Adaptive Design Study of NEST sTMS in Subjects With Major Depressive Disorder
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
N/A |
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).
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Active sTMS Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks. |
Device: 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).
|
Sham Comparator: Sham Stimulation Sham treatments to be administered using a sham device 5 times per week for six treatment weeks. |
Device: Sham Stimulation
Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Kadima Neuropsychiatry Institute | La Jolla | California | United States | 92037 |
2 | UCLA Westwood - Semel Institute for Neuroscience and Human Behavior | Los Angeles | California | United States | 90024 |
3 | Stanford University | Stanford | California | United States | 94305 |
4 | Emory University | Atlanta | Georgia | United States | 30329 |
5 | Sheppard Pratt Health System | Baltimore | Maryland | United States | 21204 |
6 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
7 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
8 | Washington University/Barnes Jewish Hospital | Saint Louis | Missouri | United States | 63110 |
9 | New York University | New York | New York | United States | 10016 |
10 | Laureate Institute for Brain Research | Tulsa | Oklahoma | United States | 74136 |
11 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
12 | Butler Hospital | Providence | Rhode Island | United States | 02906 |
13 | University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390 |
14 | Brain Health Consultants | Houston | Texas | United States | 77046 |
Sponsors and Collaborators
- Wave Neuroscience
Investigators
- Principal Investigator: Andrew Leuchter, MD, University of California, Los Angeles
Study Documents (Full-Text)
More Information
Publications
None provided.- NND-3002
Study Results
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 Detail | 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. |
Arm/Group Title | Active sTMS | Sham Stimulation |
---|---|---|
Arm/Group Description | 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). | 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. |
Period Title: Overall Study | ||
STARTED | 59 | 62 |
COMPLETED | 49 | 59 |
NOT COMPLETED | 10 | 3 |
Baseline Characteristics
Arm/Group Title | Active sTMS | Sham Stimulation | Total |
---|---|---|---|
Arm/Group Description | 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). | 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. | Total of all reporting groups |
Overall Participants | 46 | 57 | 103 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
45
(11.3)
|
46.1
(13.0)
|
45.6
(12.15)
|
Sex: Female, Male (Count of Participants) | |||
Female |
32
69.6%
|
43
75.4%
|
75
72.8%
|
Male |
14
30.4%
|
14
24.6%
|
28
27.2%
|
Race/Ethnicity, Customized (Count of Participants) | |||
Asian |
3
6.5%
|
3
5.3%
|
6
5.8%
|
Black or African American |
4
8.7%
|
4
7%
|
8
7.8%
|
Hispanic |
4
8.7%
|
5
8.8%
|
9
8.7%
|
American Indian/Alaska Native |
0
0%
|
1
1.8%
|
1
1%
|
White |
34
73.9%
|
44
77.2%
|
78
75.7%
|
Other |
1
2.2%
|
0
0%
|
1
1%
|
Region of Enrollment (participants) [Number] | |||
United States |
46
100%
|
57
100%
|
103
100%
|
Education Level (Count of Participants) | |||
Some high school or less |
0
0%
|
1
1.8%
|
1
1%
|
High school diploma |
2
4.3%
|
3
5.3%
|
5
4.9%
|
Vocational school |
3
6.5%
|
0
0%
|
3
2.9%
|
Some college |
15
32.6%
|
12
21.1%
|
27
26.2%
|
College degree |
15
32.6%
|
25
43.9%
|
40
38.8%
|
Professional or graduate degree |
11
23.9%
|
16
28.1%
|
27
26.2%
|
Outcome Measures
Title | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Active sTMS | Sham Stimulation |
---|---|---|
Arm/Group Description | 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). | 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. |
Measure Participants | 46 | 57 |
Week 1 |
5
10.9%
|
2
3.5%
|
Week 2 |
7
15.2%
|
10
17.5%
|
Week 3 |
9
19.6%
|
12
21.1%
|
Week 4 |
11
23.9%
|
10
17.5%
|
Week 5 |
12
26.1%
|
16
28.1%
|
Week 6 |
11
23.9%
|
12
21.1%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Active sTMS, Sham Stimulation |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | .814 |
Comments | ||
Method | Fisher Exact | |
Comments | The proportion of patients is compared across treatment groups using Fisher's Exact. |
