MDD: Transcranial Alternating Current Stimulation for Major Depressive Disorder

• Sponsor: University of North Carolina, Chapel Hill (Other)
• Overall Status: Completed
• CT.gov ID: NCT02339285
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 32
• Location: 1
• Arms: 3
• Actual Duration (Months): 25.4
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder; MDD	Device: tACS (alpha); Device: tACS (gamma)	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pilot Clinical Trial for the Evaluation of Feedback Transcranial Alternating Current Stimulation for the Treatment of Major Depressive Disorder
• Actual Study Start Date: May 7, 2015
• Actual Primary Completion Date: Jun 19, 2017
• Actual Study Completion Date: Jun 19, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: tACS (alpha) 10 Hz tACS with a peak-to-peak amplitude of 2 milliamps (mA) for 40 minutes. Uses tACS (alpha) device.	Device: tACS (alpha)
Experimental: tACS (gamma) 40 Hz tACS with a peak-to-peak amplitude of 2 milliamps (mA) for 40 minutes. Uses tACS (gamma) device.	Device: tACS (gamma)
Sham Comparator: Sham stimulation 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)

Outcome Measures

Primary Outcome Measures

1. Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Score [Baseline to F2 (4 weeks after completion of the intervention)]

   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.

Secondary Outcome Measures

1. Change in Alpha Oscillation Power From Resting State EEG Recordings on the First and Last Day of Stimulation [Baseline to Day 5 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.

2. Change in Alpha Oscillation Power From Resting State EEG Recordings on the First of Stimulation to 4 Weeks After Completion of Intervention [Baseline to F2]

   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.

Other Outcome Measures

1. Change in Hamilton Depression Rating Scale (HDRS) Score [Baseline to Day 5 of Stimulation; Baseline to F2]

   The HDRS is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. A higher score indicates a worse outcome. 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). The investigators will compare the scores between baseline and F2, with negative values indicating a decrease in depressive symptoms.

2. Change in Montreal Cognitive Assessment (MoCA) Score [Baseline to F2]

   This measurement will be taken at baseline (first day of stimulation) and four weeks after completion of the intervention (F2). Total score ranges from 0 to 30, with higher values indicating better cognition. The investigators will compare the scores between baseline and F2. Reported values are the raw change (increase or decrease) from baseline.

3. Change in Beck Depression Inventory (BDI) Score [Baseline to Day 5; Baseline to F2]

   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). Higher scores indicate more depressive symptoms. Total score is out of 63 possible. The investigators will compare the scores between baseline and F2. In these results, negative values indicate a decrease in depressive symptoms.

4. Clinical Global Impressions (CGI) Raw Score [Day 5; F2 (4 weeks after completion of treatment)]

   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). The investigators will compare the scores between baseline and F2.The reported values are from Item 1 "Severity of Illness" on a likert scale of 1 to 7, with 1=Normal, not at all ill and 7 = Among the most extremely ill patients.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UNC Chapel Hill Medical School Wing C	Chapel Hill	North Carolina	United States	27599

Sponsors and Collaborators

• University of North Carolina, Chapel Hill
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Flavio Frohlich, PhD, University of North Carolina at Chapel Hill, Department of Psychiatry

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 4, 2016

More Information

Publications

• Valiengo L, Benseñor IM, Goulart AC, de Oliveira JF, Zanao TA, Boggio PS, Lotufo PA, Fregni F, Brunoni AR. The sertraline versus electrical current therapy for treating depression clinical study (select-TDCS): results of the crossover and follow-up phases. Depress Anxiety. 2013 Jul;30(7):646-53. doi: 10.1002/da.22079. Epub 2013 Apr 26.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT02339285
• Other Study ID Numbers: 14-1622; 5R01MH101547-02
• First Posted: Jan 15, 2015
• Last Update Posted: Aug 20, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by University of North Carolina, Chapel Hill: tACS; Major Depressive Disorder; MDD; mood symptoms; sham
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major

Study Results

Participant Flow

Recruitment Details	Participants were recruited through advertisements (e.g., online, flyers) and self-identified with depression. Interested participants contacted the study team.
Pre-assignment Detail	Participants were randomly assigned to 1 of 3 arms: tACS (alpha), tACS (gamma), or sham stimulation. All conditions were delivered during awake, resting state for 40 minutes on 5 consecutive days. 98 participants signed consent, 40 did not meet criteria, 6 declined participation, and 20 were excluded for other reasons. 32 were randomized.

