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

Bipolar Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05179785
• Other study ID #: STUDY21110077
• Status: Completed
• Phase: N/A
• Start date: March 23, 2022
• Est. completion date: July 31, 2023

Study information

• Verified date: October 2023
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: July 31, 2023
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

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

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

• 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

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Device:
• 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
• 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.

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Mary Phillips, MD MD (Cantab)	Milken Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Beta power in left vlPFC	The difference in Beta power in left vLPFC from pre TBS to post TBS	Change in magnitude immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Primary	Beta power in right vlPFC	The difference in Beta power in right vLPFC from pre TBS to post TBS	Change in magnitude immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Primary	Beta power in left dlPFC	The difference in Beta power in left dLPFC from pre TBS to post TBS	Change in magnitude immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Primary	Beta power in right dlPFC	The difference in Beta power in right dLPFC from pre TBS to post TBS	Change in magnitude immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Primary	Beta functional connectivity between left and right vlPFC	The difference in Beta functional connectivity among left and right vLPFC from pre TBS to post TBS	Change in magnitude immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Primary	Beta functional connectivity between vlPFC and other RNet regions	The difference in Beta functional connectivity among vLPFC and other RNet regions from pre TBS to post TBS	Change in magnitude immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Primary	Beta functional connectivity between dlPFC with other CEN regions	The difference in Beta functional connectivity among dlPFC and other RNet regions from pre TBS to post TBS	Change in magnitude immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Secondary	Beta power in other RNet and CEN regions	The difference in Beta power among other RNet and CEN regions from pre TBS to post TBS	Change in magnitude immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Secondary	Functional connectivity among other RNet and CEN regions	The difference in Beta functional connectivity among other RNet and CEN regions from pre TBS to post TBS	Change in magnitude immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Secondary	Number of immediate choices made on the delay discounting task	The sum of the immediate choices made on the delay discounting task	15-30 minutes