Transcranial Alternating Current Stimulation for Major Depressive Disorder

Study Overview
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Brief Summary
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Investigating the effects of non-invasive transcranial alternating current stimulation (tACS) on patients with Major Depressive Disorder (MDD).

Detailed Description
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Central Hypothesis: Non-invasive brain stimulation that suppresses alpha oscillation reduces cortical hyperactivity and causes a clinical improvement Aim 1: To conduct a pilot clinical trial to establish feasibility and to collect first effectiveness data for the use of tACS to renormalize pathological alpha oscillations in the dorsolateral prefrontal cortex (dl-pfc) of unmedicated patients with MDD by comparing MADRS scores from baseline and one month follow up. Aim 2: Compare alpha oscillation power from resting state EEG recordings on the first and last day of stimulation. Collect EEG data at the one month follow up visit using this data to analyze alpha frequency activity as a pilot study for derivation of EEG biomarkers.

Official Title
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Pilot Clinical Trial for the Evaluation of Feedback Transcranial Alternating Current Stimulation for the Treatment of Major Depressive Disorder

Conditions
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Major Depressive Disorder, MDD

Intervention / Treatment
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* Device: tACS (alpha)
* Device: tACS (gamma)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18-65 years old Diagnostic and Statistical Manual of Mental Disorder, 4th edition (DSM-IV) diagnosis of MDD; unipolar, non-psychotic Hamilton Depression Rating Scale score >8 Capacity to understand all relevant risks and potential benefits of the study (informed consent) Meet criteria for low suicide risk Willing to comply with all study procedures and be available to do so for the duration of the study Women of reproductive potential must use highly effective contraception Exclusion Criteria: DSM-IV diagnosis of alcohol of substance abuse (other than nicotine) within the last month or a DSM-IV diagnosis of alcohol or substance dependence (other than nicotine) within the last 6 months Current use of benzodiazepines or anti-epileptic drugs Current axis I mood, or psychotic disorder other than major depressive disorder Lifetime comorbid psychiatric bipolar or psychotic disorder Eating disorder (current or within the past 6 months) Obsessive-compulsive disorder (lifetime) Post traumatic stress disorder (PTSD; current or within the last 6 months) Attention Deficit Hyperactivity Disorder (ADHD; currently under treatment) Anything that, in the opinion of the investigator, would place the participant at increased risk or preclude the participant's full compliance with or completion of the study Neurological disorders, including but not limited to history of seizures (except childhood febrile seizures and ECT induced seizures), dementia, history of stroke, Parkinson's disease, multiple sclerosis, cerebral aneurism Medical or neurological illness (unstable cardiac disease, AIDS, malignancy, liver or renal impairment) or treatment for a medical disorder that could interfere with study participation History of traumatic brain injury, reoccurring seizures or later cognitive rehabilitation, or causing cognitive sequelae Prior brain surgery Any brain devices/implants, including cochlear implants and aneurysm clips Co-morbid neurological condition (i.e. seizure disorder, brain tumor) Non English speakers Pregnancy, nursing, or if female and fertile, unwilling to use appropriate birth control measures during study participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tACS (alpha)<br>10 Hz tACS with a peak-to-peak amplitude of 2 milliamps (mA) for 40 minutes. Uses tACS (alpha) device. | Device: tACS (alpha)<br> <br> |
| Experimental: tACS (gamma)<br>40 Hz tACS with a peak-to-peak amplitude of 2 milliamps (mA) for 40 minutes. Uses tACS (gamma) device. | Device: tACS (gamma)<br> <br> |
| Sham Comparator: Sham stimulation<br>Will include 10 seconds of ramp in to 1 minute of 10 Hz tACS with a ramp out of 10 seconds for a total of 80 seconds of stimulation. Uses tACS (alpha) device. | Device: tACS (alpha)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Score | The MADRS is a 10-item scale to measure the severity of depressive episodes, where each item is rated on a scale from 0 to 6. The MADRS total score ranges from 0 to 60 with lower scores indicating less depressive symptoms. This measurement will be taken at baseline (Day 1 of Stimulation), Day 5 of Stimulation, 2 weeks after completion of the intervention (F1), and 4 weeks after completion of the intervention (F2). A comparison of MADRS scores between baseline and F2 is the primary outcome measure (measured as change from baseline). In these results, negative values will indicate a decrease in depressive symptoms. | Baseline to F2 (4 weeks after completion of the intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alpha Oscillation Power From Resting State EEG Recordings on the First and Last Day of Stimulation | The investigators will compare alpha oscillation power from resting state EEG recordings on the first day of stimulation (baseline) and last day of stimulation. The investigators will also collect EEG recordings data at a visit four weeks after completion of the intervention (F2). The investigators will use each of the three EEG recordings as data to analyze alpha frequency activity as a pilot study for derivation of EEG biomarkers. As the stimulation paradigm stimulates the frontal brain regions, the investigators will analyze alpha power change in all brain regions as well as frontal regions. | Baseline to Day 5 of Stimulation | 
| Change in Alpha Oscillation Power From Resting State EEG Recordings on the First of Stimulation to 4 Weeks After Completion of Intervention | The investigators will compare alpha oscillation power from resting state EEG recordings on the first day of stimulation (baseline) and at the follow-up visit four weeks after completion of the intervention. The investigators will also collect EEG on the fifth day of stimulation. The investigators will use each of the three EEG recordings as data to analyze alpha frequency activity as a pilot study for derivation of EEG biomarkers. As the stimulation paradigm stimulates the frontal brain regions, the investigators will analyze alpha power change in all brain regions as well as frontal regions. | Baseline to F2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tACS, Major Depressive Disorder, MDD, mood symptoms, sham