Depression, Depressive Disorder, Depressive Disorder, Major, Depressive Episode, Major Depressive Disorder
Conditions
Keywords
Transcranial Magnetic Stimulation, TMS, sTMS
Brief summary
This is a double-blind, sham controlled, multi-center study to confirm the safety and efficacy of synchronized transcranial magnetic stimulation (sTMS) for the treatment of patients currently experiencing an episode of depression who have failed to respond to at least one (1) antidepressant medication. Patients will be randomly assigned to either active or sham therapy and will undergo daily treatments for a period of time. Following completion of blinded treatments, patients may be eligible for a course of open label treatments.
Detailed description
Prospective, randomized, double-blind, sham-controlled, parallel group adaptive design study to confirm the safety and efficacy of sTMS in subject with Major Depressive Disorder (MDD) who have not responded to at least one antidepressant medication in the current episode. MDD was diagnosed according to DSM-IV criteria rendered by structured interview using the Mini International Neuropsychiatric Interview (MINI). Subjects must have discontinued any antidepressant medication a minimum of 1 week prior to initiation of treatment with the active sTMS or sham device. Following wash-out of the antidepressant medication, an additional evaluation was performed to determine whether the protocol eligibility criteria were met before randomization and treatment. Randomized subjects were treated 5 days per week for 6 weeks. Subjects who completed 6 weeks of double-blind treatment may have been eligible to receive up to 6 weeks of open-label treatment as clinically indicated during the follow-up phase of the study. Follow-up evaluation visits were conducted during those six weeks, with frequency of the visits determined by the treatment choice during that time frame (open label subjects had weekly evaluation visits for 6 weeks).
Interventions
sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF).
DEVICESham Stimulation
Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain.
Sponsors
Wave Neuroscience
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-Blind
Intervention model description
Sham Controlled
Eligibility
Sex/Gender
ALL
Age
22 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Current episode of Major Depressive Disorder * Inadequate response to at least one antidepressant medication in the current episode (Treatment Resistant Depression) * Investigator able to identify IAF using EEG * Willingness and ability to adhere to treatment schedule (5 treatments per week for six weeks)
Exclusion criteria
* Unable to unwilling to give informed consent * Diagnosed with excluded conditions or treatment histories * Currently hospitalized due to severity of depression symptoms * Use of prohibited medications (as defined by protocol) within specified time frame of randomization * Use of certain cardiac devices * Use of certain intracranial devices * Currently pregnant or unwilling to practice acceptable means of birth control, and women who are breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population | Baseline (Day 0) to End of Weeks 1, 2, 3, 4, 5, 6 | Number of participants at the end of each treatment week who saw a reduction of at least 50% in baseline Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 6, compared between the active treatment and sham-controlled groups. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6 | Change from the baseline in HAMD-17 total score from baseline to week 6, compared between the active treatment and sham-controlled groups. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression. |
| Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6 | Change from the baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to week 6, compared between the active treatment and sham-controlled groups. The MADRS scale ranges between 0-54, with higher numbers indicating more severe symptoms. 0-6 is generally accepted to be within the normal range (or in remission), 7-19 represents mild depression, while a score of 20 or higher indicates moderate to severe depression. |
| Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6 | Measure of change in mean (SD) of HAMD-17 scores from baseline to end of treatment in per-protocol patients with an Individual alpha frequency (IAF) of greater than 9.8Hz. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression. |
| Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12 | Change in HAMD-17 total score during 6 weeks of open-label treatment, compared between the active treatment and sham-controlled groups. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression. |
| Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population | Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12 | Number of participants seeing reduction of at least 50% in baseline Hamilton Depression Rating Scale (HAMD-17) scores during 6 weeks of open-label treatment, compared between the active treatment and sham-controlled groups. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited through local referral networks, as well as online study descriptions, printed flyers, and radio advertisements approved by Institutional Review Boards (IRB). Recruitment was accomplished through initial interview and in-person screening assessments determining eligibility.
Pre-assignment details
Following enrollment and completion of informed consent, participants were randomized to a treatment arm. Participants were instructed to discontinue any current antidepressant medication a minimum of 1 week prior to initiation of treatment, and confirmation of eligibility was completed after the wash-out.
Participants by arm
| Arm | Count |
|---|---|
| Active sTMS Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks.
Synchronized Transcranial Magnetic Stimulation (sTMS): sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF). | 46 |
| Sham Stimulation Sham treatments to be administered using a sham device 5 times per week for six treatment weeks.
