Bipolar DisorderNCT05445466
Causal Lesion Network Guided Treatment of Bipolar Mania With Transcranial Electrical Stimulation
A study testing High-Definition Transcranial Electrical-Current Stimulation, High-Definition Transcranial Alternate-Current Stimulation and High-Definition Personalized Beta-Gamma Electrical Stimulation in people with Bipolar Disorder and Schizo Affective Disorder, run by Beth Israel Deaconess Medical Center at 1 site in United States.
Trial summary
Mania is a core symptom of bipolar disorder involving periods of euphoria. Decreased inhibitory control, increased risk-taking behaviors, and aberrant reward processing are some of the more recognized symptoms of bipolar disorder and are included in the diagnostic criteria for mania. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar Disorder, Schizo Affective Disorder
- What is being tested?
- High-Definition Transcranial Electrical-Current Stimulation, High-Definition Transcranial Alternate-Current Stimulation and High-Definition Personalized Beta-Gamma Electrical Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Dec 2022to 1 Jun 2025
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18-65 years of age
- Proficient in English
- Able to give informed consent
- Meet diagnostic criteria for bipolar disorder or schizoaffective disorder, bipolar type as verified by the SCID
- History of mania ( >1 lifetime episode)
- Experiencing mild to moderate symptoms of mania
- No changes to mood stabilizing medications for a period of 2 weeks prior to participation
- Has not recently participated in tES/TMS treatments
Who cannot join
- Substance abuse or dependence (w/in past 6 months)
- Those who are pregnant/breastfeeding
- History of head injury with > 15 minutes of loss of consciousness/mal sequelae
- DSM-V intellectual disability
- Having a non-removable ferromagnetic metal within the body (particularly in the head)
- History of seizures
Trial locations and contacts
1 site in 1 country.
United States1 site
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Mania is a core symptom of bipolar disorder involving periods of euphoria. Decreased inhibitory control, increased risk-taking behaviors, and aberrant reward processing are some of the more recognized symptoms of bipolar disorder and are included in the diagnostic criteria for mania. Current drug therapies for mania are frequently intolerable, ineffective, and carry significant risk for side effects. Presently there are no neurobiologically informed therapies that treat or prevent mania. However, using a newly validated technique termed lesion network mapping, researchers demonstrated that focal brain lesions having a causal role in the development of mania in people without a psychiatric history can occur in different brain locations, such as the right orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex (DLPFC), and right inferior temporal gyrus (ITG). This lesion network evidence converges with existing cross-sectional and longitudinal observations in bipolar mania that have identified specific disruptions in network communication between the amygdala and ventro-lateral prefrontal cortex. The OFC is associated with inhibitory control, risk-taking behavior, and reward learning which are major components of bipolar mania. Thus, the association between OFC with mania symptoms, inhibitory control, risk-taking behavior, and reward processing suggests that this region could be targeted using non-invasive brain stimulation.
Read the detailed description
Mania is a core symptom of bipolar disorder involving periods of euphoria, delusions, and overactivity. Mania occurs in multiple medical and psychiatric illnesses and can be refractory to existing treatments. Two recent studies using brain lesion mapping of psychiatrically healthy individuals presenting with mania identified causal locations in the brain, including the orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), and inferior temporal gyrus (ITG), that were associated with new onset mania symptoms. Moreover, these identified brain regions have also been implicated in bipolar mania with specific disruption in network communication between the amygdala and ventro-lateral prefrontal cortex. The OFC is of particular interest because it is a brain structure that is associated with inhibitory control, risk-taking behavior and reward, which are major behavioral components of mania. Thus, the association between OFC with mania symptoms, inhibitory control, risk-taking behavior and reward suggests that this region could be targeted using noninvasive brain stimulation. While several studies have non-invasively targeted the DLPFC for mania, no study to date has non-invasively stimulated the OFC with either transcranial direct current stimulation (tDCS) or alternating current (tACS) in bipolar disorder and examined its effects on mania, inhibitory control, or risk-taking behavior. However, a study in healthy volunteers showed that cathodal stimulation to the OFC enhanced inhibitory control and decreased risk-taking behavior. Recently, researches have showed that targeting the OFC with tACS, personalized to the individual's intrinsic beta-gamma frequency of the reward network, that individuals showed rapid, reversible, frequency-specific modulation of reward-guided choice behavior and learning. Here we aim to answer the question of whether noninvasive brain stimulation when optimally targeted and personalized to an individual's beta-gamma frequency to the OFC can improve emotional cognitive processing and mania symptoms compared to tDCS or sham targeting. The knowledge gained from this study will provide a marker for clinical response and allow personalized treatment for patients with bipolar disorder.
