Trial Outcomes & Findings for Transcranial Alternating Current Stimulation for Major Depressive Disorder (NCT NCT02339285)

NCT ID: NCT02339285

Last Updated: 2018-08-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

32 participants

Primary outcome timeframe

Baseline to F2 (4 weeks after completion of the intervention)

Results posted on

2018-08-20

Participant Flow

Participants were recruited through advertisements (e.g., online, flyers) and self-identified with depression. Interested participants contacted the study team.

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.

Participant milestones

Participant milestones
Measure
tACS (Alpha)
10 Hz transcranial alternating current stimulation (tACS) with a peak-to-peak amplitude of 2 mA for 40 minutes
tACS (Gamma)
40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
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.
Overall Study
STARTED
10
11
11
Overall Study
Completed Intervention
10
10
10
Overall Study
2 Week Follow-up
9
10
10
Overall Study
4 Week Follow-up Visit
9
8
9
Overall Study
COMPLETED
9
8
9
Overall Study
NOT COMPLETED
1
3
2

Reasons for withdrawal

Reasons for withdrawal
Measure
tACS (Alpha)
10 Hz transcranial alternating current stimulation (tACS) with a peak-to-peak amplitude of 2 mA for 40 minutes
tACS (Gamma)
40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
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.
Overall Study
Withdrawal by Subject
0
1
1
Overall Study
Lost to Follow-up
1
1
1
Overall Study
Protocol Deviation
0
1
0

Baseline Characteristics

Transcranial Alternating Current Stimulation for Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
tACS (Alpha)
n=10 Participants
10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
tACS (Gamma)
n=11 Participants
40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
Sham Stimulation
n=11 Participants
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
n=32 Participants
Total of all reporting groups
Age, Continuous
36.30 years
STANDARD_DEVIATION 15.22 • n=5 Participants
35.36 years
STANDARD_DEVIATION 11.56 • n=7 Participants
38.36 years
STANDARD_DEVIATION 13.54 • n=5 Participants
36.69 years
STANDARD_DEVIATION 13.08 • n=4 Participants
Sex: Female, Male
Female
9 Participants
n=5 Participants
9 Participants
n=7 Participants
9 Participants
n=5 Participants
27 Participants
n=4 Participants
Sex: Female, Male
Male
1 Participants
n=5 Participants
2 Participants
n=7 Participants
2 Participants
n=5 Participants
5 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
6 Participants
n=5 Participants
10 Participants
n=7 Participants
10 Participants
n=5 Participants
26 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
4 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
6 Participants
n=4 Participants
Race (NIH/OMB)
American Indian or Alaska Native
1 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
1 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
White
9 Participants
n=5 Participants
10 Participants
n=7 Participants
11 Participants
n=5 Participants
30 Participants
n=4 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Region of Enrollment
United States
10 Participants
n=5 Participants
11 Participants
n=7 Participants
11 Participants
n=5 Participants
32 Participants
n=4 Participants
Montgomery-Asberg Depression Rating Scale (MADRS)
28.80 units on a scale
STANDARD_DEVIATION 6.36 • n=5 Participants
25.00 units on a scale
STANDARD_DEVIATION 7.21 • n=7 Participants
24.55 units on a scale
STANDARD_DEVIATION 5.18 • n=5 Participants
26.03 units on a scale
STANDARD_DEVIATION 6.39 • n=4 Participants
Hamilton Depression Rating Scale (HDRS)
17.90 units on a scale
STANDARD_DEVIATION 4.51 • n=5 Participants
14.64 units on a scale
STANDARD_DEVIATION 3.53 • n=7 Participants
14.55 units on a scale
STANDARD_DEVIATION 6.12 • n=5 Participants
15.63 units on a scale
STANDARD_DEVIATION 4.94 • n=4 Participants
Beck Depression Inventory (BDI)
26.60 units on a scale
STANDARD_DEVIATION 5.58 • n=5 Participants
28.27 units on a scale
STANDARD_DEVIATION 8.81 • n=7 Participants
26.18 units on a scale
STANDARD_DEVIATION 9.74 • n=5 Participants
27.03 units on a scale
STANDARD_DEVIATION 8.10 • n=4 Participants
Montreal Cognitive Assessment (MoCA)
28.20 units on a scale
STANDARD_DEVIATION 1.99 • n=5 Participants
27.27 units on a scale
STANDARD_DEVIATION 1.62 • n=7 Participants
27.82 units on a scale
STANDARD_DEVIATION 2.48 • n=5 Participants
27.75 units on a scale
STANDARD_DEVIATION 2.00 • n=4 Participants
Clinical Global Impression (CGI)
4.10 units on a scale
STANDARD_DEVIATION 0.99 • n=5 Participants
3.82 units on a scale
STANDARD_DEVIATION 0.60 • n=7 Participants
3.73 units on a scale
STANDARD_DEVIATION 0.79 • n=5 Participants
3.88 units on a scale
STANDARD_DEVIATION 0.79 • n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
tACS (Alpha)
n=10 Participants
10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
tACS (Gamma)
n=11 Participants
40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
Sham Stimulation
n=11 Participants
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.
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Score
-13.60 units on a scale
Standard Deviation 7.75
-8.82 units on a scale
Standard Deviation 8.94
-8.27 units on a scale
Standard Deviation 10.88

SECONDARY outcome

Timeframe: Baseline to Day 5 of Stimulation

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

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.

