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Transcranial Alternating Current Stimulation for Major Depressive Disorder (MDD)

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ClinicalTrials.gov Identifier: NCT02339285
Recruitment Status : Completed
First Posted : January 15, 2015
Results First Posted : August 20, 2018
Last Update Posted : August 20, 2018
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Major Depressive Disorder
MDD
Interventions Device: tACS (alpha)
Device: tACS (gamma)
Enrollment 32
Recruitment Details Participants were recruited through advertisements (e.g., online, flyers) and self-identified with depression. Interested participants contacted the study team.
Pre-assignment Details 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
Hide 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 [1] 10 11 11
Completed Intervention [2] 10 10 10
2 Week Follow-up [3] 9 10 10
4 Week Follow-up Visit [4] 9 8 9
Completed [5] 9 8 9
Not Completed 1 3 2
Reason Not Completed
Withdrawal by Subject             0             1             1
Lost to Follow-up             1             1             1
Protocol Deviation             0             1             0
[1]
All randomized participants included in analysis. Intent-to-treat; last observation carried forward.
[2]
Number of participants that completed 5 days of stimulation.
[3]
Number of participants that attended the follow-up visit 2 weeks after completion of intervention.
[4]
Number of participants that attended the follow-up visit 4 weeks after completion of intervention.
[5]
Number of participants that completed all sessions.
Arm/Group Title tACS (Alpha) tACS (Gamma) Sham Stimulation Total
Hide 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 Number of Baseline Participants 10 11 11 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 11 participants 11 participants 32 participants
36.30  (15.22) 35.36  (11.56) 38.36  (13.54) 36.69  (13.08)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 11 participants 11 participants 32 participants
Female
9
  90.0%
9
  81.8%
9
  81.8%
27
  84.4%
Male
1
  10.0%
2
  18.2%
2
  18.2%
5
  15.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 11 participants 11 participants 32 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
6
  60.0%
10
  90.9%
10
  90.9%
26
  81.3%
Unknown or Not Reported
4
  40.0%
1
   9.1%
1
   9.1%
6
  18.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 11 participants 11 participants 32 participants
American Indian or Alaska Native
1
  10.0%
0
   0.0%
0
   0.0%
1
   3.1%
Asian
0
   0.0%
1
   9.1%
0
   0.0%
1
   3.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
9
  90.0%
10
  90.9%
11
 100.0%
30
  93.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 10 participants 11 participants 11 participants 32 participants
10
 100.0%
11
 100.0%
11
 100.0%
32
 100.0%
Montgomery-Asberg Depression Rating Scale (MADRS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 10 participants 11 participants 11 participants 32 participants
28.80  (6.36) 25.00  (7.21) 24.55  (5.18) 26.03  (6.39)
[1]
Measure 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.
Hamilton Depression Rating Scale (HDRS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 10 participants 11 participants 11 participants 32 participants
17.90  (4.51) 14.64  (3.53) 14.55  (6.12) 15.63  (4.94)
[1]
Measure Description: The HDRS is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. Higher scores indicate more depressive symptoms.
Beck Depression Inventory (BDI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 10 participants 11 participants 11 participants 32 participants
26.60  (5.58) 28.27  (8.81) 26.18  (9.74) 27.03  (8.10)
[1]
Measure Description: The BDI is a self-administered questionnaire that measures the occurrence and severity of current depressive symptoms. Total scores range from 0-63 with higher scores indicating higher feelings of being depressed.
Montreal Cognitive Assessment (MoCA)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 10 participants 11 participants 11 participants 32 participants
28.20  (1.99) 27.27  (1.62) 27.82  (2.48) 27.75  (2.00)
[1]
Measure Description: A basic assessment of cognition. Total score is ranges from 0 to 30 points, with higher values indicating better cognition.
Clinical Global Impression (CGI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 10 participants 11 participants 11 participants 32 participants
4.10  (0.99) 3.82  (0.60) 3.73  (0.79) 3.88  (0.79)
[1]
Measure Description: Values reported on Item 1 "Severity of Illness" on the Clinical Global Impressions scale. Patients are scored on a likert scale, with 1 = "Normal, not at all ill" to 7 = "Among the most extremely ill patients."
1.Primary Outcome
Title Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Score
Time Frame Baseline to F2 (4 weeks after completion of the intervention)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title tACS (Alpha) tACS (Gamma) Sham Stimulation
Hide 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.
Overall Number of Participants Analyzed 10 11 11
Mean (Standard Deviation)
Unit of Measure: units on a scale
-13.60  (7.75) -8.82  (8.94) -8.27  (10.88)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Method ANOVA
Comments F(2, 29)
Show Statistical Analysis 2 Hide 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 [Not Specified]
Method ANOVA
Comments F(1, 31)
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection tACS (Alpha), tACS (Gamma), Sham Stimulation
Comments [Not Specified]
Type of Statistical Test Other
Comments F-test; Interaction effect (session x treatment)
Statistical Test of Hypothesis P-Value >0.10
Comments [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 9 8 9
Mean (Standard Deviation)
Unit of Measure: decibel (dB)
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)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Method ANOVA
Comments F(2,21.595)
Show Statistical Analysis 2 Hide 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 [Not Specified]
Method ANOVA
Comments F(3, 79.358)
Show Statistical Analysis 3 Hide 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 [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 9 8 9
Mean (Standard Deviation)
Unit of Measure: decibel (dB)
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)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value >0.10
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
4.Other Pre-specified Outcome
Title Change in Hamilton Depression Rating Scale (HDRS) Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title tACS (Alpha) tACS (Gamma) Sham Stimulation
Hide 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.
Overall Number of Participants Analyzed 10 11 11
Mean (Standard Deviation)
Unit of Measure: units on a scale
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title tACS (Alpha) tACS (Gamma) Sham Stimulation
Hide 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.
Overall Number of Participants Analyzed 10 11 11
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title tACS (Alpha) tACS (Gamma) Sham Stimulation
Hide 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.
Overall Number of Participants Analyzed 10 11 11
Mean (Standard Deviation)
Unit of Measure: units on a scale
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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title tACS (Alpha) tACS (Gamma) Sham Stimulation
Hide 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.
Overall Number of Participants Analyzed 10 11 11
Mean (Standard Deviation)
Unit of Measure: units on a scale
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)
Time Frame Throughout the intervention period and throughout F2 (4 weeks after completion of the intervention), for an average of 5 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title tACS (Alpha) tACS (Gamma) Sham Stimulation
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/11 (0.00%)   0/11 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
tACS (Alpha) tACS (Gamma) Sham Stimulation
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/11 (0.00%)   0/11 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
tACS (Alpha) tACS (Gamma) Sham Stimulation
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/11 (0.00%)   0/11 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Flavio Frohlich
Organization: University of North Carolina at Chapel Hill
Phone: (919) 966-4584
EMail: flavio_frohlich@med.unc.edu
Layout table for additonal information
Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02339285     History of Changes
Other Study ID Numbers: 14-1622
5R01MH101547-02 ( U.S. NIH Grant/Contract )
First Submitted: January 12, 2015
First Posted: January 15, 2015
Results First Submitted: June 12, 2018
Results First Posted: August 20, 2018
Last Update Posted: August 20, 2018