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NCT05445466

Causal Lesion Network Guided Treatment of Bipolar Mania With Transcranial Electrical Stimulation

Completed NA Results posted Last updated 6 November 2025
What this trial tests

NA trial testing High-Definition Transcranial Electrical-Current Stimulation in Bipolar Disorder in 14 participants. Completed in 1 June 2025.

Timeline
16 December 2022
Primary endpoint
1 June 2025
1 June 2025

Quick facts

Lead sponsorBeth Israel Deaconess Medical Center
PhaseNA
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment14
Start date16 December 2022
Primary completion1 June 2025
Estimated completion1 June 2025
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Beth Israel Deaconess Medical Center

Who can join

Adults 18 to 65, any sex, with Bipolar Disorder or Schizo Affective Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Young Mania Rating Scale (YMRS) Primary · 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

Baseline
GroupValue95% CI
HD-tDCS5.50.5 – 6
HD-tACS (Alpha, 10 Hz)11.89.575 – 13.25
Personalized Beta-Gamma tACS7.55.5 – 8
Day 5
GroupValue95% CI
HD-tDCS32 – 3.5
HD-tACS (Alpha, 10 Hz)84.75 – 11.125
Personalized Beta-Gamma tACS31.5 – 13
Young Mania Rating Scale (YMRS) Primary · 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

Baseline
GroupValue95% CI
HD-tDCS5.50.5 – 6
HD-tACS (Alpha, 10 Hz)11.89.575 – 13.25
Personalized Beta-Gamma tACS7.55.5 – 8
1 Month
GroupValue95% CI
HD-tDCS1.51.5 – 4
HD-tACS (Alpha, 10 Hz)118 – 14.25
Personalized Beta-Gamma tACS41.5 – 5.5
Young Mania Rating Scale (YMRS) Primary · 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

Baseline
GroupValue95% CI
HD-tDCS5.50.5 – 6
HD-tACS (Alpha, 10 Hz)11.89.575 – 13.25
Personalized Beta-Gamma tACS7.55.5 – 8
3 Month
GroupValue95% CI
HD-tDCS2.61.5 – 3.5
HD-tACS (Alpha, 10 Hz)7.55 – 9.625
Personalized Beta-Gamma tACS20.5 – 7
Altman Self-Rating Mania Scale (ASRM) Primary · 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.

Baseline
GroupValue95% CI
HD-tDCS54 – 5
HD-tACS (Alpha, 10 Hz)73.75 – 9.5
Personalized Beta-Gamma tACS33 – 5
Day 5
GroupValue95% CI
HD-tDCS74 – 8
HD-tACS (Alpha, 10 Hz)21 – 4.25
Personalized Beta-Gamma tACS55 – 7
Altman Self-Rating Mania Scale (ASRM) Primary · 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.

Baseline
GroupValue95% CI
HD-tDCS54 – 5
HD-tACS (Alpha, 10 Hz)73.75 – 9.5
Personalized Beta-Gamma tACS33 – 5
1 Month
GroupValue95% CI
HD-tDCS21 – 3
HD-tACS (Alpha, 10 Hz)42.25 – 6.25
Personalized Beta-Gamma tACS55 – 6
Altman Self-Rating Mania Scale (ASRM) Primary · 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.

Baseline
GroupValue95% CI
HD-tDCS54 – 5
HD-tACS (Alpha, 10 Hz)73.75 – 9.5
Personalized Beta-Gamma tACS33 – 5
3 Month
GroupValue95% CI
HD-tDCS22 – 4
HD-tACS (Alpha, 10 Hz)3.62.25 – 4.5
Personalized Beta-Gamma tACS65 – 7.2
Psychiatric Hospitalizations for Mania Post Study Entry Primary · 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.

