Open Label Optimization Study

Study Overview
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Brief Summary
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The goal of this observational study is to demonstrate effectiveness in the treatment of Major Depressive Disorder The primary objective is to assess the effectiveness in the treatment of Major Depressive Disorder using the CGI-I at the end of the treatment Participants will receive 10 treatments per day for 5 days (M-F) of SAINT®

Detailed Description
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This is a prospective, multi-center, open-label study. Up to 1000 adult subjects, in a major depressive episode, who have failed to receive satisfactory improvement from a prior antidepressant medication in the current episode, are eligible to participate in this study if they are deemed to be appropriate candidates for TMS. Overall study duration is expected to be approximately 4 years. The study duration per subject is anticipated to be approximately 1 year. Hypothesis: The SAINT® Neuromodulation System will demonstrate effectiveness in the treatment of MDD as measured by CGI-I at the end of the treatment (cessation of stimulation).

Official Title
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An Open Label Optimization Study to Assess the Effectiveness of the SAINT® Neuromodulation System (NMS) to Treat Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Device: SAINT® Neuromodulation System (NMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males or females, 18 and older, who have failed to receive satisfactory improvement from prior antidepressant medication in the current episode. Confirmed primary clinical diagnosis of major depressive disorder (MDD) without psychotic features consistent with DSM-V criteria. No medical conditions that would preclude the safe use of TMS. Primary psychiatrist has determined TMS to be an appropriate clinical option. Able to provide consent and comply with all study requirements. Negative pregnancy test at the intended time of SAINT™ 5-day acute course treatment and agreement to use effective birth control during SAINT® acute therapy. Exclusion Criteria: Have any contraindication to TMS (section 2 User Manual). Have any contraindication to receiving an MRI Participants with an abnormal brain MRI as determined by PI, study physician or designee. Deemed by the PI, study physician or designee to be a high risk of suicide or has made a suicide attempt within the last 6 months. Treatment dose with cortical depth adjustment is greater than 120% motor threshold and cannot be completed.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SAINT® Stimulation<br>All participants will receive 10 treatments per day for 5 days (M-F) of SAINT® stimulation therapy. | Device: SAINT® Neuromodulation System (NMS)<br>* The SAINT® NMS utilizes a type of accelerated iTBS delivered to a personalized treatment target derived from a functional MRI scan. SAINT® was designed to optimize the individual patient response to treatment. This novel approach to TMS is accomplished by focusing on three critical aspects of the treatment that drive effect. These aspects are personalized stimulation target, total course dose of stimulation, and neurophysiologically relevant stimulation pattern.<br>* Other names: TMS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Clinical Global Impression Improvement Scale (CGI-I) score at the end of treatment (Day 5 SAINT® therapy) | Clinical Global Impression-Improvement (CGI-I) score is based on a scale from zero (0) - Not Assessed to seven (7) Very Much Worse with lower scores showing improvement and higher scores showing little or no improvement. | End of Stimulation Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale (MADRS) score change from baseline to cessation of stimulation in comparison with bioimaging assessments MADRS score change from baseline to cessation of stimulation in comparison with bioimaging assessments | The rating is based on a clinical interview. Questions are asked using scales from zero (0) to six (6) with lower scores showing a better outcome and higher scores showing a worse outcome | Baseline to End Stimulation Day 5 | 
| Cambridge Brain Science Tools assessment score change in comparison with change in MADRS scores from baseline to cessation of stimulation | Assess aspects of cognition including reasoning, memory, attention and verbal ability on an online platform. Scores are automatically calculated on a scale from zero (0) to one hundred (100) and zero (0) to negative one hundred (-100) with positive numbers being associated with Best and negative numbers being associated with Worst | Baseline to End of Stimulation Day 5 | 
| To test the durability of the antidepressant effect by assessing the Clinical Global Impression Severity Scale (CGI-S) after cessation of stimulation | The Clinical Global Impression-Severity (CGI-S) is a brief clinician assessment that rates the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Score is based on a scale from zero (0) - Not Assessed to seven (7) Very Much Worse with lower scores showing improvement and higher scores showing little or no improvement. | 3, 6, 9, 12 month follow up visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, Depression, Treatment Resistant Depression