Trial Outcomes & Findings for Adaptive Design Study of NEST sTMS in Subjects With Major Depressive Disorder (NCT NCT03288714)

Last Updated: 2021-09-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

121 participants

Primary outcome timeframe

Baseline (Day 0) to End of Weeks 1, 2, 3, 4, 5, 6

Results posted on

2021-09-05

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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).	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.
Overall Study STARTED	59	62
Overall Study COMPLETED	49	59
Overall Study NOT COMPLETED	10	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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.
Overall Study Lost to Follow-up	2	1
Overall Study Non-compliance with study schedule	2	0
Overall Study Withdrawal by Subject	3	1
Overall Study Clinical Worsening	2	1
Overall Study Adverse Event	1	0

Baseline Characteristics

Adaptive Design Study of NEST sTMS in Subjects With Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active sTMS n=46 Participants 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 Stimulation n=57 Participants 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 n=103 Participants Total of all reporting groups
Age, Continuous	45 years STANDARD_DEVIATION 11.3 • n=5 Participants	46.1 years STANDARD_DEVIATION 13.0 • n=7 Participants	45.6 years STANDARD_DEVIATION 12.15 • n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	43 Participants n=7 Participants	75 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized American Indian/Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	34 Participants n=5 Participants	44 Participants n=7 Participants	78 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	46 participants n=5 Participants	57 participants n=7 Participants	103 participants n=5 Participants
Education Level Some high school or less	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Education Level High school diploma	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Education Level Vocational school	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Education Level Some college	15 Participants n=5 Participants	12 Participants n=7 Participants	27 Participants n=5 Participants
Education Level College degree	15 Participants n=5 Participants	25 Participants n=7 Participants	40 Participants n=5 Participants
Education Level Professional or graduate degree	11 Participants n=5 Participants	16 Participants n=7 Participants	27 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active sTMS n=46 Participants 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 Stimulation n=57 Participants 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.
Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population Week 1	5 Participants	2 Participants
Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population Week 2	7 Participants	10 Participants
Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population Week 3	9 Participants	12 Participants
Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population Week 4	11 Participants	10 Participants
Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population Week 5	12 Participants	16 Participants
Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population Week 6	11 Participants	12 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active sTMS n=46 Participants 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 Stimulation n=57 Participants 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.
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	22.04 score on HAMD-17 scale Standard Deviation 4.01
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	-4.33 score on HAMD-17 scale Standard Deviation 3.60
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	-6.65 score on HAMD-17 scale Standard Deviation 4.93
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	-7.74 score on HAMD-17 scale Standard Deviation 5.54
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	-7.93 score on HAMD-17 scale Standard Deviation 6.19
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	-7.95 score on HAMD-17 scale Standard Deviation 6.56
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 5.50	-6.81 score on HAMD-17 scale Standard Deviation 6.48

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active sTMS n=46 Participants 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 Stimulation n=57 Participants 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.
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	-10.12 score on MADRS scale Standard Deviation 9.04
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	-9.77 score on MADRS scale Standard Deviation 9.56
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	30.72 score on MADRS scale Standard Deviation 5.64
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	-5.39 score on MADRS scale Standard Deviation 5.80
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	-8.63 score on MADRS scale Standard Deviation 8.20
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	-9.47 score on MADRS scale Standard Deviation 9.19
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	-10.81 score on MADRS scale Standard Deviation 8.88

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Active sTMS n=19 Participants 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 Stimulation n=33 Participants 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.
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	21.91 score on HAMD-17 scale Standard Deviation 3.50
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	-4.12 score on HAMD-17 scale Standard Deviation 3.32
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	-6.15 score on HAMD-17 scale Standard Deviation 4.27
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	-7.70 score on HAMD-17 scale Standard Deviation 4.22
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	-6.97 score on HAMD-17 scale Standard Deviation 4.88
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	-6.97 score on HAMD-17 scale Standard Deviation 6.14
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	-5.18 score on HAMD-17 scale Standard Deviation 5.72

