Examining the Effect of EEG-guided Theta Burst Stimulation in Bipolar Disorder

NCT ID: NCT05179785

Last Updated: 2024-09-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-23

Study Completion Date

2023-07-31

Brief Summary

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Bipolar Disorder (BD) is a common and highly debilitating psychiatric disorder, however, the predisposing brain mechanisms are poorly understood. Here, the investigators will conduct a proof of concept study that will examine the effect of electroencephalography (EEG)-guided theta burst stimulation (TBS) on reducing mania/hypomania-related affect and reward driven behavior in adults with BD. The investigators hypothesize that TBS will reduce mania/hypomania-related affect and reward driven behavior in adults with BD.

Detailed Description

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This study aims to examine the effect of electroencephalography (EEG)-guided theta burst stimulation (TBS) on reducing mania/hypomania-related affect and reward driven behavior in adults with BD. Eligible participants will undergo 6 study visits: a screening visit, a baseline MRI visit, TBS motor thresholding visit, and 3 cTBS/EEG visits. Participants will receive brain stimulation and have brain activity recorded by EEG at each of the 3 cTBS/EEG study visits. The research associates (except for the research associate administering the TBS) and participants will be blinded to the brain area receiving TBS, which will be randomized and counterbalanced beforehand. Certain information is withheld to protect the scientific integrity of the study design.

The goal of the study is to reduce overactivity in the reward neural network (RNet) and increase activity in the central executive control network (CEN) using theta burst stimulation (TBS). The region in the RNet to be targeted by inhibitory (continuous, cTBS) is the left ventrolateral prefrontal cortex (vlPFC); and the region in the CEN to be targeted by excitatory (intermittent, iTBS) is the right dorsolateral prefrontal cortex (dlPFC)

Conditions

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Bipolar Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Left vLPFC cTBS/right dlPFC iTBS/left Som cTBS

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

left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) right dlPFC iTBS (iTBS applied to the right dorsolateral prefrontal cortex) left Som cTBS (cTBS applied to the left somatosensory cortex)

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 that can decrease the excitability of cortical neurons. 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

Intermittent Theta Burst Stimulation (iTBS)

Intervention Type DEVICE

iTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely to increase the excitability of cortical neurons. 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.

Left vLPFC cTBS/left Som cTBS/right dlPFC iTBS

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

left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) left Som cTBS (cTBS applied to the left somatosensory cortex) right dlPFC iTBS (iTBS applied to the right dorsolateral prefrontal cortex)

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 that can decrease the excitability of cortical neurons. 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

Intermittent Theta Burst Stimulation (iTBS)

Intervention Type DEVICE

iTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely to increase the excitability of cortical neurons. 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.

left Som cTBS/right dlPFC iTBS/Left vLPFC cTBS

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

left Som cTBS (cTBS applied to the left somatosensory cortex) right dlPFC iTBS (iTBS applied to the right dorsolateral prefrontal cortex) left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex)

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 that can decrease the excitability of cortical neurons. 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

Intermittent Theta Burst Stimulation (iTBS)

Intervention Type DEVICE

iTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely to increase the excitability of cortical neurons. 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.

left Som cTBS/Left vLPFC cTBS/right dlPFC iTBS

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

left Som cTBS (cTBS applied to the left somatosensory cortex) left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) right dlPFC iTBS (iTBS applied to the right dorsolateral prefrontal cortex)

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 that can decrease the excitability of cortical neurons. 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

Intermittent Theta Burst Stimulation (iTBS)

Intervention Type DEVICE

iTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely to increase the excitability of cortical neurons. 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.

right dlPFC iTBS/left Som cTBS/Left vLPFC cTBS

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

right dlPFC iTBS (iTBS applied to the right dorsolateral prefrontal cortex) left Som cTBS (cTBS applied to the left somatosensory cortex) left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex)

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 that can decrease the excitability of cortical neurons. 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

Intermittent Theta Burst Stimulation (iTBS)

Intervention Type DEVICE

iTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely to increase the excitability of cortical neurons. 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.

right dlPFC iTBS/Left vLPFC cTBS/left Som cTBS

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

right dlPFC iTBS (iTBS applied to the right dorsolateral prefrontal cortex) left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) left Som cTBS (cTBS applied to the left somatosensory cortex)

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 that can decrease the excitability of cortical neurons. 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

Intermittent Theta Burst Stimulation (iTBS)

Intervention Type DEVICE

iTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely to increase the excitability of cortical neurons. 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.

