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

NCT05179785 | Completed Results FDA Device

• 1 other identifier: STUDY21110077
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bipolar Disorder

Keywords

Bipolar Disorder; Transcranial Magnetic Stimulation; Electroencephalography

Outcome Measures

Primary Outcomes (7)

• Brain Activity (Beta Power) in Left vLPFC

  The difference in brain activity (Beta power) in left vLPFC from pre TBS to post TBS. Higher numbers indicate more brain activity after TBS, while lower numbers indicate less brain activity (Beta power) after TBS.

  Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)

• Brain Activity (Beta Power) in Right vLPFC

  The difference in brain activity (Beta power) in right vLPFC from pre TBS to post TBS. Higher numbers indicate more brain activity (Beta power) after TBS, while lower numbers indicate less brain activity (Beta power) after TBS.

  Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)

• Brain Activity (Beta Power) in Left dlPFC

  The difference in brain activity (Beta power) in left dLPFC from pre TBS to post TBS. Higher numbers indicate more brain activity (Beta power) after TBS, while lower numbers indicate less brain activity (Beta power) after TBS.

  Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)

• Brain Activity (Beta Power) in Right dlPFC

  The difference in brain activity (Beta power) in right dLPFC from pre TBS to post TBS. Higher numbers indicate more brain activity (Beta power) after TBS, while lower numbers indicate less brain activity (Beta power) after TBS.

  Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)

• Functional Connectivity Between Left and Right vLPFC

  The difference in functional connectivity (a measure of interactions between 2 brain regions) among left and right vLPFC from preTBS to post TBS. Higher numbers indicate more functional connectivity after TBS, while lower numbers indicate less functional connectivity after TBS.

  Change in magnitude of the functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)

• Functional Connectivity Between vLPFC and Other RNet Regions

  The difference in functional connectivity (a measure of interactions between 2 brain regions) among vLPFC and other RNet regions from pre TBS to post TBS. Higher numbers indicate more functional connectivity after TBS, while lower numbers indicate less functional connectivity after TBS.

  Change in magnitude of functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)

• Functional Connectivity Between dlPFC With Other CEN Regions

  The difference in functional connectivity (a measure of interactions between 2 brain regions) among dlPFC and other RNet regions from pre TBS to post TBS. Higher numbers indicate more functional connectivity after TBS, while lower numbers indicate less functional connectivity after TBS.

  Change in magnitude of functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)

Secondary Outcomes (3)

• Brain Activity (Beta Power) in Other RNet and CEN Regions

  Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)

• Functional Connectivity Among Other RNet and CEN Regions

  Change in magnitude of functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)

• Immediate Choices Made on the Delay Discounting Task

  15-30 minutes

Study Arms (6)

Left vLPFC cTBS/right dlPFC iTBS/left Som cTBS

EXPERIMENTAL

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)

Device: Continuous Theta Burst Stimulation (cTBS); Device: Intermittent Theta Burst Stimulation (iTBS)

Left vLPFC cTBS/left Som cTBS/right dlPFC iTBS

EXPERIMENTAL

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)

Device: Continuous Theta Burst Stimulation (cTBS); Device: Intermittent Theta Burst Stimulation (iTBS)

left Som cTBS/right dlPFC iTBS/Left vLPFC cTBS

EXPERIMENTAL

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)

Device: Continuous Theta Burst Stimulation (cTBS); Device: Intermittent Theta Burst Stimulation (iTBS)

left Som cTBS/Left vLPFC cTBS/right dlPFC iTBS

EXPERIMENTAL

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)

Device: Continuous Theta Burst Stimulation (cTBS); Device: Intermittent Theta Burst Stimulation (iTBS)

right dlPFC iTBS/left Som cTBS/Left vLPFC cTBS

EXPERIMENTAL

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)

Device: Continuous Theta Burst Stimulation (cTBS); Device: Intermittent Theta Burst Stimulation (iTBS)

right dlPFC iTBS/Left vLPFC cTBS/left Som cTBS

EXPERIMENTAL

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)

Device: Continuous Theta Burst Stimulation (cTBS); Device: Intermittent Theta Burst Stimulation (iTBS)

Interventions

Continuous Theta Burst Stimulation (cTBS) 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

Also known as: Transcranial Magnetic Stimulation (TMS)

Left vLPFC cTBS/left Som cTBS/right dlPFC iTBS; Left vLPFC cTBS/right dlPFC iTBS/left Som cTBS; left Som cTBS/Left vLPFC cTBS/right dlPFC iTBS; left Som cTBS/right dlPFC iTBS/Left vLPFC cTBS; right dlPFC iTBS/Left vLPFC cTBS/left Som cTBS; right dlPFC iTBS/left Som cTBS/Left vLPFC cTBS

Intermittent Theta Burst Stimulation (iTBS) 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.

Also known as: Transcranial Magnetic Stimulation (TMS)

Left vLPFC cTBS/left Som cTBS/right dlPFC iTBS; Left vLPFC cTBS/right dlPFC iTBS/left Som cTBS; left Som cTBS/Left vLPFC cTBS/right dlPFC iTBS; left Som cTBS/right dlPFC iTBS/Left vLPFC cTBS; right dlPFC iTBS/Left vLPFC cTBS/left Som cTBS; right dlPFC iTBS/left Som cTBS/Left vLPFC cTBS

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• Binge alcohol drinking
• 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
• 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
• 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

Sponsors & Collaborators

• Mary Phillips, MD MD (Cantab): lead
• Milken Institute: collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• 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.

  PMID: 38336341 RESULT

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Results Point of Contact

• Title: Mary Phillips
• Organization: University of Pittsburgh

fmristudies@upmc.edu

4123838206

Study Officials

• Mary L Phillips, MD, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Fabio Ferrarelli, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: January 5, 2022
• Study Start: March 23, 2022
• Primary Completion: July 31, 2023
• Study Completion: July 31, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: The PIs reserve the right to publish on the stated aims in a timely manner during the period of the award. Data will be available for addressing other research questions (i.e. which are not described in funded/pending grants) as soon as the data have been checked for accuracy (a period which will be no later than one year after the completion of each assessment). After the award has ended, the study investigators will continue to test the stated aims, but will also continue to solicit collaborations with outside researchers and to consider data requests in a timely manner.
• Access Criteria: Outside investigators must submit a 1)proposal of the study aims, hypotheses, variables/constructs, analytic approach, and estimated duration of the proposed research; 2)resume, qualifications, source of financial support, and conflict of interest statement; 3)sign a data-sharing agreement and confidentiality statement that stipulates using the data for the stated research purposes only, securing the data using appropriate computer technology, not manipulating the data in order to identify participants, acknowledging the grant that supported data collection and management in publications/presentations, and destroying or returning the data after analyses are complete; 4)obtain approval from their Institutional Review Board, and along with other staff members who have access to the data, submit certificates of the University of Pittsburgh Education and Certification Program in Research Practice Fundamentals or provide written documentation pf similar human subjects protection training.

Locations

US (1)