Title | Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Active sTMS | Sham Stimulation |
---|---|---|
Arm/Group Description | 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). | 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. |
Measure Participants | 46 | 57 |
Baseline |
22.96
(2.81)
|
22.04
(4.01)
|
Change from Baseline to Week 1 |
-5.30
(5.14)
|
-4.33
(3.60)
|
Change from Baseline to Week 2 |
-6.63
(4.99)
|
-6.65
(4.93)
|
Change from Baseline to Week 3 |
-7.76
(5.48)
|
-7.74
(5.54)
|
Change from Baseline to Week 4 |
-7.61
(5.63)
|
-7.93
(6.19)
|
Change from Baseline to Week 5 |
-7.93
(5.81)
|
-7.95
(6.56)
|
Change from Baseline to Week 6 |
-7.57
(5.50)
|
-6.81
(6.48)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Active sTMS, Sham Stimulation |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | .872 |
Comments | ||
Method | ANCOVA | |
Comments | P-value is from analysis of covariance adjusting for baseline. |
Title | Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Active sTMS | Sham Stimulation |
---|---|---|
Arm/Group Description | 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). | 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. |
Measure Participants | 46 | 57 |
Baseline |
31.89
(4.57)
|
30.72
(5.64)
|
Change from Baseline to Week 1 |
-6.02
(8.25)
|
-5.39
(5.80)
|
Change from Baseline to Week 2 |
-7.91
(7.46)
|
-8.63
(8.20)
|
Change from Baseline to Week 3 |
-10.76
(8.57)
|
-9.47
(9.19)
|
Change from Baseline to Week 4 |
-8.89
(9.81)
|
-10.12
(9.04)
|
Change from Baseline to Week 5 |
-9.11
(8.64)
|
-10.81
(8.88)
|
Change from Baseline to Week 6 |
-9.52
(8.75)
|
-9.77
(9.56)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Active sTMS, Sham Stimulation |
---|---|---|
Comments | The null hypothesis is that the active sTMS treatment group does not differ | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | .641 |
Comments | ||
Method | ANCOVA | |
Comments | P-value is from analysis of covariance adjusting for baseline. |
Title | 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 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Subjects in the per-protocol group with IAF greater than 9.8 Hz. |
Arm/Group Title | Active sTMS (IAF > 9.8Hz) | Sham Stimulation (IAF>9.8Hz) |
---|---|---|
Arm/Group Description | 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), subgroup of those participants were found to be greater than 9.8Hz | 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. All patients analyzed and compared with other belonging to same subgroup of those with IAF greater than 9.8Hz. |
Measure Participants | 19 | 33 |
Baseline |
23.68
(2.65)
|
21.91
(3.50)
|
Change from Baseline to Week 1 |
-7.05
(6.11)
|
-4.12
(3.32)
|
Change from Baseline to Week 2 |
-8.32
(5.75)
|
-6.15
(4.27)
|
Change from Baseline to Week 3 |
-10.11
(5.37)
|
-7.70
(4.22)
|
Change from Baseline to Week 4 |
-9.89
(4.74)
|
-6.97
(4.88)
|
Change from Baseline to Week 5 |
-9.53
(6.01)
|
-6.97
(6.14)
|
Change from Baseline to Week 6 |
-9.47
(5.11)
|
-5.18
(5.72)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Active sTMS, Sham Stimulation |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | .032 |
Comments | Alpha level: .05 | |
Method | ANCOVA | |
Comments | P-value is from analysis of covariance adjusting for baseline |
Title | Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Of the 103 subjects in the original per-protocol group, 83 continued to open-label treatment for analysis. |
Arm/Group Title | Active sTMS | Sham Stimulation |
---|---|---|
Arm/Group Description | 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). | 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. |
Measure Participants | 38 | 45 |
sTMS Active Treatment Week 6/Sham Baseline |
16.50
(4.69)
|
16.76
(5.35)
|
Change from Baseline to Open-Label Week 1 (Active Week 7/Sham Week 1) |
-8.82
(5.34)
|
-3.98
(5.53)
|
Change from Baseline to Open-Label Week 2 (Active Week 8/Sham Week 2) |
-9.36
(5.96)
|
-3.69
(5.17)
|
Change from Baseline to Open-Label Week 3 (Active Week 9/Sham Week 3) |
-9.09
(6.58)
|
-4.29
(5.25)
|
Change from Baseline to Open-Label Week 4 (Active Week 10/Sham Week 4) |
-10.68
(7.34)
|
-4.51
(5.92)
|
Change from Baseline to Open-Label Week 5 (Active Week 11/Sham Week 5) |
-12.34
(6.54)
|
-5.47
(5.71)
|
Change from Baseline to Open-Label Week 6 (Active Week 12/Sham Week 6) |
-12.72
(6.97)
|
-6.42
