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RECRUITINGINTERVENTIONAL

Intermittent Theta Burst Stimulation (iTBS) for Emotion Regulation in Bipolar Disorder

Targeting Emotion Regulation in Bipolar Disorder With Intermittent Theta Burst Stimulation: A Mechanistic Study

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: 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 willing to sign a consent form and verifiable contact information, including current psychiatric treatment provider 6. Stable medication regimen for at least one month, which must include a mood stabilizer Who Should NOT Join This Trial: 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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.

Treatments Being Tested

DEVICE

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).

DEVICE

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.

Locations (2)

Martinos Center for Biomedical Imaging
Charlestown, Massachusetts, United States
University of Pennsylvania, Center for Neuromodulation in Depression and Stress
Philadelphia, Pennsylvania, United States