Bipolar DisorderNCT05179785

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

A study testing Continuous Theta Burst Stimulation (cTBS) and Intermittent Theta Burst Stimulation (iTBS) in people with Bipolar Disorder, run by Mary Phillips, MD MD (Cantab) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 35 years
Conditions the study is for: Bipolar Disorder
What is being tested?: Continuous Theta Burst Stimulation (cTBS) and Intermittent Theta Burst Stimulation (iTBS)
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 1 siteUnited States
Study dates: 23 Mar 2022to 31 Jul 2023
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 35 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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

Who cannot join

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)

Show all 19Show fewer

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
Using psychotropic medications other than those allowed in inclusion criteria
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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Pittsburgh
Pittsburgh, Pennsylvania, 15213

Other trials in United States

About this study

Official title: Establishing the Effect of Electroencephalography (EEG)-Guided Theta Burst Stimulation on Reducing Mania/Hypomania-related Affect and Reward Driven Behavior in Bipolar Disorder

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.

Read the detailed description

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: Bipolar Disorder
Being tested: Continuous Theta Burst Stimulation (cTBS), Intermittent Theta Burst Stimulation (iTBS)
Keywords: Bipolar Disorder, Transcranial Magnetic Stimulation, Electroencephalography
Medical subject headings: Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Continuous Theta Burst Stimulation (cTBS)Device
Also called Transcranial Magnetic Stimulation (TMS)
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)Device
Also called Transcranial Magnetic Stimulation (TMS)
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.

Study groups in NCT05179785
Study group	Role	What they receive
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) Receives: 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) Receives: 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) Receives: 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) Receives: 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) Receives: 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) Receives: Device: Continuous Theta Burst Stimulation (cTBS); Device: Intermittent Theta Burst Stimulation (iTBS)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
The difference in brain activity (Beta power) among other RNet and CEN regions 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.
Measured: 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
The difference in functional connectivity (a measure of interactions between 2 brain regions) among other RNet and CEN regions from pre TBS to post TBS. Higher numbers indicate more functional connectivity after TBS, while lower numbers indicate less functional connectivity after TBS.
Measured: 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
The sum (overall total) of the immediate choices (choosing to receive a small immediate reward) made on the delay discounting task
Measured: 15-30 minutes

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Mar 202231 Jul 2023

First posted5 Jan 2022
Study start23 Mar 2022
Primary completion31 Jul 2023
Study completion31 Jul 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Bipolar DisorderStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05179785
Sponsor's protocol ID: STUDY21110077
Status last verified: Aug 2024
First submitted: 16 Dec 2021
Last updated: 19 Sep 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: Yes
Individual data sharing: Yes: Informed consent will be collected from study participants that allows for broad sharing of participants' de-identified data. Data transfer procedures will be in accordance with all Institutional Review Board guidelines and federal regulations including HIPAA.

Publications

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.
PubMed 38336341

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Establishing the Effect of Electroencephalography (EEG)-Guided Theta Burst Stimulation on Reducing Mania/Hypomania-related Affect and Reward Driven Behavior in Bipolar Disorder
ClinicalTrials.gov ID: NCT05179785
Acronym / sponsor ID: STUDY21110077
Conditions: Bipolar Disorder
Keywords: Bipolar Disorder, Transcranial Magnetic Stimulation, Electroencephalography
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: Mary Phillips, MD MD (Cantab)University, hospital or other
Collaborators: Milken Institute
Study start: 23 Mar 2022 (actual)
Primary completion: 31 Jul 2023 (actual)
Study completion: 31 Jul 2023 (actual)
First posted: 5 Jan 2022 (actual)
Results: Posted 19 Sep 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 6

Arm	Type	Receives
Left vLPFC cTBS/right dlPFC iTBS/left Som cTBS	Experimental	Device: Continuous Theta Burst Stimulation (cTBS), Device: Intermittent Theta Burst Stimulation (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) right dlPFC iTBS (iTBS applied to the right dorsolateral prefrontal cortex) left Som cTBS (cTBS applied to the left somatosensory cortex)
Left vLPFC cTBS/left Som cTBS/right dlPFC iTBS	Experimental	Device: Continuous Theta Burst Stimulation (cTBS), Device: Intermittent Theta Burst Stimulation (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)
left Som cTBS/right dlPFC iTBS/Left vLPFC cTBS	Experimental	Device: Continuous Theta Burst Stimulation (cTBS), Device: Intermittent Theta Burst Stimulation (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) 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/Left vLPFC cTBS/right dlPFC iTBS	Experimental	Device: Continuous Theta Burst Stimulation (cTBS), Device: Intermittent Theta Burst Stimulation (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)
right dlPFC iTBS/left Som cTBS/Left vLPFC cTBS	Experimental	Device: Continuous Theta Burst Stimulation (cTBS), Device: Intermittent Theta Burst Stimulation (iTBS)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)
right dlPFC iTBS/Left vLPFC cTBS/left Som cTBS	Experimental	Device: Continuous Theta Burst Stimulation (cTBS), Device: Intermittent Theta Burst Stimulation (iTBS)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)

Who may qualify

Ages: 18 to 35 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (19 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Continuous Theta Burst Stimulation (cTBS)Also: Transcranial Magnetic Stimulation (TMS)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	Device	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)Also: Transcranial Magnetic Stimulation (TMS)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.	Device	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

Primary outcome

Brain Activity (Beta Power) in Left vLPFC
Time frame: Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
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.
Brain Activity (Beta Power) in Right vLPFC
Time frame: Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
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.
Brain Activity (Beta Power) in Left dlPFC
Time frame: Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
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.
Brain Activity (Beta Power) in Right dlPFC
Time frame: Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
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.
Functional Connectivity Between Left and Right vLPFC
Time frame: Change in magnitude of the functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
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.
Functional Connectivity Between vLPFC and Other RNet Regions
Time frame: Change in magnitude of functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
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.
Functional Connectivity Between dlPFC With Other CEN Regions
Time frame: Change in magnitude of functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
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.

