Bipolar Disorder (BD)Phase 4CircuitBDNCT07680153
Neuromodulation of Mood Switch Circuitry in Bipolar Disorder
A Phase 4 study testing MagVenture MagPro TMS system in people with Bipolar Disorder (BD) and Bipolar 1 Depression, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Bipolar Disorder (BD), Bipolar 1 Depression, rTMS
- What is being tested?
- MagVenture MagPro TMS system
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Aug 2026to Dec 2031
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form.
- Adults of all genders aged 18-70 at the time of screening.
- Diagnosis of Bipolar Disorder (by DSM-V criteria)
- Depressive symptoms of at least moderate severity (GRID HDRS-17 score >= 14 or as determined by expert clinician).
- Not currently taking medications for BD OR on a stable dose of medication for at least 1 month prior to screening and plans to remain off medications OR on this stable dose for the duration of participation.
- Access to psychiatric care before, during, and after completion of the study.
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- For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.
- Proficiency in English sufficient to complete assessments and follow study procedure instructions.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
Who cannot join
- Imminent risk of suicide.
- Presence of a primary DSM-5 diagnosis other than bipolar disorder (BD-I or BD-II), or a current comorbid psychiatric disorder that, in the opinion of the investigators, would confound outcome assessment or interfere with safe participation.
- History of seizures or any condition / concurrent medication that could notably lower seizure threshold.
- Met criteria for any significant substance use disorder (by DSM-V criteria) in the 6 months prior to screening.
- History or presence of significant neurological disorder (e.g., traumatic brain injury, stroke, Parkinson's disease or other movement disorder, epilepsy).
- History or presence of significant heart condition (e.g., recent myocardial infarction, congestive heart failure > stage 2, angina pectoris, bradycardia or tachycardia at the baseline assessment, uncontrolled hypertension).
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- MRI contraindication, including presence of foreign metal bodies or implants, implanted or conductive objects in or near the head (e.g., stents, deep brain stimulators, vagus nerve stimulators, aneurysm coils, ocular implants, cochlear implants), permanent make-up.
- Individuals who are nursing, pregnant, or contemplating pregnancy within the length of study participation.
- Abnormal bloodwork for electrolytes, thyroid, or liver function.
- History or presence of any disorder or medical condition that, in the opinion of the study team, may compromise, interfere, or limit the individual's ability to complete the intervention or study procedures.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Weill Cornell Medicine
New York, New York, 10065
Research Coordinator, Interventional Psychiatry Program, 646-962-2900, tmsinfo@med.cornell.edu
Immanuel Elbau, MD, PhD
About this study
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.
- Conditions
- Bipolar Disorder (BD), Bipolar 1 Depression, rTMS, fMRI
- Being tested
- MagVenture MagPro TMS system, Sham Stimulation
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MagVenture MagPro TMS systemDevice
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).
Sham StimulationDevice
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Device: MagVenture MagPro TMS system; Device: Sham Stimulation |
| 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. Receives: Device: MagVenture MagPro TMS system; Device: Sham Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 1-week post-rTMS
Secondary outcomes (1)
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.
Measured: Baseline to 1-week post-rTMS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2026
- Study start3 Aug 2026
- Primary completionSep 2031 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar Disorder (BD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- All participants will receive both active and sham repetitive transcranial magnetic stimulation in two randomized intervention phases, separated by an inter-intervention washout period.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- BD2 LLC
- Responsible party
- Sponsor
- Investigators
- Immanuel Elbau, MD, PhD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07680153
- Sponsor's protocol ID
- 26-03029924
- Other IDs
- TMI 250797-01
- Acronym
- CircuitBD
- Status last verified
- Sep 2026
- First submitted
- 25 Jun 2026
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: 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.