifestyle Considerations (i.e. must continue with any existing treatments) throughout study duration.
• For persons of childbearing potential: must take a pregnancy test prior to initiating treatment, with results confirmed as negative by study staff
• Participants will need to have a stable internet connection and a device compatible with UCSD Microsoft Teams or UCSD Zoom to facilitate remote communication and engagement in study activities.

You may not qualify if:

• Pregnancy this includes breastfeeding or trying to becoming pregnant.
• History of psychotic or bipolar disorder or depression with psychotic features.
• Significant borderline personality disorder.
• Significant comorbid obsessive-compulsive or post-traumatic stress disorder.
• Previously diagnosed Intellectual Disability or Autism Spectrum Disorder.
• Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal.
• Clinically significant suicidality.
• Any history of tDCS.
• Any history of ECT.
• History of TMS (greater than 15 sessions) without a clinically meaningful response.
• History of ketamine (greater than 4 sessions) without a clinically meaningful response.
• History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma with persistent symptoms.
• Untreated or insufficiently treated endocrine disorder.
• Contraindication to receiving tDCS (e.g., ferromagnetic implant, history of seizure, known brain lesion).
• Treatment with an investigational drug or other intervention within the study period.

Sponsors & Collaborators

• University of California, San Diego: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

UCSD Interventional Psychiatry

San Diego, California, 92127, United States

Location

Related Publications (4)

• Tremblay S, Rogasch NC, Premoli I, Blumberger DM, Casarotto S, Chen R, Di Lazzaro V, Farzan F, Ferrarelli F, Fitzgerald PB, Hui J, Ilmoniemi RJ, Kimiskidis VK, Kugiumtzis D, Lioumis P, Pascual-Leone A, Pellicciari MC, Rajji T, Thut G, Zomorrodi R, Ziemann U, Daskalakis ZJ. Clinical utility and prospective of TMS-EEG. Clin Neurophysiol. 2019 May;130(5):802-844. doi: 10.1016/j.clinph.2019.01.001. Epub 2019 Jan 19.

  PMID: 30772238 BACKGROUND

• Woodham RD, Rimmer RM, Young AH, Fu CHY. Adjunctive home-based transcranial direct current stimulation treatment for major depression with real-time remote supervision: An open-label, single-arm feasibility study with long term outcomes. J Psychiatr Res. 2022 Sep;153:197-205. doi: 10.1016/j.jpsychires.2022.07.026. Epub 2022 Jul 8.

  PMID: 35839661 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 BACKGROUND

• Woodham RD, Selvaraj S, Lajmi N, Hobday H, Sheehan G, Ghazi-Noori AR, Lagerberg PJ, Rizvi M, Kwon SS, Orhii P, Maislin D, Hernandez L, Machado-Vieira R, Soares JC, Young AH, Fu CHY. Home-based transcranial direct current stimulation treatment for major depressive disorder: a fully remote phase 2 randomized sham-controlled trial. Nat Med. 2025 Jan;31(1):87-95. doi: 10.1038/s41591-024-03305-y. Epub 2024 Oct 21.

  PMID: 39433921 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Central Study Contacts

Interventional Psychiatry

CONTACT

858-657-6149; iptrials@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: tDCS operators, study raters, and clinicians remain blinded throughout the trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 10, 2026
• First Posted: September 22, 2026
• Study Start (Estimated): October 15, 2026
• Primary Completion (Estimated): October 15, 2031
• Study Completion (Estimated): October 15, 2031
• Last Updated: September 22, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)