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| Name | Class |
|---|---|
| Fisher Wallace Labs, LLC | UNKNOWN |
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The purpose of this study is to see if using Cranial Electrical Stimulation (CES) helps improve symptoms of major depressive disorder (MDD). The investigators are studying the device's effectiveness in treating depression, as well as its safety. This is a pilot study.
Eligible participants will be randomly assigned to receive either active CES or sham CES, every weekday for 3 weeks. During the visits, subjects will receive CES or sham CES treatment for 20 minutes.
The primary outcome measure will be change in score on the HAM-D 17. The secondary outcome measure will be change in patient-reported sleep score.
We examined efficacy and safety of one specific cranial electrical stimulator (CES) device at a fixed setting in subjects with treatment-resistant major depressive disorder (MDD). Thirty subjects with MDD and inadequate response to standard antidepressants were randomized to 3 weeks of treatment with CES (15/500/15000 Hz, symmetrical rectangular biphasic current of 1-4 mAmp, 40 Volts) or sham CES (device off) for 20 minutes, 5 days per week. The primary outcome measure was improvement in the 17-item Hamilton Depression Rating Scale (HAM-D-17). Adverse effects (AEs) were assessed using the Patient Related Inventory of Side Effects (PRISE). We hypothesized that subjects who received active as opposed to sham CES would have a significantly greater improvement in their depression symptoms. Due to the small sample, we could not hypothesize an effect size, but would calculate one to determine signal strength to guide the design of a larger, more rigorous study. As an exploratory aim, we also examined whether CES would benefit sleep.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active CES | Experimental | 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. |
|
| Sham CES | Sham Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Active CES | Device | CES current |
|
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| Measure | Description | Time Frame |
|---|---|---|
| Change in Hamilton Depression Rating Scale (HAM-D 17) Score From Baseline to Week 3 | 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). | Baseline-Week 3 |
| Reported Side Effects Based on PRISE AE Scores | 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. | Baseline-Week 3 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Global Sleep Scores on the Pittsburgh Sleep Quality Index (PSQI) From Baseline to Week 3. | 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). |
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Inclusion Criteria
Subjects must meet all of the following criteria to participate in the study:
Exclusion Criteria
Subjects meeting any of the following criteria will not be allowed to participate in the study:
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| Name | Affiliation | Role |
|---|---|---|
| David Mischoulon, MD, PhD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Depression Clinical and Research Program at Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26424428 | Result | Mischoulon D, De Jong MF, Vitolo OV, Cusin C, Dording CM, Yeung AS, Durham K, Parkin SR, Fava M, Dougherty DD. Efficacy and safety of a form of cranial electrical stimulation (CES) as an add-on intervention for treatment-resistant major depressive disorder: A three week double blind pilot study. J Psychiatr Res. 2015 Nov;70:98-105. doi: 10.1016/j.jpsychires.2015.08.016. Epub 2015 Aug 29. |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Active CES | 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 |
| FG001 | Sham CES | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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.
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| ID | Title | Description |
|---|---|---|
| BG000 | Active CES | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Hamilton Depression Rating Scale (HAM-D 17) Score From Baseline to Week 3 | 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). | Intent to treat sample with last observation carried forward for all randomized subject. | Posted | Mean | Standard Deviation | units on a scale | Baseline-Week 3 |
|
3 weeks
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Active CES | 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | PRISE | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr David Mischoulon | Massachusetts General Hospital, Dept of Psychiatry | 617-724-5198 | dmischoulon@partners.org |
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| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| D003863 | Depression |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
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| Sham CES | Device | Sham CES (device off) for 20-minutes each day 5 days/week for 3 weeks. |
|
|
| Baseline-Week 3 |
| BG001 | Sham CES | 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Hamilton Depression Rating Scale | 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. | Mean | Standard Deviation | units on a scale |
|
| OG000 |
| Active CES |
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 |
| OG001 | Sham CES | 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. |
|
|
| Primary | Reported Side Effects Based on PRISE AE Scores | 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. | Intent to treat sample with all subjects randomized. | Posted | Number | number of subjects reporting | Baseline-Week 3 |
|
|
|
| Secondary | Change in Global Sleep Scores on the Pittsburgh Sleep Quality Index (PSQI) From Baseline to Week 3. | 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). | This is an intent to treat (ITT) analysis of all patients randomized. | Posted | Mean | Standard Deviation | units on a scale | Baseline-Week 3 |
|
|
|
| 0 |
| 17 |
| 11 |
| 17 |
| EG001 | Sham CES | 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. | 0 | 13 | 8 | 13 |
| Constipation | Gastrointestinal disorders | PRISE | Systematic Assessment | Constipation |
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| Nausea/vomiting | Gastrointestinal disorders | PRISE | Systematic Assessment | Nausea or vomiting |
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| Palpitations | Cardiac disorders | PRISE | Systematic Assessment | Palpitations |
|
| Orthostatic hypotension | Cardiac disorders | PRISE | Systematic Assessment | Dizziness on standing |
|
| Increased perspiration | Skin and subcutaneous tissue disorders | PRISE | Systematic Assessment | increased sweating |
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| Headache | Nervous system disorders | PRISE | Systematic Assessment | Headache |
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| Tremors | Nervous system disorders | PRISE | Systematic Assessment | Tremors |
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| Dizziness | Nervous system disorders | PRISE | Systematic Assessment | Dizziness |
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| Blurred vision | Eye disorders | PRISE | Systematic Assessment | blurred vision |
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| Ringing in ears | Ear and labyrinth disorders | PRISE | Systematic Assessment | Ringing in ears |
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| Difficulty urinating | Renal and urinary disorders | PRISE | Systematic Assessment | Difficulty urinating |
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| Frequent urination | Renal and urinary disorders | PRISE | Systematic Assessment | Frequent urination |
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| Menstrual irregularity | Reproductive system and breast disorders | PRISE | Systematic Assessment | Menstrual irregularity |
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| Difficulty sleeping | General disorders | PRISE | Systematic Assessment | Difficulty sleeping |
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| Sleeping too much | General disorders | PRISE | Systematic Assessment | Sleeping too much |
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| Loss of sexual desire | Reproductive system and breast disorders | PRISE | Systematic Assessment | Loss of sexual desire |
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| Trouble achieving orgasm | Reproductive system and breast disorders | PRISE | Systematic Assessment | Trouble achieving orgasm |
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| Trouble with erections | Reproductive system and breast disorders | PRISE | Systematic Assessment | Trouble with erections |
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| Anxiety | Psychiatric disorders | PRISE | Systematic Assessment | Anxiety |
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| Poor concentration | Psychiatric disorders | PRISE | Systematic Assessment | Poor concentration |
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| General malaise | Psychiatric disorders | PRISE | Systematic Assessment | General malaise |
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| Restlessness | Psychiatric disorders | PRISE | Systematic Assessment | Restlessness |
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| Fatigue | Psychiatric disorders | PRISE | Systematic Assessment | Fatigue |
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| Decreased energy | Psychiatric disorders | PRISE | Systematic Assessment | Decreased energy |
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| Flashing light and tingling sensation | Nervous system disorders | Spontaneous report | Non-systematic Assessment | Mild flashing light sensation in their peripheral vision and/or a tingling sensation in temples |
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| D001519 |
| Behavior |
| Fatigue |
|
| Anxiety |
|
| Flashing light/tingling |
|