- Conditions
- Bipolar Disorder, Schizo Affective Disorder
- Being tested
- High-Definition Transcranial Electrical-Current Stimulation, High-Definition Transcranial Alternate-Current Stimulation, High-Definition Personalized Beta-Gamma Electrical Stimulation
- Keywords
- Brain Stimulation, Mania
- Medical subject headings
- Bipolar Disorder, Psychotic Disorders, Mania
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-Definition Transcranial Electrical-Current StimulationDevice
Also called Soterix Medical, GTEN 200
Non-frequency dependent transcranial electrical stimulation condition for 5 days of twice a day treatment
High-Definition Transcranial Alternate-Current StimulationDevice
Also called Soterix Medical, GTEN 200
Active-control stimulation condition will target alpha (10 Hz) for 5 days of twice a day treatment
High-Definition Personalized Beta-Gamma Electrical StimulationDevice
Also called Soterix Medical, GTEN 200
Personalized beta-gamma electrical stimulation for 5 days of twice a day treatment
| Study group | Role | What they receive |
|---|---|---|
| HD-tDCS | Active comparator | HD-tDCS; Two, twenty-minute sessions of tDCS to the OFC for 5 days (10 total sessions) Receives: Device: High-Definition Transcranial Electrical-Current Stimulation |
| HD-tACS (alpha, 10 Hz) | Active comparator | 10 Hz HD-tACS; Two, twenty-minute sessions of tACS to the OFC for 5 days (10 total sessions). Receives: Device: High-Definition Transcranial Alternate-Current Stimulation |
| Personalized Beta-Gamma HD-tACS | Active comparator | Personalized HD-tACS; Two, twenty-minute sessions of tACS to the OFC for 5 days (10 total sessions). Receives: Device: High-Definition Personalized Beta-Gamma Electrical Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Young Mania Rating Scale (YMRS)
Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms
Measured: Change from baseline to 5 Day follow-up
Young Mania Rating Scale (YMRS)
Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms
Measured: Change from baseline to 1-month follow-up
Young Mania Rating Scale (YMRS)
Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms
Measured: Change from baseline to 3-month follow-up
Altman Self-Rating Mania Scale (ASRM)
The ASRM is a 5-item self rating mania scale, assessing the presence and severity of manic symptoms. The scores for all five items are added together, resulting in a total score that can range from 0 to 20. A score of 6 or higher indicates a high probability of a manic or hypomanic condition.
Measured: Change from baseline to 5 Day follow-up
Altman Self-Rating Mania Scale (ASRM)
The ASRM is a 5-item self rating mania scale, assessing the presence and severity of manic symptoms. The scores for all five items are added together, resulting in a total score that can range from 0 to 20. A score of 6 or higher indicates a high probability of a manic or hypomanic condition.
Measured: Change from baseline to 1-month follow-up
Altman Self-Rating Mania Scale (ASRM)
The ASRM is a 5-item self rating mania scale, assessing the presence and severity of manic symptoms. The scores for all five items are added together, resulting in a total score that can range from 0 to 20. A score of 6 or higher indicates a high probability of a manic or hypomanic condition.
