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| ID | Type | Description | Link |
|---|---|---|---|
| TMI 250797-01 | Other Grant/Funding Number | BD2 LLC |
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| Name | Class |
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| BD2 LLC | UNKNOWN |
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This study is exploring a new approach to treating depression in people with bipolar disorder (BD). Investigators are testing whether a non-invasive form of brain stimulation can help us understand depressed-to-euthymic mood shifts and their related brain circuits in BD.
Investigators in this study will use a technique called repetitive transcranial magnetic stimulation, or rTMS. It uses non-invasive magnetic pulses delivered to the scalp to stimulate specific areas of the brain. rTMS is already used to treat depression, and investigators are now studying whether it can be made even more effective for people with bipolar disorder by precisely targeting an individualized brain region for each participant. Participants in this study will receive two courses of rTMS, one active and one placebo (called "sham"), in a randomized order so investigators can directly compare the effects. Before treatment, investigators will use brain scans (MRI) to create a personalized map of each participant's brain activity. This lets investigators identify the exact stimulation target most likely to influence the brain circuits involved in BD mood shifts. Investigators will track mood symptoms closely throughout the study to measure what changes.
Investigators believe that depression in BD is partly driven by disrupted communication between two brain regions involved in processing what feels important or rewarding. Investigators want to find out whether rTMS can restore that communication and whether doing so leads to measurable improvements in depression.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active rTMS followed by Sham rTMS | Experimental | Active rTMS administered during Intervention Phase 1; Sham rTMS (no active TMS pulses) administered during Intervention Phase 2. Participants will undergo two 5-day rTMS intervention phases (5 days of active stimulation followed by 5 days of sham stimulation) separated by a variable 4-12 week washout period. |
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| Sham rTMS followed by Active rTMS | Experimental | Sham rTMS (no active TMS pulses) administered during Intervention Phase 1; Active rTMS administered during Intervention Phase 2. Participants will undergo two 5-day rTMS intervention phases (5 days of sham stimulation followed by 5 days of active stimulation) separated by a variable 4-12 week washout period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MagVenture MagPro TMS system | Device | TANS-guided SAL Acc iTBS approach: Targeted Functional Network Stimulation (TANS) combines precision functional mapping (PFM) with electric field (E-field) modeling to individualize circuit targeting. Active rTMS will be intermittent theta burst simulation (iTBS) delivered to the salience network (SAL) with an accelerated intervention protocol (up to 5 consecutive days of 10 hourly active rTMS sessions). |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline to 1-Week Post-rTMS in Montgomery-Asberg Depression Rating Scale (MADRS) Score | Within-participant difference in change in depression, measured by score on the Montgomery-Asberg Depression Rating Scale (MADRS), in the active intervention phase vs. the sham intervention phase. The minimum MADRS score is 0 and the maximum MADRS score is 60, with higher scores indicating greater depression severity. The primary analysis uses a linear mixed-effects model with fixed effects for time (pre/post), condition (active/sham), intervention phase, and randomization sequence, with a subject-specific random intercept. The primary endpoint is the time × condition interaction, reflecting differential symptom change for active versus sham rTMS. | Baseline to 1-week post-rTMS |
| Measure | Description | Time Frame |
|---|---|---|
| Change in salience network functional connectivity in active vs. sham rTMS | Within-participant difference in change in salience network functional connectivity (FC) in the active intervention phase vs. the sham intervention phase. Difference will be measured as pre-to-post rTMS change in FC between ventral striatum and anterior cingulate nodes of the salience network, with higher scores indicating greater FC. The secondary analysis also uses a linear mixed-effects model with fixed effects for time (pre/post), condition (active/sham), intervention phase, and randomization sequence, with a subject-specific random intercept. The primary endpoint is the time × condition interaction, reflecting differential change in FC for active versus sham rTMS. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Research Coordinator, Interventional Psychiatry Program | Contact | 646-962-2900 | tmsinfo@med.cornell.edu |
| Name | Affiliation | Role |
|---|---|---|
| Immanuel Elbau, MD, PhD | Weill Medical College of Cornell University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Weill Cornell Medicine | New York | New York | 10065 | United States |
Individual participant data that underlie the results reported in the primary outcomes publication, after de-identification, will be shared. Supporting documents including the study protocol and informed consent form will be available. Analytic pipelines used in published analyses will be made publicly available via GitHub.
IPD will be available to researchers who provide a methodologically sound proposal, beginning 6 months and ending 6 years following article publication.
De-identified IPD provided in the primary outcomes publication may be provided to qualified researchers who submit a methodologically sound proposal to the study PI. To gain access, data requestors will need to sign a data sharing agreement. Data will shared via a secure, encrypted file transfer system.
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| ID | Term |
|---|---|
| D001714 | Bipolar Disorder |
| ID | Term |
|---|---|
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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All participants will receive both active and sham repetitive transcranial magnetic stimulation in two randomized intervention phases, separated by an inter-intervention washout period.
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| Sham Stimulation | Device | An Active/Placebo (A/P) sham TMS coil will be used to deliver placebo stimulation. The A/P coil is a double-sided coil in which one side delivers effective magnetic stimulation, while the opposite side is configured to produce a sham condition without inducing cortical activation. Sham stimulation will also be delivered to the salience network (SAL) with an accelerated intervention protocol (up to 5 consecutive days of 10 hourly sham rTMS sessions). |
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| Baseline to 1-week post-rTMS |