(5.01)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Active sTMS, Sham Stimulation |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | .015 |
Comments | Alpha level: .05 | |
Method | ANCOVA | |
Comments | P-value is from analysis of covariance adjusting for baseline |
Title | Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Of the 103 subjects in the original per-protocol group, 83 continued to open-label treatment for analysis. |
Arm/Group Title | Active sTMS | Sham Stimulation |
---|---|---|
Arm/Group Description | 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). | 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. |
Measure Participants | 38 | 45 |
Open Label Week 1 (Active Week 7/Sham Week 1) |
12
26.1%
|
9
15.8%
|
Open Label Week 2 (Active Week 8/Sham Week 2) |
17
37%
|
9
15.8%
|
Open Label Week 3 (Active Week 9/Sham Week 3) |
14
30.4%
|
10
17.5%
|
Open Label Week 4 (Active Week 10/Sham Week 4) |
19
41.3%
|
10
17.5%
|
Open Label Week 5 (Active Week 11/Sham Week 5) |
23
50%
|
10
17.5%
|
Open Label Week 6 (Active Week 12/Sham Week 6) |
20
43.5%
|
12
21.1%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Active sTMS, Sham Stimulation |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | .028 |
Comments | Alpha level: .05 | |
Method | Fisher Exact | |
Comments | The proportion of patients is compared across treatment groups using Fisher's Exact. |
Adverse Events
Time Frame | All subjects screened at Screening, Baseline, and each Evaluation Visit (End of Weeks 1, 2, 3, 4, 5, 6; if continuing open-label 7, 8, 9, 10, 11, 12) | |||
---|---|---|---|---|
Adverse Event Reporting Description | All adverse events were entered by study personnel verbatim based on patient reports. Any adverse event occurring before randomization occurred was not included in the final report. | |||
Arm/Group Title | Active sTMS | Sham Stimulation | ||
Arm/Group Description | 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). | 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. | ||
All Cause Mortality |
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Active sTMS | Sham Stimulation | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/59 (0%) | 0/62 (0%) | ||
Serious Adverse Events |
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Active sTMS | Sham Stimulation | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/59 (3.4%) | 0/62 (0%) | ||
General disorders | ||||
Anaphylactic Reaction (peanut allergy) | 1/59 (1.7%) | 0/62 (0%) | ||
Psychiatric disorders | ||||
Hospitalization (Suicidal Ideation) | 1/59 (1.7%) | 0/62 (0%) | ||
Other (Not Including Serious) Adverse Events |
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Active sTMS | Sham Stimulation | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 35/59 (59.3%) | 43/62 (69.4%) | ||
Eye disorders | ||||
Visual Disturbance | 3/59 (5.1%) | 5/62 (8.1%) | ||
Gastrointestinal disorders | ||||
Diarrhea | 3/59 (5.1%) | 3/62 (4.8%) | ||
Nausea | 6/59 (10.2%) | 2/62 (3.2%) | ||
GI Infection | 0/59 (0%) | 2/62 (3.2%) | ||
General disorders | ||||
Dizziness | 3/59 (5.1%) | 1/62 (1.6%) | ||
Cramping | 0/59 (0%) | 2/62 (3.2%) | ||
Oral Herpes | 2/59 (3.4%) | 0/62 (0%) | ||
Blepharospasm | 2/59 (3.4%) | 1/62 (1.6%) | ||
Hypersensitivity | 0/59 (0%) | 2/62 (3.2%) | ||
Muscle Twitching | 2/59 (3.4%) | 0/62 (0%) | ||
Nasopharyngitis | 0/59 (0%) | 2/62 (3.2%) | ||
Musculoskeletal and connective tissue disorders | ||||
Neck Pain | 7/59 (11.9%) | 3/62 (4.8%) | ||
Jaw Discomfort | 2/59 (3.4%) | 0/62 (0%) | ||
Musculoskeletal Pain | 0/59 (0%) | 2/62 (3.2%) | ||
Back Pain | 2/59 (3.4%) | 2/62 (3.2%) | ||
Shoulder Pain | 2/59 (3.4%) | 0/62 (0%) | ||
Nervous system disorders | ||||
Headache | 23/59 (39%) | 28/62 (45.2%) | ||
Paraesthesia | 1/59 (1.7%) | 5/62 (8.1%) | ||
Psychiatric disorders | ||||
Insomnia | 5/59 (8.5%) | 8/62 (12.9%) | ||
Anxiety | 1/59 (1.7%) | 2/62 (3.2%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Respiratory Infection | 10/59 (16.9%) | 10/62 (16.1%) | ||
Skin and subcutaneous tissue disorders | ||||
Application Site Discomfort | 3/59 (5.1%) | 2/62 (3.2%) |
Limitations/Caveats
More Information
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 | Meagan Kovacs, Clinical and Regulatory Affairs Manager |
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Organization | Wave Neuroscience |
Phone | 9492292869 |
meagan@waveneuro.com |
- NND-3002