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Efficacy and Safety of Cranial Electrical Stimulation (CES) for Major Depressive Disorder (MDD)

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ClinicalTrials.gov Identifier: NCT01325532
Recruitment Status : Completed
First Posted : March 29, 2011
Results First Posted : June 1, 2016
Last Update Posted : June 1, 2016
Sponsor:
Collaborator:
Fisher Wallace Labs, LLC
Information provided by (Responsible Party):
David Mischoulon, MD, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Device: Active CES
Device: Sham CES
Enrollment 30
Recruitment Details Subjects were recruited by advertisement from our Depression Clinical and Research Program (DCRP). Informed consent was obtained per IRB guidelines. Investigators who screened subjects were our program’s psychiatrists and psychologists, trained and certified in the use of appropriate diagnostic instruments such as the SCID and HAM-D.
Pre-assignment Details Subjects who passed the screen visit returned a week later for the baseline visit. At that time, subjects received their first treatment (or sham) at the site for 20 minutes, including personal instruction of proper technique and electrode placement.
Arm/Group Title Active CES Sham CES
Hide Arm/Group Description

Active CES: The FW-100 Cranial Stimulator headset was placed on the scalp over the two dorsolateral prefrontal cortex areas. The power knob was turned to maximum setting. The waveform contains a 15000Hz square wave carrier from 0-4 mAmp. The first 15Hz modulating signal provides 50msec of “on” and 16.7msec of “off” time (total 66.7msec, 50% duty cycle). A second 500Hz modulating signal changes the “on” time series of 15000Hz pulses (750 pulses/50msec) into 25 smaller bursts of 15 pulses of the 15000Hz carrier signal, for 375 pulses in 50msec. The consecutive positive burst and “off” time is followed by an opposite negative burst and “off” time, balancing the current component to zero. Output voltage ranges from 0-40V, positive and negative. CES automatically shut off after 20 mins.

Active CES: CES current

Shame CES: The sham devices were modified to not deliver current to the headset. The current from the active device departs from the posts at the top of the device into the headsets, creating a loop when the headset is worn by the subject with the wet electrode sponges. This loop is eliminated in the sham devices by wrapping wire around the posts, thus containing the loop within the device, with no electricity leaving the headsets. This approach allows the loop to be maintained, and therefore all of the device’s green and yellow amperage lights still light up, protecting the blind.

Sham CES: Sham CES (device off) for 20-minutes each day 5 days/week for 3 weeks.

Period Title: Overall Study
Started 17 13
Completed 15 13
Not Completed 2 0
Reason Not Completed
Withdrawal by Subject             2             0
Arm/Group Title Active CES Sham CES Total
Hide Arm/Group Description

Active CES: The FW-100 Cranial Stimulator headset was placed on the scalp over the two dorsolateral prefrontal cortex areas. The power knob was turned to maximum setting. The waveform contains a 15000Hz square wave carrier from 0-4 mAmp. The first 15Hz modulating signal provides 50msec of “on” and 16.7msec of “off” time (total 66.7msec, 50% duty cycle). A second 500Hz modulating signal changes the “on” time series of 15000Hz pulses (750 pulses/50msec) into 25 smaller bursts of 15 pulses of the 15000Hz carrier signal, for 375 pulses in 50msec. The consecutive positive burst and “off” time is followed by an opposite negative burst and “off” time, balancing the current component to zero. Output voltage ranges from 0-40V, positive and negative. CES automatically shut off after 20 mins.

Active CES: CES current

Shame CES: The sham devices were modified to not deliver current to the headset. The current from the active device departs from the posts at the top of the device into the headsets, creating a loop when the headset is worn by the subject with the wet electrode sponges. This loop is eliminated in the sham devices by wrapping wire around the posts, thus containing the loop within the device, with no electricity leaving the headsets. This approach allows the loop to be maintained, and therefore all of the device’s green and yellow amperage lights still light up, protecting the blind.

Sham CES: Sham CES (device off) for 20-minutes each day 5 days/week for 3 weeks.

