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

September 16, 2026 updated by: Jean-Philippe Miron, University of California, San Diego

Spaced Transcranial Direct Current Stimulation for Treatment-Resistant Depression: A Home-Based Randomized Sham-Controlled Trial and Mechanistic Exploration

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

74

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92127
        • UCSD Interventional Psychiatry
        • Contact:
        • Contact:
          • UCSD Interventional Psychiatry Clinic
          • Phone Number: 858-207-0938

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Unstable symptoms between screening and baseline as defined by a ≥ 30% change in MADRS score.
  • Require a benzodiazepine with a dose > lorazepam 2 mg/day
  • Has started a new psychotherapeutic process in the past 3 months from screening.
  • Use of potentially irritant topical treatments (ex: retinoids, alpha hydroxy acids).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active spaced-tDCS

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)

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).
Sham Comparator: Sham spaced-tDCS

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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Active vs Sham spaced tDCS Efficacy as measured by the Montgomery-Åsberg Depression Rating Scale
Time Frame: Baseline to 4-weeks post treatment

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in MADRS with active versus sham spaced tDCS during all post treatment visits
Time Frame: 1-week post treatment to 10-week post treatment

Clinical outcomes associated with active versus sham spaced tDCS as measured by MADRS response (≥50% reduction) and remission (score ≤10) rates.
1-week post treatment to 10-week post treatment
Changes in Hamilton Depression Rating Scale, 17-item version scores
Time Frame: 1-week post treatment to 10-week post treatment

Reduction in HAMD-17 scores at all follow-up timepoints. Score range from 0 to 52.
1-week post treatment to 10-week post treatment
Changes in Patient Health Questionnaire-9
Time Frame: 1-week post treatment to 10-week post treatment

Changes in PHQ scores at all follow-up timepoints. With scores ranging from 0-27
1-week post treatment to 10-week post treatment
Changes in General Anxiety Disorder-7
Time Frame: 1-week post treatment to 10-week post treatment

Changes in GAD-7 scores at all follow-up timepoints. Score range from 0-21
1-week post treatment to 10-week post treatment
Changes in The Modified Scale for Suicidal Ideation
Time Frame: 1-week post treatment to 10-week post treatment

Changes in the presence and severity of suicidal thoughts at all follow-up timepoints. Scores ranging from 0-54
1-week post treatment to 10-week post treatment
Feasibility (Recruitment)
Time Frame: Baseline clinical assessment to 10 weeks post treatment.

Recruitment rate will be measured as the number of patients enrolled by the conclusion of the study, reported as a whole number.
Baseline clinical assessment to 10 weeks post treatment.
Feasibility (Retention)
Time Frame: Baseline clinical assessment to 10 weeks post treatment.

Retention rate will be measured as the percentage of enrolled patients who complete all study visits, reported as a percentage.
Baseline clinical assessment to 10 weeks post treatment.
Feasibility (Adherence)
Time Frame: Baseline clinical assessment to 10 weeks post treatment

The proportion of completed sessions relative to the total prescribed sessions, expressed as a percentage.
Baseline clinical assessment to 10 weeks post treatment
Safety of at-home spaced tDCS
Time Frame: Baseline clinical assessment to 10 weeks post treatment

Safety will be measured by the number of serious adverse events (SAEs)
Baseline clinical assessment to 10 weeks post treatment
Tolerability to spaced tDCS
Time Frame: Baseline clinical assessment to 10 weeks post treatment.

Tolerability will be measured by the number of adverse events (AEs).
Baseline clinical assessment to 10 weeks post treatment.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biomarker Discovery: Short-Interval Intracortical Inhibition (SICI) and Long-Interval Intracortical Inhibition (LICI) via TMS-EMG
Time Frame: Baseline to 4-weeks post treatment

TMS-EMG will be used to evaluate changes in SICI and LICI.
Baseline to 4-weeks post treatment
Biomarker Discovery: Intracortical Facilitation (ICF) via TMS-EMG
Time Frame: Baseline to 4-weeks post treatment

TMS-EMG will be used to evaluate changes in intracortical facilitation
Baseline to 4-weeks post treatment
Biomarker Discovery: Cortical Silent Period (CSP) via Transcranial Magnetic Stimulation-Electromyography (TMS-EMG)
Time Frame: Baseline to 4-weeks post treatment

TMS-EMG will be used to assess changes in the cortical silent period (CSP). Unit of Measurement: Duration (milliseconds).
Baseline to 4-weeks post treatment
TMS-Evoked Potential (TEP) Component Amplitudes via TMS-EEG
Time Frame: Baseline to 4-weeks post treatment

TMS-EEG will be used to evaluate changes in TMS-evoked potential (TEP) component amplitudes.

Unit of Measurement: Voltage (µV).
Baseline to 4-weeks post treatment
Resting-State Electroencephalography (rsEEG)
Time Frame: Baseline to 4-weeks post treatment

rsEEG will be used to analyze changes in brain activity patterns at rest. Unit of Measurement: Frequency (Hz)
Baseline to 4-weeks post treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Diego

Collaborators

National Institute of Mental Health (NIMH)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 15, 2026

Primary Completion (Estimated)

October 15, 2031

Study Completion (Estimated)

October 15, 2031

Study Registration Dates

First Submitted

September 10, 2026

First Submitted That Met QC Criteria

September 16, 2026

First Posted (Actual)

September 22, 2026

Study Record Updates

Last Update Posted (Actual)

September 22, 2026

Last Update Submitted That Met QC Criteria

September 16, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 814732
  • 1K23MH144148-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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