Neuromodulation of Mood Switch Circuitry in Bipolar Disorder
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-70
SponsorWeill Medical College of Cornell University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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).
Disqualifiers
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.
Trial design
Design model
Crossover
Treatments tested in this trial
MagVenture MagPro TMS system
DeviceTANS-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 Stimulation
DeviceAn 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).
Treatment groups
62 Participants
are divided into 2 treatment groupsGroup A: Active rTMS followed by Sham rTMSExperimental treatment 2 interventions
Group B: Sham rTMS followed by Active rTMSExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
Baseline to 1-week post-rTMSSecondary 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.
Time frame
Baseline to 1-week post-rTMSSponsors and contacts
Click on the lead sponsor to view all of their trials.
Weill Medical College of Cornell University
Lead sponsor
BD2 LLC
Collaborator
Source ClinicalTrials.gov