iTBS in Bipolar I Depression

Study Overview
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Brief Summary
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A multisite, open label pilot study to investigate the efficacy and safety of a novel accelerated intermittent theta-burst stimulation (iTBS) protocol while assessing for changes in neuroimaging biomarkers associated with treatment response.

Official Title
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A Pilot Study of iTBS in Bipolar I Depression

Conditions
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Bipolar Depression, Bipolar I Disorder

Intervention / Treatment
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* Device: Magnus Transcranial Magnetic Neuromodulation System (MNS) with SAINT®(Stanford Accelerated Intelligent Neuromodulation Therapy)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 22-65 years of age Bipolar I disorder diagnosis as defined by The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Currently experiencing a Major Depressive Episode with Montgomery-Asberg Depression Rating Scale (MADRS) >/= 20 at screening [Day -5/-14] and baseline [Day 0] On a stable and adequate dose of an anti-manic agent (Lithium with a level of at least 0.6, Depakote with a level of at least 50, or a therapeutic dose of carbamazepine, oxcarbazepine, or a neuroleptic for treatment of mania per clinician judgment) without dose changes for at least 6 weeks prior to the active study time period. Final assessment of appropriateness of participant's pharmacologic regimen is subject to study team clinician judgment. Having failed a therapeutic trial of a first line bipolar depression antidepressant (as specified by the Antidepressant Treatment History Form and updated with new medications approved by the FDA for treatment of bipolar depression) in this current episode. This includes a minimum 4 week trial of one of the following medications (minimum dosage): lithium 900mg daily (or blood level >= 0.6 milliequivalent/Liter (mEq/L), carbamazepine 400mg daily (or blood level >= 0.8 mEq/L), lamotrigine 200mg daily, asenapine 20mg daily, lurasidone 20mg daily, olanzapine 10mg daily, quetiapine 300mg daily, or lumateperone 42mg daily. Final determination of a failed adequate therapeutic trial is subject to study team clinician judgement. Established outpatient psychiatrist Exclusion Criteria: Female that is pregnant or breastfeeding, or of childbearing potential but not using medically acceptable birth control during study Current mixed episode assessed by clinician judgment as defined by DSM-5 criteria Current active substance use disorder (as defined by DSM-5) with exception of nicotine and caffeine. Participants may be subject to urine drug screen base on study team clinician judgment. Participation in any clinical trial with an investigational drug or device within the last 3 month or concurrent to study participation History of epilepsy, shrapnel or metal in the head or skull, cardiovascular disease/event, Obsessive Compulsive Disorder, or autism spectrum disorder 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 documented evidence of brain injury Active suicidal risk based on investigator's clinical judgment Clinically significant unstable medical condition Other condition judged by investigator that could prevent the participant from completion of the study (such as but not limited to, significant physical disability (e.g., hearing/visual deficits) to perform a neutral memory task and/or neuropsychological test battery) Ferromagnetic metal implant or another contraindication to imaging in a 3 Tesla MRI Electroconvulsive therapy (ECT) treatment in the past 3 months Minimum of 6 months since last manic or hypomanic episode as defined by DSM-5 criteria

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 65 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment Arm<br>Open label study, all participants will receive novel iTBS | Device: Magnus Transcranial Magnetic Neuromodulation System (MNS) with SAINT®(Stanford Accelerated Intelligent Neuromodulation Therapy)<br>* Novel intermittent theta burst stimulation protocol with individualized targets in the brain for stimulation using structural and functional MRI inputs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery-Asberg Depression Rating Scale (MADRS) score | The MADRS is a ten-item clinician rated questionnaire that helps rate the severity of depression. Total scores can range from 0 to 60, with higher scores indicating greater severity of depression (0-6 normal range, 7-19 mild depression, 20-34 moderate depression, >34 severe depression). | Baseline, at post treatment up to 5 days |