3 secondary outcomes

Brain Activity (Beta Power) in Other RNet and CEN Regions
Time frame: 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
Time frame: 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
Time frame: 15-30 minutes

Results and safety

Results posted to the registry on 19 Sep 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Left vLPFC cTBS/Right dlPFC iTBS/Left Som cTBS	3	3
Left vLPFC cTBS/Left Som cTBS/Right dlPFC iTBS	2	2
Left Som cTBS/Right dlPFC iTBS/Left vLPFC cTBS	1	1
Left Som cTBS/Left vLPFC cTBS/Right dlPFC iTBS	2	2
Right dlPFC iTBS/Left Som cTBS/Left vLPFC cTBS	3	3
Right dlPFC iTBS/Left vLPFC cTBS/Left Som cTBS	2	2

Primary outcome: Brain Activity (Beta Power) in Left vLPFC

Time frame: Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins). Mean (Standard Deviation). Unit: Percentage of change post versus pre

Measure	Left vLPFC cTBS n = 12	Right dlPFC iTBS n = 12	Left SS cTBS n = 12
Delayed Choice (larger reward in the future)	-88.78 (224.54)	1437.64 (4411.75)	13.43 (346.26)
Immediate Choice (small immediate reward)	-128.00 (105.32)	-612.44 (1487.43)	89.70 (940.52)

Left vLPFC cTBS: p = 0.29389090, t-test, 2 sided
Left vLPFC cTBS: p = 0.97863544, t-test, 2 sided
Right dlPFC iTBS: p = 0.60236264, t-test, 2 sided

Population analysed: One participant was excluded from the EEG data analysis due to lack of immediate choices on the delayed discounting task

Primary outcome: Brain Activity (Beta Power) in Right vLPFC

Measure	Left vLPFC cTBS n = 12	Right dlPFC iTBS n = 12	Left SS cTBS n = 12
Delayed Choice (larger reward in the future)	-162.37 (799.00)	5.13 (312.18)	-498.71 (1022.00)
Immediate Choice (small immediate reward)	131.99 (409.07)	-136.62 (702.68)	-117.6 (893.74)

Left vLPFC cTBS: p = 0.50030946, t-test, 2 sided
Left vLPFC cTBS: p = 0.37517380, t-test, 2 sided
Right dlPFC iTBS: p = 0.47876971, t-test, 2 sided

Population analysed: Initially, 10 main outcome measures were stated based on the assumption that 25 participants with bipolar disorder (BD) would be recruited and all data (neuroimaging and behavioral) would be collected from at least 20 participants. However, all data was collected from only 12 BD participants. As such, to not jeopardize the power for the 10 main outcome measures, statistical analyses were performed on only 4 of the 10 outcome measures.

Primary outcome: Brain Activity (Beta Power) in Left dlPFC

Measure	Left vLPFC cTBS n = 12	Right dlPFC iTBS n = 12	Left SS cTBS n = 12
Delayed Choice (larger reward in the future)	33.83 (446.73)	-286.13 (628.89)	-623.68 (1950.2)
Immediate Choice (small immediate reward)	32.04 (322.62)	-182.53 (494.97)	99.64 (512.78)

Left vLPFC cTBS: p = 0.75298499, t-test, 2 sided
Left vLPFC cTBS: p = 0.16043787, t-test, 2 sided
Right dlPFC iTBS: p = 0.67902693, t-test, 2 sided

Primary outcome: Brain Activity (Beta Power) in Right dlPFC

Measure	Left vLPFC cTBS n = 12	Right dlPFC iTBS n = 12	Left SS cTBS n = 12
Immediate Choice (small immediate reward)	-128.27 (363.79)	-70.27 (520.40)	-383.76 (849.28)
Delayed Choice (larger reward in the future)	-74.21 (104.49)	-83.74 (2072.87)	-398.00 (1039.5)

Left vLPFC cTBS: p = 0.73357221, t-test, 2 sided
Left vLPFC cTBS: p = 0.43954526, t-test, 2 sided
Right dlPFC iTBS: p = 0.44198980, t-test, 2 sided

Population analysed: One participant was excluded from the EEG data analysis due to lack of immediate choices on the delayed discounting task

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Total participation up to 1 day. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Left vLPFC cTBS	0 of 13 (0%)	0 of 13 (0%)	0 of 13
Right dlPFC iTBS	0 of 13 (0%)	0 of 13 (0%)	0 of 13
Left Som cTBS	0 of 13 (0%)	0 of 13 (0%)	0 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 38336341Mayeli 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.
Individual participant dataSharing planned: Yes. Informed consent will be collected from study participants that allows for broad sharing of participants' de-identified data. Data transfer procedures will be in accordance with all Institutional Review Board guidelines and federal regulations including HIPAA.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mary L Phillips, MD, MD principal investigator

University of Pittsburgh

Fabio Ferrarelli, MD, PhD principal investigator

University of Pittsburgh

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Brain Activity (Beta Power) in Left vLPFC (time frame: Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05179785, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.