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Active sTMS n=38 Participants 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 Stimulation n=45 Participants 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.
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	16.76 score on HAMD-17 scale Standard Deviation 5.35
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	-3.98 score on HAMD-17 scale Standard Deviation 5.53
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	-3.69 score on HAMD-17 scale Standard Deviation 5.17
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	-4.29 score on HAMD-17 scale Standard Deviation 5.25
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	-4.51 score on HAMD-17 scale Standard Deviation 5.92
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	-5.47 score on HAMD-17 scale Standard Deviation 5.71
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	-6.42 score on HAMD-17 scale Standard Deviation 5.01

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Active sTMS n=38 Participants 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 Stimulation n=45 Participants 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.
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	10 Participants
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	9 Participants
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	9 Participants
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	10 Participants
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	10 Participants
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	12 Participants

Adverse Events

Active sTMS

Serious events: 2 serious events

Other events: 35 other events

Deaths: 0 deaths

Sham Stimulation

Serious events: 0 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Active sTMS n=59 participants at risk 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 Stimulation n=62 participants at risk 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.
Psychiatric disorders Hospitalization (Suicidal Ideation)	1.7% 1/59 • 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) 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.	0.00% 0/62 • 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) 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.
General disorders Anaphylactic Reaction (peanut allergy)	1.7% 1/59 • 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) 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.	0.00% 0/62 • 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) 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.

Other adverse events

Additional Information

Meagan Kovacs, Clinical and Regulatory Affairs Manager

Wave Neuroscience

Phone: 9492292869

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Active sTMS n=59 participants at risk 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 Stimulation n=62 participants at risk 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.
Skin and subcutaneous tissue disorders Application Site Discomfort	5.1% 3/59 • 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) 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.	3.2% 2/62 • 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) 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.
Gastrointestinal disorders Diarrhea	5.1% 3/59 • 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) 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.	4.8% 3/62 • 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) 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.
General disorders Dizziness	5.1% 3/59 • 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) 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.	1.6% 1/62 • 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) 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.
Nervous system disorders Headache	39.0% 23/59 • 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) 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.	45.2% 28/62 • 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) 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.
Psychiatric disorders Insomnia	8.5% 5/59 • 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) 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.	12.9% 8/62 • 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) 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.
Gastrointestinal disorders Nausea	10.2% 6/59 • 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) 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.	3.2% 2/62 • 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) 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.
Musculoskeletal and connective tissue disorders Neck Pain	11.9% 7/59 • 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) 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.	4.8% 3/62 • 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) 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.
Respiratory, thoracic and mediastinal disorders Respiratory Infection	16.9% 10/59 • 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) 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.	16.1% 10/62 • 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) 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.
Eye disorders Visual Disturbance	5.1% 3/59 • 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) 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.	8.1% 5/62 • 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) 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.
Nervous system disorders Paraesthesia	1.7% 1/59 • 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) 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.	8.1% 5/62 • 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) 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.
Psychiatric disorders Anxiety	1.7% 1/59 • 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) 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.	3.2% 2/62 • 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) 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.
General disorders Cramping	0.00% 0/59 • 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) 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.	3.2% 2/62 • 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) 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.
Gastrointestinal disorders GI Infection	0.00% 0/59 • 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) 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.	3.2% 2/62 • 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) 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.
General disorders Oral Herpes	3.4% 2/59 • 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) 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.	0.00% 0/62 • 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) 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.
General disorders Blepharospasm	3.4% 2/59 • 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) 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.	1.6% 1/62 • 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) 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.
General disorders Hypersensitivity	0.00% 0/59 • 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) 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.	3.2% 2/62 • 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) 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.
Musculoskeletal and connective tissue disorders Jaw Discomfort	3.4% 2/59 • 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) 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.	0.00% 0/62 • 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) 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.
General disorders Muscle Twitching	3.4% 2/59 • 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) 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.	0.00% 0/62 • 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) 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.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.00% 0/59 • 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) 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.	3.2% 2/62 • 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) 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.
General disorders Nasopharyngitis	0.00% 0/59 • 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) 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.	3.2% 2/62 • 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) 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.
Musculoskeletal and connective tissue disorders Back Pain	3.4% 2/59 • 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) 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.	3.2% 2/62 • 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) 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.
Musculoskeletal and connective tissue disorders Shoulder Pain	3.4% 2/59 • 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) 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.	0.00% 0/62 • 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) 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.