Measured: Change from baseline to 3-month follow-up
Psychiatric Hospitalizations for Mania Post Study Entry
Psychiatric hospitalization for mania. Count of hospitalizations from baseline to end of study period assessed at Day 5, 1 Month \& 3 Month.
Measured: Cumulative count of hospitalizations for mania from baseline to end of study
Secondary outcomes (30)
Balloon Analogue Risk Task (BART)
The BART is a computerized task the measures risk-taking behavior. Participants are tasked with inflating the virtual balloon. The number of pumps a participant chooses to make on each balloon is used as a measure of their risk-taking behavior. More pumps generally indicate a higher tolerance for risk. The balloon bursts at a given point if the participant overfills it. Number of popped balloons reported for a given trial.
Measured: Change from baseline to 5 Day follow-up
Balloon Analogue Risk Task (BART)
The BART is a computerized task the measures risk-taking behavior. Participants are tasked with inflating the virtual balloon. The number of pumps a participant chooses to make on each balloon is used as a measure of their risk-taking behavior. More pumps generally indicate a higher tolerance for risk. The balloon bursts at a given point if the participant overfills it. Number of popped balloons reported for a given trial.
Measured: Change from baseline to 1-month follow-up
Balloon Analogue Risk Task (BART)
The BART is a computerized task the measures risk-taking behavior. Participants are tasked with inflating the virtual balloon. The number of pumps a participant chooses to make on each balloon is used as a measure of their risk-taking behavior. More pumps generally indicate a higher tolerance for risk. The balloon bursts at a given point if the participant overfills it. Number of popped balloons reported for a given trial.
Measured: Change from baseline to 3-month follow-up
The Go/No Go Task
The Go/No Go Task is a computerized task that measures impulsiveness. Participants presented with Go (to respond) and no Go (when not to respond) instructions. Two trials are performed. The first trial consist of two distinct auditory stimuli (both Go stimuli) where the participant is asked to respond with a different number of mouse clicks to the stimuli respectively. The second trial, has a no Go stimuli (where the participant is suppose to withhold a response) and a go stimuli. Reaction time for correct trials only for the entire task are reported in milliseconds.
Measured: Change from baseline to 5 Day follow-up
The Go/No Go Task
The Go/No Go Task is a computerized task that measures impulsiveness. Participants presented with Go (to respond) and no Go (when not to respond) instructions. Two trials are performed. The first trial consist of two distinct auditory stimuli (both Go stimuli) where the participant is asked to respond with a different number of mouse clicks to the stimuli respectively. The second trial, has a no Go stimuli (where the participant is suppose to withhold a response) and a go stimuli. Reaction time for correct trials only for the entire task are reported in milliseconds.
Measured: Change from baseline to 1-month follow-up
The Go/No Go Task
The Go/No Go Task is a computerized task that measures impulsiveness. Participants presented with Go (to respond) and no Go (when not to respond) instructions. Two trials are performed. The first trial consist of two distinct auditory stimuli (both Go stimuli) where the participant is asked to respond with a different number of mouse clicks to the stimuli respectively. The second trial, has a no Go stimuli (where the participant is suppose to withhold a response) and a go stimuli. Reaction time for correct trials only for the entire task are reported in milliseconds.
Measured: Change from baseline to 3-month follow-up
Electroencephalography (EEG) Resting State
Measuring neural activity at rest consisting of 5 minutes of eyes-open resting-state EEG (rsEEG) was recorded. Fast Fourier transformations were conducted on data, resulting in 4 frequency bands: delta/theta, alpha, beta, and gamma.
Measured: Change from baseline to 5 Day follow-up
Electroencephalography (EEG) Resting State
Measuring neural activity at rest consisting of 5 minutes of eyes-open resting-state EEG (rsEEG) was recorded. Fast Fourier transformations were conducted on data, resulting in 4 frequency bands: delta/theta, alpha, beta, and gamma.