Sham Stimulation: Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain. | 57 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Clinical Worsening | 2 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Non-compliance with study schedule | 2 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Total | Active sTMS | Sham Stimulation |
|---|---|---|---|
| Age, Continuous | 45.6 years STANDARD_DEVIATION 12.15 | 45 years STANDARD_DEVIATION 11.3 | 46.1 years STANDARD_DEVIATION 13 |
| Education Level College degree | 40 Participants | 15 Participants | 25 Participants |
| Education Level High school diploma | 5 Participants | 2 Participants | 3 Participants |
| Education Level Professional or graduate degree | 27 Participants | 11 Participants | 16 Participants |
| Education Level Some college | 27 Participants | 15 Participants | 12 Participants |
| Education Level Some high school or less | 1 Participants | 0 Participants | 1 Participants |
| Education Level Vocational school | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian/Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 6 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized Hispanic | 9 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 78 Participants | 34 Participants | 44 Participants |
| Region of Enrollment United States | 103 participants | 46 participants | 57 participants |
| Sex: Female, Male Female | 75 Participants | 32 Participants | 43 Participants |
| Sex: Female, Male Male | 28 Participants | 14 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 62 |
| other Total, other adverse events | 35 / 59 | 43 / 62 |
| serious Total, serious adverse events | 2 / 59 | 0 / 62 |
Outcome results
Primary
Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population
Number of participants at the end of each treatment week who saw a reduction of at least 50% in baseline Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 6, compared between the active treatment and sham-controlled groups. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.
Time frame: Baseline (Day 0) to End of Weeks 1, 2, 3, 4, 5, 6
Population: 121 subjects were randomized into the study. Of those, 13 subjects dropped out of the study for various reasons and 5 were excluded from per-protocol analysis, as they failed to meet protocol requirements. Per-protocol analysis was performed on the remaining 103 subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active sTMS | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population | Week 1 | 5 Participants |
| Active sTMS | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population | Week 2 | 7 Participants |
| Active sTMS | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population | Week 3 | 9 Participants |
| Active sTMS | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population | Week 4 | 11 Participants |
| Active sTMS | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population | Week 5 | 12 Participants |
| Active sTMS | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population | Week 6 | 11 Participants |
| Sham Stimulation | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population | Week 5 | 16 Participants |
| Sham Stimulation | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population | Week 1 | 2 Participants |
| Sham Stimulation | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population | Week 4 | 10 Participants |
| Sham Stimulation | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population | Week 2 | 10 Participants |
| Sham Stimulation | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population | Week 6 | 12 Participants |
| Sham Stimulation | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population | Week 3 | 12 Participants |
Comparison: Null hypothesis is that the active sTMS treatment group does not differ from the sham group with respect to the proportion of patients with clinical response at Week 6.p-value: 0.814Fisher Exact
Secondary
Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population
Number of participants seeing reduction of at least 50% in baseline Hamilton Depression Rating Scale (HAMD-17) scores during 6 weeks of open-label treatment, compared between the active treatment and sham-controlled groups. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.
Time frame: Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12
Population: Of the 103 subjects in the original per-protocol group, 83 continued to open-label treatment for analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active sTMS | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population | Open Label Week 1 (Active Week 7/Sham Week 1) | 12 Participants |
| Active sTMS | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population | Open Label Week 2 (Active Week 8/Sham Week 2) | 17 Participants |
| Active sTMS | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population | Open Label Week 3 (Active Week 9/Sham Week 3) | 14 Participants |
| Active sTMS | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population | Open Label Week 4 (Active Week 10/Sham Week 4) | 19 Participants |
| Active sTMS | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population | Open Label Week 5 (Active Week 11/Sham Week 5) | 23 Participants |
| Active sTMS | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population | Open Label Week 6 (Active Week 12/Sham Week 6) | 20 Participants |
| Sham Stimulation | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population | Open Label Week 5 (Active Week 11/Sham Week 5) | 10 Participants |
| Sham Stimulation | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population | Open Label Week 1 (Active Week 7/Sham Week 1) | 9 Participants |
| Sham Stimulation | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population | Open Label Week 4 (Active Week 10/Sham Week 4) | 10 Participants |
| Sham Stimulation | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population | Open Label Week 2 (Active Week 8/Sham Week 2) | 9 Participants |
| Sham Stimulation | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population | Open Label Week 6 (Active Week 12/Sham Week 6) | 12 Participants |
| Sham Stimulation | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population | Open Label Week 3 (Active Week 9/Sham Week 3) | 10 Participants |
p-value: 0.028Fisher Exact
Secondary
Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment
Change from the baseline in HAMD-17 total score from baseline to week 6, compared between the active treatment and sham-controlled groups. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.