Total of all reporting groups
Overall Number of Baseline Participants 17 13 30
Hide Baseline Analysis Population Description
Adults with MDD; the HAM-D score eligibility range was set to include subjects who were partial or non-responders (HAM-D 15-18) but not too severely depressed (HAMD ≤ 23), given CES’s experimental nature.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 13 participants 30 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
17
 100.0%
13
 100.0%
30
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants 13 participants 30 participants
45.5  (12.3) 51.4  (11.9) 48.1  (12.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 13 participants 30 participants
Female
10
  58.8%
7
  53.8%
17
  56.7%
Male
7
  41.2%
6
  46.2%
13
  43.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 17 participants 13 participants 30 participants
17 13 30
Hamilton Depression Rating Scale   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 17 participants 13 participants 30 participants
18.1  (1.5) 18.7  (3.9) 18.3  (2.8)
[1]
Measure Description: The Hamilton Depression Rating Scale used here is a 17-item scale that measures severity of depression. Items are individually scored from 0-4 or from 0-2 depending on the item, and the individual scores for each item are added to comprise one score. Higher scores indicate greater severity of depression. Possible scores on the scale range from a minimum of zero (0) to a maximum of 52.
1.Primary Outcome
Title Change in Hamilton Depression Rating Scale (HAM-D 17) Score From Baseline to Week 3
Hide Description The Hamilton Depression Rating Scale (HAM-D-17) used here is a 17-item scale that measures severity of depression. Items are individually scored from 0-4 or from 0-2 depending on the item, and the individual scores for each item are added to comprise one score. Higher scores indicate greater severity of depression. Possible scores on the scale range from a minimum of zero (0) to a maximum of 52. This section reports the improvement in depressive symptoms during the course of treatment, i.e. the change in overall score between baseline visit and week 3 visit. Change can occur in either direction (i.e. improvement or worsening). A score of greater than zero indicates a reduction of depressive symptoms (improvement), whereas a score of less than zero indicates an increase in depressive symptoms (worsening).
Time Frame Baseline-Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat sample with last observation carried forward for all randomized subject.
Arm/Group Title Active CES Sham CES
Hide Arm/Group Description:

Active CES: The FW-100 Cranial Stimulator headset was placed on the scalp over the two dorsolateral prefrontal cortex areas. The power knob was turned to maximum setting. The waveform contains a 15000Hz square wave carrier from 0-4 mAmp. The first 15Hz modulating signal provides 50msec of “on” and 16.7msec of “off” time (total 66.7msec, 50% duty cycle). A second 500Hz modulating signal changes the “on” time series of 15000Hz pulses (750 pulses/50msec) into 25 smaller bursts of 15 pulses of the 15000Hz carrier signal, for 375 pulses in 50msec. The consecutive positive burst and “off” time is followed by an opposite negative burst and “off” time, balancing the current component to zero. Output voltage ranges from 0-40V, positive and negative. CES automatically shut off after 20 mins.

Active CES: CES current

Shame CES: The sham devices were modified to not deliver current to the headset. The current from the active device departs from the posts at the top of the device into the headsets, creating a loop when the headset is worn by the subject with the wet electrode sponges. This loop is eliminated in the sham devices by wrapping wire around the posts, thus containing the loop within the device, with no electricity leaving the headsets. This approach allows the loop to be maintained, and therefore all of the device’s green and yellow amperage lights still light up, protecting the blind.

Sham CES: Sham CES (device off) for 20-minutes each day 5 days/week for 3 weeks.

Overall Number of Participants Analyzed 17 13
Mean (Standard Deviation)
Unit of Measure: units on a scale
14.8  (6.3) 13.6  (5.8)
2.Primary Outcome
Title Reported Side Effects Based on PRISE AE Scores
Hide Description This measures the emergence of different adverse (side) effects from treatment during the study. This section will describe the most commonly reported adverse effects. The section on adverse events will describe and detail the full range of AEs reported.
Time Frame Baseline-Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat sample with all subjects randomized.
Arm/Group Title Active CES Sham CES
Hide Arm/Group Description:

Active CES: The FW-100 Cranial Stimulator headset was placed on the scalp over the two dorsolateral prefrontal cortex areas. The power knob was turned to maximum setting. The waveform contains a 15000Hz square wave carrier from 0-4 mAmp. The first 15Hz modulating signal provides 50msec of “on” and 16.7msec of “off” time (total 66.7msec, 50% duty cycle). A second 500Hz modulating signal changes the “on” time series of 15000Hz pulses (750 pulses/50msec) into 25 smaller bursts of 15 pulses of the 15000Hz carrier signal, for 375 pulses in 50msec. The consecutive positive burst and “off” time is followed by an opposite negative burst and “off” time, balancing the current component to zero. Output voltage ranges from 0-40V, positive and negative. CES automatically shut off after 20 mins.

Active CES: CES current

Shame CES: The sham devices were modified to not deliver current to the headset. The current from the active device departs from the posts at the top of the device into the headsets, creating a loop when the headset is worn by the subject with the wet electrode sponges. This loop is eliminated in the sham devices by wrapping wire around the posts, thus containing the loop within the device, with no electricity leaving the headsets. This approach allows the loop to be maintained, and therefore all of the device’s green and yellow amperage lights still light up, protecting the blind.

