Intensive TMS for Bipolar Depression

Study Overview
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Brief Summary
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The research study is being conducted to test whether using high dose spaced theta-burst rTMS (a form of transcranial magnetic stimulation) produces a significant reduction in depressive symptoms compared with sham. This project will recruit patients aged 18-70 with symptoms of bipolar depression who have failed (or not shown signs of improvement) after at least two prior treatments.

Detailed Description
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The research study is being conducted to test whether using high dose spaced theta-burst rTMS (a form of transcranial magnetic stimulation) produces a significant reduction in depressive symptoms compared with sham. This project will recruit patients aged 18-70 with symptoms of bipolar depression who have failed (or not shown signs of improvement) after at least two prior treatments. The null hypothesis is that there will be no difference in reductions in depressive symptoms by the end of a five-day treatment period. The alternative hypothesis is that, compared with sham, active TMS will result in a greater reduction in depressive symptoms by the end of the treatment period. Participants will be randomly assigned to active or sham conditions: 50% to active and 50% to sham.

Official Title
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Intensive TMS for Rapid Relief of Bipolar Depression Symptoms

Conditions
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Bipolar Depression, Treatment Resistant Depression

Intervention / Treatment
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* Device: Intensive intermittent theta-burst stimulation (iTBS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Bipolar depression (BP I and BP II) by Diagnostic and Statistical Manual 5 (DSM 5) criteria Age 18-70 Right or left handed All genders Treatment resistant depression, as in they must have treatment resistant depression with 2 or more prior antidepressant trials that have failed to produce a response (> 50% reduction in symptoms) using ATHF criteria Able to provide informed consent to participate in the study Must be on a stable medication regimen, requiring at least one mood stabilizer Depression severity as represented by scoring at least 20 on Montgomery-Asberg Depression Rating Scale (MADRS) Exclusion Criteria: No current substance abuse disorder for the past 6 months (previous substance abuse not exclusionary) Any psychotic disorder or current active psychotic symptoms (personality disorders not exclusionary unless in the opinion of the referring psychiatrist it would jeopardize participation) No dementia or other major neurological disorders Not having depression as primary disorder No major medical illness, for example metastatic cancer, end stage renal disease Not able to verify contact information. Participants must be able to follow through with the study & must have verified contact information and at least one verified contact Pregnancy. While there are no known risks to a fetus this is a new use of TMS, which has not been tested, thus pregnancy is exclusionary Score on Young Mania Rating Scale (YMRS) greater than 12 (patients with mixed features have been shown not to respond well to TMS treatment) Rapid cycling Bipolar illness (patients with > 4 mood episodes within the past year will be excluded, as they have a higher risk of switch to mania) Any implants, conditions, or contraindications that would be deemed unsafe for TMS or MRI Currently using benzodiazepines (such as lorazepam) with a dose >1 mg per day or equivalent.

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Transcranial Magnetic Stimulation<br>Active Intensive iTBS involves intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (L-DLPFC). | Device: Intensive intermittent theta-burst stimulation (iTBS)<br>* Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region.<br>|
| Sham Comparator: Sham Transcranial Magnetic Stimulation<br>Sham Intensive iTBS involves using the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the TMS pulse, which mimics the scalp sensation from active stimulation. | Device: Intensive intermittent theta-burst stimulation (iTBS)<br>* Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy of high dose spaced theta burst (HDS-TBS) | The primary outcome will be based on the set of repeated Montgomery Asberg Depression scores (10 items rated on a 0-6 scale, 0-60 possible score range, with higher scores indicating greater depressive symptomology), obtained at baseline and on each of the five treatment days. | Through study completion, approximately 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between change in brain resting state functional connectivity and treatment effects | The main secondary outcome will be the change in correlation of the dorsal lateral prefrontal cortex (DLPFC) with limbic regions, as gathered during baseline and post stimulation MRI scans. | Upon study completion, approximately 1 week |