Baseline
GroupValue95% CI
HD-tDCS0
HD-tACS (Alpha, 10 Hz)0
Personalized Beta-Gamma tACS0
Day 5
GroupValue95% CI
HD-tDCS0
HD-tACS (Alpha, 10 Hz)0
Personalized Beta-Gamma tACS0
1 Month
GroupValue95% CI
HD-tDCS0
HD-tACS (Alpha, 10 Hz)1
Personalized Beta-Gamma tACS0
3 Month
GroupValue95% CI
HD-tDCS0
HD-tACS (Alpha, 10 Hz)0
Personalized Beta-Gamma tACS0
Balloon Analogue Risk Task (BART) Secondary · Change from baseline to 5 Day follow-up

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.

Baseline
GroupValue95% CI
HD-tDCS1610 – 17
HD-tACS (Alpha, 10 Hz)13.511.5 – 15.25
Personalized Beta-Gamma tACS1311 – 19
Day 5
GroupValue95% CI
HD-tDCS1716 – 17
HD-tACS (Alpha, 10 Hz)13.57.75 – 20
Personalized Beta-Gamma tACS1814 – 25
Balloon Analogue Risk Task (BART) Secondary · Change from baseline to 1-month follow-up

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.

Baseline
GroupValue95% CI
HD-tDCS1610 – 17
HD-tACS (Alpha, 10 Hz)13.511.5 – 15.25
Personalized Beta-Gamma tACS1311 – 19
1 Month
GroupValue95% CI
HD-tDCS1515 – 16
HD-tACS (Alpha, 10 Hz)14.110.5 – 18.65
Personalized Beta-Gamma tACS2717 – 28
Balloon Analogue Risk Task (BART) Secondary · Change from baseline to 3-month follow-up

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.

Baseline
GroupValue95% CI
HD-tDCS1610 – 17
HD-tACS (Alpha, 10 Hz)13.511.5 – 15.25
Personalized Beta-Gamma tACS1311 – 19
3 Month
GroupValue95% CI
HD-tDCS12.211 – 14
HD-tACS (Alpha, 10 Hz)14.711.75 – 18.3
Personalized Beta-Gamma tACS1814 – 22
The Go/No Go Task Secondary · Change from baseline to 5 Day follow-up

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.

Baseline
GroupValue95% CI
HD-tDCS876.9768638675.4974359 – 923.1895604
HD-tACS (Alpha, 10 Hz)954.3716154894.5683204 – 964.7482317
Personalized Beta-Gamma tACS859.6685714857.6372796 – 1139.709184
Day 5
GroupValue95% CI
HD-tDCS927.1679389925.6649616 – 1011.031746
HD-tACS (Alpha, 10 Hz)878.0193364871.9321033 – 915.1828861
Personalized Beta-Gamma tACS917.7871795805.0713097 – 994.2446809
The Go/No Go Task Secondary · Change from baseline to 1-month follow-up

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.

Baseline
GroupValue95% CI
HD-tDCS876.9768638675.4974359 – 923.1895604
HD-tACS (Alpha, 10 Hz)954.3716154894.5683204 – 964.7482317
Personalized Beta-Gamma tACS859.6685714857.6372796 – 1139.709184
1 Month
GroupValue95% CI
HD-tDCS923.5850515914.8220551 – 939.1815857
HD-tACS (Alpha, 10 Hz)919.8986144910.2266457 – 942.2465073
Personalized Beta-Gamma tACS880.3450882838.5765306 – 993.5419847

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected up to 3 months after tES treatment (10 sessions over 1 week) was completed.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Active HD-tDCS
Serious: 0/5 (0%)
Deaths: 0/5
Active Control (Alpha, 10 Hz)
Serious: 0/4 (0%)
Deaths: 0/4
Personalized Beta-Gamma tACS
Serious: 0/5 (0%)
Deaths: 0/5
Other adverse events (1 terms — click to expand)

ReactionSystemActive HD-tDCSActive Control (Alpha, 10 …Personalized Beta-Gamma tACS
Eye Fatigue/PainEye disorders

Data from ClinicalTrials.gov NCT05445466 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Transcranial alternating current stimulation for neuropsychiatric disorders: a systematic review of treatment parameters and outcomes.
    Gholamali Nezhad F, Martin J, Tassone VK, Swiderski A, et al · · 2024 · cited 7× · PMID 39211537 · DOI 10.3389/fpsyt.2024.1419243

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