Arm/Group Title	tACS (Alpha)	tACS (Gamma)	Sham Stimulation
Arm/Group Description	10 Hz transcranial alternating current stimulation (tACS) with a peak-to-peak amplitude of 2 mA for 40 minutes	40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	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.
Period Title: Overall Study
STARTED	10	11	11
Completed Intervention	10	10	10
2 Week Follow-up	9	10	10
4 Week Follow-up Visit	9	8	9
COMPLETED	9	8	9
NOT COMPLETED	1	3	2

Baseline Characteristics

Arm/Group Title	tACS (Alpha)	tACS (Gamma)	Sham Stimulation	Total
Arm/Group Description	10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	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.	Total of all reporting groups
Overall Participants	10	11	11	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.30 (15.22)	35.36 (11.56)	38.36 (13.54)	36.69 (13.08)
Sex: Female, Male (Count of Participants)
Female	9 90%	9 81.8%	9 81.8%	27 84.4%
Male	1 10%	2 18.2%	2 18.2%	5 15.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	6 60%	10 90.9%	10 90.9%	26 81.3%
Unknown or Not Reported	4 40%	1 9.1%	1 9.1%	6 18.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 10%	0 0%	0 0%	1 3.1%
Asian	0 0%	1 9.1%	0 0%	1 3.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	9 90%	10 90.9%	11 100%	30 93.8%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%	11 100%	11 100%	32 100%
Montgomery-Asberg Depression Rating Scale (MADRS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	28.80 (6.36)	25.00 (7.21)	24.55 (5.18)	26.03 (6.39)
Hamilton Depression Rating Scale (HDRS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	17.90 (4.51)	14.64 (3.53)	14.55 (6.12)	15.63 (4.94)
Beck Depression Inventory (BDI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	26.60 (5.58)	28.27 (8.81)	26.18 (9.74)	27.03 (8.10)
Montreal Cognitive Assessment (MoCA) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	28.20 (1.99)	27.27 (1.62)	27.82 (2.48)	27.75 (2.00)
Clinical Global Impression (CGI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.10 (0.99)	3.82 (0.60)	3.73 (0.79)	3.88 (0.79)

Outcome Measures

1. Primary Outcome

Title	Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Score
Description	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.
Time Frame	Baseline to F2 (4 weeks after completion of the intervention)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	tACS (Alpha)	tACS (Gamma)	Sham Stimulation
Arm/Group Description	10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	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.
Measure Participants	10	11	11
Mean (Standard Deviation) [units on a scale]	-13.60 (7.75)	-8.82 (8.94)	-8.27 (10.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	tACS (Alpha), tACS (Gamma), Sham Stimulation
	Comments	Null hypothesis: There is no difference baseline and the 4 week follow up in MADRS score between treatment groups. Alternative hypothesis: There is a difference between baseline and the 4 week follow up MADRS score between treatment groups.
	Type of Statistical Test	Other
	Comments	F-test; Treatment effect
Statistical Test of Hypothesis	p-Value	>0.10
	Comments
	Method	ANOVA
	Comments	F(2, 29)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	tACS (Alpha), tACS (Gamma), Sham Stimulation
	Comments	Null hypothesis: There is no difference baseline and the 4 week follow up in MADRS score between treatment groups. Alternative hypothesis: There is a difference between baseline and the 4 week follow up MADRS score between treatment groups.
	Type of Statistical Test	Other
	Comments	F-test; Session effect
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	F(1, 31)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	tACS (Alpha), tACS (Gamma), Sham Stimulation
	Comments
	Type of Statistical Test	Other
	Comments	F-test; Interaction effect (session x treatment)
Statistical Test of Hypothesis	p-Value	>0.10
	Comments
	Method	ANOVA
	Comments	F(2,29)

2. Secondary Outcome

Title	Change in Alpha Oscillation Power From Resting State EEG Recordings on the First and Last Day of Stimulation
Description	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.
Time Frame	Baseline to Day 5 of Stimulation

Outcome Measure Data

Analysis Population Description

Only participants that completed all sessions are used in this task (per protocol participants); N = 26

Arm/Group Title	tACS (Alpha)	tACS (Gamma)	Sham Stimulation
Arm/Group Description	10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	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.
Measure Participants	9	8	9
All Brain Regions	-1.75 (1.75)	0.53 (1.79)	0.24 (1.22)
Frontal Brain Regions	-1.23 (1.29)	0.12 (1.68)	-0.02 (1.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	tACS (Alpha), tACS (Gamma), Sham Stimulation
	Comments	Null hypothesis: There is no difference in changes of alpha frequency power between baseline EEG and EEG on Day 5 of Stimulation between treatment groups. Alternative hypothesis: There is a difference in changes of alpha frequency power between baseline EEG and EEG on Day 5 of Stimulation between treatment groups.
	Type of Statistical Test	Other
	Comments	F-test; Condition effect
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments	F(2,21.595)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	tACS (Alpha), tACS (Gamma), Sham Stimulation
	Comments	Null hypothesis: There is no difference in changes of alpha frequency power between baseline EEG and EEG on Day 5 of Stimulation between treatment groups. Alternative hypothesis: There is a difference in changes of alpha frequency power between baseline EEG and EEG on Day 5 of Stimulation between treatment groups.
	Type of Statistical Test	Other
	Comments	F-test; Region effect (region defined as region of brain - frontal, parietal, occipital temporal)
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	F(3, 79.358)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	tACS (Alpha), tACS (Gamma), Sham Stimulation
	Comments	Null hypothesis: There is no difference in changes of alpha frequency power between baseline EEG and EEG on Day 5 of Stimulation between treatment groups. Alternative hypothesis: There is a difference in changes of alpha frequency power between baseline EEG and EEG on Day 5 of Stimulation between treatment groups.
	Type of Statistical Test	Other
	Comments	F-test; Interaction effect (region x condition)
Statistical Test of Hypothesis	p-Value	>0.10
	Comments
	Method	ANOVA
	Comments	F(6, 68.284)

