Dose-Optimized and Spaced Transcranial Direct Current Stimulation for Treatment-Resistant Depression (DOS)

This study aims to evaluate the feasibility, safety, and tolerability of an innovative approach to treating Major Depressive Disorder (MDD), particularly in cases where patients have not responded well to traditional therapies. Specifically, the objective is to evaluate the antidepressant effects of a Dose-Optimized and Spaced Transcranial Direct Current Stimulation (DOS-tDCS) protocol in participants with treatment-resistant depression (TRD) compared to spaced tDCS only and sham tDCS in a 3-arm randomized controlled trial (RCT). The proposed method involves applying low-intensity electrical currents through the scalp in a manner that is both more intense and more frequently spaced than standard treatments. This approach is hypothesized to lead to a significant reduction in depressive symptoms. Participants in the study will be randomly assigned to one of three groups: the experimental group receiving the DOS-tDCS treatment, a group receiving spaced tDCS only, or a control group receiving a sham (placebo) treatment. Outcomes will be measured over a period of six weeks. The study's goal is to offer a potentially more accessible and effective treatment option for individuals who have not benefited from existing MDD therapies.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder; Treatment Resistant Depression
• Intervention / Treatment: Device: Dose-Optimized and Spaced Transcranial Direct Current Stimulation; Device: Spaced Transcranial Direct Current Stimulation; Device: Sham Transcranial Direct Current Stimulation

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92127
      • UCSD Interventional Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. People between the ages of 18 and 85 at the time of screening.
2. 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.
3. 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).
4. Medical records confirming a history of at least moderate treatment-resistance as defined an 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.
5. MADRS score of ≥20 at screening (Visit 1).
6. Existing relationship with mental health provider and access to ongoing psychiatric care before and after completion of the study.
7. Must be on a stable antidepressant therapeutic regimen, or not receiving treatment for 4 weeks prior to study enrollment and agree to continue this regimen throughout the study period.
8. In good general health, as evidenced by medical history.
9. 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.
10. Agreement to adhere to Lifestyle Considerations (i.e. must continue with any existing treatments) throughout study duration.
11. For persons of child-bearing potential: must take a pregnancy test at the screening visit, with results confirmed as negative by study staff.

Exclusion Criteria:

An individual will be excluded from participation in this study if they meet any of the following criteria, as determined from a review of medical records prior to screening or at the screening visit:

