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

NCT06730841 | Completed DMC FDA Device

• 1 other identifier: 810432
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Treatment Resistant Depression; Major Depressive Disorder

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (8)

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

  From baseline neurophysiological assessment prior to treatment, to during treatment, to 6 weeks after first treatment.

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

  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)

  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

  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

  From baseline neurophysiological assessment prior to treatment, to during treatment, to 6 weeks after first treatment.

Study Arms (3)

DOS-tDCS: A dose-optimized and spaced form of tDCS

ACTIVE COMPARATOR

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

Spaced tDCS: A spaced form of tDCS only

ACTIVE COMPARATOR

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

Sham tDCS

SHAM COMPARATOR

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

Interventions

Dose-Optimized and Spaced Transcranial Direct Current Stimulation DEVICE

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).

Also known as: tDCS, Soterix Medical 1x1 CT

DOS-tDCS: A dose-optimized and spaced form of tDCS

Spaced Transcranial Direct Current Stimulation DEVICE

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).

Also known as: Soterix Medical 1x1 CT

Spaced tDCS: A spaced form of tDCS only

Sham Transcranial Direct Current Stimulation DEVICE

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).

Also known as: Soterix Medical 1x1 CT

Sham tDCS

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• People between the ages of 18 and 85 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 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.
• MADRS score of ≥20 at screening (Visit 1).
• 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, or not receiving treatment for 4 weeks prior to study enrollment and agree to continue this regimen throughout the study period.
• In good general health, as evidenced by medical history.
• 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 child-bearing potential: must take a pregnancy test at the screening visit, with results confirmed as negative by study staff.

You may not qualify if:

• 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:
• Pregnancy;
• 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;
• Chronic depression (defined as of over 5 years duration);
• 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;

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

UCSD Interventional Psychiatry

San Diego, California, 92127, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Study Record Dates

• First Submitted: August 23, 2024
• First Posted: December 12, 2024
• Study Start: September 26, 2024
• Primary Completion: August 1, 2025
• Study Completion: September 1, 2025
• Last Updated: November 20, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)