3. Secondary Outcome

Title	Change in Alpha Oscillation Power From Resting State EEG Recordings on the First of Stimulation to 4 Weeks After Completion of Intervention
Description	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.
Time Frame	Baseline to F2

Outcome Measure Data

Analysis Population Description

Only participants that completed all sessions are used in this task (per protocol participants); N = 26

Arm/Group Title	tACS (Alpha)	tACS (Gamma)	Sham Stimulation
Arm/Group Description	10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	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.
Measure Participants	9	8	9
All Brain Regions	-0.42 (2.35)	0.09 (1.76)	0.55 (1.17)
Frontal Brain Regions	-0.57 (1.89)	0.00 (1.60)	0.41 (1.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	tACS (Alpha), tACS (Gamma), Sham Stimulation
	Comments	Null hypothesis: There is no difference in changes of alpha frequency power between baseline EEG and EEG 4 weeks after completion of the intervention between treatment groups. Alternative hypothesis: There is a difference in changes of alpha frequency power between baseline EEG and EEG 4 weeks after completion of the intervention between treatment groups.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.10
	Comments
	Method	ANOVA
	Comments

4. Other Pre-specified Outcome

Title	Change in Hamilton Depression Rating Scale (HDRS) Score
Description	The HDRS is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. A higher score indicates a worse outcome. 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). The investigators will compare the scores between baseline and F2, with negative values indicating a decrease in depressive symptoms.
Time Frame	Baseline to Day 5 of Stimulation; Baseline to F2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	tACS (Alpha)	tACS (Gamma)	Sham Stimulation
Arm/Group Description	10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	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.
Measure Participants	10	11	11
Day 5 change	-6.00 (3.09)	-4.45 (5.41)	-3.09 (4.48)
F2 change	-8.50 (5.04)	-4.73 (5.61)	-4.64 (6.98)

5. Other Pre-specified Outcome

Title	Change in Montreal Cognitive Assessment (MoCA) Score
Description	This measurement will be taken at baseline (first day of stimulation) and four weeks after completion of the intervention (F2). Total score ranges from 0 to 30, with higher values indicating better cognition. The investigators will compare the scores between baseline and F2. Reported values are the raw change (increase or decrease) from baseline.
Time Frame	Baseline to F2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	tACS (Alpha)	tACS (Gamma)	Sham Stimulation
Arm/Group Description	10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	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.
Measure Participants	10	11	11
Mean (Standard Deviation) [units on a scale]	0.50 (0.53)	1.27 (1.35)	1.09 (1.51)

6. Other Pre-specified Outcome

Title	Change in Beck Depression Inventory (BDI) Score
Description	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). Higher scores indicate more depressive symptoms. Total score is out of 63 possible. The investigators will compare the scores between baseline and F2. In these results, negative values indicate a decrease in depressive symptoms.
Time Frame	Baseline to Day 5; Baseline to F2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	tACS (Alpha)	tACS (Gamma)	Sham Stimulation
Arm/Group Description	10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	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.
Measure Participants	10	11	11
Day 5 Change	-8.60 (6.42)	-9.64 (10.07)	-7.18 (7.19)
F2 change	-14.80 (12.39)	-11.09 (11.68)	-10.64 (10.39)

7. Other Pre-specified Outcome

Title	Clinical Global Impressions (CGI) Raw Score
Description	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). The investigators will compare the scores between baseline and F2.The reported values are from Item 1 "Severity of Illness" on a likert scale of 1 to 7, with 1=Normal, not at all ill and 7 = Among the most extremely ill patients.
Time Frame	Day 5; F2 (4 weeks after completion of treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	tACS (Alpha)	tACS (Gamma)	Sham Stimulation
Arm/Group Description	10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes	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.
Measure Participants	10	11	11
Day 5 Score	4.30 (0.95)	3.73 (0.65)	3.73 (0.79)
F2 Score	3.90 (1.37)	3.82 (0.75)	3.45 (1.29)

Adverse Events

Time Frame	Throughout the intervention period and throughout F2 (4 weeks after completion of the intervention), for an average of 5 weeks.
Arm/Group Title	tACS (Alpha)		tACS (Gamma)		Sham Stimulation
Arm/Group Description	10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes		40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes		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.
All Cause Mortality
	tACS (Alpha)		tACS (Gamma)		Sham Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)		0/11 (0%)
Serious Adverse Events
	tACS (Alpha)		tACS (Gamma)		Sham Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	tACS (Alpha)		tACS (Gamma)		Sham Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.