Time frame: Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6
Population: 121 subjects were randomized into the study. Of those, 13 subjects dropped out of the study for various reasons and 5 were excluded from per-protocol analysis, as they failed to meet protocol requirements. Per-protocol analysis was performed on the remaining 103 subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active sTMS | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Change from Baseline to Week 2 | -6.63 score on HAMD-17 scale | Standard Deviation 4.99 |
| Active sTMS | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Change from Baseline to Week 4 | -7.61 score on HAMD-17 scale | Standard Deviation 5.63 |
| Active sTMS | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Change from Baseline to Week 1 | -5.30 score on HAMD-17 scale | Standard Deviation 5.14 |
| Active sTMS | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Change from Baseline to Week 5 | -7.93 score on HAMD-17 scale | Standard Deviation 5.81 |
| Active sTMS | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Change from Baseline to Week 3 | -7.76 score on HAMD-17 scale | Standard Deviation 5.48 |
| Active sTMS | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Change from Baseline to Week 6 | -7.57 score on HAMD-17 scale | Standard Deviation 5.5 |
| Active sTMS | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Baseline | 22.96 score on HAMD-17 scale | Standard Deviation 2.81 |
| Sham Stimulation | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Change from Baseline to Week 6 | -6.81 score on HAMD-17 scale | Standard Deviation 6.48 |
| Sham Stimulation | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Baseline | 22.04 score on HAMD-17 scale | Standard Deviation 4.01 |
| Sham Stimulation | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Change from Baseline to Week 1 | -4.33 score on HAMD-17 scale | Standard Deviation 3.6 |
| Sham Stimulation | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Change from Baseline to Week 2 | -6.65 score on HAMD-17 scale | Standard Deviation 4.93 |
| Sham Stimulation | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Change from Baseline to Week 3 | -7.74 score on HAMD-17 scale | Standard Deviation 5.54 |
| Sham Stimulation | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Change from Baseline to Week 4 | -7.93 score on HAMD-17 scale | Standard Deviation 6.19 |
| Sham Stimulation | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment | Change from Baseline to Week 5 | -7.95 score on HAMD-17 scale | Standard Deviation 6.56 |
Comparison: Null hypothesis is that the active sTMS treatment group does not differ from the sham group with respect to the proportion of patients with clinical response at Week 6.p-value: 0.872ANCOVA
Secondary
Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments
Change in HAMD-17 total score during 6 weeks of open-label treatment, compared between the active treatment and sham-controlled groups. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.
Time frame: Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12
Population: Of the 103 subjects in the original per-protocol group, 83 continued to open-label treatment for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active sTMS | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | Change from Baseline to Open-Label Week 2 (Active Week 8/Sham Week 2) | -9.36 score on HAMD-17 scale | Standard Deviation 5.96 |
| Active sTMS | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | Change from Baseline to Open-Label Week 4 (Active Week 10/Sham Week 4) | -10.68 score on HAMD-17 scale | Standard Deviation 7.34 |
| Active sTMS | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | Change from Baseline to Open-Label Week 1 (Active Week 7/Sham Week 1) | -8.82 score on HAMD-17 scale | Standard Deviation 5.34 |
| Active sTMS | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | Change from Baseline to Open-Label Week 5 (Active Week 11/Sham Week 5) | -12.34 score on HAMD-17 scale | Standard Deviation 6.54 |
| Active sTMS | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | Change from Baseline to Open-Label Week 3 (Active Week 9/Sham Week 3) | -9.09 score on HAMD-17 scale | Standard Deviation 6.58 |
| Active sTMS | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | Change from Baseline to Open-Label Week 6 (Active Week 12/Sham Week 6) | -12.72 score on HAMD-17 scale | Standard Deviation 6.97 |
| Active sTMS | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | sTMS Active Treatment Week 6/Sham Baseline | 16.50 score on HAMD-17 scale | Standard Deviation 4.69 |
| Sham Stimulation | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | Change from Baseline to Open-Label Week 6 (Active Week 12/Sham Week 6) | -6.42 score on HAMD-17 scale | Standard Deviation 5.01 |
| Sham Stimulation | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | sTMS Active Treatment Week 6/Sham Baseline | 16.76 score on HAMD-17 scale | Standard Deviation 5.35 |
| Sham Stimulation | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | Change from Baseline to Open-Label Week 1 (Active Week 7/Sham Week 1) | -3.98 score on HAMD-17 scale | Standard Deviation 5.53 |
| Sham Stimulation | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | Change from Baseline to Open-Label Week 2 (Active Week 8/Sham Week 2) | -3.69 score on HAMD-17 scale | Standard Deviation 5.17 |
| Sham Stimulation | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | Change from Baseline to Open-Label Week 3 (Active Week 9/Sham Week 3) | -4.29 score on HAMD-17 scale | Standard Deviation 5.25 |
| Sham Stimulation | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | Change from Baseline to Open-Label Week 4 (Active Week 10/Sham Week 4) | -4.51 score on HAMD-17 scale | Standard Deviation 5.92 |
| Sham Stimulation | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments | Change from Baseline to Open-Label Week 5 (Active Week 11/Sham Week 5) | -5.47 score on HAMD-17 scale | Standard Deviation 5.71 |
p-value: 0.015ANCOVA
Secondary
Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population
Change from the baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to week 6, compared between the active treatment and sham-controlled groups. The MADRS scale ranges between 0-54, with higher numbers indicating more severe symptoms. 0-6 is generally accepted to be within the normal range (or in remission), 7-19 represents mild depression, while a score of 20 or higher indicates moderate to severe depression.