Measured: Change from baseline to 1-month follow-up
Electroencephalography (EEG) Resting State
Measuring neural activity at rest consisting of 5 minutes of eyes-open resting-state EEG (rsEEG) was recorded. Fast Fourier transformations were conducted on data, resulting in 4 frequency bands: delta/theta, alpha, beta, and gamma.
Measured: Change from baseline to 3-month follow-up
Reinforcement Learning Task
The reinforcement learning task is a monetary based learning tasks that included reward and punishment trails. The task presents multiple trials of stimuli where the participant chooses 1 of 2 stimuli presented at a time (one of which is associated with punishment represented by loss of monetary reward while the other is associated with gain of monetary reward). EEG is record during the task and signal is captured during the participants choose and the feedback received. Reported is the peak beta/gamma range response derived from the EEG during reward feedback. This measurement is used from the baseline assessment to inform the personalized beta-gamma range stimulation for the Personalized Beta-Gamma tACS group.
Measured: Change from baseline to 5 Day follow-up
Reinforcement Learning Task
The reinforcement learning task is a monetary based learning tasks that included reward and punishment trails. The task presents multiple trials of stimuli where the participant chooses 1 of 2 stimuli presented at a time (one of which is associated with punishment represented by loss of monetary reward while the other is associated with gain of monetary reward). EEG is record during the task and signal is captured during the participants choose and the feedback received. Reported is the peak beta/gamma range response derived from the EEG during reward feedback. This measurement is used from the baseline assessment to inform the personalized beta-gamma range stimulation for the Personalized Beta-Gamma tACS group.
Measured: Change from baseline to 1-month follow-up
Reinforcement Learning Task
The reinforcement learning task is a monetary based learning tasks that included reward and punishment trails. The task presents multiple trials of stimuli where the participant chooses 1 of 2 stimuli presented at a time (one of which is associated with punishment represented by loss of monetary reward while the other is associated with gain of monetary reward). EEG is record during the task and signal is captured during the participants choose and the feedback received. Reported is the peak beta/gamma range response derived from the EEG during reward feedback. This measurement is used from the baseline assessment to inform the personalized beta-gamma range stimulation for the Personalized Beta-Gamma tACS group.
Measured: Change from baseline to 3-month follow-up
Social Functioning Scale (SFS)
The SFS a self-report questionnaire initially designed for people diagnosed with Schizophrenia; consists of 79 items designed to reflect the social skills and performances in different areas of life. Subscores are summed together for a total score. Total score of SFS ranges between 0-223 points. Higher scores mean better social functioning.
Measured: Change from baseline to 5 Day follow-up
Social Functioning Scale (SFS)
The SFS a self-report questionnaire initially designed for people diagnosed with Schizophrenia; consists of 79 items designed to reflect the social skills and performances in different areas of life. Subscores are summed together for a total score. Total score of SFS ranges between 0-223 points. Higher scores mean better social functioning.
Measured: Change from baseline to 1-month follow-up
Social Functioning Scale (SFS)
The SFS a self-report questionnaire initially designed for people diagnosed with Schizophrenia; consists of 79 items designed to reflect the social skills and performances in different areas of life. Subscores are summed together for a total score. Total score of SFS ranges between 0-223 points. Higher scores mean better social functioning.
Measured: Change from baseline to 3-month follow-up
Global Assessment of Functioning (GAF)
The GAF measures how symptoms affect individuals day-to-day life; scored from 0 to 100
Measured: Change from baseline to 5 Day follow-up
Global Assessment of Functioning (GAF)
The GAF measures how symptoms affect individuals day-to-day life; scored from 0 to 100
Measured: Change from baseline to 1-month follow-up
Global Assessment of Functioning (GAF)
The GAF measures how symptoms affect individuals day-to-day life; scored from 0 to 100
Measured: Change from baseline to 3-month follow-up
Positive and Negative Syndrome Scale (PANSS)
30 items included in the PANSS measuring positive, negative and general symptoms; 7 related to positive symptoms, 7 for negative symptoms, and 16 for general psychopathology Scale. Ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale. Scores summed for Total Score on scale (30 to 210). Higher scores mean worse clinical symptoms. Total score reported.
