Bipolar DisorderNCT04696471
Effects of Theta Burst Stimulation on the Brain, Behavior, and Clinical Symptoms in Adults With Bipolar Disorder
A study testing Continuous Theta Burst Stimulation (cTBS) in people with Bipolar Disorder, run by Mary Phillips, MD MD (Cantab) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Continuous Theta Burst Stimulation (cTBS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 146 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Apr 2021to 24 Oct 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
- 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
Show all 13Show fewer
- 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, as these are commonly-prescribed medications for BD
- 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
Who cannot join
- 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
Show all 25Show fewer
- 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
- MRI exclusion criteria: metallic objects, e.g., surgical implants; claustrophobia; proneness; positive pregnancy test for females (performed at the MRRC) or self-report pregnancy
- 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
- Participants with Bipolar Disorder
- BD diagnosis other than BDI/II
- More severe hypo/mania (YMRS>15)
- Psychosis
- Using psychotropic medications other than those allowed in inclusion criteria
- Participants without Bipolar Disorder
- Present/ lifetime history of any psychiatric disorder other than anxiety and non BD mood disorders
- Family history of of BD
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Elucidating Neural Mechanisms of Hypo/Mania Using Theta Burst Stimulation
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.
Read the 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
- Being tested
- Continuous Theta Burst Stimulation (cTBS), Sham Continuous Theta Burst Stimulation (Sham cTBS)
- Keywords
- Bipolar Disorder, Magnetic Resonance Imaging, Transcranial Magnetic Stimulation
- 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. 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)Device
Also called Sham Transcranial Magnetic Stimulation (Sham TMS)
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
| Study group | Role | What they receive |
|---|---|---|
| Left ventrolateral prefrontal cortex (vlPFC)/Left SS/Left vlPFC sham | Experimental | 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. Receives: Device: Continuous Theta Burst Stimulation (cTBS); Device: Sham Continuous Theta Burst Stimulation (Sham cTBS) |
| Left vlPFC/Left vlPFC sham/Left SS | Experimental | 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. Receives: Device: Continuous Theta Burst Stimulation (cTBS); Device: Sham Continuous Theta Burst Stimulation (Sham cTBS) |
| Left SS/Left vlPFC sham/Left vlPFC | Experimental | 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. Receives: Device: Continuous Theta Burst Stimulation (cTBS); Device: Sham Continuous Theta Burst Stimulation (Sham cTBS) |
| Left SS/Left vlPFC/Left vlPFC sham | Experimental | 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. Receives: Device: Continuous Theta Burst Stimulation (cTBS); Device: Sham Continuous Theta Burst Stimulation (Sham cTBS) |
| Left vlPFC sham/Left SS/Left vlPFC | Experimental | 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. Receives: Device: Continuous Theta Burst Stimulation (cTBS); Device: Sham Continuous Theta Burst Stimulation (Sham cTBS) |
| Left vlPFC sham/Left vlPFC/Left SS | Experimental | 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. Receives: Device: Continuous Theta Burst Stimulation (cTBS); Device: Sham Continuous Theta Burst Stimulation (Sham cTBS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reward expectancy-related left ventrolateral prefrontal cortex activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted blood oxygen level-dependent (BOLD) signal from the left ventrolateral prefrontal cortex to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related right ventrolateral prefrontal cortex activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the right ventrolateral prefrontal cortex to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related left ventral striatum activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left ventral striatum to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related right ventral striatum activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left ventral striatum to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related left orbitofrontal cortex activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left orbitofrontal cortex to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related right orbitofrontal cortex activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left orbitofrontal cortex to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related midline rostral anterior cingulate cortex (rACC) activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the midline rostral anterior cingulate cortex (rACC) to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related midline dorsal anterior cingulate cortex activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the midline dorsal anterior cingulate cortex to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related left amygdala activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left amygdala to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related right amygdala activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left amygdala to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related left ventrolateral prefrontal cortex-right ventrolateral prefrontal cortex functional connectivity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left and right ventrolateral prefrontal cortices to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related left ventrolateral prefrontal cortex-left ventral striatum functional connectivity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and left ventral striatum to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related left ventrolateral prefrontal cortex-right ventral striatum functional connectivity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and right ventral striatum to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related left ventrolateral prefrontal cortex-left orbitofrontal cortex functional connectivity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and left orbitofrontal cortex to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related left ventrolateral prefrontal cortex-right orbitofrontal cortex functional connectivity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and right orbitofrontal cortex to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related left ventrolateral prefrontal cortex-midline rostral anterior cingulate cortex functional connectivity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and midline rACC to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related left ventrolateral prefrontal cortex-midline dorsal anterior cingulate cortex functional connectivity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and midline dorsal anterior cingulate cortex to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related left ventrolateral prefrontal cortex-left amygdala functional connectivity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and left amygdala to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Reward expectancy-related left ventrolateral prefrontal cortex-right amygdala functional connectivity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and right amygdala to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Secondary outcomes (16)
Reward expectancy-related left ventrolateral prefrontal cortex wholebrain functional connectivity
The difference in magnitude between pre and post cTBS for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and the whole brain to the uncertain reward expectancy regressor during performance of the reward task
