Effects of Theta Burst Stimulation on the Brain, Behavior, and Clinical Symptoms in Adults With Bipolar Disorder

NCT ID: NCT04696471

Last Updated: 2026-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-06
• Study Completion Date: 2025-10-24

Brief Summary

Bipolar Disorder (BD) is a common and highly debilitating psychiatric disorder, however, the predisposing brain mechanisms are poorly understood. Here, the investigators aim to examine the immediate effect of transcranial brain stimulation (TBS) on brain activity and emotions in adults with and without BD as a first stage toward understanding the predisposing brain mechanisms of BD. The investigators hypothesize that TBS will reduce brain activity while playing a game with rewards in all adults, but the TBS will reduce brain activity more in the adults with BD compared to adults without BD. Furthermore, the investigators hypothesize that this reduced brain activity will be associated with reduced BD symptoms, such as negative emotions.

Detailed Description

This study aims to examine the effects of noninvasive stimulation on brain activity as measured by functional magnetic resonance imaging (fMRI) in participants with and without Bipolar I Disorder. Eligible participants will undergo 5 study visits: a screening visit, a baseline MRI visit, and 3 cTBS visits. Participants will receive brain stimulation and undergo fMRI scanning at each of the 3 cTBS study visits, however, at one of the visits, the brain stimulation will be a sham. The research associates and participants will be blinded to when the sham occurs, which will be randomized beforehand. Certain information is withheld to protect the scientific integrity of the study design

Conditions

Bipolar Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Left ventrolateral prefrontal cortex (vlPFC)/Left SS/Left vlPFC sham

A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned:

• left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex)
• left SS cTBS (cTBS applied to the left somatosensory area)
• left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham.

Group Type: EXPERIMENTAL

Continuous Theta Burst Stimulation (cTBS)

Intervention Type: DEVICE

cTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely. It is FDA-approved as a treatment for psychological conditions including depression; however, this device is not approved for the treatment of adults with Bipolar Disorder I or for use in healthy adults. This research study is using the cTBS off label in all participants (those with and without Bipolar Disorder I) to examine research questions

Sham Continuous Theta Burst Stimulation (Sham cTBS)

Intervention Type: DEVICE

Sham cTBS goes through the motions of applying cTBS to the brain but administers very low current so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells. Participants will know that one session will be a sham, but they will be blinded to which session is the sham

Left vlPFC/Left vlPFC sham/Left SS

A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned:

• left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex)
• left SS cTBS (cTBS applied to the left somatosensory area)
• left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham.

Group Type: EXPERIMENTAL

Continuous Theta Burst Stimulation (cTBS)

Intervention Type: DEVICE

cTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely. It is FDA-approved as a treatment for psychological conditions including depression; however, this device is not approved for the treatment of adults with Bipolar Disorder I or for use in healthy adults. This research study is using the cTBS off label in all participants (those with and without Bipolar Disorder I) to examine research questions

Sham Continuous Theta Burst Stimulation (Sham cTBS)

Intervention Type: DEVICE

Sham cTBS goes through the motions of applying cTBS to the brain but administers very low current so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells. Participants will know that one session will be a sham, but they will be blinded to which session is the sham

Left SS/Left vlPFC sham/Left vlPFC

A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned:

• left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex)
• left SS cTBS (cTBS applied to the left somatosensory area)
• left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham.

Group Type: EXPERIMENTAL

Continuous Theta Burst Stimulation (cTBS)

Intervention Type: DEVICE

cTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely. It is FDA-approved as a treatment for psychological conditions including depression; however, this device is not approved for the treatment of adults with Bipolar Disorder I or for use in healthy adults. This research study is using the cTBS off label in all participants (those with and without Bipolar Disorder I) to examine research questions

Sham Continuous Theta Burst Stimulation (Sham cTBS)

Intervention Type: DEVICE

Sham cTBS goes through the motions of applying cTBS to the brain but administers very low current so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells. Participants will know that one session will be a sham, but they will be blinded to which session is the sham

Left SS/Left vlPFC/Left vlPFC sham

A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned:

• left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex)
• left SS cTBS (cTBS applied to the left somatosensory area)
• left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham.

Group Type: EXPERIMENTAL

Continuous Theta Burst Stimulation (cTBS)

Intervention Type: DEVICE

cTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely. It is FDA-approved as a treatment for psychological conditions including depression; however, this device is not approved for the treatment of adults with Bipolar Disorder I or for use in healthy adults. This research study is using the cTBS off label in all participants (those with and without Bipolar Disorder I) to examine research questions

Sham Continuous Theta Burst Stimulation (Sham cTBS)

Intervention Type: DEVICE

Sham cTBS goes through the motions of applying cTBS to the brain but administers very low current so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells. Participants will know that one session will be a sham, but they will be blinded to which session is the sham

Left vlPFC sham/Left SS/Left vlPFC

A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned:

• left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex)
• left SS cTBS (cTBS applied to the left somatosensory area)
• left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham.