Measured: Change from baseline to 5 Day follow-up
Positive and Negative Syndrome Scale (PANSS)
30 items included in the PANSS measuring positive, negative and general symptoms; 7 related to positive symptoms, 7 for negative symptoms, and 16 for general psychopathology Scale. Ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale. Scores summed for Total Score on scale (30 to 210). Higher scores mean worse clinical symptoms. Total score reported.
Measured: Change from baseline to 1-month follow-up
Positive and Negative Syndrome Scale (PANSS)
30 items included in the PANSS measuring positive, negative and general symptoms; 7 related to positive symptoms, 7 for negative symptoms, and 16 for general psychopathology Scale. Ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale. Scores summed for Total Score on scale (30 to 210). Higher scores mean worse clinical symptoms. Total score reported.
Measured: Change from baseline to 3-month follow-up
Montgomery-Åsberg Depression Rating Scale (MADRS)
The MADRS is designed to measure depression and severity of symptoms; 0 to 6 indicates no depression, 7 to 19 indicates mild depression, 20 to 34 indicates moderate depression, 35 and greater indicates severe depression. Total score reported (0 to 60).
Measured: Change from baseline to 5 Day follow-up
Montgomery-Åsberg Depression Rating Scale (MADRS)
The MADRS is designed to measure depression and severity of symptoms; 0 to 6 indicates no depression, 7 to 19 indicates mild depression, 20 to 34 indicates moderate depression, 35 and greater indicates severe depression. Total score reported (0 to 60).
Measured: Change from baseline to 1-month follow-up
Montgomery-Åsberg Depression Rating Scale (MADRS)
The MADRS is designed to measure depression and severity of symptoms; 0 to 6 indicates no depression, 7 to 19 indicates mild depression, 20 to 34 indicates moderate depression, 35 and greater indicates severe depression. Total score reported (0 to 60).
Measured: Change from baseline to 3-month follow-up
Barratt Impulsiveness Scale-11 (BIS-11)
The BIS-11 is designed to assess the personality/behavioral impulsiveness. The BIS-11 has 30 items and is scored appropriately. Scored to yield a total score, three second-order factors, and six first-order factors. Each question has a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). Higher scores mean more impulsive behavior. Total score reported (30-120).
Measured: Change from baseline to 5 Day follow-up
Barratt Impulsiveness Scale-11 (BIS-11)
The BIS-11 is designed to assess the personality/behavioral impulsiveness. The BIS-11 has 30 items and is scored appropriately. Scored to yield a total score, three second-order factors, and six first-order factors. Each question has a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). Higher scores mean more impulsive behavior. Total score reported (30-120).
Measured: Change from baseline to 1-month follow-up
Barratt Impulsiveness Scale-11 (BIS-11)
The BIS-11 is designed to assess the personality/behavioral impulsiveness. The BIS-11 has 30 items and is scored appropriately. Scored to yield a total score, three second-order factors, and six first-order factors. Each question has a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). Higher scores mean more impulsive behavior. Total score reported (30-120).
Measured: Change from baseline to 3-month follow-up
Brief Assessment of Cognition (BACS)
The BACS is designed to assess several domains of cognition; Verbal Memory; Processing Speed; Working Memory; Verbal Fluency; Motor Function; Executive Functioning. Higher scores indicate better cognitive functioning. Total score reported after being transformed into z score based on normative scoring provide by test makers.
Measured: Change from baseline to 5 Day follow-up
Brief Assessment of Cognition (BACS)
The BACS is designed to assess several domains of cognition; Verbal Memory; Processing Speed; Working Memory; Verbal Fluency; Motor Function; Executive Functioning. Higher scores indicate better cognitive functioning. Total score reported after being transformed into z score based on normative scoring provide by test makers.