Time frame: Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6
Population: 121 subjects were randomized into the study. Of those, 13 subjects dropped out of the study for various reasons and 5 were excluded from per-protocol analysis, as they failed to meet protocol requirements. Per-protocol analysis was performed on the remaining 103 subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active sTMS | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Change from Baseline to Week 2 | -7.91 score on MADRS scale | Standard Deviation 7.46 |
| Active sTMS | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Change from Baseline to Week 4 | -8.89 score on MADRS scale | Standard Deviation 9.81 |
| Active sTMS | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Change from Baseline to Week 1 | -6.02 score on MADRS scale | Standard Deviation 8.25 |
| Active sTMS | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Change from Baseline to Week 5 | -9.11 score on MADRS scale | Standard Deviation 8.64 |
| Active sTMS | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Change from Baseline to Week 3 | -10.76 score on MADRS scale | Standard Deviation 8.57 |
| Active sTMS | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Change from Baseline to Week 6 | -9.52 score on MADRS scale | Standard Deviation 8.75 |
| Active sTMS | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Baseline | 31.89 score on MADRS scale | Standard Deviation 4.57 |
| Sham Stimulation | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Change from Baseline to Week 6 | -9.77 score on MADRS scale | Standard Deviation 9.56 |
| Sham Stimulation | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Baseline | 30.72 score on MADRS scale | Standard Deviation 5.64 |
| Sham Stimulation | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Change from Baseline to Week 1 | -5.39 score on MADRS scale | Standard Deviation 5.8 |
| Sham Stimulation | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Change from Baseline to Week 2 | -8.63 score on MADRS scale | Standard Deviation 8.2 |
| Sham Stimulation | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Change from Baseline to Week 3 | -9.47 score on MADRS scale | Standard Deviation 9.19 |
| Sham Stimulation | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Change from Baseline to Week 4 | -10.12 score on MADRS scale | Standard Deviation 9.04 |
| Sham Stimulation | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population | Change from Baseline to Week 5 | -10.81 score on MADRS scale | Standard Deviation 8.88 |
Comparison: The null hypothesis is that the active sTMS treatment group does not differp-value: 0.641ANCOVA
Secondary
Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz
Measure of change in mean (SD) of HAMD-17 scores from baseline to end of treatment in per-protocol patients with an Individual alpha frequency (IAF) of greater than 9.8Hz. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.
Time frame: Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6
Population: Subjects in the per-protocol group with IAF greater than 9.8 Hz.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active sTMS | Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Change from Baseline to Week 2 | -8.32 score on HAMD-17 scale | Standard Deviation 5.75 |
| Active sTMS | Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Change from Baseline to Week 4 | -9.89 score on HAMD-17 scale | Standard Deviation 4.74 |
| Active sTMS | Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Change from Baseline to Week 1 | -7.05 score on HAMD-17 scale | Standard Deviation 6.11 |
| Active sTMS | Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Change from Baseline to Week 5 | -9.53 score on HAMD-17 scale | Standard Deviation 6.01 |
| Active sTMS | Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Change from Baseline to Week 3 | -10.11 score on HAMD-17 scale | Standard Deviation 5.37 |
| Active sTMS | Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Change from Baseline to Week 6 | -9.47 score on HAMD-17 scale | Standard Deviation 5.11 |
| Active sTMS | Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Baseline | 23.68 score on HAMD-17 scale | Standard Deviation 2.65 |
| Sham Stimulation | Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Change from Baseline to Week 6 | -5.18 score on HAMD-17 scale | Standard Deviation 5.72 |
| Sham Stimulation | Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Baseline | 21.91 score on HAMD-17 scale | Standard Deviation 3.5 |
| Sham Stimulation | Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Change from Baseline to Week 1 | -4.12 score on HAMD-17 scale | Standard Deviation 3.32 |
| Sham Stimulation | Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Change from Baseline to Week 2 | -6.15 score on HAMD-17 scale | Standard Deviation 4.27 |
| Sham Stimulation | Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Change from Baseline to Week 3 | -7.70 score on HAMD-17 scale | Standard Deviation 4.22 |
| Sham Stimulation | Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Change from Baseline to Week 4 | -6.97 score on HAMD-17 scale | Standard Deviation 4.88 |
| Sham Stimulation | Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz | Change from Baseline to Week 5 | -6.97 score on HAMD-17 scale | Standard Deviation 6.14 |
p-value: 0.032ANCOVA