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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
3
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).
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).
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).
UCSD Interventional Psychiatry
San Diego, California, United States
Feasibility (Recruitment)
Recruitment rate will be measured as the number of patients enrolled by the conclusion of the study, reported as a whole number.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: From baseline clinical assessment prior to treatment, to 6 weeks after first treatment.
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.
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: From baseline clinical assessment prior to treatment, to 6 weeks after first treatment.
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