Measured: Change from baseline to 1-month follow-up
Brief Assessment of Cognition (BACS)
The BACS is designed to assess several domains of cognition; Verbal Memory; Processing Speed; Working Memory; Verbal Fluency; Motor Function; Executive Functioning. Higher scores indicate better cognitive functioning. Total score reported after being transformed into z score based on normative scoring provide by test makers.
Measured: Change from baseline to 3-month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2022
- Study start16 Dec 2022
- Primary completion1 Jun 2025
- Study completion1 Jun 2025
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.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paulo Lizano, Beth Israel Deaconess Medical Center
- Investigators
- Paulo Lizano, MD,PhD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05445466
- Sponsor's protocol ID
- 2022P000295
- Status last verified
- Oct 2025
- First submitted
- 17 Jun 2022
- Last updated
- 6 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Causal Lesion Network Guided Treatment of Bipolar Mania With Transcranial Electrical Stimulation
- ClinicalTrials.gov ID
- NCT05445466
- Acronym / sponsor ID
- 2022P000295
- Conditions
- Bipolar Disorder, Schizo Affective Disorder
- Keywords
- Brain Stimulation, Mania
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Study start
- 16 Dec 2022 (actual)
- Primary completion
- 1 Jun 2025 (actual)
- Study completion
- 1 Jun 2025 (actual)
- First posted
- 6 Jul 2022 (actual)
- Results
- Posted 6 Nov 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Mania is a core symptom of bipolar disorder involving periods of euphoria. Decreased inhibitory control, increased risk-taking behaviors, and aberrant reward processing are some of the more recognized symptoms of bipolar disorder and are included in the diagnostic criteria for mania. Current drug therapies for mania are frequently intolerable, ineffective, and carry significant risk for side effects. Presently there are no neurobiologically informed therapies that treat or prevent mania. However, using a newly validated technique termed lesion network mapping, researchers demonstrated that focal brain lesions having a causal role in the development of mania in people without a psychiatric history can occur in different brain locations, such as the right orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex (DLPFC), and right inferior temporal gyrus (ITG). This lesion network evidence converges with existing cross-sectional and longitudinal observations in bipolar mania that have identified specific disruptions in network communication between the amygdala and ventro-lateral prefrontal cortex. The OFC is associated with inhibitory control, risk-taking behavior, and reward learning which are major components of bipolar mania. Thus, the association between OFC with mania symptoms, inhibitory control, risk-taking behavior, and reward processing suggests that this region could be targeted using non-invasive brain stimulation.
Detailed description
Mania is a core symptom of bipolar disorder involving periods of euphoria, delusions, and overactivity. Mania occurs in multiple medical and psychiatric illnesses and can be refractory to existing treatments. Two recent studies using brain lesion mapping of psychiatrically healthy individuals presenting with mania identified causal locations in the brain, including the orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), and inferior temporal gyrus (ITG), that were associated with new onset mania symptoms. Moreover, these identified brain regions have also been implicated in bipolar mania with specific disruption in network communication between the amygdala and ventro-lateral prefrontal cortex. The OFC is of particular interest because it is a brain structure that is associated with inhibitory control, risk-taking behavior and reward, which are major behavioral components of mania. Thus, the association between OFC with mania symptoms, inhibitory control, risk-taking behavior and reward suggests that this region could be targeted using noninvasive brain stimulation. While several studies have non-invasively targeted the DLPFC for mania, no study to date has non-invasively stimulated the OFC with either transcranial direct current stimulation (tDCS) or alternating current (tACS) in bipolar disorder and examined its effects on mania, inhibitory control, or risk-taking