Recruiting

iTBS

Sponsor:

Massachusetts General Hospital

Code:

NCT06274567

Conditions

Bipolar Disorder

Eligibility Criteria

Sex: All

Age: 24 - 65

Healthy Volunteers: Not accepted

Interventions

Transcranial Magnetic Stimulation (TMS)

Sham (placebo) TMS

Study Details

Brief summary:

The objective of this study protocol is to test whether intermittent theta-burst transcranial magnetic stimulation (iTBS-TMS) to the inferior parietal lobule (IPL) can strengthen functional connectivity with a key region in emotion regulation (ER) neurocircuitry (anterior insula, AI) and improve performance on ER-related tasks in patients with bipolar disorder. Individual IPL sites for stimulation will be identified through baseline, pre-TMS functional magnetic resonance imaging (fMRI) scans. Patient-specific IPL subregions showing positive functional connectivity with the anterior insula and falling within the patient-specific frontoparietal control network will be used as individualized target sites for TMS stimulation. Patients will be randomized to receive 24 sessions of active versus sham iTBS to patient-specific IPL targets (6 sessions/day, 4 days, 43,200 pulses total). Post-iTBS resting-state and task-based fMRI scans will be acquired 3 days after the final day of iTBS administration (Day 4) following identical procedures as baseline. Effects of iTBS-TMS on ER will be evaluated by comparing pre-TMS versus post-TMS functional connectivity and behavior during performance on ER tasks.

Conditions

Bipolar Disorder

Study ID

NCT06274567

Start date

Sep 20, 2024

Status verified date

Jul, 2026

Completion date

Mar 31, 2029

Anticipated

Primary completion date

Feb 28, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 24 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. Individuals of all genders
2. ages 24-65
3. Diagnostic Statistical Manual (DSM-5) defined diagnosis of bipolar I or II disorder (BD); assessed using the Mini-International Neuropsychiatric Interview (M.I.N.I.) version 7.0.2.
4. Current depressive episode, assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) score ≥20,
5. Ability to provide informed consent and verifiable contact information, including current psychiatric treatment provider
6. Stable medication regimen for at least one month, which must include a mood stabilizer

Exclusion Criteria:

1. current mania/hypomania assessed by the Young Mania Rating Scale (YMRS > 12)
2. rapid-cycling bipolar illness, defined as >4 episodes per year, indicating increased risk of switch to mania
3. current active suicidality (suicidal ideation with intent or plan), as assessed by a score >4 on the MADRS item #10
4. current substance use disorder for the past 6 months; substance use disorder in remission permitted
5. history of psychosis
6. dementia or other major neurological disorders, as assessed by a Mini-Mental State Exam (MMSE) score <24 and Montreal Cognitive Assessment (MOCA) score <26
7. medical illness or non-psychiatric medical treatment that would likely interfere with study participation
8. contraindications for magnetic resonance imaging (MRI) or transcranial magnetic stimulation (TMS), including the presence of metallic implants that would interfere with safety (i.e. cardiac pacemaker, metal plates, non-removable body piercings, etc.), history of seizure disorder, history of head trauma
9. a clinical course of a neuromodulatory therapy (e.g. transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy) within the past 6 months
10. current use of benzodiazepines, which can interfere with iTBS stimulation
11. current pregnancy, to limit potential risks to an unborn child

Other: Given that >86% of BD patients experience lifetime comorbid anxiety, co-occurring anxiety disorders will be allowable for inclusion, thus providing a more representative sample of bipolar patients who typically present at our Clinics for treatment. Comorbid anxiety disorders are not a criteria for inclusion or exclusion.

Study Design

Enrollment

136 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Active intermittent theta burst stimulation (iTBS)

The Active intermittent theta burst stimulation (iTBS) arm will receive active iTBS applied to the inferior parietal lobule (IPL)

placebo comparator: Sham intermittent theta burst stimulation (iTBS)

The Sham intermittent theta burst stimulation (iTBS) arm will receive sham iTBS applied to the inferior parietal lobule (IPL)

Interventions

Transcranial Magnetic Stimulation (TMS)

Transcranial magnetic stimulation (TMS) is a non-invasive tool for modulating patterns of brain activation and circuit connectivity. It uses electromagnetic pulses to induce electric currents over the cortex that serve to depolarize or hyperpolarize neurons, thereby changing patterns of synaptic activity. This study uses intermittent theta burst stimulation (iTBS), an efficient TMS protocol that uses high frequency (50Hz) triplets of TMS given every 200 milliseconds (i.e. at 5 Hz).

Sham (placebo) TMS

Sham stimulation works by blocking the magnetic field with an internal spacer on the sham side of the TMS coil, allowing the operator to place the coil surface against the scalp. A brief electric pulse calibrated to the stimulator output is delivered to the scalp simultaneous to the TMS pulse to mimic the scalp sensation during the sham condition. 75 Importantly, the electric pulse is calibrated to the stimulator output to ensure a realistic sham condition.

Primary outcome measure

  • Correlated functional magnetic resonance imaging (fMRI) time series (functional connectivity) [ Time Frame: Baseline, 1-3 days post 4-day intervention (up to 4 weeks post Baseline) ]

Central Contacts and Locations

Central contacts

Locations

Martinos Center for Biomedical Imaging

Recruiting

Charlestown, Massachusetts, United States, 02129

Contacts

Principal Investigator:

Kristen K Ellard, PhD

University of Pennsylvania, Center for Neuromodulation in Depression and Stress

Recruiting

Philadelphia, Pennsylvania, United States, 19104-4283(215) 573-4229

Contacts

Principal Investigator:

Yvette Sheline, MD, MS

More Information

Sponsor

Massachusetts General Hospital

Last update posted

Jul 16, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Massachusetts General Hospital on 2026-07-16.