NeoSync TMS Treatment for Bipolar I Depression

Study Overview
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Brief Summary
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This study is designed to evaluate the safety and preliminary efficacy of synchronized transcranial magnetic stimulation (sTMS) using the NeoSync EEG Synchronized TMS device (NEST) in subjects with Bipolar Disorder type I in a Major Depressive Episode. This is an open label study in which subjects will receive treatment 5 days per week for 6 weeks.

Official Title
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Evaluation of NeoSync EEG Synchronized TMS For the Treatment of Major Depressive Episode in Bipolar Disorder and Associated Neural Response: An Open Label Trial

Conditions
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Major Depressive Episode, Bipolar Depression, Bipolar Disorder, Mood Disorders

Intervention / Treatment
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* Device: NEST (NeoSync EEG Synchronized TMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following inclusion criteria to qualify for enrollment into the study: 18 - 70 years of age; DSM-5 primary diagnosis of Bipolar Disorder type 1 (with a documented past manic episode), currently in a Major Depressive Episode by diagnostic criteria elicited by structured clinical interview (SCID-5-RV); MADRS score ≥ 20; Duration of current episode >4 weeks YMRS score ≤ 12; baseline EEG of sufficient quality for quantitative analysis processing; willing and able to adhere to the intensive treatment schedule and all required study visits; currently on adequate dose of mood stabilizer with significant evidence base or FDA approval as antimanic or for maintenance therapy of bipolar disorder (e.g, valproic acid/divalproex, carbamazepine, lithium, aripiprazole, ziprasidone, risperidone, quetiapine, olanzapine, asenapine, haloperidol, chlorpromazine, paliperidone, cariprazine). Exclusion Criteria: Subjects will be excluded from study participation if one of the following exclusion criteria applies: unable or unwilling to give informed consent; diagnosed with current primary psychotic disorder (rather than BD); diagnosed with current mania or hypomanic mood episode; history of moderate to severe substance use disorder within the past 6 months (except nicotine and caffeine); currently being treated with a stimulant; clinically defined major neurological disorder; including, but not limited to, seizure disorder and history of loss of consciousness due to head injury for greater than 10 minutes, or with documented evidence of brain injury; increased risk of seizure for any reason, including diagnosis of increased intracranial pressure, comorbid neurological disorder, use of certain medications, highly unstable use of alcohol or benzodiazepines; initiation of new antidepressant treatments (new medication, new device-based stimulation, or new psychotherapy) within 6 weeks prior to study baseline; active suicidal intent or plan as detected on screening assessments, or in the Investigator's opinion, is likely to attempt suicide within the next six months; presence of implanted cardiac pacemakers, implanted medication pumps, or intracardiac lines; intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, stents, or electrodes) or any other metal object within or near the head (excluding the mouth), which cannot be safely removed; clinically significant unstable medical condition; if female: pregnant, not using medically acceptable means of birth control, or currently breastfeeding; other condition, which in the judgment of the Investigator could prevent the subject from completion of the study; for participants in the MRI study: ferromagnetic metal implant or other contraindication to imaging in a 3 Tesla MRI; past treatment with TMS therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label, unblinded treatment series, all participants receive active treatment with the investigational device (NeoSync sTMS), as adjunct to ongoing stable pharmacotherapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sTMS active<br>Treatment with the NEST Device | Device: NEST (NeoSync EEG Synchronized TMS)<br>* The NeoSync EEG Synchronized TMS (NEST) is an electromechanical medical device that produces and delivers a sinusoidal magnetic field to areas of the brain in the treatment of Bipolar Depression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean MADRS Total Score Change (Last Observation Carried Forward) | The Montgomery-Asberg Depression Rating Scale (MADRS) will be performed as a baseline and endpoint assessments and efficacy measure. It's considered the gold standard for rating depression severity and used frequently in clinical trials. The MADRS score ranges from 0 to 60; a score of 0-6 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity. | Baseline to week 6 reported | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean HDRS-17 Total Score Change (Last Observation Carried Forward) | The Hamilton Rating Scale for Depression (HRSD-28) will be done at baseline and endpoint assessments. The HRSD-17 score, derived from the HRSD-28, will be analyzed. The HRSD-17 score ranges from 0-52; a score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity. | Baseline and week 6 | 
| Mean IDS-SR Score Change (Last Observation Carried Forward) | The Inventory of Depressive Symptomatology (IDS-SR) will be performed as a baseline and after every 5 treatments. It's a standardized self-rating scale for depressive symptom severity used in many clinical trials. IDS-SR total score ranges from 0 to 84; a score of 0-13 is generally accepted to be within the normal range (or reflect clinical remission), while a score of 26 or higher indicates at least moderate severity. Single value was average mean IDS-SR score change. | Baseline through week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sTMS, NEST, NeoSync, synchronous, non-invasive neuromodulation, TMS, transcranial magnetic stimulation, EEG, bipolar, depression