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventrolateral prefrontal cortex activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the left ventrolateral prefrontal cortex to the contrast of possible win vs. neutral control conditions
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Right ventrolateral prefrontal cortex activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the right ventrolateral prefrontal cortex to the contrast of possible win vs. neutral control conditions
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventral striatum activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the left ventral striatum to the contrast of possible win vs. neutral control conditions
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Right ventral striatum activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the right ventral striatum to the contrast of possible win vs. neutral control conditions
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left orbitofrontal cortex activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the left orbitofrontal cortex to the contrast of possible win vs. neutral control conditions
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Right orbitofrontal cortex activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the right orbitofrontal cortex to the contrast of possible win vs. neutral control conditions
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Midline rostral anterior cingulate cortex activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the midline rostral anterior cingulate cortex to the contrast of possible win vs. neutral control conditions
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Midline dorsal anterior cingulate cortex activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the midline dorsal anterior cingulate cortex to the contrast of possible win vs. neutral control conditions
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left amygdala activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the left amygdala to the contrast of possible win vs. neutral control conditions
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Right amygdala activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the right amygdala to the contrast of possible win vs. neutral control conditions
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventral lateral prefrontal cortex-wholebrain functional connectivity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimates of functional connectivity between the left ventrolateral prefrontal cortex and the wholebrain to the contrast of possible win vs. neutral control conditions
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Prediction error-related left ventral striatum activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the left ventral striatum to the prediction error regressor
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Prediction error-related right ventral striatum activity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the right ventral striatum to the prediction error regressor
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Prediction error-related left ventral striatum-wholebrain functional connectivity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimates of resting state functional connectivity between the left ventral striatum and the wholebrian to the prediction error regressor
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Prediction error-related right ventral striatum-wholebrain functional connectivity
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimates of resting state functional connectivity between the right ventral striatum and the wholebrain
Measured: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2021
- Study start6 Apr 2021
- Primary completion24 Oct 2025
- Study completion24 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 146 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mary Phillips, MD MD (Cantab)
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, Mary Phillips, MD MD (Cantab), University of Pittsburgh
- Investigators
- Mary Phillips, MD, MD, Principal investigator, University of PittsburghFabio Ferrarelli, MD, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04696471
- Sponsor's protocol ID
- STUDY20060322
- Other IDs
- R01MH122990
- Status last verified
- Oct 2026
- First submitted
- 18 Dec 2020
- Last updated
- 3 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: The investigators will complete and submit a National Data Archive (NDA) Data Sharing Agreement within 6 months of the Notice of Award Issue date. Study staff will upload data dictionary to the NDA website, and will review the NDA data definition for the measures collected and define the project's data definition harmonized to that standard. For measures not yet defined, project staff will work with the NDA staff to define the measure following NDA best practices. Informed consent will be collected from study participants that allows for broad sharing of participants' de-identified data. Study staff will use participants' personally identifiable information to generate NDA Global Unique Identifier (GUID) numbers for study participants. All data will be identified by GUID numbers only prior to submission to the NDA database. Data transfer procedures will be in accordance with all Institutional Review Board guidelines and federal regulations including HIPAA.
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Elucidating Neural Mechanisms of Hypo/Mania Using Theta Burst Stimulation
- ClinicalTrials.gov ID
- NCT04696471
- Acronym / sponsor ID
- STUDY20060322
- Conditions
- Bipolar Disorder
- Keywords
- Bipolar Disorder, Magnetic Resonance Imaging, Transcranial Magnetic Stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 146 participants (actual)
- Lead sponsor
- Mary Phillips, MD MD (Cantab)University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 6 Apr 2021 (actual)
- Primary completion
- 24 Oct 2025 (actual)
- Study completion
- 24 Oct 2025 (actual)
- First posted
- 6 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 ventrolateral prefrontal cortex (vlPFC)/Left SS/Left vlPFC sham | Experimental | Device: Continuous Theta Burst Stimulation (cTBS), Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)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. |
| Left vlPFC/Left vlPFC sham/Left SS | Experimental | Device: Continuous Theta Burst Stimulation (cTBS), Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)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. |
| Left SS/Left vlPFC sham/Left vlPFC | Experimental | Device: Continuous Theta Burst Stimulation (cTBS), Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)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. |
| Left SS/Left vlPFC/Left vlPFC sham | Experimental | Device: Continuous Theta Burst Stimulation (cTBS), Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)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. |
| Left vlPFC sham/Left SS/Left vlPFC | Experimental | Device: Continuous Theta Burst Stimulation (cTBS), Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)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. |
| Left vlPFC sham/Left vlPFC/Left SS | Experimental | Device: Continuous Theta Burst Stimulation (cTBS), Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)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. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- All participants
- Participants with Bipolar Disorder (BD)
- Participants without Bipolar Disorder
Key exclusion criteria (25 listed)
- All participants
- Participants with Bipolar Disorder
- Participants without Bipolar Disorder
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. 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 SS/Left vlPFC sham/Left vlPFC, Left SS/Left vlPFC/Left vlPFC sham, Left ventrolateral prefrontal cortex (vlPFC)/Left SS/Left vlPFC sham, Left vlPFC sham/Left SS/Left vlPFC, Left vlPFC sham/Left vlPFC/Left SS, Left vlPFC/Left vlPFC sham/Left SS |