behavior. However, a study in healthy volunteers showed that cathodal stimulation to the OFC enhanced inhibitory control and decreased risk-taking behavior. Recently, researches have showed that targeting the OFC with tACS, personalized to the individual's intrinsic beta-gamma frequency of the reward network, that individuals showed rapid, reversible, frequency-specific modulation of reward-guided choice behavior and learning. Here we aim to answer the question of whether noninvasive brain stimulation when optimally targeted and personalized to an individual's beta-gamma frequency to the OFC can improve emotional cognitive processing and mania symptoms compared to tDCS or sham targeting. The knowledge gained from this study will provide a marker for clinical response and allow personalized treatment for patients with bipolar disorder.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| HD-tDCS | Active comparator | Device: High-Definition Transcranial Electrical-Current StimulationHD-tDCS; Two, twenty-minute sessions of tDCS to the OFC for 5 days (10 total sessions) |
| HD-tACS (alpha, 10 Hz) | Active comparator | Device: High-Definition Transcranial Alternate-Current Stimulation10 Hz HD-tACS; Two, twenty-minute sessions of tACS to the OFC for 5 days (10 total sessions). |
| Personalized Beta-Gamma HD-tACS | Active comparator | Device: High-Definition Personalized Beta-Gamma Electrical StimulationPersonalized HD-tACS; Two, twenty-minute sessions of tACS to the OFC for 5 days (10 total sessions). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Aged 18-65 years of age
- Proficient in English
- Able to give informed consent
- Meet diagnostic criteria for bipolar disorder or schizoaffective disorder, bipolar type as verified by the SCID
- History of mania ( >1 lifetime episode)
Key exclusion criteria (6 listed)
- Substance abuse or dependence (w/in past 6 months)
- Those who are pregnant/breastfeeding
- History of head injury with > 15 minutes of loss of consciousness/mal sequelae
- DSM-V intellectual disability
- Having a non-removable ferromagnetic metal within the body (particularly in the head)
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 |
|---|---|---|
| High-Definition Transcranial Electrical-Current StimulationAlso: Soterix Medical, GTEN 200Non-frequency dependent transcranial electrical stimulation condition for 5 days of twice a day treatment | Device | HD-tDCS |
| High-Definition Transcranial Alternate-Current StimulationAlso: Soterix Medical, GTEN 200Active-control stimulation condition will target alpha (10 Hz) for 5 days of twice a day treatment | Device | HD-tACS (alpha, 10 Hz) |
| High-Definition Personalized Beta-Gamma Electrical StimulationAlso: Soterix Medical, GTEN 200Personalized beta-gamma electrical stimulation for 5 days of twice a day treatment | Device | Personalized Beta-Gamma HD-tACS |
Primary outcome
Young Mania Rating Scale (YMRS)
Time frame: Change from baseline to 5 Day follow-up
Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms
Young Mania Rating Scale (YMRS)
Time frame: Change from baseline to 1-month follow-up
Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms
Young Mania Rating Scale (YMRS)
Time frame: Change from baseline to 3-month follow-up
Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms
Altman Self-Rating Mania Scale (ASRM)
Time frame: Change from baseline to 5 Day follow-up
The ASRM is a 5-item self rating mania scale, assessing the presence and severity of manic symptoms. The scores for all five items are added together, resulting in a total score that can range from 0 to 20. A score of 6 or higher indicates a high probability of a manic or hypomanic condition.
Altman Self-Rating Mania Scale (ASRM)
Time frame: Change from baseline to 1-month follow-up
The ASRM is a 5-item self rating mania scale, assessing the presence and severity of manic symptoms. The scores for all five items are added together, resulting in a total score that can range from 0 to 20. A score of 6 or higher indicates a high probability of a manic or hypomanic condition.
Altman Self-Rating Mania Scale (ASRM)
Time frame: Change from baseline to 3-month follow-up
The ASRM is a 5-item self rating mania scale, assessing the presence and severity of manic symptoms. The scores for all five items are added together, resulting in a total score that can range from 0 to 20. A score of 6 or higher indicates a high probability of a manic or hypomanic condition.