Sham CES: Sham CES (device off) for 20-minutes each day 5 days/week for 3 weeks.

Overall Number of Participants Analyzed 17 13
Measure Type: Number
Unit of Measure: number of subjects reporting
Poor concentration 10 2
Decreased energy 6 2
Fatigue 5 2
Anxiety 5 4
Flashing light/tingling 5 0
3.Secondary Outcome
Title Change in Global Sleep Scores on the Pittsburgh Sleep Quality Index (PSQI) From Baseline to Week 3.
Hide Description The Pittsburgh Sleep Quality Index (PSQI) is a patient-rated instrument to assess sleep quality and quantity and its changes throughout the study. Scoring is based on 7 individual components. Each component is scored from 0-3. Higher scores indicate worse sleep. Total global sleep score ranges from zero (0) to 21. We report here the overall change in global sleep score for each treatment arm, i.e. the change in overall score between baseline visit and week 3 visit. Change can occur in either direction (i.e. improvement or worsening). A score of greater than zero indicates a reduction of sleep disturbance (improvement), whereas a score of less than zero indicates an increase in sleep disturbance (worsening).
Time Frame Baseline-Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
This is an intent to treat (ITT) analysis of all patients randomized.
Arm/Group Title Active CES Sham CES
Hide Arm/Group Description:

Active CES: The FW-100 Cranial Stimulator headset was placed on the scalp over the two dorsolateral prefrontal cortex areas. The power knob was turned to maximum setting. The waveform contains a 15000Hz square wave carrier from 0-4 mAmp. The first 15Hz modulating signal provides 50msec of “on” and 16.7msec of “off” time (total 66.7msec, 50% duty cycle). A second 500Hz modulating signal changes the “on” time series of 15000Hz pulses (750 pulses/50msec) into 25 smaller bursts of 15 pulses of the 15000Hz carrier signal, for 375 pulses in 50msec. The consecutive positive burst and “off” time is followed by an opposite negative burst and “off” time, balancing the current component to zero. Output voltage ranges from 0-40V, positive and negative. CES automatically shut off after 20 mins.

Active CES: CES current

Shame CES: The sham devices were modified to not deliver current to the headset. The current from the active device departs from the posts at the top of the device into the headsets, creating a loop when the headset is worn by the subject with the wet electrode sponges. This loop is eliminated in the sham devices by wrapping wire around the posts, thus containing the loop within the device, with no electricity leaving the headsets. This approach allows the loop to be maintained, and therefore all of the device’s green and yellow amperage lights still light up, protecting the blind.

Sham CES: Sham CES (device off) for 20-minutes each day 5 days/week for 3 weeks.

Overall Number of Participants Analyzed 17 13
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.33  (2.02) 0.77  (2.17)
Time Frame 3 weeks
Adverse Event Reporting Description All subjects filled out the PRISE adverse effect instrument at each visit. Emergence of each side effect was assessed during the course of the study.
 
Arm/Group Title Active CES Sham CES
Hide Arm/Group Description

Active CES: The FW-100 Cranial Stimulator headset was placed on the scalp over the two dorsolateral prefrontal cortex areas. The power knob was turned to maximum setting. The waveform contains a 15000Hz square wave carrier from 0-4 mAmp. The first 15Hz modulating signal provides 50msec of “on” and 16.7msec of “off” time (total 66.7msec, 50% duty cycle). A second 500Hz modulating signal changes the “on” time series of 15000Hz pulses (750 pulses/50msec) into 25 smaller bursts of 15 pulses of the 15000Hz carrier signal, for 375 pulses in 50msec. The consecutive positive burst and “off” time is followed by an opposite negative burst and “off” time, balancing the current component to zero. Output voltage ranges from 0-40V, positive and negative. CES automatically shut off after 20 mins.

Active CES: CES current

Shame CES: The sham devices were modified to not deliver current to the headset. The current from the active device departs from the posts at the top of the device into the headsets, creating a loop when the headset is worn by the subject with the wet electrode sponges. This loop is eliminated in the sham devices by wrapping wire around the posts, thus containing the loop within the device, with no electricity leaving the headsets. This approach allows the loop to be maintained, and therefore all of the device’s green and yellow amperage lights still light up, protecting the blind.

Sham CES: Sham CES (device off) for 20-minutes each day 5 days/week for 3 weeks.