| Sham Continuous Theta Burst Stimulation (Sham cTBS)Also: Sham Transcranial Magnetic Stimulation (Sham TMS)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 | Device | Left SS/Left vlPFC sham/Left vlPFC, Left SS/Left vlPFC/Left vlPFC sham, Left ventrolateral prefrontal cortex (vlPFC)/Left SS/Left vlPFC sham, Left vlPFC sham/Left SS/Left vlPFC, Left vlPFC sham/Left vlPFC/Left SS, Left vlPFC/Left vlPFC sham/Left SS |
Primary outcome
Reward expectancy-related left ventrolateral prefrontal cortex activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted blood oxygen level-dependent (BOLD) signal from the left ventrolateral prefrontal cortex to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related right ventrolateral prefrontal cortex activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the right ventrolateral prefrontal cortex to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related left ventral striatum activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left ventral striatum to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related right ventral striatum activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left ventral striatum to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related left orbitofrontal cortex activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left orbitofrontal cortex to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related right orbitofrontal cortex activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left orbitofrontal cortex to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related midline rostral anterior cingulate cortex (rACC) activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the midline rostral anterior cingulate cortex (rACC) to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related midline dorsal anterior cingulate cortex activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the midline dorsal anterior cingulate cortex to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related left amygdala activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left amygdala to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related right amygdala activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left amygdala to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related left ventrolateral prefrontal cortex-right ventrolateral prefrontal cortex functional connectivity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left and right ventrolateral prefrontal cortices to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related left ventrolateral prefrontal cortex-left ventral striatum functional connectivity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and left ventral striatum to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related left ventrolateral prefrontal cortex-right ventral striatum functional connectivity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and right ventral striatum to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related left ventrolateral prefrontal cortex-left orbitofrontal cortex functional connectivity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and left orbitofrontal cortex to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related left ventrolateral prefrontal cortex-right orbitofrontal cortex functional connectivity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and right orbitofrontal cortex to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related left ventrolateral prefrontal cortex-midline rostral anterior cingulate cortex functional connectivity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and midline rACC to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related left ventrolateral prefrontal cortex-midline dorsal anterior cingulate cortex functional connectivity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and midline dorsal anterior cingulate cortex to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related left ventrolateral prefrontal cortex-left amygdala functional connectivity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and left amygdala to the uncertain reward expectancy regressor during performance of the reward task
Reward expectancy-related left ventrolateral prefrontal cortex-right amygdala functional connectivity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and right amygdala to the uncertain reward expectancy regressor during performance of the reward task
16 secondary outcomes
Reward expectancy-related left ventrolateral prefrontal cortex wholebrain functional connectivity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventrolateral prefrontal cortex activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Right ventrolateral prefrontal cortex activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventral striatum activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Right ventral striatum activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left orbitofrontal cortex activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Right orbitofrontal cortex activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Midline rostral anterior cingulate cortex activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Midline dorsal anterior cingulate cortex activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left amygdala activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Right amygdala activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventral lateral prefrontal cortex-wholebrain functional connectivity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Prediction error-related left ventral striatum activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Prediction error-related right ventral striatum activity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Prediction error-related left ventral striatum-wholebrain functional connectivity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Prediction error-related right ventral striatum-wholebrain functional connectivity
Time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Individual participant dataSharing planned: Yes. The investigators will complete and submit a National Data Archive (NDA) Data Sharing Agreement within 6 months of the Notice of Award Issue date. Study staff will upload data dictionary to the NDA website, and will review the NDA data definition for the measures collected and define the project's data definition harmonized to that standard. For measures not yet defined, project staff will work with the NDA staff to define the measure following NDA best practices. Informed consent will be collected from study participants that allows for broad sharing of participants' de-identified data. Study staff will use participants' personally identifiable information to generate NDA Global Unique Identifier (GUID) numbers for study participants. All data will be identified by GUID numbers only prior to submission to the NDA database. Data transfer procedures will be in accordance with all Institutional Review Board guidelines and federal regulations including HIPAA.
Related trials for Bipolar Disorder
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Recruiting
Safety and Feasibility of DBS for Bipolar Depression
Bipolar I Disorder, Bipolar Depression
Not yet recruiting
Compulsive Eating and Brain's Reward System in Different Pathologies
PARKINSON DISEASE (Disorder), Bipolar 1 Disorder
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Recruiting
Affective Cognitive Training in Mood Disorders and High-risk Relatives
Major Depressive Disorder (MDD), Bipolar Disorder (BD)
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 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?
A study testing Continuous Theta Burst Stimulation (cTBS) in people with Bipolar Disorder, run by Mary Phillips, MD MD (Cantab) at 1 site in United States.
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 13 inclusion and 25 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 3 Nov 2026. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Reward expectancy-related left ventrolateral prefrontal cortex activity (time frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)). The study lists 19 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Nov 2026.