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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active sTMS | Experimental | Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks. |
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| Sham Stimulation | Sham Comparator | Sham treatments to be administered using a sham device 5 times per week for six treatment weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Synchronized Transcranial Magnetic Stimulation (sTMS) | Device | sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline (Day 0) to End of Weeks 1, 2, 3, 4, 5, 6 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Andrew Leuchter, MD | University of California, Los Angeles | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kadima Neuropsychiatry Institute | La Jolla | California | 92037 | United States | ||
| UCLA Westwood - Semel Institute for Neuroscience and Human Behavior |
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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 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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 7, 2018 | Jul 7, 2021 |
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Sham Controlled
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Double-Blind
| Sham Stimulation | Device | Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain. |
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| Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6 |
| 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. | Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6 |
| 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. | Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6 |
| 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. | Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12 |
| 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. | Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12 |
| Los Angeles |
| California |
| 90024 |
| United States |
| Stanford University | Stanford | California | 94305 | United States |
| Emory University | Atlanta | Georgia | 30329 | United States |
| Sheppard Pratt Health System | Baltimore | Maryland | 21204 | United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| Washington University/Barnes Jewish Hospital | St Louis | Missouri | 63110 | United States |
| New York University | New York | New York | 10016 | United States |
| Laureate Institute for Brain Research | Tulsa | Oklahoma | 74136 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Butler Hospital | Providence | Rhode Island | 02906 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| Brain Health Consultants | Houston | Texas | 77046 | United States |
| FG001 | 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. |
| COMPLETED |
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| NOT COMPLETED |
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Baseline demographics taken from the per-protocol (PP) population; the PP group includes all participants who signed an informed consent, met study criteria, were randomized to a treatment arm, received at least 80% (24/30) of scheduled treatments within 60 days and completed the required treatment and post-baseline assessments in the double-blind phase
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Education Level | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. | 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. | Posted | Count of Participants | Participants | Baseline (Day 0) to End of Weeks 1, 2, 3, 4, 5, 6 |
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| 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. | 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. | Posted | Mean | Standard Deviation | score on HAMD-17 scale | Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6 |
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| 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. | 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. | Posted | Mean | Standard Deviation | score on MADRS scale | Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6 |
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| 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. | Subjects in the per-protocol group with IAF greater than 9.8 Hz. | Posted | Mean | Standard Deviation | score on HAMD-17 scale | Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6 |
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| 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. | Of the 103 subjects in the original per-protocol group, 83 continued to open-label treatment for analysis. | Posted | Mean | Standard Deviation | score on HAMD-17 scale | Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12 |
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| 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. | Of the 103 subjects in the original per-protocol group, 83 continued to open-label treatment for analysis. | Posted | Count of Participants | Participants | Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12 |
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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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Active 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). | 0 | 59 | 2 | 59 | 35 | 59 |
| EG001 | 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. | 0 | 62 | 0 | 62 | 43 | 62 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization (Suicidal Ideation) | Psychiatric disorders | Non-systematic Assessment | Patient exhibited increased depressive symptoms and suicidal ideation and was subsequently admitted to the hospital for suicidal ideation. |
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| Anaphylactic Reaction (peanut allergy) | General disorders | Non-systematic Assessment | Subject in Open-label portion of study had anaphylactic reaction to peanuts and was admitted to hospital for treatment. Subject continued treatment normally. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Application Site Discomfort | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Dizziness | General disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Insomnia | Psychiatric disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Neck Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Respiratory Infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Visual Disturbance | Eye disorders | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | Systematic Assessment |
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| Anxiety | Psychiatric disorders | Systematic Assessment |
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| Cramping | General disorders | Systematic Assessment |
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| GI Infection | Gastrointestinal disorders | Systematic Assessment |
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| Oral Herpes | General disorders | Systematic Assessment |
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| Blepharospasm | General disorders | Systematic Assessment |
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| Hypersensitivity | General disorders | Systematic Assessment |
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| Jaw Discomfort | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Muscle Twitching | General disorders | Systematic Assessment |
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| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Nasopharyngitis | General disorders | Systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Shoulder Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Meagan Kovacs, Clinical and Regulatory Affairs Manager | Wave Neuroscience | 9492292869 | meagan@waveneuro.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 26, 2018 | Jul 7, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D003863 | Depression |
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| Male |
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| Black or African American |
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| Hispanic |
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| American Indian/Alaska Native |
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| White |
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| Other |
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| High school diploma |
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| Vocational school |
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| Some college |
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| College degree |
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| Professional or graduate degree |
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