Outcome measures

Outcome measures
Measure
tACS (Alpha)
n=9 Participants
10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
tACS (Gamma)
n=8 Participants
40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
Sham Stimulation
n=9 Participants
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.
Change in Alpha Oscillation Power From Resting State EEG Recordings on the First and Last Day of Stimulation
All Brain Regions
-1.75 decibel (dB)
Standard Deviation 1.75
0.53 decibel (dB)
Standard Deviation 1.79
0.24 decibel (dB)
Standard Deviation 1.22
Change in Alpha Oscillation Power From Resting State EEG Recordings on the First and Last Day of Stimulation
Frontal Brain Regions
-1.23 decibel (dB)
Standard Deviation 1.29
0.12 decibel (dB)
Standard Deviation 1.68
-0.02 decibel (dB)
Standard Deviation 1.20

SECONDARY outcome

Timeframe: Baseline to F2

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

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.

Outcome measures

Outcome measures
Measure
tACS (Alpha)
n=9 Participants
10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
tACS (Gamma)
n=8 Participants
40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
Sham Stimulation
n=9 Participants
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.
Change in Alpha Oscillation Power From Resting State EEG Recordings on the First of Stimulation to 4 Weeks After Completion of Intervention
All Brain Regions
-0.42 decibel (dB)
Standard Deviation 2.35
0.09 decibel (dB)
Standard Deviation 1.76
0.55 decibel (dB)
Standard Deviation 1.17
Change in Alpha Oscillation Power From Resting State EEG Recordings on the First of Stimulation to 4 Weeks After Completion of Intervention
Frontal Brain Regions
-0.57 decibel (dB)
Standard Deviation 1.89
0.00 decibel (dB)
Standard Deviation 1.60
0.41 decibel (dB)
Standard Deviation 1.18

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
tACS (Alpha)
n=10 Participants
10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
tACS (Gamma)
n=11 Participants
40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
Sham Stimulation
n=11 Participants
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.
Change in Hamilton Depression Rating Scale (HDRS) Score
Day 5 change
-6.00 units on a scale
Standard Deviation 3.09
-4.45 units on a scale
Standard Deviation 5.41
-3.09 units on a scale
Standard Deviation 4.48
Change in Hamilton Depression Rating Scale (HDRS) Score
F2 change
-8.50 units on a scale
Standard Deviation 5.04
-4.73 units on a scale
Standard Deviation 5.61
-4.64 units on a scale
Standard Deviation 6.98

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
tACS (Alpha)
n=10 Participants
10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
tACS (Gamma)
n=11 Participants
40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
Sham Stimulation
n=11 Participants
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.
Change in Montreal Cognitive Assessment (MoCA) Score
0.50 units on a scale
Standard Deviation 0.53
1.27 units on a scale
Standard Deviation 1.35
1.09 units on a scale
Standard Deviation 1.51

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
tACS (Alpha)
n=10 Participants
10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
tACS (Gamma)
n=11 Participants
40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
Sham Stimulation
n=11 Participants
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.
Change in Beck Depression Inventory (BDI) Score
Day 5 Change
-8.60 units on a scale
Standard Deviation 6.42
-9.64 units on a scale
Standard Deviation 10.07
-7.18 units on a scale
Standard Deviation 7.19
Change in Beck Depression Inventory (BDI) Score
F2 change
-14.80 units on a scale
Standard Deviation 12.39
-11.09 units on a scale
Standard Deviation 11.68
-10.64 units on a scale
Standard Deviation 10.39

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
tACS (Alpha)
n=10 Participants
10 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
tACS (Gamma)
n=11 Participants
40 Hz transcranial alternating current stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes
Sham Stimulation
n=11 Participants
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.
Clinical Global Impressions (CGI) Raw Score
Day 5 Score
4.30 units on a scale
Standard Deviation 0.95
3.73 units on a scale
Standard Deviation 0.65
3.73 units on a scale
Standard Deviation 0.79
Clinical Global Impressions (CGI) Raw Score
F2 Score
3.90 units on a scale
Standard Deviation 1.37
3.82 units on a scale
Standard Deviation 0.75
3.45 units on a scale
Standard Deviation 1.29

Adverse Events

tACS (Alpha)

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

tACS (Gamma)

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Sham Stimulation

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Flavio Frohlich

University of North Carolina at Chapel Hill

Phone: (919) 966-4584

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place