Group Type: EXPERIMENTAL

Continuous Theta Burst Stimulation (cTBS)

Intervention Type: DEVICE

cTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely. It is FDA-approved as a treatment for psychological conditions including depression; however, this device is not approved for the treatment of adults with Bipolar Disorder I or for use in healthy adults. This research study is using the cTBS off label in all participants (those with and without Bipolar Disorder I) to examine research questions

Sham Continuous Theta Burst Stimulation (Sham cTBS)

Intervention Type: DEVICE

Sham cTBS goes through the motions of applying cTBS to the brain but administers very low current so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells. Participants will know that one session will be a sham, but they will be blinded to which session is the sham

Left vlPFC sham/Left vlPFC/Left SS

A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned:

• left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex)
• left SS cTBS (cTBS applied to the left somatosensory area)
• left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham.

Group Type: EXPERIMENTAL

Continuous Theta Burst Stimulation (cTBS)

Intervention Type: DEVICE

cTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely. It is FDA-approved as a treatment for psychological conditions including depression; however, this device is not approved for the treatment of adults with Bipolar Disorder I or for use in healthy adults. This research study is using the cTBS off label in all participants (those with and without Bipolar Disorder I) to examine research questions

Sham Continuous Theta Burst Stimulation (Sham cTBS)

Intervention Type: DEVICE

Sham cTBS goes through the motions of applying cTBS to the brain but administers very low current so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells. Participants will know that one session will be a sham, but they will be blinded to which session is the sham

Interventions

Continuous Theta Burst Stimulation (cTBS)

cTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely. It is FDA-approved as a treatment for psychological conditions including depression; however, this device is not approved for the treatment of adults with Bipolar Disorder I or for use in healthy adults. This research study is using the cTBS off label in all participants (those with and without Bipolar Disorder I) to examine research questions

Intervention Type: DEVICE

Sham Continuous Theta Burst Stimulation (Sham cTBS)

Sham cTBS goes through the motions of applying cTBS to the brain but administers very low current so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells. Participants will know that one session will be a sham, but they will be blinded to which session is the sham

Intervention Type: DEVICE

Other Intervention Names

Transcranial Magnetic Stimulation (TMS); Sham Transcranial Magnetic Stimulation (Sham TMS)

Eligibility Criteria

Inclusion Criteria

1. All participants

• 18-35 years of age
• Scoring less than or equal to 8 on the Hamilton Rating Scale for Depression (HRSD) at screen visit

2. Participants with Bipolar Disorder (BD)

• Diagnosis of Bipolar Disorder I/II (BDI/II) (DSM-5 criteria) in remission (euthymic for >2 months) or with mild-moderate hypomania
• <15 on the Young Mania Rating Scale
• Not psychotic
• <3 on delusions, hallucinations, unusual thought content, and conceptual disorganization items of the Positive and Negative Syndrome Scale (PANSS)
• Unmedicated or on any combination (except antidepressant monotherapy) of anxiolytics (benzodiazepines, buspirone, pregabalin, hydroxyzine) as needed, and/or atypical antipsychotics, and/or lithium, and/or other mood stabilizers, and/or non-SNRI antidepressants and/or non benzodiazepine hypnotics taken for >2 months, as these are commonly-prescribed medications for BD

3. Participants without Bipolar Disorder

• No present or lifetime history of BD or psychiatric disorder other than anxiety or non BD mood disorders
• Not in a current depressive episode
• No family history of BD

3. Participants without Bipolar Disorder

• Present/ lifetime history of any psychiatric disorder other than anxiety and non BD mood disorders
• Family history of of BD

Exclusion Criteria

1. All participants

• History of head injury, neurological, pervasive developmental disorder (e.g. autism), systemic medical disease and treatment (medical records, participant report)
• Family history of epilepsy (TBS exclusion criterion)
• Use of substances with seizure risk (e.g., stimulants) in the past month, assessed as at screening, baseline, and before each fMRI-cTBS-fMRI session
• Mini-Mental State Examination score (cognitive state) <24
• Premorbid National Adult Reading Test Intelligent Quotient estimate<85
• Visual disturbance: <20/40 Snellen visual acuity
• Left/mixed handedness
• History of alcohol/substance use disorder (SUD; all substances, including nicotine), and/or illicit substance use (except cannabis) over the last 6 months (SCID-5). Note: lifetime/present cannabis use (at non-abuse (<3 times in the past month) and non SUD levels) will be allowed, given its common usage in BD and young adults. Cannabis SUD over the last 6 months will not be allowed. Urine tests on scan days will exclude current illicit substance use (except cannabis). Salivary alcohol tests on scan days will exclude intoxicated individuals
• Binge drinking in the week before, and/or >3 units/day for the 3 days before, and/or alcohol in the last 12 hrs before, any cTBS scan day, confirmed at screening and scan days (to avoid TBS during alcohol withdrawal). Alcohol/nicotine/ caffeine/cannabis use (below SCID-5 SUD, binge levels) will be allowed, and used as covariates
• Inability to understand English
• <18 years of age or >35 year of age

• SNRI antidepressants and bupropion will not be allowed, as they can elevate seizure risk, a contraindication for TBS
• Scoring greater than or equal to 8 on HRSD and in depressive episode is confirmed on SCID-5 at screen visit
• Scoring greater than or equal to 18 on HRSD at any visit
• In current depressive episode

2. Participants with Bipolar Disorder

• BD diagnosis other than BDI/II
• More severe hypo/mania (YMRS>15)
• Psychosis

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Mary Phillips, MD MD (Cantab)

OTHER

Sponsor Role: lead

Responsible Party

Mary Phillips, MD MD (Cantab)

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mary Phillips, MD, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Fabio Ferrarelli, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

R01MH122990

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY20060322

Identifier Type: -

Identifier Source: org_study_id