1. Pregnancy;
2. History of psychotic or bipolar disorder or depression with psychotic features;
3. Significant borderline personality disorder;
4. Significant comorbid obsessive-compulsive or post-traumatic stress disorder;
5. Previously diagnosed Intellectual Disability or Autism Spectrum Disorder;
6. Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal;
7. Clinically significant suicidality;
8. Any history of tDCS;
9. Any history of ECT;
10. History of TMS (greater than 15 sessions) without a clinically meaningful response.
11. History of ketamine (greater than 4 sessions) without a clinically meaningful response;
12. Chronic depression (defined as of over 5 years duration);
13. 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;
14. Untreated or insufficiently treated endocrine disorder;
15. Contraindication to receiving tDCS (e.g., ferromagnetic implant, history of seizure, known brain lesion);
16. Treatment with an investigational drug or other intervention within the study period;
17. Unstable symptoms between screening and baseline as defined by a ≥ 30% change in MADRS score;
18. Require a benzodiazepine with a dose > lorazepam 2 mg/day
19. Has started a new psychotherapeutic process in the past 3 months from screening;
20. Use of potentially irritant topical treatments (ex: retinoids, alpha hydroxy acids)
21. Aesthetic procedure the area of the forehead directly below the stimulation area within the last 6 months (laser, fillers, surgery, etc.)
22. Any active dermatological condition on face or scalp that would in the opinion of the PI represent a contraindication to the treatment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: DOS-tDCS: A dose-optimized and spaced form of tDCS; On each treatment day, participants will receive 5 tDCS sessions, each lasting 20 minutes, with a 20-minute intersession interval. The dose-optimized and spaced tDCS (DOS-tDCS) group will be treated using a stimulation intensity of up to 4 mA.	Device: Dose-Optimized and Spaced Transcranial Direct Current Stimulation; tDCS, a non-invasive neuromodulation technique that applies low-intensity, direct electrical stimulation to the cortex via scalp electrodes, has been extensively researched as a potential treatment for MDD. tDCS enhances neuroplasticity, which is theorized to be responsible for its therapeutic effects and has been presented as a cost-effective solution for MDD. Preclinical evidence supports the potential advantage of spaced stimulation with tDCS to maximally engage neuroplasticity. This group will be treated using a stimulation intensity of up to 4 milliamp (mA). Participants will first complete an acute intensive induction phase consisting of daily treatment every weekday over 2 weeks (10 days total) followed by a consolidation phase consisting of weekly treatments (once a week) over 4 additional weeks (6 weeks total).; Other Names: tDCS; Soterix Medical 1x1 CT
Active Comparator: Spaced tDCS: A spaced form of tDCS only; On each treatment day, participants will receive 5 tDCS sessions, each lasting 20 minutes, with a 20-minute intersession interval. The spaced tDCS only group will receive stimulation at the standard 2 mA dose.	Device: Spaced Transcranial Direct Current Stimulation; tDCS, a non-invasive neuromodulation technique that applies low-intensity, direct electrical stimulation to the cortex via scalp electrodes, has been extensively researched as a potential treatment for MDD. tDCS enhances neuroplasticity, which is theorized to be responsible for its therapeutic effects and has been presented as a cost-effective solution for MDD. Preclinical evidence supports the potential advantage of spaced stimulation with tDCS to maximally engage neuroplasticity. This group will be treated using a stimulation intensity of 2 mA. Participants will first complete an acute intensive induction phase consisting of daily treatment every weekday over 2 weeks (10 days total) followed by a consolidation phase consisting of weekly treatments (once a week) over 4 additional weeks (6 weeks total).; Other Names: Soterix Medical 1x1 CT
Sham Comparator: Sham tDCS; On each treatment day, participants will receive 5 sham tDCS sessions, each lasting 20 minutes, with a 20-minute intersession interval.	Device: Sham Transcranial Direct Current Stimulation; tDCS, a non-invasive neuromodulation technique that applies low-intensity, direct electrical stimulation to the cortex via scalp electrodes, has been extensively researched as a potential treatment for MDD. tDCS enhances neuroplasticity, which is theorized to be responsible for its therapeutic effects and has been presented as a cost-effective solution for MDD. This group will be treated using sham stimulation. Participants will first complete an acute intensive induction phase consisting of daily treatment every weekday over 2 weeks (10 days total) followed by a consolidation phase consisting of weekly treatments (once a week) over 4 additional weeks (6 weeks total).; Other Names: Soterix Medical 1x1 CT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility (Recruitment)	Recruitment rate will be measured as the number of patients enrolled by the conclusion of the study, reported as a whole number.	From baseline clinical assessment prior to treatment, to 6 weeks after first treatment.
Feasibility (Retention)	Retention rate will be measured as the percentage of enrolled patients who complete all study visits, reported as a percentage.	From baseline clinical assessment prior to treatment, to 6 weeks after first treatment.
Feasibility (Adherence)	The proportion of completed sessions relative to the total prescribed sessions, expressed as a percentage.	From baseline clinical assessment prior to treatment, to 6 weeks after first treatment.
Safety	Safety will be measured by the number of serious adverse events (SAEs).	From baseline clinical assessment prior to treatment, to 6 weeks after first treatment.
Tolerability	Tolerability will be measured by the number of adverse events (AEs).	From baseline clinical assessment prior to treatment, to 6 weeks after first treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker Discovery: Short-Interval Intracortical Inhibition (SICI) via TMS-EMG	TMS-EMG will be used to evaluate changes in SICI. Unit of Measurement: Amplitude or percentage inhibition.	From baseline neurophysiological assessment prior to treatment, to during treatment, to 6 weeks after first treatment.
Biomarker Discovery: Intracortical Facilitation (ICF) via TMS-EMG	TMS-EMG will be used to evaluate changes in intracortical facilitation Unit of Measurement: Amplitude or percentage facilitation.	From baseline neurophysiological assessment prior to treatment, to during treatment, to 6 weeks after first treatment.
Biomarker Discovery: Cortical Silent Period (CSP) via Transcranial Magnetic Stimulation-Electromyography (TMS-EMG)	TMS-EMG will be used to assess changes in the cortical silent period (CSP). Unit of Measurement: Duration (milliseconds).	From baseline neurophysiological assessment prior to treatment, to during treatment, to 6 weeks after first treatment.
Biomarker Discovery: TMS-Evoked Potential (TEP) Component Amplitudes via TMS-EEG	TMS-EEG will be used to evaluate changes in TMS-evoked potential (TEP) component amplitudes. Unit of Measurement: Voltage (µV).	From baseline neurophysiological assessment prior to treatment, to during treatment, to 6 weeks after first treatment.
Biomarker Discovery: Significant Current Density (SCD) via TMS-EEG	TMS-EEG will be used to evaluate changes in significant current density (SCD). Unit of Measurement: Current density (A/m²).	From baseline neurophysiological assessment prior to treatment, to during treatment, to 6 weeks after first treatment.
Biomarker Discovery: Biomarker Discovery: Significant Current Scattering (SCS) via TMS-EEG	TMS-EEG will be used to evaluate changes in significant current scattering (SCS). Unit of Measurement: Scattering coefficient (unitless).	From baseline neurophysiological assessment prior to treatment, to during treatment, to 6 weeks after first treatment.
Biomarker Discovery: Resting-State Electroencephalography (rsEEG)	rsEEG will be used to analyze changes in brain activity patterns at rest. Unit of Measurement: Frequency (Hz) and amplitude (µV).	From baseline neurophysiological assessment prior to treatment, to during treatment, to 6 weeks after first treatment.
Changes from pre-treatment depressive symptomatology in post-treatment	Changes in depressive symptoms will be assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), which ranges from 0 to 60, with higher scores indicating more severe depression. A decrease in the MADRS score will be interpreted as an improvement in symptoms.	From baseline clinical assessment prior to treatment, to 6 weeks after first treatment.

Collaborators and Investigators

• Sponsor: University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2024
• Primary Completion (Actual): August 1, 2025
• Study Completion (Actual): September 1, 2025

Study Registration Dates

• First Submitted: August 23, 2024
• First Submitted That Met QC Criteria: December 11, 2024
• First Posted (Actual): December 12, 2024

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Therapeutics; Behavioral Disciplines and Activities; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Transcranial Direct Current Stimulation
• Other Study ID Numbers: 810432

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.: No