Psychiatric Hospitalizations for Mania Post Study Entry
Time frame: Cumulative count of hospitalizations for mania from baseline to end of study
Psychiatric hospitalization for mania. Count of hospitalizations from baseline to end of study period assessed at Day 5, 1 Month \& 3 Month.
30 secondary outcomes
Balloon Analogue Risk Task (BART)
Time frame: Change from baseline to 5 Day follow-up
Balloon Analogue Risk Task (BART)
Time frame: Change from baseline to 1-month follow-up
Balloon Analogue Risk Task (BART)
Time frame: Change from baseline to 3-month follow-up
The Go/No Go Task
Time frame: Change from baseline to 5 Day follow-up
The Go/No Go Task
Time frame: Change from baseline to 1-month follow-up
The Go/No Go Task
Time frame: Change from baseline to 3-month follow-up
Electroencephalography (EEG) Resting State
Time frame: Change from baseline to 5 Day follow-up
Electroencephalography (EEG) Resting State
Time frame: Change from baseline to 1-month follow-up
Electroencephalography (EEG) Resting State
Time frame: Change from baseline to 3-month follow-up
Reinforcement Learning Task
Time frame: Change from baseline to 5 Day follow-up
Reinforcement Learning Task
Time frame: Change from baseline to 1-month follow-up
Reinforcement Learning Task
Time frame: Change from baseline to 3-month follow-up
Social Functioning Scale (SFS)
Time frame: Change from baseline to 5 Day follow-up
Social Functioning Scale (SFS)
Time frame: Change from baseline to 1-month follow-up
Social Functioning Scale (SFS)
Time frame: Change from baseline to 3-month follow-up
Global Assessment of Functioning (GAF)
Time frame: Change from baseline to 5 Day follow-up
Global Assessment of Functioning (GAF)
Time frame: Change from baseline to 1-month follow-up
Global Assessment of Functioning (GAF)
Time frame: Change from baseline to 3-month follow-up
Positive and Negative Syndrome Scale (PANSS)
Time frame: Change from baseline to 5 Day follow-up
Positive and Negative Syndrome Scale (PANSS)
Time frame: Change from baseline to 1-month follow-up
Positive and Negative Syndrome Scale (PANSS)
Time frame: Change from baseline to 3-month follow-up
Montgomery-Åsberg Depression Rating Scale (MADRS)
Time frame: Change from baseline to 5 Day follow-up
Montgomery-Åsberg Depression Rating Scale (MADRS)
Time frame: Change from baseline to 1-month follow-up
Montgomery-Åsberg Depression Rating Scale (MADRS)
Time frame: Change from baseline to 3-month follow-up
Barratt Impulsiveness Scale-11 (BIS-11)
Time frame: Change from baseline to 5 Day follow-up
Barratt Impulsiveness Scale-11 (BIS-11)
Time frame: Change from baseline to 1-month follow-up
Barratt Impulsiveness Scale-11 (BIS-11)
Time frame: Change from baseline to 3-month follow-up
Brief Assessment of Cognition (BACS)
Time frame: Change from baseline to 5 Day follow-up
Brief Assessment of Cognition (BACS)
Time frame: Change from baseline to 1-month follow-up
Brief Assessment of Cognition (BACS)
Time frame: Change from baseline to 3-month follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Paulo Lizano, MD,PhD principal investigator
Beth Israel Deaconess Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High-Definition Transcranial Electrical-Current Stimulation, High-Definition Transcranial Alternate-Current Stimulation and High-Definition Personalized Beta-Gamma Electrical Stimulation in people with Bipolar Disorder and Schizo Affective Disorder, run by Beth Israel Deaconess Medical Center 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 8 inclusion and 6 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 6 Nov 2025. 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 6 Nov 2025). 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?
Young Mania Rating Scale (YMRS) (time frame: Change from baseline to 5 Day follow-up). 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?
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 6 Nov 2025.