Interventions

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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 that can decrease the excitability of cortical neurons. 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

Intermittent Theta Burst Stimulation (iTBS)

iTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely to increase the excitability of cortical neurons. 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

Other Intervention Names

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Transcranial Magnetic Stimulation (TMS) Transcranial Magnetic Stimulation (TMS)

Eligibility Criteria

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Inclusion Criteria

* 18-35 years of age
* Diagnosis of BD (DSM-5 criteria) in remission (euthymic for \>2 months) or in a manic/hypomanic episode \[manic/hypomanic or euthymic adults with BD (3-fifths manic/hypomanic); euthymic for \> 2 months from most recent BD episode OR current manic/hypomanic episode\]
* Not psychotic
* Score \<3 on delusions, hallucinations, unusual thought content, and conceptual disorganization items of the Positive and Negative Syndrome Scale (PANSS)
* Unmedicated or on any combination 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, as these are commonly-prescribed medications for BD
* Provides the contact information of a medical provider (including but not limited to a PCP) that we may communicate with for any concerns of escalating symptoms of mania

* Scoring greater than or equal to 38 on the YMRS at any study visit
* Does not provide the contact information of a medical provider (including but not limited to a PCP) that we may communicate with for any concerns of escalating symptoms of mania

Exclusion Criteria

* Not 18-35 years of age
* Diagnosis of BD in a depressive episode or Diagnosis of BP in partial remission, euthymia that fails to meet full remission criterion of a period of at least 2 months in which there are no significant symptoms, e.g., only partial remission of symptoms or full remission of symptoms but for \<2 months
* Diagnosis of BD in a depressive episode
* Personal and family history of epilepsy (TBS exclusion)
* Binge alcohol drinking
* Taking substances in the last month that can elevate seizure risk including but not limited to SNRI antidepressants, bupropion and stimulants (TBS exclusion)
* History of head injury, neurological, pervasive developmental disorder (e.g. autism), systemic medical disease and treatment (medical records, participant report)
* Mini-Mental State Examination score (cognitive state) \<24
* Premorbid NAART IQ estimate\<85
* Visual disturbance: \<20/40 Snellen visual acuity
* History of alcohol/substance use disorder (SUD; all substances, except 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 TBS visit, 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
* MRI exclusion: metallic objects, e.g., surgical implants; claustrophobia; positive pregnancy test for females (at the MRRC) or self-report pregnancy \*Unable to understand English
* Scoring greater than or equal to 8 on HRSD at screen visit and depressive episode is confirmed on SCID-5
* Scoring greater than or equal to 18 on HRSD at any study visit
* Psychosis
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Milken Institute

OTHER

Sponsor Role collaborator

Mary Phillips, MD MD (Cantab)

OTHER

Sponsor Role lead

Responsible Party

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Mary Phillips, MD MD (Cantab)

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Mary L Phillips, MD, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Fabio Ferrarelli, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

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University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

References

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Mayeli A, Wang Y, Graur S, Ghane M, Keihani A, Kim A, Janssen S, Huston C, Coffman BA, Ferrarelli F, Phillips ML. Effects of theta burst stimulation on reward processing and decision-making in bipolar disorder: A pilot study. Brain Stimul. 2024 Mar-Apr;17(2):163-165. doi: 10.1016/j.brs.2024.02.002. Epub 2024 Feb 7. No abstract available.

Reference Type RESULT
PMID: 38336341 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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STUDY21110077

Identifier Type: -

Identifier Source: org_study_id

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