All-Cause Mortality
Active CES Sham CES
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Active CES Sham CES
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/17 (0.00%)      0/13 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Active CES Sham CES
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/17 (64.71%)      8/13 (61.54%)    
Cardiac disorders     
Palpitations  1 [1]  1/17 (5.88%)  1 1/13 (7.69%)  1
Orthostatic hypotension  1 [2]  2/17 (11.76%)  2 0/13 (0.00%)  0
Ear and labyrinth disorders     
Ringing in ears  1 [3]  1/17 (5.88%)  1 1/13 (7.69%)  1
Eye disorders     
Blurred vision  1 [4]  1/17 (5.88%)  1 0/13 (0.00%)  0
Gastrointestinal disorders     
Diarrhea  1  2/17 (11.76%)  2 0/13 (0.00%)  0
Constipation  1 [5]  1/17 (5.88%)  1 1/13 (7.69%)  1
Nausea/vomiting  1 [6]  0/17 (0.00%)  0 1/13 (7.69%)  1
General disorders     
Difficulty sleeping  1 [7]  3/17 (17.65%)  3 2/13 (15.38%)  2
Sleeping too much  1 [8]  3/17 (17.65%)  3 1/13 (7.69%)  1
Nervous system disorders     
Headache  1 [9]  1/17 (5.88%)  1 1/13 (7.69%)  1
Tremors  1 [10]  1/17 (5.88%)  1 0/13 (0.00%)  0
Dizziness  1 [11]  1/17 (5.88%)  1 0/13 (0.00%)  0
Flashing light and tingling sensation * 2 [12]  5/17 (29.41%)  5 0/13 (0.00%)  0
Psychiatric disorders     
Anxiety  1 [13]  5/17 (29.41%)  5 4/13 (30.77%)  4
Poor concentration  1 [14]  10/17 (58.82%)  10 2/13 (15.38%)  2
General malaise  1 [15]  5/17 (29.41%)  5 0/13 (0.00%)  0
Restlessness  1 [16]  3/17 (17.65%)  3 2/13 (15.38%)  2
Fatigue  1 [17]  5/17 (29.41%)  5 2/13 (15.38%)  2
Decreased energy  1 [18]  6/17 (35.29%)  6 2/13 (15.38%)  2
Renal and urinary disorders     
Difficulty urinating  1 [19]  0/17 (0.00%)  0 1/13 (7.69%)  1
Frequent urination  1 [20]  0/17 (0.00%)  0 1/13 (7.69%)  1
Reproductive system and breast disorders     
Menstrual irregularity  1 [21]  1/17 (5.88%)  1 0/13 (0.00%)  0
Loss of sexual desire  1 [22]  3/17 (17.65%)  3 1/13 (7.69%)  1
Trouble achieving orgasm  1 [23]  2/17 (11.76%)  2 0/13 (0.00%)  0
Trouble with erections  1 [24]  1/17 (5.88%)  1 0/13 (0.00%)  0
Skin and subcutaneous tissue disorders     
Increased perspiration  1 [25]  1/17 (5.88%)  1 0/13 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, PRISE
2
Term from vocabulary, Spontaneous report
[1]
Palpitations
[2]
Dizziness on standing
[3]
Ringing in ears
[4]
blurred vision
[5]
Constipation
[6]
Nausea or vomiting
[7]
Difficulty sleeping
[8]
Sleeping too much
[9]
Headache
[10]
Tremors
[11]
Dizziness
[12]
Mild flashing light sensation in their peripheral vision and/or a tingling sensation in temples
[13]
Anxiety
[14]
Poor concentration
[15]
General malaise
[16]
Restlessness
[17]
Fatigue
[18]
Decreased energy
[19]
Difficulty urinating
[20]
Frequent urination
[21]
Menstrual irregularity
[22]
Loss of sexual desire
[23]
Trouble achieving orgasm
[24]
Trouble with erections
[25]
increased sweating
The main limitations include a small sample and lack of an active comparator. Because CES did not separate from its sham counterpart in this sample of MDD patients, we cannot rule out that the benefit obtained from CES was due to placebo effects.
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
Name/Title: Dr David Mischoulon
Organization: Massachusetts General Hospital, Dept of Psychiatry
Phone: 617-724-5198
Responsible Party: David Mischoulon, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01325532     History of Changes
Other Study ID Numbers: 2010 P000461
First Submitted: March 24, 2011
First Posted: March 29, 2011
Results First Submitted: March 20, 2016
Results First Posted: June 1, 2016
Last Update Posted: June 1, 2016